WorldWideScience

Sample records for dual roles depending

  1. TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth

    OpenAIRE

    Haricharan, Svasti; Brown, Powel

    2015-01-01

    This study fundamentally alters our understanding of how TLR4 drives breast cancer. Although TLR4 was previously considered a tumor promoter, we demonstrate a complex, TP53-dependent role for TLR4 in regulating tumor growth. TP53 is a tumor suppressor commonly inactivated across cancer types. In TP53 wild-type cancer cells, TLR4 activation causes secretion of IFN-γ into the microenvironment, resulting in induction of p21 and inhibition of cell growth. Conversely, TLR4 activation in TP53 mutan...

  2. TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth.

    Science.gov (United States)

    Haricharan, Svasti; Brown, Powel

    2015-06-23

    Breast cancer is a leading cause of cancer-related death, and it is important to understand pathways that drive the disease to devise effective therapeutic strategies. Our results show that Toll-like receptor 4 (TLR4) drives breast cancer cell growth differentially based on the presence of TP53, a tumor suppressor. TP53 is mutationally inactivated in most types of cancer and is mutated in 30-50% of diagnosed breast tumors. We demonstrate that TLR4 activation inhibits growth of TP53 wild-type cells, but promotes growth of TP53 mutant breast cancer cells by regulating proliferation. This differential effect is mediated by changes in tumor cell cytokine secretion. Whereas TLR4 activation in TP53 mutant breast cancer cells increases secretion of progrowth cytokines, TLR4 activation in TP53 wild-type breast cancer cells increases type I IFN (IFN-γ) secretion, which is both necessary and sufficient for mediating TLR4-induced growth inhibition. This study identifies a novel dichotomous role for TLR4 as a growth regulator and a modulator of tumor microenvironment in breast tumors. These results have translational relevance, demonstrating that TP53 mutant breast tumor growth can be suppressed by pharmacologic TLR4 inhibition, whereas TLR4 inhibitors may in fact promote growth of TP53 wild-type tumors. Furthermore, using data generated by The Cancer Genome Atlas consortium, we demonstrate that the effect of TP53 mutational status on TLR4 activity may extend to ovarian, colon, and lung cancers, among others, suggesting that the viability of TLR4 as a therapeutic target depends on TP53 status in many different tumor types.

  3. Comparative MD Simulations Indicate a Dual Role for Arg1323.50 in Dopamine-Dependent D2R Activation.

    Directory of Open Access Journals (Sweden)

    Ralf C Kling

    Full Text Available Residue Arg3.50 belongs to the highly conserved DRY-motif of class A GPCRs, which is located at the bottom of TM3. On the one hand, Arg3.50 has been reported to help stabilize the inactive state of GPCRs, but on the other hand has also been shown to be crucial for stabilizing active receptor conformations and mediating receptor-G protein coupling. The combined results of these studies suggest that the exact function of Arg3.50 is likely to be receptor-dependent and must be characterized independently for every GPCR. Consequently, we now present comparative molecular-dynamics simulations that use our recently described inactive-state and Gα-bound active-state homology models of the dopamine D2 receptor (D2R, which are either bound to dopamine or ligand-free, performed to identify the function of Arg1323.50 in D2R. Our results are consistent with a dynamic model of D2R activation in which Arg1323.50 adopts a dual role, both by stabilizing the inactive-state receptor conformation and enhancing dopamine-dependent D2R-G protein coupling.

  4. Low-threshold mechanoreceptors play a frequency-dependent dual role in subjective ratings of mechanical allodynia.

    Science.gov (United States)

    Löken, Line S; Duff, Eugene P; Tracey, Irene

    2017-12-01

    In the setting of injury, myelinated primary afferent fibers that normally signal light touch are thought to switch modality and instead signal pain. In the absence of injury, touch is perceived as more intense when firing rates of Aβ afferents increase. However, it is not known if varying the firing rates of Aβ afferents have any consequence to the perception of dynamic mechanical allodynia (DMA). We hypothesized that, in the setting of injury, the unpleasantness of DMA would be intensified as the firing rates of Aβ afferents increase. Using a stimulus-response protocol established in normal skin, where an increase in brush velocity results in an increase of Aβ afferent firing rates, we tested if brush velocity modulated the unpleasantness of capsaicin-induced DMA. We analyzed how changes in estimated low-threshold mechanoreceptor firing activity influenced perception and brain activity (functional MRI) of DMA. Brushing on normal skin was perceived as pleasant, but brushing on sensitized skin produced both painful and pleasant sensations. Surprisingly, there was an inverse relationship between Aβ firing rates and unpleasantness such that brush stimuli that produced low firing rates were most painful and those that elicited high firing rates were rated as pleasant. Concurrently to this, we found increased cortical activity in response to low Aβ firing rates in regions previously implicated in pain processing during brushing of sensitized skin, but not normal skin. We suggest that Aβ signals do not merely switch modality to signal pain during injury. Instead, they exert a high- and low-frequency-dependent dual role in the injured state, with respectively both pleasant and unpleasant consequences. NEW & NOTEWORTHY We suggest that Aβ signals do not simply switch modality to signal pain during injury but play a frequency-dependent and dual role in the injured state with both pleasant and unpleasant consequences. These results provide a framework to resolve the

  5. Dual Career Mothers' Role Conflict, Parental Roles, and Gender Roles.

    Science.gov (United States)

    Kinsella-Shaw, Mary; And Others

    The increasing numbers of married women working make the study of dual career mothers an important topic for the psychology of women. Such research is vital to helping women integrate careers with family life. A study was conducted to examine the extent to which gender role, number of hours worked per week, and number and age of children relate to…

  6. Dual-role plasticizer and dispersant for ceramic layers

    DEFF Research Database (Denmark)

    2016-01-01

    Thus, one aspect of the invention relates to a green ceramic layer comprising a ceramic material, a binder, and a dual-role dispersant and plasticizer, wherein said dual-role dispersant and plasticizer is an organic di- or tri-ester selected from compounds of formula (I), (II), (III) and (IV......). Another aspect of the present invention relates to a slurry for use in the manufacturing of a green ceramic layer comprising a ceramic material, a solvent, a binder, and a dual-role dispersant and plasticizer, wherein said dual role dispersant and plasticizer is an organic di- or tri- ester. Further...... aspects include uses of and methods of manufacturing said green ceramic layers....

  7. Comparing DIF methods for data with dual dependency

    Directory of Open Access Journals (Sweden)

    Ying Jin

    2016-09-01

    Full Text Available Abstract Background The current study compared four differential item functioning (DIF methods to examine their performances in terms of accounting for dual dependency (i.e., person and item clustering effects simultaneously by a simulation study, which is not sufficiently studied under the current DIF literature. The four methods compared are logistic regression accounting neither person nor item clustering effect, hierarchical logistic regression accounting for person clustering effect, the testlet model accounting for the item clustering effect, and the multilevel testlet model accounting for both person and item clustering effects. The secondary goal of the current study was to evaluate the trade-off between simple models and complex models for the accuracy of DIF detection. An empirical example analyzing the 2011 TIMSS Mathematics data was also included to demonstrate the differential performances of the four DIF methods. A number of DIF analyses have been done on the TIMSS data, and rarely had these analyses accounted for the dual dependence of the data. Results Results indicated the complex models did not outperform simple models under certain conditions, especially when DIF parameters were considered in addition to significance tests. Conclusions Results of the current study could provide supporting evidence for applied researchers in selecting the appropriate DIF methods under various conditions.

  8. Are factors related to dual-task performance in people with Parkinson's disease dependent on the type of dual task?

    Science.gov (United States)

    Strouwen, Carolien; Molenaar, Esther A L M; Keus, Samyra H J; Münks, Liesbeth; Heremans, Elke; Vandenberghe, Wim; Bloem, Bastiaan R; Nieuwboer, Alice

    2016-02-01

    Impaired dual-task performance significantly impacts upon functional mobility in people with Parkinson's disease (PD). The aim of this study was to identify determinants of dual-task performance in people with PD in three different dual tasks to assess their possible task-dependency. We recruited 121 home-dwelling patients with PD (mean age 65.93 years; mean disease duration 8.67 years) whom we subjected to regular walking (control condition) and to three dual-task conditions: walking combined with a backwards Digit Span task, an auditory Stroop task and a Mobile Phone task. We measured dual-task gait velocity using the GAITRite mat and dual-task reaction times and errors on the concurrent tasks as outcomes. Motor, cognitive and descriptive variables which correlated to dual-task performance (p task gait velocity and executive function, tested by the alternating intake test, was significantly associated with gait velocity during the Digit Span (R(2) = 0.65; p task (R(2) = 0.62; p task. Age was a surplus determinant of gait velocity while using a mobile phone. Single-task gait velocity and executive function as measured by a verbal fluency switching task were independent determinants of dual-task gait performance in people with PD. In contrast to expectation, these factors were the same across different tasks, supporting the robustness of the findings. Future study needs to determine whether these factors predict dual-task abnormalities prospectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. The Dual Role of Multinational Corporations in Cluster Evolution

    DEFF Research Database (Denmark)

    Østergaard, Christian Richter; Reinau, Kristian Hegner; Park, Eun Kyung

    2017-01-01

    This chapter shows that multinational corporations play a dual role in cluster evolution through the case of the wireless communications cluster in Northern Denmark. On the one hand, they bring in resources to the cluster, such as financial resources, technology, knowledge, innovation networks, a...

  10. Role salience of dual-career women managers

    Directory of Open Access Journals (Sweden)

    Anthony V Naidoo

    2002-10-01

    Full Text Available This study examines and contrasts the level of role participation, commitment and value expectation that dual career women invest in contending work and family roles. While the 162 married women managers were found to participate significantly more in the work role, they indicated greater commitment to and value expectation from the home and family role. A significant positive correlation between the commitment to the work role and commitment to the home and family role suggests that dual-career women may experience work and home as complimentary rather than conflicting roles. For dual-career women, work salience and career salience were found to be moderately correlated. Opsomming In hierdie studie word die vlakke van rol-deelname, rol-toegewydheid en rol-waardeverwagting wat dubbelloopbaan vroue onderskeidelik in die werk-en familierol investeer, gekonstrasteer. Terwyl dit geblyk het dat 162 getroude vroulike bestuurders beduidend meer deelneem in die werkrol, het hulle hoër toegewydheid en waardeverwagtings teenoor die huis-en-familie rol getoon. ‘n Beduidende positiewe korrelasie is gevind tussen toegewydheid tot die werksrol en toegewydheid tot die huis-en-familierol. Hierdie bevinding suggereer dat dubbelloopbaan vroue hulle werk en familie-rolle as komplimenterend eerder as konflikterend ervaar. Dit het verder geblyk dat werkrolbelangrikheid en loopbaanbelangrikheid matig gekorreleer is.

  11. Finding Balance for Dual-Role Bombers

    Science.gov (United States)

    2011-06-01

    official ground training course by completing the SAC Contingency Aircrew Training (SCAT) program, which taught ―role- and theatre -specific techniques...paired with 149 crews; there were 53 B-52Ds paired with 52 crews; and at the Thai base of U-Tapao there were 54 B-52Ds paired with 85 crews for a

  12. The dual role of external technology sourcing in technological exploration

    DEFF Research Database (Denmark)

    Vanhaverbeke, Wim; Li-Ying, Jason; van de Vrande, Vareska

    2013-01-01

    from non-partners, partners may play a role because of whom they know. That is, they inform the firm about technological opportunities beyond its corporate venturing network. The empirical analysis supports the dual role of venturing partners in facilitating the two types of explorative learning.......We refine the concept of boundary-spanning exploration, by making a distinction between explorative learning from partners and from non-partners (Partners are organizations with whom a focal firm has some kind of external venturing relations, i.e. technological alliances, corporate venturing...... capital, or M&As). These partners play a dual role: in explorative learning from partners, a firm teams up with external venturing partners to co-develop or transfer technology. Partners’ technology base (what they know) is driving explorative learning from partners. In contrast, in explorative learning...

  13. The dual role of microbes in corrosion.

    Science.gov (United States)

    Kip, Nardy; van Veen, Johannes A

    2015-03-01

    Corrosion is the result of a series of chemical, physical and (micro) biological processes leading to the deterioration of materials such as steel and stone. It is a world-wide problem with great societal and economic consequences. Current corrosion control strategies based on chemically produced products are under increasing pressure of stringent environmental regulations. Furthermore, they are rather inefficient. Therefore, there is an urgent need for environmentally friendly and sustainable corrosion control strategies. The mechanisms of microbially influenced corrosion and microbially influenced corrosion inhibition are not completely understood, because they cannot be linked to a single biochemical reaction or specific microbial species or groups. Corrosion is influenced by the complex processes of different microorganisms performing different electrochemical reactions and secreting proteins and metabolites that can have secondary effects. Information on the identity and role of microbial communities that are related to corrosion and corrosion inhibition in different materials and in different environments is scarce. As some microorganisms are able to both cause and inhibit corrosion, we pay particular interest to their potential role as corrosion-controlling agents. We show interesting interfaces in which scientists from different disciplines such as microbiology, engineering and art conservation can collaborate to find solutions to the problems caused by corrosion.

  14. The dual role of microbes in corrosion

    Science.gov (United States)

    Kip, Nardy; van Veen, Johannes A

    2015-01-01

    Corrosion is the result of a series of chemical, physical and (micro) biological processes leading to the deterioration of materials such as steel and stone. It is a world-wide problem with great societal and economic consequences. Current corrosion control strategies based on chemically produced products are under increasing pressure of stringent environmental regulations. Furthermore, they are rather inefficient. Therefore, there is an urgent need for environmentally friendly and sustainable corrosion control strategies. The mechanisms of microbially influenced corrosion and microbially influenced corrosion inhibition are not completely understood, because they cannot be linked to a single biochemical reaction or specific microbial species or groups. Corrosion is influenced by the complex processes of different microorganisms performing different electrochemical reactions and secreting proteins and metabolites that can have secondary effects. Information on the identity and role of microbial communities that are related to corrosion and corrosion inhibition in different materials and in different environments is scarce. As some microorganisms are able to both cause and inhibit corrosion, we pay particular interest to their potential role as corrosion-controlling agents. We show interesting interfaces in which scientists from different disciplines such as microbiology, engineering and art conservation can collaborate to find solutions to the problems caused by corrosion. PMID:25259571

  15. Brain activations during bimodal dual tasks depend on the nature and combination of component tasks

    Directory of Open Access Journals (Sweden)

    Emma eSalo

    2015-02-01

    Full Text Available We used functional magnetic resonance imaging to investigate brain activations during nine different dual tasks in which the participants were required to simultaneously attend to concurrent streams of spoken syllables and written letters. They performed a phonological, spatial or simple (speaker-gender or font-shade discrimination task within each modality. We expected to find activations associated specifically with dual tasking especially in the frontal and parietal cortices. However, no brain areas showed systematic dual task enhancements common for all dual tasks. Further analysis revealed that dual tasks including component tasks that were according to Baddeley’s model modality atypical, that is, the auditory spatial task or the visual phonological task, were not associated with enhanced frontal activity. In contrast, for other dual tasks, activity specifically associated with dual tasking was found in the left or bilateral frontal cortices. Enhanced activation in parietal areas, however, appeared not to be specifically associated with dual tasking per se, but rather with intermodal attention switching. We also expected effects of dual tasking in left frontal supramodal phonological processing areas when both component tasks required phonological processing and in right parietal supramodal spatial processing areas when both tasks required spatial processing. However, no such effects were found during these dual tasks compared with their component tasks performed separately. Taken together, the current results indicate that activations during dual tasks depend in a complex manner on specific demands of component tasks.

  16. Majority and minority influence: A dual role interpretation

    OpenAIRE

    de Vries, N.K.; de Dreu, C.; Gordijn, E.; Schuurman, M.

    1996-01-01

    This chapter offers an analysis of majority vs. minority influence using the Heuristic-Systematic Model of persuasion (HSM). We evaluate evidence for and against leading perspectives such as Conversion Theory. Next, research and theory is reviewed suggesting that majority vs. minority influence differentially affect the processing of persuasive arguments. A dual-role interpretation of majority and minority influence is presented. First, numerical support for discrepant messages affects the de...

  17. Abuse or dependence on cannabis and other psychiatric disorders. Madrid study on dual pathology prevalence.

    Science.gov (United States)

    Arias, Francisco; Szerman, Nestor; Vega, Pablo; Mesias, Beatriz; Basurte, Ignacio; Morant, Consuelo; Ochoa, Enriqueta; Poyo, Félix; Babin, Francisco

    2013-01-01

    Cannabis use has been associated to a wide variety of mental disorders, the possible causal role of this use in the etiology of severe mental disorders as schizophrenia or bipolar disorder standing out. Moreover, the cannabinoid system is involved in emotional regulation, so cannabis use could disturb this process and provoke anxiety and mood disorders. The main objective of this study was to analyze the cannabis addict subgroup from Madrid study of prevalence of dual disorders in community mental health and substance misuse services. The sample consisted of 837 outpatients under treatment in the mental health network or drug network of the Community of Madrid (Spain). Of these, 353 subjects had a lifetime diagnosis of cannabis abuse or dependence and 357 subjects did not have cannabis substance use disorder. We used the Mini International Neuropsychiatric Interview (MINI) to evaluate axis I mental disorders, and Personality Disorder Questionnaire to evaluate personality disorders. It was considered that 76.5% of the cannabis addicts had a current dual disorder. The most prevalent ones were mood and anxiety disorders. Of those addicted to cannabis, 51% had a personality disorder. Most of them had several substance use disorders. Cannabis abuse or dependence subjects had an earlier onset in consumption of other drugs such as alcohol, cocaine, and tobacco than addicts without cannabis abuse or dependence. The cannabis addicts also differed from the other addicts because of an association to antisocial personality disorder, bipolar disorder, psychosis and agoraphobia. The presence of these mental disorders was significantly associated to a lower age at initiation of cannabis use. Dual pathology is very high in cannabis addicts under treatment. Said consumption of cannabis, probably within a polysubstance use pattern, is associated to severe mental disorders as psychosis and bipolar disorder. An earlier age of onset in cannabis use is associated to a greater risk of

  18. Dual roles for spike signaling in cortical neural populations

    Directory of Open Access Journals (Sweden)

    Dana eBallard

    2011-06-01

    Full Text Available A prominent feature of signaling in cortical neurons is that of randomness in the action potential. The output of a typical pyramidal cell can be well fit with a Poisson model, and variations in the Poisson rate repeatedly have been shown to be correlated with stimuli. However while the rate provides a very useful characterization of neural spike data, it may not be the most fundamental description of the signaling code. Recent data showing γ frequency range multi-cell action potential correlations, together with spike timing dependent plasticity, are spurring a re-examination of the classical model, since precise timing codes imply that the generation of spikes is essentially deterministic. Could the observed Poisson randomness and timing determinism reflect two separate modes of communication, or do they somehow derive from a single process? We investigate in a timing-based model whether the apparent incompatibility between these probabilistic and deterministic observations may be resolved by examining how spikes could be used in the underlying neural circuits. The crucial component of this model draws on dual roles for spike signaling. In learning receptive fields from ensembles of inputs, spikes need to behave probabilistically, whereas for fast signaling of individual stimuli, the spikes need to behave deterministically. Our simulations show that this combination is possible if deterministic signals using γ latency coding are probabilistically routed through different members of a cortical cell population at different times. This model exhibits standard features characteristic of Poisson models such as orientation tuning post-stimulus histograms and exponential interval histograms. In addition it makes testable predictions that follow from the γ latency coding.

  19. The dual effects of nitrite on hemoglobin-dependent redox reactions.

    Science.gov (United States)

    Lu, Naihao; Chen, Chao; He, Yingjie; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

    2014-08-31

    Evidence to support the role of heme proteins-dependent reactions as major inducers of oxidative damage is increasingly present. Nitrite (NO2(-)) is one of the major end products of NO metabolism, and from the daily consumption. Although the biological significance of heme proteins/NO2(-)-mediated protein tyrosine nitration is a subject of great interest, the important roles of NO2(-) on heme proteins-dependent redox reactions have been greatly underestimated. In this study, we investigated the influence of NO2(-) on met-hemoglobin (Hb)-dependent oxidative and nitrative stress. It was found that NO2(-) effectively reduced cytotoxic ferryl intermediate back to ferric Hb in a biphasic kinetic reaction. However, the presence of NO2(-) surprisingly exerted pro-oxidant effect on Hb-H2O2-induced protein (bovine serum albumin, enolase) oxidation at low concentrations and enhanced the loss of HepG2 cell viability. In the reduction of ferryl Hb to ferric state, NO2(-) was decreased and oxidized to a nitrating agent NO2, Tyr12 and Tyr191 in enolase were subsequently nitrated. In contrast to the frequently inhibitive effect of nitrotyrosine, NO2(-)-triggered tyrosine nitration might play an important role in enolase activation. These data provided novel evidence that the dietary intake and potential therapeutic application of NO2(-) would possess anti- and pro-oxidant activities through interfering in hemoglobin-dependent redox reactions. Besides the classic role in protein tyrosine nitration, the dual effects on hemoglobin-triggered oxidative stress may provide new insights into the physiological and toxicological implications of NO2(-) with heme proteins. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Differences between craving and health-related quality of life in patients with alcohol dependence with or without dual pathology in outpatient treatment: A descriptive study.

    Science.gov (United States)

    Robles-Martínez, María; García-Carretero, Miguel Ángel; Gibert, Juan; Palma-Álvarez, Raúl Felipe; Abad, Alfonso Carlos; Sorribes, Marta; Roncero, Carlos

    2018-01-23

    Dual diagnosis is the coexistence of an addictive disorder and another mental disorder. The objective is to estimate cravings and self-reported quality of life in a sample of patients with alcoholic dependence, with or without dual pathology, who attend an outpatient treatment centre. A cross-sectional study of 112 patients (56 dual and 56 non-dual), diagnosed with alcohol dependence according to DSM-IV-TR. The presence of cravings is determined by the Multidimensional Alcohol Craving Scale and quality of life through the SF-36 Health Questionnaire. There are no statistically significant differences in cravings in either subgroup; the latter tend to refer to lower alcohol cravings than non-dual patients. The dual patients have a worse quality of life in all categories evaluated, highlighting a worse quality of life in the categories: social function, emotional role, vitality and general health. Females present a lower quality of life emphasising those of social function and emotional role. No differences were detected in relation to cravings between the 2 groups. In order to perform a correct clinical and therapeutic approach for patients with alcohol dependence, we should consider focusing on the evaluation of cravings and quality of life. In order to perform a correct clinical and therapeutic approach for patients with alcohol dependence, it is necessary to consider cravings and quality of life, since these parameters are important for the evaluation of patients with alcohol dependence. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Jealousy, Gender, Sex Roles, and Dependency.

    Science.gov (United States)

    Madden, Margaret E.; And Others

    One hundred adults ages 18 to 42 completed measures of jealousy and dependency in romantic relationships and of sex role traditionalism. Traditionalism and jealousy were correlated, as predicted, but dependency and jealousy were not. For men, but not for women, traditionalism and jealousy were positively correlated. Dependency and traditionalism…

  2. Betwixt and between: Role conflict, role ambiguity and role definition in project-based dual-leadership structures.

    Science.gov (United States)

    Ebbers, Joris J; Wijnberg, Nachoem M

    2017-11-01

    Project-based organizations in the film industry usually have a dual-leadership structure, based on a division of tasks between the dual leaders - the director and the producer - in which the former is predominantly responsible for the artistic and the latter for the commercial aspects of the film. These organizations also have a role hierarchically below and between the dual leaders: the 1st assistant director. This organizational constellation is likely to lead to role conflict and role ambiguity experienced by the person occupying that particular role. Although prior studies found negative effects of role conflict and role ambiguity, this study shows they can also have beneficial effects because they create space for defining the role expansively that, in turn, can be facilitated by the dual leaders defining their own roles more narrowly. In a more general sense, this study also shows the usefulness of analyzing the antecedents and consequences of roles, role definition, and role crafting in connection to the behavior of occupants of adjacent roles.

  3. Betwixt and between: Role conflict, role ambiguity and role definition in project-based dual-leadership structures

    Science.gov (United States)

    Ebbers, Joris J; Wijnberg, Nachoem M

    2017-01-01

    Project-based organizations in the film industry usually have a dual-leadership structure, based on a division of tasks between the dual leaders – the director and the producer – in which the former is predominantly responsible for the artistic and the latter for the commercial aspects of the film. These organizations also have a role hierarchically below and between the dual leaders: the 1st assistant director. This organizational constellation is likely to lead to role conflict and role ambiguity experienced by the person occupying that particular role. Although prior studies found negative effects of role conflict and role ambiguity, this study shows they can also have beneficial effects because they create space for defining the role expansively that, in turn, can be facilitated by the dual leaders defining their own roles more narrowly. In a more general sense, this study also shows the usefulness of analyzing the antecedents and consequences of roles, role definition, and role crafting in connection to the behavior of occupants of adjacent roles. PMID:29081536

  4. Psychopathological profile and prevalence of dual pathology on patients with alcoholic dependence undergoing outpatient treatment.

    Science.gov (United States)

    García-Carretero, Miguel A; Novalbos-Ruiz, José P; Robles-Martínez, María; Jordán-Quintero, María A; O'Ferrall-González, Cristina

    2017-01-01

    Assess the prevalence of dual pathology in patients with alcohol dependence and describe the psychopathological profile of mental disorders, impulsiveness, ADHD presence and craving. It is a cross-sectional study about dual pathology, carried out on 102 patients undergoing outpatient treatment. The presence of dual pathology is established by means of the MINI-5 interview and the MCMI-III test; DSM-IV being used as the alcohol abuse criteria. Impulsiveness, ADHD presence, craving and quality of life were measured through SIS, ASRSv1, MACS and SF-36. The prevalence of dual pathology ranges from 45.1% to 80.4% according to MCMI-III and MINI-5, respectively. The most frequent pathologies are current major depressive episodes, followed by current generalized anxiety disorders, suicide risk and current dysthymia disorders; 73.2% of dual patients present a moderate and intense global score according to MACS, 56.1% got a meaningful score in impulsiveness according to SIS and 41.5% has highly consistent symptoms with ADHD. As regards quality of life, 53.7% of the sample had bad mental health. In the case of dual patients consuming other substances, 30% had a history of bipolar disorders and 10% had a high suicide risk. The prevalence of psychiatric comorbidity in patients with alcohol dependence undergoing outpatient treatment varies depending on the detection method, MINI being the one identifying a greater number of cases. More than half of dual patients present impulsive behavior, a bad mental health state and high craving levels. Special attention should be paid to dual patients consuming other substances.

  5. The dual role of external corporate venturing in technological exploration

    DEFF Research Database (Denmark)

    Li, Ying; van de Vrande, Vareska; Vanhaverbeke, Wim

    2009-01-01

    Innovating firms can not only explore new technologies from its innovation partners, but also explore new technologies from the organizations to which the innovating firm has had no prior relationships. Prior studies have mostly focused on a firm's exploratory learning from its venturing partners...... ("exploration from partners" or "EFP"). There has been little insight on how external corporate venturing may affect the exploratory learning beyond the venturing partnerships ("exploration beyond partners" or "EBP"). We claim that prior venturing relations have a dual role: First, the innovation firm can learn...... from knowledge embedded in its partners. Second, it can also learn from through its partners about knowledge developed by other firms or organizations with whom the innovating firm had no external venturing relations before. In this paper, we are interested how external corporate venturing partnerships...

  6. Balancing dual roles in end-of-life research.

    Science.gov (United States)

    Martin, Wanda; Grey, Meredith; Webber, Terry; Robinson, Linnea; Hartt, Nancy; Cairns, Moira; Stajduhar, Kelli

    2007-01-01

    Ethical and practical issues are sure to arise from the majority of research studies done with palliative populations. Whether it is feeling opportunistic, being emotionally available, or struggling with witnessing a gap in service and needs of the participants receiving care, nurses involved in research find a way to balance both roles to meet the needs of the participants as well as the study (McIlfatrick, Sullivan, & McKenna, 2006). This paper highlights some of the practical and ethical issues that arise when frontline nurses also take on the role of research assistant for studies with palliative populations. Specifically, the authors highlight their personal experiences based on their research assistant work on a study examining family caregiver coping in end-of-life cancer care. The authors discuss the "balancing act" of taking on these dual roles and offer recommendations on how to be with and approach people when doing research at the end of life using a framework based on Swanson's Theory of Caring (1991).

  7. Dual roles and dual identities: enhancing the experience of in-service teacher training in English Further Education

    Directory of Open Access Journals (Sweden)

    Orr, Kevin

    2009-06-01

    Full Text Available In marked distinction from other sectors of education, around 90 percent of Further Education (FE staff in England are employed untrained and complete their Initial Teacher Training (ITT on a part-time in-service basis. By consequence, these staff sustain the dual role of employed teacher and teacher-trainee usually at the beginning of their career. This paper reports on a project funded by ESCalate which researched the dual roles and dual identities of employee and trainee on in-service FE teacher-training courses. It argues that the lack of a culture of pedagogical development in colleges along with the pressure for trainees to quickly cope with teaching can lead to conservative practice as expedience may be prioritised over flair. In response, the paper makes recommendations to enhance the experience and development of in-service teacher trainees.

  8. The Dual Role of HLA-G in Cancer

    Directory of Open Access Journals (Sweden)

    Nathalie Rouas-Freiss

    2014-01-01

    Full Text Available We here review the current data on the role of HLA-G in cancer based on recent findings of an unexpected antitumor activity of HLA-G in hematological malignancies. For the past decade, HLA-G has been described as a tumor-escape mechanism favoring cancer progression, and blocking strategies have been proposed to counteract it. Aside from these numerous studies on solid tumors, recent data showed that HLA-G inhibits the proliferation of malignant B cells due to the interaction between HLA-G and its receptor ILT2, which mediates negative signaling on B cell proliferation. These results led to the conjecture that, according to the malignant cell type, HLA-G should be blocked or conversely induced to counteract tumor progression. In this context, we will here present (i the dual role of HLA-G in solid and liquid tumors with special emphasis on (ii the HLA-G active structures and their related ILT2 and ILT4 receptors and (iii the current knowledge on regulatory mechanisms of HLA-G expression in tumors.

  9. Dual role of beta-carotene in combination with cigarette smoke aqueous extract on the formation of mutagenic lipid peroxidation products in lung membranes: dependence on pO2.

    Science.gov (United States)

    Palozza, P; Serini, S; Trombino, S; Lauriola, L; Ranelletti, F O; Calviello, G

    2006-12-01

    Results from some intervention trials indicated that supplemental beta-carotene enhanced lung cancer incidence and mortality in chronic smokers. The aim of this study was to verify the hypothesis that high concentrations of the carotenoid, under the pO2 present in lung (100-150 mmHg), may exert deleterious effects through a prooxidant mechanism. To test this hypothesis, we examined the interactions of beta-carotene and cigarette smoke condensate (tar) on the formation of lipid peroxidation products in rat lung microsomal membranes enriched in vitro with varying beta-carotene concentrations (from 1 to 10 nmol/mg prot) and then incubated with tar (6-25 microg/ml) under different pO2. As markers of lipid peroxidation, we evaluated the levels of conjugated dienes and malondialdehyde, possessing mutagenic and pro-carcinogenic activity. The exposure of microsomal membranes to tar induced a dose-dependent enhancement of lipid peroxidation, which progressively increased as a function of pO2. Under a low pO2 (15 mmHg), beta-carotene acted clearly as an antioxidant, inhibiting tar-induced lipid peroxidation. However, the carotenoid progressively lost its antioxidant efficiency by increasing pO2 (50-100 mmHg) and acted as a prooxidant at pO2 ranging from 100 to 760 mmHg in a dose-dependent manner. Consistent with this finding, the addition of alpha-tocopherol (25 microM) prevented the prooxidant effects of the carotenoid. beta-Carotene auto-oxidation, measured as formation of 5,6-epoxy-beta,beta-carotene, was faster at high than at low pO2 and the carotenoid was more rapidly consumed in the presence of tar. These data point out that the carotenoid may enhance cigarette smoke-induced oxidative stress and exert potential deleterious effects at the pO2 normally present in lung tissue.

  10. Dual role of betel leaf extract on thyroid function in male mice.

    Science.gov (United States)

    Panda, S; Kar, A

    1998-12-01

    The effects of betel leaf extract (0.10, 0.40, 0.80 and 2.0 g kg-1 day-1 for 15 days) on the alterations in thyroid hormone concentrations. lipid peroxidation (LPO) and on the activities of superoxide dismutase (SOD) and catalase (CAT) were investigated in male Swiss mice. Administration of betel leaf extract exhibited a dual role, depending on the different doses. While the lowest dose decreased thyroxine (T4) and increased serum triiodothyronine (T3) concentrations, reverse effects were observed at two higher doses. Higher doses also increased LPO with a concomitant decrease in SOD and CAT activities. However, with the lowest dose most of these effects were reversed. These findings suggest that betel leaf can be both stimulatory and inhibitory to thyroid function, particularly for T3 generation and lipid peroxidation in male mice, depending on the amount consumed.

  11. Cocaine abuse or dependency and other pyschiatric disorders. Madrid study on dual pathology.

    Science.gov (United States)

    Arias, Francisco; Szerman, Nestor; Vega, Pablo; Mesias, Beatriz; Basurte, Ignacio; Morant, Consuelo; Ochoa, Enriqueta; Poyo, Félix; Babin, Francisco

    2013-01-01

    The main objective of this study was to analyse the cocaine addict subgroup from the Madrid study of prevalence of dual disorders in community mental health and substance misuse services. The sample consisted of 837 outpatients from Madrid, Spain. We compared 488 subjects who had a lifetime diagnosis of cocaine abuse or dependence, and 222 subjects who did not have a cocaine substance use disorder. We used the Mini International Neuropsychiatric Interview to evaluate axis I mental disorders, and the Personality Disorder Questionnaire to evaluate personality disorders. Almost three-quarters (73.4%) of cocaine addicts had a current dual disorder. Most prevalent were mood and anxiety disorders. Almost half (49.6%) had a personality disorder. Most of them (94.9%) had other substance use disorders. Cocaine addicts did not have higher prevalence rates of dual pathology than addicts with no cocaine abuse or dependence. Cocaine addicts were associated to a diagnosis of antisocial personality disorder, agoraphobia, and post-traumatic stress disorder, and they had an early age of onset of alcohol and cannabis use. Dual pathology is no higher in cocaine addicts in treatment than in addicts who do not use cocaine, however cocaine addicts started other drugs earlier, and were associated with specific mental disorders. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  12. Static spin-dependent forces between heavy quarks in the classical approximation to dual QCD

    International Nuclear Information System (INIS)

    Baker, M.; Ball, J.S.; Zachariasen, F.

    1991-01-01

    We compute the static spin-dependent forces V S (R) (proportional to σ 1 ·σ 2 ) and V T (R) (proportional to 3σ 1 ·Rσ 2 ·R-σ 1 ·σ 2 ) between two quarks separated by R. This is done by treating the (weak) spin-dependent effects as a perturbation on the spin-independent potentials and fields computed earlier for dual QCD. What results is a definite prediction for the heavy-quark potentials which are similar to, but different in form from, those used in phenomenological treatments. Calculations of the masses and splittings of heavy-quark states using our potentials will provide a further test of the dual superconductor picture of QCD

  13. Dual gene activation and knockout screen reveals directional dependencies in genetic networks. | Office of Cancer Genomics

    Science.gov (United States)

    Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair.

  14. Local chemical potential, local hardness, and dual descriptors in temperature dependent chemical reactivity theory.

    Science.gov (United States)

    Franco-Pérez, Marco; Ayers, Paul W; Gázquez, José L; Vela, Alberto

    2017-05-31

    In this work we establish a new temperature dependent procedure within the grand canonical ensemble, to avoid the Dirac delta function exhibited by some of the second order chemical reactivity descriptors based on density functional theory, at a temperature of 0 K. Through the definition of a local chemical potential designed to integrate to the global temperature dependent electronic chemical potential, the local chemical hardness is expressed in terms of the derivative of this local chemical potential with respect to the average number of electrons. For the three-ground-states ensemble model, this local hardness contains a term that is equal to the one intuitively proposed by Meneses, Tiznado, Contreras and Fuentealba, which integrates to the global hardness given by the difference in the first ionization potential, I, and the electron affinity, A, at any temperature. However, in the present approach one finds an additional temperature-dependent term that introduces changes at the local level and integrates to zero. Additionally, a τ-hard dual descriptor and a τ-soft dual descriptor given in terms of the product of the global hardness and the global softness multiplied by the dual descriptor, respectively, are derived. Since all these reactivity indices are given by expressions composed of terms that correspond to products of the global properties multiplied by the electrophilic or nucleophilic Fukui functions, they may be useful for studying and comparing equivalent sites in different chemical environments.

  15. Management and leadership: a dual role in nursing education.

    Science.gov (United States)

    Calpin-Davies, Philomena J

    2003-01-01

    The purpose of this paper is to review the dual concepts of leadership and management in nursing education. It provides a consideration of caring as the end purpose of nursing education and argues that empowered caring makes use of professional academic credentials to form collaborative alliances that influence health care delivery. Inspiring and empowering leadership also transform educational services. In particular the key issues of investing in technology, supporting life long learning and creating a community workplace are addressed. It concludes with the suggestion that the nurse education ought to be led and managed differently.

  16. Ethical principles of informed consent: exploring nurses' dual role of care provider and researcher.

    Science.gov (United States)

    Judkins-Cohn, Tanya M; Kielwasser-Withrow, Kiersten; Owen, Melissa; Ward, Jessica

    2014-01-01

    This article describes the ethical principles of autonomy, beneficence, and justice within the nurse researcher-participant relationship as these principles relate to the informed consent process for research. Within this process, the nurse is confronted with a dual role. This article describes how nurses, who are in the dual role of care provider and researcher, can apply these ethical principles to their practice in conjunction with the American Nurses Association's code of ethics for nurses. This article also describes, as an element of ethical practice, the importance of using participant-centered quality measures to aid informed decision making of participants in research. In addition, the article provides strategies for improving the informed consent process in nursing research. Finally, case scenarios are discussed, along with the application of ethical principles within the awareness of the dual role of the nurse as care provider and researcher. Copyright 2014, SLACK Incorporated.

  17. Dual-memory processes in crack cocaine dependents: The effects of childhood neglect on recall.

    Science.gov (United States)

    Tractenberg, Saulo G; Viola, Thiago W; Gomes, Carlos F A; Wearick-Silva, Luis Eduardo; Kristensen, Christian H; Stein, Lilian M; Grassi-Oliveira, Rodrigo

    2015-01-01

    Exposure to adversities during sensitive periods of neurodevelopment is associated with the subsequent development of substance dependence and exerts harmful, long-lasting effects upon memory functioning. In this study, we investigated the relationship between childhood neglect (CN) and memory using a dual-process model that quantifies recollective and non-recollective retrieval processes in crack cocaine dependents. Eighty-four female crack cocaine-dependent inpatients who did (N = 32) or did not (N = 52) report a history of CN received multiple opportunities to study and recall a short list composed of familiar and concrete words and then received a delayed-recall test. Crack cocaine dependents with a history of CN showed worse performance on free-recall tests than did dependents without a history of CN; this finding was associated with declines in recollective retrieval (direct access) rather than non-recollective retrieval. In addition, we found no evidence of group differences in forgetting rates between immediate- and delayed-recall tests. The results support developmental models of traumatology and suggest that neglect of crack cocaine dependents in early life disrupts the adult memory processes that support the retrieval of detailed representations of events from the past.

  18. The Dual Role of Media Internalization in Adolescent Sexual Behavior.

    Science.gov (United States)

    Rousseau, Ann; Beyens, Ine; Eggermont, Steven; Vandenbosch, Laura

    2017-08-01

    Sexualizing media content is prevalent in various media types. Sexualizing media messages and portrayals emphasize unattainable body and appearance ideals as the primary components of sexual desirability. The internalization of these ideals is positively related to self-objectification and sexual body consciousness. In turn, self-objectification and sexual body consciousness affect adolescents' sexual behavior, albeit in opposing directions. While objectifying self-perceptions are linked to higher levels of sexual behavior, body consciousness during physical intimacy is linked to lower levels of sexual behavior. Based on this knowledge, the present three-wave panel study of 824 Belgian, predominant heterosexual adolescents (M age  = 15.33; SD = 1.45) proposes a dual-pathway model that investigates two different pathways through which the internalization of media ideals may impact adolescents' sexual behavior. An inhibitory pathway links media internalization to lower levels of sexual behavior through sexual body consciousness, and a supportive pathway links media internalization to higher levels of sexual behavior through self-objectification. Structural equation analyses supported the proposed dual-pathway, showing that the impact of media internalization on adolescents' sexual behavior proceeds through an inhibitory pathway and a supportive pathway. Regarding the supportive pathway, media internalization (W1) positively predicted sexual behavior (W3), through valuing appearance over competence (W2). Regarding the inhibitory pathway, media internalization (W1) positively predicted body surveillance, which, in turn, positively predicted sexual body consciousness (all W2). Sexual body consciousness (W2) is negatively related to sexual behavior (W3). From a sexual developmental perspective, these findings emphasize the importance of guiding adolescents in interpreting and processing sexualizing media messages.

  19. Balancing dual roles in self-employed women: An exploratory study

    Directory of Open Access Journals (Sweden)

    Kirsty-Lee McLellan

    2009-04-01

    Full Text Available This study is aimed at exploring how self-employed women cope in balancing their dual roles as mothers and executives. Through the elicitation of constructs by making use of Kelly’s repertory grid technique, the personal construct system of five self-employed white women in Gauteng across varying industries was established. While being successful dual earners, they still bore the primary responsibility for nurturing their families and assuring their well-being. The successful balancing of their dual roles was attributed to the following central themes, which emerged from all the participants: quality time spent with children and family, structure and planning, coping with guilt, support structures and self-reliance, and balance between work and life.

  20. The dual role of cyclin C connects stress regulated gene expression to mitochondrial dynamics

    Directory of Open Access Journals (Sweden)

    Randy Strich

    2014-09-01

    Full Text Available Following exposure to cytotoxic agents, cellular damage is first recognized by a variety of sensor mechanisms. Thenceforth, the damage signal is transduced to the nucleus to install the correct gene expression program including the induction of genes whose products either detoxify destructive compounds or repair the damage they cause. Next, the stress signal is disseminated throughout the cell to effect the appropriate changes at organelles including the mitochondria. The mitochondria represent an important signaling platform for the stress response. An initial stress response of the mitochondria is extensive fragmentation. If the damage is prodigious, the mitochondria fragment (fission and lose their outer membrane integrity leading to the release of pro-apoptotic factors necessary for programmed cell death (PCD execution. As this complex biological process contains many moving parts, it must be exquisitely coordinated as the ultimate decision is life or death. The conserved C-type cyclin plays an important role in executing this molecular Rubicon by coupling changes in gene expression to mitochondrial fission and PCD. Cyclin C, along with its cyclin dependent kinase partner Cdk8, associates with the RNA polymerase holoenzyme to regulate transcription. In particular, cyclin C-Cdk8 repress many stress responsive genes. To relieve this repression, cyclin C is destroyed in cells exposed to pro-oxidants and other stressors. However, prior to its destruction, cyclin C, but not Cdk8, is released from its nuclear anchor (Med13, translocates from the nucleus to the cytoplasm where it interacts with the fission machinery and is both necessary and sufficient to induce extensive mitochondria fragmentation. Furthermore, cytoplasmic cyclin C promotes PCD indicating that it mediates both mitochondrial fission and cell death pathways. This review will summarize the role cyclin C plays in regulating stress-responsive transcription. In addition, we will detail

  1. Uncovering a Dual Regulatory Role for Caspases During Endoplasmic Reticulum Stress-induced Cell Death.

    Science.gov (United States)

    Anania, Veronica G; Yu, Kebing; Gnad, Florian; Pferdehirt, Rebecca R; Li, Han; Ma, Taylur P; Jeon, Diana; Fortelny, Nikolaus; Forrest, William; Ashkenazi, Avi; Overall, Christopher M; Lill, Jennie R

    2016-07-01

    Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the "unfolded protein response" (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the underlying mechanisms by which they exert their effect continue to remain elusive. To understand the role caspases play during ER stress, a systems level approach integrating analysis of the transcriptome, proteome, and proteolytic substrate profile was employed. This quantitative analysis revealed transcriptional profiles for most human genes, provided information on protein abundance for 4476 proteins, and identified 445 caspase substrates. Based on these data sets many caspase substrates were shown to be downregulated at the protein level during ER stress suggesting caspase activity inhibits their cellular function. Additionally, RNA sequencing revealed a role for caspases in regulation of ER stress-induced transcriptional pathways and gene set enrichment analysis showed expression of multiple gene targets of essential transcription factors to be upregulated during ER stress upon inhibition of caspases. Furthermore, these transcription factors were degraded in a caspase-dependent manner during ER stress. These results indicate that caspases play a dual role in regulating the cellular response to ER stress through both post-translational and transcriptional regulatory mechanisms. Moreover, this study provides unique insight into progression of the unfolded protein response into cell death, which may help identify therapeutic strategies to treat ER stress-related diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Managing multiple roles - Personality, stress, and work-family interference in dual-earner couples

    NARCIS (Netherlands)

    Wierda-Boer, H.H.; Gerris, J.R.M.; Vermulst, A.A.

    2009-01-01

    Today many parents have multiple roles. This study examined how personality, domain-specific stress, and work-family interference are interrelated. Questionnaire data of 276 Dutch dual-earner couples with young children were analyzed using structural equation modeling. Findings demonstrated that job

  3. The imidazopyridine derivative JK184 reveals dual roles for microtubules in Hedgehog signaling.

    Science.gov (United States)

    Cupido, Tommaso; Rack, Paul G; Firestone, Ari J; Hyman, Joel M; Han, Kyuho; Sinha, Surajit; Ocasio, Cory A; Chen, James K

    2009-01-01

    Eradicating hedgehogs: The title molecule has been previously identified as a potent inhibitor of the Hedgehog signaling pathway, which gives embryonic cells information needed to develop properly. This molecule is shown to modulate Hedgehog target gene expression by depolymerizing microtubules, thus revealing dual roles of the cytoskeleton in pathway regulation (see figure).

  4. Bone mineral density in patients with noninsulin-dependent diabetes mellitus by dual photon absorptiometry

    International Nuclear Information System (INIS)

    Kao, C.H.; Tsou, C.T.; Chen, C.C.; Wang, S.J.

    1993-01-01

    Bone mineral density (BMD) in 38 male patients with noninsulin-dependent diabetes mellitus (NIDDM) was measured by dual photon absorptiometry (DPA) using a M and SE Osteo Tech 300 scanner. The BMD of the second to fourth lumbar vertebrae was measured and the mean density was presented as g cm -2 . The patients were distinguished according to the following three criteria: (1) blood sugar control was good or poor; (2) the duration of diabetes was long or short; (3) renal function was evaluated by effective renal plasma flow (ERPF) as good or poor. The results showed about half the cases of NIDDM had lower BMD. The patients with poor blood sugar control, longer disease duration and poor renal function had lower BMD. However, the difference between any two groups distinguished by the three criteria is not significant. We think that the causes of osteoporosis in patients with NIDDM may not be explained by only a single factor. (author)

  5. Dual role of lignin in plant litter decomposition in terrestrial ecosystems.

    Science.gov (United States)

    Austin, Amy T; Ballaré, Carlos L

    2010-03-09

    Plant litter decomposition is a critical step in the formation of soil organic matter, the mineralization of organic nutrients, and the carbon balance in terrestrial ecosystems. Biotic decomposition in mesic ecosystems is generally negatively correlated with the concentration of lignin, a group of complex aromatic polymers present in plant cell walls that is recalcitrant to enzymatic degradation and serves as a structural barrier impeding microbial access to labile carbon compounds. Although photochemical mineralization of carbon has recently been shown to be important in semiarid ecosystems, litter chemistry controls on photodegradative losses are not understood. We evaluated the importance of litter chemistry on photodegradation of grass litter and cellulose substrates with varying levels of lignin [cellulose-lignin (CL) substrates] under field conditions. Using wavelength-specific light attenuation filters, we found that light-driven mass loss was promoted by both UV and visible radiation. The spectral dependence of photodegradation correlated with the absorption spectrum of lignin but not of cellulose. Field incubations demonstrated that increasing lignin concentration reduced biotic decomposition, as expected, but linearly increased photodegradation. In addition, lignin content in CL substrates consistently decreased in photodegradative incubations. We conclude that lignin has a dual role affecting litter decomposition, depending on the dominant driver (biotic or abiotic) controlling carbon turnover. Under photodegradative conditions, lignin is preferentially degraded because it acts as an effective light-absorbing compound over a wide range of wavelengths. This mechanistic understanding of the role of lignin in plant litter decomposition will allow for more accurate predictions of carbon dynamics in terrestrial ecosystems.

  6. Determination of the lysosomal role in tumor accumulation of 67Ga by dual-tracer studies

    International Nuclear Information System (INIS)

    Ando, Atsushi; Ando, Itsuko; Hiraki, Tatsunosuke; Yamada, Norihisa; Hisada, Kinichi

    1989-01-01

    The lysosomal role in tumor accumulation of 67 Ga was determined by dual-tracer( 67 Ga and 46 Sc) studies. It became clear that 67 Ga essentially did not accumulate in the tumor lysosome, and that the lysosome did not play a major role in tumor accumulation of 67 Ga. In addition, it was revealed that tumor lysosome was hardly disrupted at all in some phases of fractionation procedures. (author)

  7. Brain substrates of social decision-making in dual diagnosis: cocaine dependence and personality disorders.

    Science.gov (United States)

    Verdejo-Garcia, Antonio; Verdejo-Román, Juan; Albein-Urios, Natalia; Martínez-González, José M; Soriano-Mas, Carles

    2017-03-01

    Cocaine dependence frequently co-occurs with personality disorders, leading to increased interpersonal problems and greater burden of disease. Personality disorders are characterised by patterns of thinking and feeling that divert from social expectations. However, the comorbidity between cocaine dependence and personality disorders has not been substantiated by measures of brain activation during social decision-making. We applied functional magnetic resonance imaging to compare brain activations evoked by a social decision-making task-the Ultimatum Game-in 24 cocaine dependents with personality disorders (CDPD), 19 cocaine dependents without comorbidities and 19 healthy controls. In the Ultimatum Game participants had to accept or reject bids made by another player to split monetary stakes. Offers varied in fairness (in fair offers the proposer shares ~50 percent of the money; in unfair offers the proposer shares <30 percent of the money), and participants were told that if they accept both players get the money, and if they reject both players lose it. We contrasted brain activations during unfair versus fair offers and accept versus reject choices. During evaluation of unfair offers CDPD displayed lower activation in the insula and the anterior cingulate cortex and higher activation in the lateral orbitofrontal cortex and superior frontal and temporal gyri. Frontal activations negatively correlated with emotion recognition. During rejection of offers CDPD displayed lower activation in the anterior cingulate cortex, striatum and midbrain. Dual diagnosis is linked to hypo-activation of the insula and anterior cingulate cortex and hyper-activation of frontal-temporal regions during social decision-making, which associates with poorer emotion recognition. © 2015 Society for the Study of Addiction.

  8. The lipid dependence of melittin action investigated by dual-color fluorescence burst analysis

    NARCIS (Netherlands)

    Bogaart, Geert van den; Mika, Jacek T.; Krasnikov, Viktor; Poolman, Bert

    Dual-color fluorescence-burst analysis was used to study melittin-induced leakage of macromolecules from liposomes of various lipid compositions. To perform dual-color fluorescence-burst analysis, fluorescently labeled size-marker molecules were encapsulated into liposomes, labeled with a second

  9. Whole Saliva has a Dual Role on the Adherence of Candida albicans to Polymethylmetacrylate

    OpenAIRE

    Elguezabal, N; Maza, J.L.; Dorronsoro, S.; Pont?n, J.

    2008-01-01

    Adhesion of Candida albicans to acrylic of dental prostheses or to salivary macromolecules adsorbed on their surface is believed to be a critical event in the development of denture stomatitis. In previous studies our group has shown that adhesion of C. albicans germ tubes to polystyrene is decreased by saliva whereas C. albicans yeast cells adhesion to the same material is enhanced. The results presented in this study confirm this dual role played by whole saliva, since it decreased the adhe...

  10. Role of endocannabinoids in regulating drug dependence

    Directory of Open Access Journals (Sweden)

    Daniela Parolaro

    2007-01-01

    Full Text Available Daniela Parolaro, Daniela Vigano’, Natalia Realini, Tiziana RubinoNeuroscience Center, DBSF, University of Insubria, Busto Arsizio, ItalyAbstract: This review will discuss the latest knowledge of how the endocannabinoid system might be involved in treating addiction to the most common illicit drugs. Experimental models are providing increasing evidence for the pharmacological management of endocannabinoid signaling not only to block the direct reinforcing effects of cannabis, opioids, nicotine and ethanol, but also for preventing relapse to the various drugs of abuse, including opioids, cocaine, nicotine, alcohol and metamphetamine. Preclinical and clinical studies suggest that the endocannabinoid system can be manipulated by the CB1 receptor antagonist SR141716A, that might constitute a new generation of compounds for treating addiction across different classes of abused drugs.Keywords: Endocannabinoids, drug dependence, opioids, nicotine, alcohol, psychostimulants

  11. Solvent-Dependent Dual Fluorescence of the Push-Pull System 2-Diethylamino-7-Nitrofluorene

    KAUST Repository

    Larsen, Martin A. B.; Stephansen, Anne B.; Alarousu, Erkki; Pittelkow, Michael; Mohammed, Omar F.; Sø lling, Theis I

    2018-01-01

    The solvent-dependent excited state behavior of the molecular push-pull system 2-diethylamino-7-nitrofluorene has been explored using femtosecond transient absorption spectroscopy in combination with density functional theory calculations. Several excited state minima have been identified computationally, all possessing significant intramolecular charge transfer character. The experimentally observed dual fluorescence is suggested to arise from a planar excited state minimum and another minimum reached by twisting of the aryl-nitrogen bond of the amino group. The majority of the excited state population, however, undergo non-radiative transitions and potential excited deactivation pathways are assessed in the computational investigation. A third excited state conformer, characterized by twisting around the aryl-nitrogen bond of the nitro group, is reasoned to be responsible for the majority of the non-radiative decays and a crossing between the excited state and ground state is localized. Additionally, ultrafast intersystem crossing is observed in the apolar solvent cyclohexane and rationalized to occur via an El-Sayed assisted transition from one of the identified excited state minima. The solvent thus determines more than just the fluorescence lifetime and shapes the potential energy landscape, thereby dictating the available excited state pathways.

  12. Solvent-Dependent Dual Fluorescence of the Push-Pull System 2-Diethylamino-7-Nitrofluorene

    KAUST Repository

    Larsen, Martin A. B.

    2018-01-31

    The solvent-dependent excited state behavior of the molecular push-pull system 2-diethylamino-7-nitrofluorene has been explored using femtosecond transient absorption spectroscopy in combination with density functional theory calculations. Several excited state minima have been identified computationally, all possessing significant intramolecular charge transfer character. The experimentally observed dual fluorescence is suggested to arise from a planar excited state minimum and another minimum reached by twisting of the aryl-nitrogen bond of the amino group. The majority of the excited state population, however, undergo non-radiative transitions and potential excited deactivation pathways are assessed in the computational investigation. A third excited state conformer, characterized by twisting around the aryl-nitrogen bond of the nitro group, is reasoned to be responsible for the majority of the non-radiative decays and a crossing between the excited state and ground state is localized. Additionally, ultrafast intersystem crossing is observed in the apolar solvent cyclohexane and rationalized to occur via an El-Sayed assisted transition from one of the identified excited state minima. The solvent thus determines more than just the fluorescence lifetime and shapes the potential energy landscape, thereby dictating the available excited state pathways.

  13. Betwixt and between : role conflict, role ambiguity and role definition in project-based dual-leadership structures

    NARCIS (Netherlands)

    Ebbers, J.J.; Wijnberg, N.M.

    2017-01-01

    Project-based organizations in the film industry usually have a dual leadership structure, based on a division of tasks between the dual leaders, the director and the producer, in which the former is predominantly responsible for the artistic and the latter for the commercial aspects of the film.

  14. A dual role of p53 in the control of autophagy.

    Science.gov (United States)

    Tasdemir, Ezgi; Chiara Maiuri, M; Morselli, Eugenia; Criollo, Alfredo; D'Amelio, Marcello; Djavaheri-Mergny, Mojgan; Cecconi, Francesco; Tavernarakis, Nektarios; Kroemer, Guido

    2008-08-01

    Genotoxic stress can induce autophagy in a p53-dependent fashion and p53 can transactivate autophagy-inducing genes. We have observed recently that inactivation of p53 by deletion, depletion or inhibition can trigger autophagy. Thus, human and mouse cells subjected to knockout, knockdown or pharmacological inhibition of p53 manifest signs of autophagy such as depletion of p62/SQSTM1, LC3 lipidation, redistribution of GFP-LC3 in cytoplasmic puncta, and accumulation of autophagosomes and autolysosomes, both in vitro and in vivo. Inhibition of p53 causes autophagy in enucleated cells, indicating that the cytoplasmic, non-nuclear pool of p53 can regulate autophagy. Accordingly, retransfection of p53(-/-) cells with wild-type p53 as well as a p53 mutant that is excluded from the nucleus (due to the deletion of the nuclear localization sequence) can inhibit autophagy, whereas retransfection with a nucleus-restricted p53 mutant (in which the nuclear localization sequence has been deleted) does not inhibit autophagy. Several distinct autophagy inducers (e.g., starvation, rapamycin, lithium, tunicamycin and thapsigargin) stimulate the rapid degradation of p53. In these conditions, inhibition of the p53-specific E3 ubiquitin ligase HDM2 can avoid p53 depletion and simultaneously prevent the activation of autophagy. Moreover, a p53 mutant that lacks the HDM2 ubiquitinylation site and hence is more stable than wild-type p53 is particularly efficient in suppressing autophagy. In conclusion, p53 plays a dual role in the control of autophagy. On the one hand, nuclear p53 can induce autophagy through transcriptional effects. On the other hand, cytoplasmic p53 may act as a master repressor of autophagy.

  15. Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Huixian [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Shi, Zhenqi [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Qiao, Ping [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Department of Pharmacology, Norman Bethune Medical College, Jilin University, Changchun, Jilin 130021 (China); Li, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); McCoy, Erin M. [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Mao, Ping [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Xu, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Feng, Xu [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Wang, Shunqing, E-mail: shqwang_cn@yahoo.com [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China)

    2013-11-01

    Highlights: •IL-3 treatment of bone marrow cells generates a population of hematopoietic cells. •IL-3-dependent hematopoietic cells are capable of differentiating into osteoclasts. •Osteoclasts derived from IL-3-dependent hematopoietic cells are functional. •IL-3 promotes the development of osteoclast progenitors. •IL-3 inhibits the osteoclastogenic process. -- Abstract: Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the

  16. [Dual pathology].

    Science.gov (United States)

    Rougier, A

    2008-05-01

    Dual pathology is defined as the association of two potentially epileptogenic lesions, hippocampal (sclerosis, neuronal loss) and extrahippocampal (temporal or extratemporal). Epileptic activity may be generated by either lesion and the relative importance of every lesion's epileptogenicity conditions the surgical strategy adopted. Most frequently associated with hippocampal sclerosis are cortical dysplasias. The common physiopathology of the two lesions is not clearly established. Extrahippocampal lesions may be undetectable on MRI (microdysgenesis, for example) and ictal discharge patterns may vary among dual pathology patients. The surgical strategy depends on the location of the extrahippocampal lesion and its relative role in seizure generation; however, reported surgical results suggest that simultaneous resection of mesial temporal structures along with the extrahippocampal lesion should be performed.

  17. Bridging the language gap: Exploring science teachers' dual role as teachers of content and English literacy

    Science.gov (United States)

    Arnold, Suzanne C.

    Responsibility for educating English language learners is increasingly falling on the shoulders of content specialists at the secondary level, as students are mainstreamed into classes. Therefore, providing these students an opportunity to achieve academic success depends largely on the quality of mainstream instruction (Cornell, 1995). Most teachers receive little or no preparation in how to work with English language learners. In my study, I address the instructional issues confronting three white, monolingual English-speaking middle school science teachers who must meet the demands of an increasing English language learner population. Specifically, this study explores teacher beliefs and enactment of reform-oriented science and sheltered instructional approaches to develop English language learners scientific and English literacy skills. I also explore the relationships that exist between these two dynamics in an effort to determine the extent to which teachers take on a dual role as teachers promoting English language and science proficiency. Using a participant observation case study method and my adaptation of Schwab's commonplaces heuristic, I analyzed the relationship between teacher beliefs, milieu, subject matter, and enactment in bridging the language gap in the science classroom for English language learners. The most noteworthy finding of this study was the significant role of milieu in enacting lessons that bridge the language gap and foster the development of English language learners science and English literacy skills. The findings suggest that greater attention be given to helping teachers establish a relationship-driven classroom milieu. You can provide all kinds of courses or professional learning experiences to improve teachers' instructional practices, but they must also recognize the importance of establishing relationships with their students; the coursework they take will not supplant the need to foster a warm and safe environment for all

  18. Dependent leaders : Role-specific challenges for middle managers

    NARCIS (Netherlands)

    Voorn, Bart

    2018-01-01

    Mocked and ridiculed by many, praised by few, middle managers have challenging roles in organizations. It is typified by unique dependencies on different aspects of their work circumstances, including their superiors’ leadership, assigned goals, and tenure. Empirical research exploring specific

  19. Juggling the dual role of practitioner and educator: practice teachers' perceptions.

    Science.gov (United States)

    Carr, Helen; Gidman, Janice

    2012-02-01

    This paper reports on a study exploring the role (caseload manager; practitioner; educator) of Specialist Community Public Health Nursing (SCPHN) Practice Teachers (PTs) and mentors for Specialist Practice Community (SPC) district nursing students. Methodological triangulation was used, comprising questionnaires completed by 15 PTs and mentors, followed by six semistructured interviews, to provide quantitative and qualitative data. The results of the study identify that post-registration students demanded considerable time due to their need to develop leadership and higher cognitive skills in practice. PTs and mentors identified feeling undervalued by the organisation and colleagues as they tried to maintain their dual role with limited time or resources allocated. Respondents reported that they often worked over their hours to maintain both roles which impacted on their work life balance. They reported that both peer and university support groups were valuable and suggested that increased contact from lecturers and greater flexibility in university courses would accommodate their continuing professional development. It is, therefore, concluded that further support is needed by both the organisation and the university to enable this dual role.

  20. Colon-targeted delivery of budesonide using dual pH- and time-dependent polymeric nanoparticles for colitis therapy

    Directory of Open Access Journals (Sweden)

    Naeem M

    2015-07-01

    Full Text Available Muhammad Naeem,1 Moonjeong Choi,1 Jiafu Cao,1 Yujeong Lee,1 Muhammad Ikram,2 Sik Yoon,2 Jaewon Lee,1 Hyung Ryong Moon,1 Min-Soo Kim,1 Yunjin Jung,1 Jin-Wook Yoo11College of Pharmacy, Pusan National University, Busan, 2Pusan National University School of Medicine, Yangsan, South KoreaAbstract: Single pH-dependent drug delivery systems have been widely used for colon-targeted delivery, but their efficiency is often hampered by the variation in gut pH. To overcome the limitation of single pH-dependent delivery systems, in this study, we developed and evaluated the therapeutic potential of budesonide-loaded dual pH/time-dependent nanoparticles (NPs for the treatment of colitis. Eudragit FS30D was used as a pH-dependent polymer, and Eudragit RS100 as a time-dependent controlled release polymer. Single pH-dependent NPs (pH_NPs, single time-dependent NPs (Time_NPs, and dual pH/time-dependent NPs (pH/Time_NPs were prepared using the oil-in-water emulsion method. The physicochemical properties and drug release profiles of these NPs in gastrointestinal (GI tract conditions were investigated. The therapeutic potential and in vivo distribution of the NPs were evaluated in a dextran sulfate sodium (DSS-induced colitis mice model. The pH/Time_NPs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. The in vivo distribution study in the mice GI tract demonstrated that pH/Time_NPs were more efficiently delivered to the inflamed colon than pH_NPs were. Compared to the single pH_NPs-treated group, the pH/Time_NPs-treated group showed increased body weight and colon length and markedly decreased disease activity index, colon weight/length ratios, histological damage, and inflammatory cell infiltration in colon tissue. Our results demonstrate that the dual pH/time-dependent NPs are an effective oral colon-targeted delivery system for colitis therapy.Keywords: colon-specific delivery, dual-sensitive delivery

  1. The Granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity

    Directory of Open Access Journals (Sweden)

    Stephanie eWallner

    2015-08-01

    Full Text Available Granulocyte-colony stimulating factor (G-CSF is a growth factor that has originally been identified several decades ago as a hematopoietic factor required mainly for the generation of neutrophilic granulocytes, and is in clinical use for that. More recently, it has been discovered that G-CSF also plays a role in the brain as a growth factor for neurons and neural stem cells, and as a factor involved in the plasticity of the vasculature. We review and discuss these dual properties in view of the neuroregenerative potential of this growth factor.

  2. Low mass diffractive dissociation in a simple t-dependent dual bootstrap model

    International Nuclear Information System (INIS)

    Bishari, M.

    1978-08-01

    The smallness of inelastic diffractive dissociation is explicitly demonstrated, in the framework of the '1/N dual unitarization' scheme, by incorporating a Deck type mechanism with the crucial planar bootstrap equation. Although both inelastic and elastic pomeron couplings are of the same order in 1/N, the origin for their smallness, however, is not identical. (author)

  3. High-efficiency dual-modes vortex beam generator with polarization-dependent transmission and reflection properties.

    Science.gov (United States)

    Tang, Shiwei; Cai, Tong; Wang, Guang-Ming; Liang, Jian-Gang; Li, Xike; Yu, Jiancheng

    2018-04-23

    Vortex beam is believed to be an effective way to extend communication capacity, but available efforts suffer from the issues of complex configurations, fixed operation mode as well as low efficiency. Here, we propose a general strategy to design dual-modes vortex beam generator by using metasurfaces with polarization-dependent transmission and reflection properties. Combining the focusing and vortex functionalities, we design/fabricate a type of compact dual-modes vortex beam generator operating at both reflection/transmission sides of the system. Experimental results demonstrate that the designed metadevice can switch freely and independently between the reflective vortex with topological charge m 1  = 2 and transmissive vortex with m 2  = 1. Moreover, the metadevice exhibits very high efficiencies of 91% and 85% for the reflective and transmissive case respectively. Our findings open a door for multifunctional metadevices with high performances, which indicate wide applications in modern integration-optics and wireless communication systems.

  4. Dual Roles of FmtA in Staphylococcus aureus Cell Wall Biosynthesis and Autolysis

    Science.gov (United States)

    Qamar, Aneela

    2012-01-01

    The fmtA gene is a member of the Staphylococcus aureus core cell wall stimulon. The FmtA protein interacts with β-lactams through formation of covalent species. Here, we show that FmtA has weak d-Ala-d-Ala-carboxypeptidase activity and is capable of covalently incorporating C14-Gly into cell walls. The fluorescence microscopy study showed that the protein is localized to the cell division septum. Furthermore, we show that wall teichoic acids interact specifically with FmtA and mediate recruitment of FmtA to the S. aureus cell wall. Subjection of S. aureus to FmtA concentrations of 0.1 μM or less induces autolysis and biofilm production. This effect requires the presence of wall teichoic acids. At FmtA concentrations greater than 0.2 μM, autolysis and biofilm formation in S. aureus are repressed and growth is enhanced. Our findings indicate dual roles of FmtA in S. aureus growth, whereby at low concentrations, FmtA may modulate the activity of the major autolysin (AtlA) of S. aureus and, at high concentrations, may participate in synthesis of cell wall peptidoglycan. These two roles of FmtA may reflect dual functions of FmtA in the absence and presence of cell wall stress, respectively. PMID:22564846

  5. The role of the opioid system in alcohol dependence.

    Science.gov (United States)

    Nutt, David J

    2014-01-01

    The role of the brain opioid system in alcohol dependence has been the subject of much research for over 25 years. This review explores the evidence: firstly describing the opioid receptors in terms of their individual subtypes, neuroanatomy, neurophysiology and ligands; secondly, summarising emerging data from specific neurochemical, behavioural and neuroimaging studies, explaining the characteristics of addiction with a focus on alcohol dependence and connecting the opioid system with alcohol dependence; and finally reviewing the known literature regarding opioid antagonists in clinical use for alcohol dependence. Further interrogation of how modulation of the opioid system, via use of MOP (mu), DOP (delta) and KOP (kappa) agents, restores the balance of a dysregulated system in alcohol dependence should increase our insight into this disease process and therefore guide better methods for understanding and treating alcohol dependence in the future.

  6. The Role of Control Functions in Mentalizing: Dual-Task Studies of Theory of Mind and Executive Function

    Science.gov (United States)

    Bull, Rebecca; Phillips, Louise H.; Conway, Claire A.

    2008-01-01

    Conflicting evidence has arisen from correlational studies regarding the role of executive control functions in Theory of Mind. The current study used dual-task manipulations of executive functions (inhibition, updating and switching) to investigate the role of these control functions in mental state and non-mental state tasks. The "Eyes"…

  7. Dual role of delay effects in a tumour-immune system.

    Science.gov (United States)

    Yu, Min; Dong, Yueping; Takeuchi, Yasuhiro

    2017-08-01

    In this paper, a previous tumour-immune interaction model is simplified by neglecting a relatively weak direct immune activation by the tumour cells, which can still keep the essential dynamics properties of the original model. As the immune activation process is not instantaneous, we now incorporate one delay for the activation of the effector cells (ECs) by helper T cells (HTCs) into the model. Furthermore, we investigate the stability and instability regions of the tumour-presence equilibrium state of the delay-induced system with respect to two parameters, the activation rate of ECs by HTCs and the HTCs stimulation rate by the presence of identified tumour antigens. We show the dual role of this delay that can induce stability switches exhibiting destabilization as well as stabilization of the tumour-presence equilibrium. Besides, our results reveal that an appropriate immune activation time delay plays a significant role in control of tumour growth.

  8. Prediction of life stress on athletes’ burnout: the dual role of perceived stress

    Science.gov (United States)

    Wang, Erica T.W.; Hsu, Ya-Wen; Chang, Ko-Hsin

    2018-01-01

    Although many studies adopted Smith’s (1986) cognitive–affective model of athletic burnout in examining stress–burnout relationship, very few studies examined the mediating/moderating role of perceived stress on the stress–burnout relationship. We sampled 195 college student-athletes and assessed their life stress, perceived stress, and burnout. Correlation analyses found all study variables correlated. Two separate hierarchical regression analyses found that the “distress” component of perceived stress mediated athletes’ two types of life stress–burnout relationship but “counter-stress” component of perceived stress-moderated athletes’ general-life stress–burnout relationship. We concluded that interweaving relationships among athletes’ life stress, perceived stress, and burnout are not straightforward. Future research should consider the nature of athletes life stress, and dual role of perceived stress in examining its’ association with related psychological responses in athletic settings. PMID:29362691

  9. Prediction of life stress on athletes' burnout: the dual role of perceived stress.

    Science.gov (United States)

    Chyi, Theresa; Lu, Frank Jing-Horng; Wang, Erica T W; Hsu, Ya-Wen; Chang, Ko-Hsin

    2018-01-01

    Although many studies adopted Smith's (1986) cognitive-affective model of athletic burnout in examining stress-burnout relationship, very few studies examined the mediating/moderating role of perceived stress on the stress-burnout relationship. We sampled 195 college student-athletes and assessed their life stress, perceived stress, and burnout. Correlation analyses found all study variables correlated. Two separate hierarchical regression analyses found that the "distress" component of perceived stress mediated athletes' two types of life stress-burnout relationship but "counter-stress" component of perceived stress-moderated athletes' general-life stress-burnout relationship. We concluded that interweaving relationships among athletes' life stress, perceived stress, and burnout are not straightforward. Future research should consider the nature of athletes life stress, and dual role of perceived stress in examining its' association with related psychological responses in athletic settings.

  10. Prediction of life stress on athletes’ burnout: the dual role of perceived stress

    Directory of Open Access Journals (Sweden)

    Theresa Chyi

    2018-01-01

    Full Text Available Although many studies adopted Smith’s (1986 cognitive–affective model of athletic burnout in examining stress–burnout relationship, very few studies examined the mediating/moderating role of perceived stress on the stress–burnout relationship. We sampled 195 college student-athletes and assessed their life stress, perceived stress, and burnout. Correlation analyses found all study variables correlated. Two separate hierarchical regression analyses found that the “distress” component of perceived stress mediated athletes’ two types of life stress–burnout relationship but “counter-stress” component of perceived stress-moderated athletes’ general-life stress–burnout relationship. We concluded that interweaving relationships among athletes’ life stress, perceived stress, and burnout are not straightforward. Future research should consider the nature of athletes life stress, and dual role of perceived stress in examining its’ association with related psychological responses in athletic settings.

  11. Whole Saliva has a Dual Role on the Adherence of Candida albicans to Polymethylmetacrylate.

    Science.gov (United States)

    Elguezabal, N; Maza, J L; Dorronsoro, S; Pontón, J

    2008-01-01

    Adhesion of Candida albicans to acrylic of dental prostheses or to salivary macromolecules adsorbed on their surface is believed to be a critical event in the development of denture stomatitis. In previous studies our group has shown that adhesion of C. albicans germ tubes to polystyrene is decreased by saliva whereas C. albicans yeast cells adhesion to the same material is enhanced. The results presented in this study confirm this dual role played by whole saliva, since it decreased the adhesion of germ tubes but increased the adhesion of yeast cells to polymethylmetacrylate (PMMA). These effects mediated by whole saliva do not seem to be related to an inhibition of the germination of C. albicans, since similar levels of filamentation were observed in presence and absence of saliva. These results may give new insights into the conflicting role of saliva in the adhesion of C. albicans to acrylic resins of dental prostheses.

  12. Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2007-01-01

    Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

  13. Role of Islamic Banking and Conventional Against Poverty with The Dual Banking System

    Directory of Open Access Journals (Sweden)

    Iwan Setiawan

    2016-12-01

    Full Text Available Islamic banking in Indonesia is present in a dual banking system. Islamic banking is expected to contribute more in the process of economic development and improving people’s welfare. The  main  objective of  this  study is  to  analyze the  role  of  financing Islamic banking and conventional banking credit to the improvement of people’s welfare as measured by reductions in poverty. The study was conducted using  the explanatory method, applying the  panel  regression estimation techniques simultaneously with the  Two Stage Least Square  method (TSLS  using  data from the period 1992-2012. Results  of the study reveals that the increased of  financing Islamic banking and conventional banking credit assign roles  to poverty reduction in Indonesia. The role of Islamic banking financing is lower  than conventional bank  credit role  in reducing poverty. In addition to improve financing and credit, changes should be applied in the value  of the instruments of monetary policy, economic growth, unequal distribution  of income and  the depreciation  of the local  currency that contribute towards poverty conditions.

  14. Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Fulcher, F. Kent; Smith, Bethany T.; Russ, Misty; Patel, Yashomati M.

    2008-01-01

    Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles to the plasma membrane. Our previous studies demonstrated that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. The experiments described in this report are the first to show a dual role for the myosin IIA isoform specifically in regulating insulin-stimulated glucose uptake in adipocytes. We demonstrate that inhibition of MLCK but not RhoK results in impaired insulin-stimulated glucose uptake. Furthermore, our studies show that insulin specifically stimulates the phosphorylation of the RLC associated with the myosin IIA isoform via MLCK. In time course experiments, we determined that GLUT4 translocates to the plasma membrane prior to myosin IIA recruitment. We further show that recruitment of myosin IIA to the plasma membrane requires that myosin IIA be activated via phosphorylation of the RLC by MLCK. Our findings also reveal that myosin II is required for proper GLUT4-vesicle fusion at the plasma membrane. We show that once at the plasma membrane, myosin II is involved in regulating the intrinsic activity of GLUT4 after insulin stimulation. Collectively, our results are the first to reveal that myosin IIA plays a critical role in mediating insulin-stimulated glucose uptake in 3T3-LI adipocytes, via both GLUT4 vesicle fusion at the plasma membrane and GLUT4 activity

  15. Dual roles of borax in kinetics of calcium sulfate dihydrate formation.

    Science.gov (United States)

    Jiang, Wenge; Pan, Haihua; Tao, Jinhui; Xu, Xurong; Tang, Ruikang

    2007-04-24

    An additive is not exclusively retardant or promoter for a crystallization system. The kinetic studies of calcium sulfate dihydrate (CSD) crystal growth demonstrated that borax played dual roles in the reaction, which accelerated CSD formations at the low concentration levels but inhibited the crystal growth at the high ones. In situ atomic force microscopy studies revealed that borax modulated the CSD crystallization via two different pathways: promoted the secondary nucleation to increase the step density on the growing crystal faces but simultaneously retarded the spread of these growth steps by the Langmuir adsorption. These two contradictory factors were incorporated in the crystallization, and their balance was regulated by the borax concentration. Both the macroscopic and microscopic experimental data nicely displayed the crystallization model of birth and spread that was able to account for the behaviors of borax in CSD formations.

  16. Temperature dependent dual hydrogen sensor response of Pd nanoparticle decorated Al doped ZnO surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, D.; Barman, P. B.; Hazra, S. K., E-mail: surajithazra@yahoo.co.in [Department of Physics and Materials Science, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh-173234 (India); Dutta, D. [IC Design and Fabrication Centre, Department of Electronics and Telecommunication Engineering, Jadavpur University, Kolkata-700032 (India); Kumar, M.; Som, T. [SUNAG Laboratory, Institute of Physics, Sachivalaya Marg, Bhubaneswar 751005 (India)

    2015-10-28

    Sputter deposited Al doped ZnO (AZO) thin films exhibit a dual hydrogen sensing response in the temperature range 40 °C–150 °C after surface modifications with palladium nanoparticles. The unmodified AZO films showed no response in hydrogen in the temperature range 40 °C–150 °C. The operational temperature windows on the low and high temperature sides have been estimated by isolating the semiconductor-to-metal transition temperature zone of the sensor device. The gas response pattern was modeled by considering various adsorption isotherms, which revealed the dominance of heterogeneous adsorption characteristics. The Arrhenius adsorption barrier showed dual variation with change in hydrogen gas concentration on either side of the semiconductor-to-metal transition. A detailed analysis of the hydrogen gas response pattern by considering the changes in nano palladium due to hydrogen adsorption, and semiconductor-to-metal transition of nanocrystalline Al doped ZnO layer due to temperature, along with material characterization studies by glancing incidence X-ray diffraction, atomic force microscopy, and transmission electron microscopy, are presented.

  17. Endogenous IL-22 Plays a Dual Role in Arthritis: Regulation of Established Arthritis via IFN-γ Responses

    Science.gov (United States)

    Justa, Shivali; Zhou, Xiaoqun; Sarkar, Sujata

    2014-01-01

    Objective IL-22 is elevated in patients with inflammatory arthritis and correlates with disease activity. IL-22 deficient mice have reduced incidence of arthritis. Recombinant IL-22 restrains progression of arthritis via increase in IL-10 responses when administered prior to onset of arthritis. These findings imply a possible dual role of IL-22 in inflammatory arthritis depending on the phase of arthritis. Experiments outlined here were designed to elucidate the contribution of endogenous IL-22 before and after the onset of arthritis. Methods Collagen induced arthritis (CIA) was induced in DBA1 or IFN-γ deficient mice following immunization with collagen and complete Freund's adjuvant. Anti-IL-22 antibody or isotype control were administered prior to or after onset of arthritis and disease progression assessed by clinical scoring and histopathology. IL-22, IL-17 and IFN-γ responses were measured by ELISA and flowcytometry. Anti-collagen antibody responses were analyzed by ELISA. Expression of IL-22R1 in CD4+ cells was elucidated by flowcytometry and real time PCR. Results Collagen specific IL-22 responses were expanded during arthritis and IL-22 producing cells were discrete from IL-17 or IFN-γ producing cells. Neutralization of IL-22 after onset of arthritis resulted in significant increase in Th1 responses and significantly reduced severity of arthritis. CD4+ cells from arthritic mice showed increased surface expression of IL-22R1. In vitro, CD4+T cells cultured with antigen presenting cells in the presence or absence of IL-22 suppressed or induced IFN-γ, respectively. The protective effect of anti-IL-22 was reversed in IFN-γ deficient mice. Moreover, administration of anti-IL-22 prior to onset of arthritis augmented arthritis severity. Conclusion We show for the first time that IL-22 plays a dual role: protective prior to the onset of arthritis and pathogenic after onset of arthritis. The pathogenic effect of IL-22 is dependent on suppression of IFN

  18. Role of Narrative Skills on Reading Comprehension: Spanish-English and Cantonese-English Dual Language Learners

    Science.gov (United States)

    Uchikoshi, Yuuko; Yang, Lu; Liu, Siwei

    2018-01-01

    This longitudinal study examined the role of narrative skills in English reading comprehension, after controlling for vocabulary and decoding, with a sample of 112 dual language learners (DLLs), including both Spanish-English and Cantonese-English children. Decoding, vocabulary, and narrative samples were collected in the winter of first grade and…

  19. Promoting Preservice Teachers' Dual Self-Regulation Roles as Learners and as Teachers: Effects of Generic vs. Specific Prompts

    Science.gov (United States)

    Kramarski, Bracha; Kohen, Zehavit

    2017-01-01

    Researchers have recently suggested that teachers must undertake important dual self-regulation roles if they want to become effective at improving their students' self-regulation. First, teachers need to become proficient at self-regulated learning (SRL) themselves, and then teachers need to learn explicitly how to proactively teach SRL -- termed…

  20. Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

    International Nuclear Information System (INIS)

    Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.; Storm, Gert; Arts, Josje H.E.; Kuper, C. Frieke; Bloksma, Nanne; Henricks, Paul A.J.

    2006-01-01

    Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-α levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later

  1. A dual role of the extracellular domain of Drosophila Crumbs for morphogenesis of the embryonic neuroectoderm

    Directory of Open Access Journals (Sweden)

    Shradha Das

    2018-01-01

    Full Text Available Epithelia are highly polarised tissues and several highly conserved polarity protein complexes serve to establish and maintain polarity. The transmembrane protein Crumbs (Crb, the central component of the Crb protein complex, is required, among others, for the maintenance of polarity in most epithelia in the Drosophila embryo. However, different epithelia exhibit different phenotypic severity upon loss of crb. Using a transgenomic approach allowed us to more accurately define the role of crb in different epithelia. In particular, we provide evidence that the loss of epithelial tissue integrity in the ventral epidermis of crb mutant embryos is due to impaired actomyosin activity and an excess number of neuroblasts. We demonstrate that the intracellular domain of Crb could only partially rescue this phenotype, while it is able to completely restore tissue integrity in other epithelia. Based on these results we suggest a dual role of the extracellular domain of Crb in the ventral neuroectoderm. First, it is required for apical enrichment of the Crb protein, which in turn regulates actomyosin activity and thereby ensures tissue integrity; and second, the extracellular domain of Crb stabilises the Notch receptor and thereby ensures proper Notch signalling and specification of the correct number of neuroblasts.

  2. Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology.

    Science.gov (United States)

    Pérez, Cecilia V; Gómez, Leticia G; Gualdoni, Gisela S; Lustig, Livia; Rabinovich, Gabriel A; Guazzone, Vanesa A

    2015-07-30

    Galectin-1 (Gal-1), a proto-type member of galectin family, is highly expressed in immune privileged sites, including the testis. However, in spite of considerable progress the relevance of endogenous and exogenous Gal-1 in testis pathophysiology have not yet been explored. Here we evaluated the in vivo roles of Gal-1 in experimental autoimmune orchitis (EAO), a well-established model of autoimmune testicular inflammation associated with subfertility and infertility. A significant reduction in the incidence and severity of EAO was observed in mice genetically deficient in Gal-1 (Lgals1(-/-)) versus wild-type (WT) mice. Testicular histopathology revealed the presence of multifocal testicular damage in WT mice characterized by an interstitial mononuclear cell infiltrate and different degrees of germ cell sloughing of seminiferous tubules. TUNEL assay and assessment of active caspase-3 expression, revealed the prevalence of apoptotic spermatocytes mainly localized in the adluminal compartment of seminiferous tubules in EAO mice. A significant increased number of TUNEL-positive germ cells was detected in EAO testis from WT compared with Lgals1(-/-) mice. In contrast, exogenous administration of recombinant Gal-1 to WT mice undergoing EAO attenuated the severity of the disease. Our results unveil a dual role of endogenous versus exogenous Gal-1 in the control of autoimmune testis inflammation.

  3. The role of dual diagnosis in health-related quality of life among treatment-seeking patients in Spain.

    Science.gov (United States)

    Daigre, Constanza; Grau-López, Lara; Rodríguez-Cintas, Laia; Ros-Cucurull, Elena; Sorribes-Puertas, Marta; Esculies, Oriol; Bones-Rocha, Katia; Roncero, Carlos

    2017-12-01

    The comorbidity of any substance use disorder and another mental disorder is defined as dual diagnosis. Dual diagnosis is very common and clinical and therapeutic consequences have been described. This cross-sectional study aimed to analyse health-related quality of life (HRQoL) according to clinical characteristics and psychiatric comorbidities in patients with substance dependence. A total of 1276 substance-dependent patients seeking treatment were recruited. HRQoL was evaluated by the Short-Form 36 (SF-36) questionnaire. The SCID-I, SCID-II and Conners' adult ADHD diagnostic interview were used to evaluate dual diagnosis. A visual analogue scale was used to measure craving. Bivariate and multivariate analyses were performed, and correction for multiple tests was conducted. Substance-dependent patients had impaired quality of life, especially in the mental component. SF-36 physical and mental component scores were 47.7 ± 10.9 and 36.1 ± 14.1, respectively. Furthermore, 65% of the patients had dual diagnosis, 51% had an Axis I DSM-IV-TR mental disorder and 35% had some personality disorder. Impaired physical quality of life was independently associated with medical condition, age, being female, depressive disorder and anxiety disorder. Depression disorder, any personality disorder, active consumption last month, Attention deficit hyperactivity disorder, anxiety disorder, suicide attempt were independently associated with worse mental quality of life. These findings emphasize the significance of dual diagnosis in the impairment of HRQoL in substance-dependent patients, particularly with regard to mental component. In addicted patients with low scores on SF-36, psychiatric comorbidity should be evaluated and treated in an integrated approach.

  4. Dual Identity and Prejudice: The Moderating Role of Group Boundary Permeability

    Science.gov (United States)

    Shi, Yuanyuan; Dang, Jianning; Zheng, Wenwen; Liu, Li

    2017-01-01

    Past work suggested that dual identity was effective to reduce prejudice. This study extended research on dual identity and prejudice by identifying a boundary condition in this relationship, that is, group permeability. In Study 1, we replicated previous studies with Chinese individuals and found that inducing dual identity (emphasizing subgroup differences and a common nation identity), compared to the control condition, decreased the urban residents’ prejudice against rural-to-urban migrants. In Study 2, we manipulated the group boundary permeability using the Hukou system reform, and found that when the group boundary was permeable, dual identity was effective in reducing prejudice against rural-to-urban migrants. However, this effect vanished in the condition where the group boundary was impermeable. These results point to the importance of inducing dual identity under specific conditions for research on decreasing prejudice. Some practical implications of the findings for urbanization and immigration are discussed. PMID:28261130

  5. Dual role of preputial gland secretion and its major components in sex recognition of mice.

    Science.gov (United States)

    Zhang, Jian-Xu; Liu, Ying-Juan; Zhang, Jin-Hua; Sun, Lixing

    2008-10-20

    This study was aimed at validating the sexual attractiveness of hexadecanol and hexadecyl acetate, two putative pheromone compounds, from preputial gland secretion of mice. These two compounds have been reported to be among the major components of preputial gland secretion in both sexes but higher in quantity in males than females. In this study, we show that castration suppressed the production of the two compounds, further suggesting their association with maleness. Adding preputial gland secretion and the synthetic analogs of the two compounds to castrated male urine at their physiological levels in intact males increased the attractiveness of castrated male urine to female mice, showing that the two compounds were indeed male pheromones. Furthermore, their sexual attractiveness disappeared upon removing the vomeronasal organs (VNOs) from female recipients. Replenishing castrated male urine with preputial gland secretion and the two compounds at their physiological levels in females increased the attractiveness of castrated male urine to males. Such a reversal of sexual attractiveness for hexadecanol and hexadecyl acetate suggests that they had opposing dual effects in sexual attractiveness in a dosage-dependent manner.

  6. The dual role of tumor necrosis factor (TNF) in cancer biology.

    Science.gov (United States)

    Bertazza, Loris; Mocellin, Simone

    2010-01-01

    Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the cascade of molecular events underlying TNF-mediated tumor regression observed in vivo is still incompletely elucidated. Furthermore, some preclinical findings suggest that TNF may even promote cancer development and progression. With this work we intend to summarize the molecular biology of TNF (with particular regard to its tumor-related activities) and review the experimental and clinical evidence currently available describing the complex and sometime apparently conflicting relationship between this cytokine, cancer biology and antitumor therapy. We also propose a model to explain the dual effect of TNF based on the exposure time and cytokine levels reached within the tumor microenvironment. Finally, we overview recent research findings that might lead to new ways for exploiting the anticancer potential of TNF in the clinical setting.

  7. On the role, ecology, phylogeny, and structure of dual-family immunophilins.

    Science.gov (United States)

    Barik, Sailen

    2017-11-01

    The novel class of dual-family immunophilins (henceforth abbreviated as DFI) represents naturally occurring chimera of classical FK506-binding protein (FKBP) and cyclophilin (CYN), connected by a flexible linker that may include a three-unit tetratricopeptide (TPR) repeat. Here, I report a comprehensive analysis of all current DFI sequences and their host organisms. DFIs are of two kinds: CFBP (cyclosporin- and FK506-binding protein) and FCBP (FK506- and cyclosporin-binding protein), found in eukaryotes. The CFBP type occurs in select bacteria that are mostly extremophiles, such as psychrophilic, thermophilic, halophilic, and sulfur-reducing. Essentially all DFI organisms are unicellular. I suggest that DFIs are specialized bifunctional chaperones that use their flexible interdomain linker to associate with large polypeptides or multisubunit megacomplexes to promote simultaneous folding or renaturation of two clients in proximity, essential in stressful and denaturing environments. Analysis of sequence homology and predicted 3D structures of the FKBP and CYN domains as well as the TPR linkers upheld the modular nature of the DFIs and revealed the uniqueness of their TPR domain. The CFBP and FCBP genes appear to have evolved in parallel pathways with no obvious single common ancestor. The occurrence of both types of DFI in multiple unrelated phylogenetic clades supported their selection in metabolic and environmental niche roles rather than a traditional taxonomic relationship. Nonetheless, organisms with these rare immunophilins may define an operational taxonomic unit (OTU) bound by the commonality of chaperone function.

  8. The dual role of autophagy under hypoxia-involvement of interaction between autophagy and apoptosis.

    Science.gov (United States)

    Li, Mengmeng; Tan, Jin; Miao, Yuyang; Lei, Ping; Zhang, Qiang

    2015-06-01

    Hypoxia is one of severe cellular stress and it is well known to be associated with a worse outcome since a lack of oxygen accelerates the induction of apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis caused by hypoxia. Generally autophagy blocks the induction of apoptosis and inhibits the activation of apoptosis-associated caspase which could reduce cellular injury. However, in special cases, autophagy or autophagy-relevant proteins may help to induce apoptosis, which could aggravate cell damage under hypoxia condition. In addition, the activation of apoptosis-related proteins-caspase can also degrade autophagy-related proteins, such as Atg3, Atg4, Beclin1 protein, inhibiting autophagy. Although the relationship between autophagy and apoptosis has been known for rather complex for more than a decade, the underlying regulatory mechanisms have not been clearly understood. This short review discusses and summarizes the dual role of autophagy and the interaction and molecular regulatory mechanisms between autophagy and apoptosis under hypoxia.

  9. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling.

    Science.gov (United States)

    Wang, Ying; Branicky, Robyn; Noë, Alycia; Hekimi, Siegfried

    2018-04-18

    Superoxide dismutases (SODs) are universal enzymes of organisms that live in the presence of oxygen. They catalyze the conversion of superoxide into oxygen and hydrogen peroxide. Superoxide anions are the intended product of dedicated signaling enzymes as well as the byproduct of several metabolic processes including mitochondrial respiration. Through their activity, SOD enzymes control the levels of a variety of reactive oxygen species (ROS) and reactive nitrogen species, thus both limiting the potential toxicity of these molecules and controlling broad aspects of cellular life that are regulated by their signaling functions. All aerobic organisms have multiple SOD proteins targeted to different cellular and subcellular locations, reflecting the slow diffusion and multiple sources of their substrate superoxide. This compartmentalization also points to the need for fine local control of ROS signaling and to the possibility for ROS to signal between compartments. In this review, we discuss studies in model organisms and humans, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling. © 2018 Wang et al.

  10. Dual roles for coactivator activator and its counterbalancing isoform coactivator modulator in human kidney cell tumorigenesis.

    Science.gov (United States)

    Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y; Tsai, Ming-Jer; O'Malley, Bert W

    2008-10-01

    Coactivator activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein, we show that CoAA is a dual-function coregulator that inhibits G(1)-S transition in human kidney cells and suppresses anchorage-independent growth and xenograft tumor formation. Suppression occurs in part by down-regulating c-myc and its downstream effectors ccnd1 and skp2 and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, coactivator modulator (CoAM), antagonizes CoAA-induced G(1)-S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma compared with normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice isoform. This is, thus far, the only example of a nuclear receptor coregulator involved in suppression of kidney cancer and suggests potentially significant new roles for coregulators in renal cancer biology.

  11. Gender equity in STEM: The role of dual enrollment science courses in selecting a college major

    Science.gov (United States)

    Persons, Christopher Andrew

    A disproportionately low number of women, despite rigorous high school preparation and evidenced interest in STEM through voluntary participation in additional coursework, declare a STEM-related college major. The result of this drop in participation in STEM-related college majors is a job market flooded with men and the support of an incorrect stereotype: STEM is for men. This research seeks to assess the effects, if any, that Dual Enrollment (DE) science courses have on students' self-identified intent to declare a STEM-related college major as well as the respective perceptions of both male and female students. Self-Determination Theory and Gender Equity Framework were used respectively as the theoretical frames. High school students from six schools in two district participated in an online survey and focus groups in this mixed methods study. The results of the research identified the role the DE course played in their choice of college major, possible interventions to correct the underrepresentation, and societal causes for the stereotype.

  12. Role of Mecp2 in Experience-Dependent Epigenetic Programming

    Directory of Open Access Journals (Sweden)

    Christoph A. Zimmermann

    2015-03-01

    Full Text Available Mutations in the X-linked gene MECP2, the founding member of a family of proteins recognizing and binding to methylated DNA, are the genetic cause of a devastating neurodevelopmental disorder in humans, called Rett syndrome. Available evidence suggests that MECP2 protein has a critical role in activity-dependent neuronal plasticity and transcription during brain development. Moreover, recent studies in mice show that various posttranslational modifications, notably phosphorylation, regulate Mecp2’s functions in learning and memory, drug addiction, depression-like behavior, and the response to antidepressant treatment. The hypothalamic-pituitary-adrenal (HPA axis drives the stress response and its deregulation increases the risk for a variety of mental disorders. Early-life stress (ELS typically results in sustained HPA-axis deregulation and is a major risk factor for stress related diseases, in particular major depression. Interestingly, Mecp2 protein has been shown to contribute to ELS-dependent epigenetic programming of Crh, Avp, and Pomc, all of these genes enhance HPA-axis activity. Hereby ELS regulates Mecp2 phosphorylation, DNA binding, and transcriptional activities in a tissue-specific and temporospatial manner. Overall, these findings suggest MECP2 proteins are so far underestimated and have a more dynamic role in the mediation of the gene-environment dialog and epigenetic programming of the neuroendocrine stress system in health and disease.

  13. Dual role of proapoptotic BAD in insulin secretion and beta cell survival

    OpenAIRE

    Danial, Nika N.; Walensky, Loren D.; Zhang, Chen-Yu; Choi, Cheol Soo; Fisher, Jill K.; Molina, Anthony J. A.; Datta, Sandeep Robert; Pitter, Kenneth L.; Bird, Gregory H.; Wikstrom, Jakob D.; Deeney, Jude T.; Robertson, Kirsten; Morash, Joel; Kulkarni, Ameya; Neschen, Susanne

    2008-01-01

    The proapoptotic BCL-2 family member BAD resides in a glucokinase-containing complex that regulates glucose-driven mitochondrial respiration. Here, we present genetic evidence of a physiologic role for BAD in glucose-stimulated insulin secretion by beta cells. This novel function of BAD is specifically dependent upon the phosphorylation of its BH3 sequence, previously defined as an essential death domain. We highlight the pharmacologic relevance of phosphorylated BAD BH3 by using cell-permeab...

  14. Role of Mitochondrial Complex IV in Age-Dependent Obesity

    Directory of Open Access Journals (Sweden)

    Ines Soro-Arnaiz

    2016-09-01

    Full Text Available Aging is associated with progressive white adipose tissue (WAT enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion.

  15. Acute effects of alcohol on intrusive memory development and viewpoint dependence in spatial memory support a dual representation model.

    Science.gov (United States)

    Bisby, James A; King, John A; Brewin, Chris R; Burgess, Neil; Curran, H Valerie

    2010-08-01

    A dual representation model of intrusive memory proposes that personally experienced events give rise to two types of representation: an image-based, egocentric representation based on sensory-perceptual features; and a more abstract, allocentric representation that incorporates spatiotemporal context. The model proposes that intrusions reflect involuntary reactivation of egocentric representations in the absence of a corresponding allocentric representation. We tested the model by investigating the effect of alcohol on intrusive memories and, concurrently, on egocentric and allocentric spatial memory. With a double-blind independent group design participants were administered alcohol (.4 or .8 g/kg) or placebo. A virtual environment was used to present objects and test recognition memory from the same viewpoint as presentation (tapping egocentric memory) or a shifted viewpoint (tapping allocentric memory). Participants were also exposed to a trauma video and required to detail intrusive memories for 7 days, after which explicit memory was assessed. There was a selective impairment of shifted-view recognition after the low dose of alcohol, whereas the high dose induced a global impairment in same-view and shifted-view conditions. Alcohol showed a dose-dependent inverted "U"-shaped effect on intrusions, with only the low dose increasing the number of intrusions, replicating previous work. When same-view recognition was intact, decrements in shifted-view recognition were associated with increases in intrusions. The differential effect of alcohol on intrusive memories and on same/shifted-view recognition support a dual representation model in which intrusions might reflect an imbalance between two types of memory representation. These findings highlight important clinical implications, given alcohol's involvement in real-life trauma. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Centrality Dependence of Hadron Multiplicities in Nuclear Collisions in the Dual Parton Model

    CERN Document Server

    Capella, A

    2001-01-01

    We show that, even in purely soft processes, the hadronic multiplicity in nucleus-nucleus interactions contains a term that scales with the number of binary collisions. In the absence of shadowing corrections, this term dominates at mid rapidities and high energies. Shadowing corrections are calculated as a function of impact parameter and the centrality dependence of mid-rapidity multiplicities is determined. The multiplicity per participant increases with centrality with a rate that increases between SPS and RHIC energies, in agreement with experiment.

  17. A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1

    Science.gov (United States)

    Kilisch, Markus; Lytovchenko, Olga; Arakel, Eric C.; Bertinetti, Daniela; Schwappach, Blanche

    2016-01-01

    ABSTRACT The transport of the K+ channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent binding of 14-3-3 sterically masks a COPI-binding motif. However, the direct effects of phosphorylation on COPI binding and on the binding parameters of 14-3-3 isoforms are still unknown. We find that phosphorylation of the trafficking control region prevents COPI binding even in the absence of 14-3-3, and we present a quantitative analysis of the binding of all human 14-3-3 isoforms to the trafficking control regions of TASK-1 and TASK-3. Surprisingly, the affinities of 14-3-3 proteins for TASK-1 are two orders of magnitude lower than for TASK-3. Furthermore, we find that phosphorylation of a second serine residue in the C-terminus of TASK-1 inhibits 14-3-3 binding. Thus, phosphorylation of the trafficking control region can stimulate or inhibit transport of TASK-1 to the cell surface depending on the target serine residue. Our findings indicate that control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic. PMID:26743085

  18. The role of dual-energy computed tomography in the assessment of pulmonary function

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Jeon [Department of Radiology, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, 22, Gwanpyeong-ro 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do 431-796 (Korea, Republic of); Hoffman, Eric A. [Departments of Radiology, Medicine, and Biomedical Engineering, University of Iowa, 200 Hawkins Dr, CC 701 GH, Iowa City, IA 52241 (United States); Lee, Chang Hyun; Goo, Jin Mo [Department of Radiology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799 (Korea, Republic of); Levin, David L. [Department of Radiology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905 (United States); Kauczor, Hans-Ulrich [Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 400, 69120 Heidelberg (Germany); Seo, Joon Beom, E-mail: seojb@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Pungnap 2-dong, Songpa-ku, Seoul, 05505 (Korea, Republic of)

    2017-01-15

    Highlights: • The dual-energy CT technique enables the differentiation of contrast materials with material decomposition algorithm. • Pulmonary functional information can be evaluated using dual-energy CT with anatomic CT information, simultaneously. • Pulmonary functional information from dual-energy CT can improve diagnosis and severity assessment of diseases. - Abstract: The assessment of pulmonary function, including ventilation and perfusion status, is important in addition to the evaluation of structural changes of the lung parenchyma in various pulmonary diseases. The dual-energy computed tomography (DECT) technique can provide the pulmonary functional information and high resolution anatomic information simultaneously. The application of DECT for the evaluation of pulmonary function has been investigated in various pulmonary diseases, such as pulmonary embolism, asthma and chronic obstructive lung disease and so on. In this review article, we will present principles and technical aspects of DECT, along with clinical applications for the assessment pulmonary function in various lung diseases.

  19. A Developmental Behavioral Analysis of Dual Motives’ Role in Political Economies of Corruption

    Directory of Open Access Journals (Sweden)

    Sara Nora Ross

    2014-03-01

    Full Text Available This paper is a developmental meta-analysis of behaviors that contribute to political economies of corruption, deploying bioneurological dual motive and behavioral development theories. Together, these systems of analysis enable a developmental perspective to illustrate and analyze a progression of dual motives’ variations as humans and their conditions change. The progression of examples indicates that there are multiple evolutions of political economies that vary in their complexity, with different behavioral features at each level. Dual motive theory helps in identifying and understanding the complex linkages and layers of socio-political and economic behaviors as they become more complex. Increasingly complex horizontal and vertical stacks of social networks, like lattice-works of dual motives, enable individuals and groups to develop and maintain sturdy yet adaptable social systems of patronage, brokerage, and clientelism. These so-often informally structured relationships underlie corruption-like transactions long before, and long after, they are regarded as the enduring institution of corruption. Three hypotheses under gird the development of that thesis. The first is that dual motive theory facilitates meta-analyses of social networks’ often hidden layers of complexity. A second hypothesis is that analyses using dual motive theory can explicate more complexity when the theory is integrated with developmental behavioral theory. The third hypothesis is that analyses made possible by that integration offer substantive contributions to understanding socio-political-economic behaviors, including multiple political economies of corruption. Three strategies are employed to develop the paper’s thesis. First, the concepts of social ties, networks, reciprocity and dual motive theory are introduced to set the context. second, a behavioral task measurement theory is introduced: the model of hierarchical complexity. Scoped for this paper to

  20. Role of the limbic system in dependence on drugs.

    Science.gov (United States)

    Rodríguez de Fonseca, F; Navarro, M

    1998-08-01

    The limbic system is a group of structurally and functionally related areas of the brain that provides the anatomical substrate for emotions and motivated behaviour, including the circuitry for the stress response and reward-related events. This system is strongly implicated in drug abuse from the pleasure and/or positive side associated with acute exposure to the dysphoria and craving associated with withdrawal. The contribution of the main cortical and subcortical elements of the limbic system to drug dependence is briefly reviewed in the present work with a focus on the role of the extended amygdala and its connections as well as on the peripheral feedback signals mediated by adrenal glucocorticoids. The elucidation of the neuroadaptive responses of the limbic system to chronic drug exposure will undoubtedly help to design rational strategies for the treatment of addiction.

  1. Physiological roles of Regulated Ire1 Dependent Decay

    Directory of Open Access Journals (Sweden)

    Dina S. Coelho

    2014-04-01

    Full Text Available Ire1 is an important transducer of the Unfolded Protein Response (UPR that is activated by the accumulation of misfolded proteins in the Endoplamic Reticulum (ER stress. Activated Ire1 mediates the splicing of an intron from the mRNA of Xbp1, causing a frame-shift during translation and introducing a new carboxyl domain in the Xbp1 protein, which only then becomes a fully functional transcription factor. Studies using cell culture systems demonstrated that Ire1 also promotes the degradation of mRNAs encoding mostly ER-targeted proteins, to reduce the load of incoming ER client proteins during ER stress. This process was called RIDD (regulated Ire1-dependent decay, but its physiological significance remained poorly characterized beyond cell culture systems. Here we review several recent studies that have highlighted the physiological roles of RIDD in specific biological paradigms, such as photoreceptor differentiation in Drosophila or mammalian liver and endocrine pancreas function. These studies demonstrate the importance of RIDD in tissues undergoing intense secretory function and highlight the physiologic role of RIDD during UPR activation in cells and organisms.

  2. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    International Nuclear Information System (INIS)

    Rodriguez-Acebes, Sara; Cueva, Paloma de la; Ferruelo, Antonio J.; Fernandez-Hernando, Carlos; Lasuncion, Miguel A.; Martinez-Botas, Javier; Gomez-Coronado, Diego

    2008-01-01

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 μM lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  3. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Acebes, Sara [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Cueva, Paloma de la; Ferruelo, Antonio J; Fernandez-Hernando, Carlos [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); Lasuncion, Miguel A [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain); Martinez-Botas, Javier [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Gomez-Coronado, Diego [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es

    2008-12-12

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 {mu}M lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  4. Analysis of dual-phase-lag thermal behaviour in layered films with temperature-dependent interface thermal resistance

    International Nuclear Information System (INIS)

    Liu, K-C

    2005-01-01

    This work analyses theoretically the dual-phase-lag thermal behaviour in two-layered thin films with an interface thermal resistance, which is predicted by the radiation boundary condition model. The effect of the interface thermal resistance on the transmission-reflection phenomenon, induced by a pulsed volumetric source adjacent to the exterior surface of one layer, is investigated. Due to the difference between the two layers in the relaxation times, τ q and τ T , and the nonlinearity of the interfacial boundary condition, complexity is introduced and some mathematical difficulties are involved in solving the present problem. A hybrid application of the Laplace transform method and a control-volume formulation are used along with the linearization technique. The results show that the effect of the thermophysical properties on the behaviour of the energy passing across the interface gradually reduces with increasing interface thermal resistance. The lagging thermal behaviour depends on the magnitude of τ T and τ q more than on the ratio of τ T /τ q

  5. A dual-process approach to exploring the role of delay discounting in obesity.

    Science.gov (United States)

    Price, Menna; Higgs, Suzanne; Maw, James; Lee, Michelle

    2016-08-01

    Delay discounting of financial rewards has been related to overeating and obesity. Neuropsychological evidence supports a dual-system account of both discounting and overeating behaviour where the degree of impulsive decision making is determined by the relative strength of reward desire and executive control. A dual-parameter model of discounting behaviour is consistent with this theory. In this study, the fit of the commonly used one-parameter model was compared to a new dual-parameter model for the first time in a sample of adults with wide ranging BMI. Delay discounting data from 79 males and females (males=26) across a wide age (M=28.44years (SD=8.81)) and BMI range (M=25.42 (SD=5.16)) was analysed. A dual-parameter model (saturating-hyperbolic; Doya, [Doya (2008) ]) was applied to the data and compared on model fit indices to the single-parameter model. Discounting was significantly greater in the overweight/obese participants using both models, however, the two parameter model showed a superior fit to data (pdual-system account of inter-temporal choice behaviour. The dual-parameter model showed superior fit to data and the two parameters were shown to be related yet distinct indices sensitive to differences between weight groups. Findings are discussed in terms of the impulsive reward and executive control systems that contribute to unhealthy food choice and within the context of obesity related research. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A dual system formed by the ARC and NR molybdoenzymes mediates nitrite-dependent NO production in Chlamydomonas.

    Science.gov (United States)

    Chamizo-Ampudia, Alejandro; Sanz-Luque, Emanuel; Llamas, Ángel; Ocaña-Calahorro, Francisco; Mariscal, Vicente; Carreras, Alfonso; Barroso, Juan B; Galván, Aurora; Fernández, Emilio

    2016-10-01

    Nitric oxide (NO) is a relevant signal molecule involved in many plant processes. However, the mechanisms and proteins responsible for its synthesis are scarcely known. In most photosynthetic organisms NO synthases have not been identified, and Nitrate Reductase (NR) has been proposed as the main enzymatic NO source, a process that in vitro is also catalysed by other molybdoenzymes. By studying transcriptional regulation, enzyme approaches, activity assays with in vitro purified proteins and in vivo and in vitro NO determinations, we have addressed the role of NR and Amidoxime Reducing Component (ARC) in the NO synthesis process. N\\R and ARC were intimately related both at transcriptional and activity level. Thus, arc mutants showed high NIA1 (NR gene) expression and NR activity. Conversely, mutants without active NR displayed an increased ARC expression in nitrite medium. Our results with nia1 and arc mutants and with purified enzymes support that ARC catalyses the NO production from nitrite taking electrons from NR and not from Cytb5-1/Cytb5-Reductase, the component partners previously described for ARC (proposed as NOFNiR, Nitric Oxide-Forming Nitrite Reductase). This NR-ARC dual system would be able to produce NO in the presence of nitrate, condition under which NR is unable to do it. © 2016 John Wiley & Sons Ltd.

  7. Dual role of the carboxyl-terminal region of pig liver L-kynurenine 3-monooxygenase: mitochondrial-targeting signal and enzymatic activity.

    Science.gov (United States)

    Hirai, Kumiko; Kuroyanagi, Hidehito; Tatebayashi, Yoshitaka; Hayashi, Yoshitaka; Hirabayashi-Takahashi, Kanako; Saito, Kuniaki; Haga, Seiich; Uemura, Tomihiko; Izumi, Susumu

    2010-12-01

    l-kynurenine 3-monooxygenase (KMO) is an NAD(P)H-dependent flavin monooxygenase that catalyses the hydroxylation of l-kynurenine to 3-hydroxykynurenine, and is localized as an oligomer in the mitochondrial outer membrane. In the human brain, KMO may play an important role in the formation of two neurotoxins, 3-hydroxykynurenine and quinolinic acid, both of which provoke severe neurodegenerative diseases. In mosquitos, it plays a role in the formation both of eye pigment and of an exflagellation-inducing factor (xanthurenic acid). Here, we present evidence that the C-terminal region of pig liver KMO plays a dual role. First, it is required for the enzymatic activity. Second, it functions as a mitochondrial targeting signal as seen in monoamine oxidase B (MAO B) or outer membrane cytochrome b(5). The first role was shown by the comparison of the enzymatic activity of two mutants (C-terminally FLAG-tagged KMO and carboxyl-terminal truncation form, KMOΔC50) with that of the wild-type enzyme expressed in COS-7 cells. The second role was demonstrated with fluorescence microscopy by the comparison of the intracellular localization of the wild-type, three carboxyl-terminal truncated forms (ΔC20, ΔC30 and ΔC50), C-terminally FLAG-tagged wild-type and a mutant KMO, where two arginine residues, Arg461-Arg462, were replaced with Ser residues.

  8. Dual role for plasminogen activator inhibitor type 1 as soluble and as matricellular regulator of epithelial alveolar cell wound healing.

    Science.gov (United States)

    Maquerlot, François; Galiacy, Stephane; Malo, Michel; Guignabert, Christophe; Lawrence, Daniel A; d'Ortho, Maria-Pia; Barlovatz-Meimon, Georgia

    2006-11-01

    Epithelium repair, crucial for restoration of alveolo-capillary barrier integrity, is orchestrated by various cytokines and growth factors. Among them keratinocyte growth factor plays a pivotal role in both cell proliferation and migration. The urokinase plasminogen activator (uPA) system also influences cell migration through proteolysis during epithelial repair. In addition, the complex formed by uPAR-uPA and matrix-bound plasminogen activator inhibitor type-1 (PAI-1) exerts nonproteolytic roles in various cell types. Here we present new evidence about the dual role of PAI-1 under keratinocyte growth factor stimulation using an in vitro repair model of rat alveolar epithelial cells. Besides proteolytic involvement of the uPA system, the availability of matrix-bound-PAI-1 is also required for an efficient healing. An unexpected decrease of healing was shown when PAI-1 activity was blocked. However, the proteolytic action of uPA and plasmin were still required. Moreover, immediately after wounding, PAI-1 was dramatically increased in the newly deposited matrix at the leading edge of wounds. We thus propose a dual role for PAI-1 in epithelial cell wound healing, both as a soluble inhibitor of proteolysis and also as a matrix-bound regulator of cell migration. Matrix-bound PAI-1 could thus be considered as a new member of the matricellular protein family.

  9. Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

    Directory of Open Access Journals (Sweden)

    Qing Li

    2016-06-01

    Full Text Available Background/Aims: Our previous studies have indicated that a novel endothelin receptor antagonist CPU0213 effectively normalized renal function in diabetic nephropathy. However, the molecular mechanisms mediating the nephroprotective role of CPU0213 remain unknown. Methods and Results: In the present study, we first detected the role of CPU0213 on apoptosis in human renal tubular epithelial cell (HK-2. It was shown that high glucose significantly increased the protein expression of Bax and decreased Bcl-2 protein in HK-2 cells, which was reversed by CPU0213. The percentage of HK-2 cells that showed Annexin V-FITC binding was markedly suppressed by CPU0213, which confirmed the inhibitory role of CPU0213 on apoptosis. Given the regulation of endothelin (ET system to oxidative stress, we determined the role of redox signaling in the regulation of CPU0213 on apoptosis. It was demonstrated that the production of superoxide (O2-. was substantially attenuated by CPU0213 treatment in HK-2 cells. We further found that CPU0213 dramatically inhibited expression of Nox4 protein, which gene silencing mimicked the role of CPU0213 on the apoptosis under high glucose stimulation. We finally examined the role of CPU0213 on ET-1 receptors and found that high glucose-induced protein expression of endothelin A and B receptors was dramatically inhibited by CPU0213. Conclusion: Taken together, these results suggest that this Nox4-dependenet O2- production is critical for the apoptosis of HK-2 cells in high glucose. Endothelin receptor antagonist CPU0213 has an anti-apoptosis role through Nox4-dependent O2-.production, which address the nephroprotective role of CPU0213 in diabetic nephropathy.

  10. Students with Dual Diagnosis: Can School-Based Mental Health Services Play a Role?

    Science.gov (United States)

    Lambros, Katina; Kraemer, Bonnie; Wager, James Derek; Culver, Shirley; Angulo, Aidee; Saragosa, Marie

    2016-01-01

    This article describes and investigates initial findings from the Esperanza Mental Health Services (EMHS) Program, which is an intensive outpatient program that provides individual and group mental health services for students with "dual diagnosis" or developmental disabilities and co-occurring mental health problems. Previous research…

  11. From proactive to retroactive dual-task interference: The important role of Task-2 probability

    NARCIS (Netherlands)

    Nieuwenstein, Mark; Scholz, S.; Broers, Nico

    2014-01-01

    Dual-task studies on the attentional blink (AB) and psychological refractory period (PRP) effect show that the processing of a first target (T1) obstructs the processing of a shortly following target (T2). Recently, Nieuwenstein and Wyble (2014) found an opposite pattern, such that a memory encoding

  12. Adult Age Differences in Dual Information Processes: Implications for the Role of Affective and Deliberative Processes in Older Adults' Decision Making.

    Science.gov (United States)

    Peters, Ellen; Hess, Thomas M; Västfjäll, Daniel; Auman, Corinne

    2007-03-01

    Age differences in affective/experiential and deliberative processes have important theoretical implications for judgment and decision theory and important pragmatic implications for older-adult decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age. However, age-related adaptive processes, including motivated selectivity in the use of deliberative capacity, an increased focus on emotional goals, and greater experience, predict better or worse decisions for older adults depending on the situation. The aim of the current review is to examine adult age differences in affective and deliberative information processes in order to understand their potential impact on judgments and decisions. We review evidence for the role of these dual processes in judgment and decision making and then review two representative life-span perspectives (based on aging-related changes to cognitive or motivational processes) on the interplay between these processes. We present relevant predictions for older-adult decisions and make note of contradictions and gaps that currently exist in the literature. Finally, we review the sparse evidence about age differences in decision making and how theories and findings regarding dual processes could be applied to decision theory and decision aiding. In particular, we focus on prospect theory (Kahneman & Tversky, 1979) and how prospect theory and theories regarding age differences in information processing can inform one another. © 2007 Association for Psychological Science.

  13. The role of gender in the association between personality and task priority in older adults' dual-tasking while walking.

    Science.gov (United States)

    Agmon, Maayan; Armon, Galit; Denesh, Shani; Doumas, Mihalis

    2018-01-02

    Falls are a major problem for older adults. Many falls occur when a person's attention is divided between two tasks, such as a dual task (DT) involving walking. Most recently, the role of personality in walking performance was addressed; however, its association with DT performance remains to be determined. This cross-sectional study of 73 older, community-dwelling adults explores the association between personality and DT walking and the role of gender in this relationship. Personality was evaluated using the five-factor model. Single-task (ST) and DT assessment of walking-cognitive DT performance comprised a 1-min walking task and an arithmetic task performed separately (ST) and concurrently (DT). Dual-task costs (DTCs), reflecting the proportional difference between ST and DT performance, were also calculated. Gender plays a role in the relationship between personality and DT. Extraversion was negatively associated with DTC-motor for men (ΔR 2  = 0.06, p fall prevention.

  14. Speed-dependent Voigt lineshape parameter database from dual frequency comb measurements up to 1305 K. Part I: Pure H2O absorption, 6801-7188 cm-1

    Science.gov (United States)

    Schroeder, Paul J.; Cich, Matthew J.; Yang, Jinyu; Giorgetta, Fabrizio R.; Swann, William C.; Coddington, Ian; Newbury, Nathan R.; Drouin, Brian J.; Rieker, Gregory B.

    2018-05-01

    We measure speed-dependent Voigt lineshape parameters with temperature-dependence exponents for several hundred spectroscopic features of pure water spanning 6801-7188 cm-1. The parameters are extracted from broad bandwidth, high-resolution dual frequency comb absorption spectra with multispectrum fitting techniques. The data encompass 25 spectra ranging from 296 K to 1305 K and 1 to 17 Torr of pure water vapor. We present the extracted parameters, compare them to published data, and present speed-dependence, self-shift, and self-broadening temperature-dependent parameters for the first time. Lineshape data is extracted using a quadratic speed-dependent Voigt profile and a single self-broadening power law temperature-dependence exponent over the entire temperature range. The results represent an important step toward a new high-temperature database using advanced lineshape profiles.

  15. Graphene Oxides Used as a New "Dual Role" Binder for Stabilizing Silicon Nanoparticles in Lithium-Ion Battery.

    Science.gov (United States)

    Shan, Changsheng; Wu, Kaifeng; Yen, Hung-Ju; Narvaez Villarrubia, Claudia; Nakotte, Tom; Bo, Xiangjie; Zhou, Ming; Wu, Gang; Wang, Hsing-Lin

    2018-05-09

    For the first time, we report that graphene oxide (GO) can be used as a new "dual-role" binder for Si nanoparticles (SiNPs)-based lithium-ion batteries (LIBs). GO not only provides a graphene-like porous 3D framework for accommodating the volume changes of SiNPs during charging/discharging cycles, but also acts as a polymer-like binder that forms strong chemical bonds with SiNPs through its Si-OH functional groups to trap and stabilize SiNPs inside the electrode. Leveraging this unique dual-role of GO binder, we fabricated GO/SiNPs electrodes with remarkably improved performances as compared to using the conventional polyvinylidene fluoride (PVDF) binder. Specifically, the GO/SiNPs electrode showed a specific capacity of 2400 mA h g -1 at the 50th cycle and 2000 mA h g -1 at the 100th cycle, whereas the SiNPs/PVDF electrode only showed 456 mAh g -1 at the 50th cycle and 100 mAh g -1 at 100th cycle. Moreover, the GO/SiNPs film maintained its structural integrity and formed a stable solid-electrolyte interphase (SEI) film after 100 cycles. These results, combined with the well-established facile synthesis of GO, indicate that GO can be an excellent binder for developing high performance Si-based LIBs.

  16. Once a clinician, always a clinician: a systematic review to develop a typology of clinician-researcher dual-role experiences in health research with patient-participants

    Directory of Open Access Journals (Sweden)

    E. Jean C. Hay-Smith

    2016-08-01

    Full Text Available Abstract Background Many health researchers are clinicians. Dual-role experiences are common for clinician-researchers in research involving patient-participants, even if not their own patients. To extend the existing body of literature on why dual-role is experienced, we aimed to develop a typology of common catalysts for dual-role experiences to help clinician-researchers plan and implement methodologically and ethically sound research. Methods Systematic searching of Medline, CINAHL, PsycINFO, Embase and Scopus (inception to 28.07.2014 for primary studies or first-person reflexive reports of clinician-researchers’ dual-role experiences, supplemented by reference list checking and Google Scholar scoping searches. Included articles were loaded in NVivo for analysis. The coding was focused on how dual-role was evidenced for the clinician-researchers in research involving patients. Procedures were completed by one researcher (MB and independently cross-checked by another (JHS. All authors contributed to extensive discussions to resolve all disagreements about initial coding and verify the final themes. Results Database searching located 7135 records, resulting in 29 included studies, with the addition of 7 studies through reference checks and scoping searches. Two overarching themes described the most common catalysts for dual-role experiences – ways a research role can involve patterns of behaviour typical of a clinical role, and the developing connection that starts to resemble a clinician-patient relationship. Five subthemes encapsulated the clinical patterns commonly repeated in research settings (clinical queries, perceived agenda, helping hands, uninvited clinical expert, and research or therapy and five subthemes described concerns about the researcher-participant relationship (clinical assumptions, suspicion and holding back, revelations, over-identification, and manipulation. Clinician-researchers use their clinical skills in health

  17. A role for barley calcium-dependent protein kinase CPK2a in the response to drought

    Directory of Open Access Journals (Sweden)

    Agata Cieśla

    2016-10-01

    Full Text Available Increasing the drought tolerance of crops is one of the most challenging goals in plant breeding. To improve crop productivity during periods of water deficit, it is essential to understand the complex regulatory pathways that adapt plant metabolism to environmental conditions. Among various plant hormones and second messengers, calcium ions are known to be involved in drought stress perception and signaling. Plants have developed specific calcium-dependent protein kinases that convert calcium signals into phosphorylation events. In this study we attempted to elucidate the role of a calcium-dependent protein kinase in the drought stress response of barley (Hordeum vulgare L., one of the most economically important crops worldwide. The ongoing barley genome project has provided useful information about genes potentially involved in the drought stress response, but information on the role of calcium-dependent kinases is still limited. We found that the gene encoding the calcium-dependent protein kinase HvCPK2a was significantly upregulated in response to drought. To better understand the role of HvCPK2a in drought stress signaling, we generated transgenic Arabidopsis plants that overexpressed the corresponding coding sequence. Overexpressing lines displayed drought sensitivity, reduced nitrogen balance index, an increase in total chlorophyll content and decreased relative water content. In addition, in vitro kinase assay experiments combined with mass spectrometry allowed HvCPK2a autophosphorylation sites to be identified. Our results suggest that HvCPK2a is a dual-specificity calcium-dependent protein kinase that functions as a negative regulator of the drought stress response in barley.

  18. Dual role of proapoptotic BAD in insulin secretion and beta cell survival.

    Science.gov (United States)

    Danial, Nika N; Walensky, Loren D; Zhang, Chen-Yu; Choi, Cheol Soo; Fisher, Jill K; Molina, Anthony J A; Datta, Sandeep Robert; Pitter, Kenneth L; Bird, Gregory H; Wikstrom, Jakob D; Deeney, Jude T; Robertson, Kirsten; Morash, Joel; Kulkarni, Ameya; Neschen, Susanne; Kim, Sheene; Greenberg, Michael E; Corkey, Barbara E; Shirihai, Orian S; Shulman, Gerald I; Lowell, Bradford B; Korsmeyer, Stanley J

    2008-02-01

    The proapoptotic BCL-2 family member BAD resides in a glucokinase-containing complex that regulates glucose-driven mitochondrial respiration. Here, we present genetic evidence of a physiologic role for BAD in glucose-stimulated insulin secretion by beta cells. This novel function of BAD is specifically dependent upon the phosphorylation of its BH3 sequence, previously defined as an essential death domain. We highlight the pharmacologic relevance of phosphorylated BAD BH3 by using cell-permeable, hydrocarbon-stapled BAD BH3 helices that target glucokinase, restore glucose-driven mitochondrial respiration and correct the insulin secretory response in Bad-deficient islets. Our studies uncover an alternative target and function for the BAD BH3 domain and emphasize the therapeutic potential of phosphorylated BAD BH3 mimetics in selectively restoring beta cell function. Furthermore, we show that BAD regulates the physiologic adaptation of beta cell mass during high-fat feeding. Our findings provide genetic proof of the bifunctional activities of BAD in both beta cell survival and insulin secretion.

  19. The Dual Role of Disorder on the Dissociation of Interfacial Charge Transfer Excitons

    Science.gov (United States)

    Shi, Liang; Lee, Chee-Kong; Willard, Adam

    In organic-based photovoltaics (OPV), dissociation of neutral photo-excitations (i.e., Frenkel excitons) into free charge carriers requires the excitons to overcome binding energy that can significantly exceed thermal energies. The inability of bound charges to overcome this large binding energy has been implicated as a primary source of efficiency loss in OPVs. Despite the potential impact on the performance of organic solar cells much remains to be understood about the microscopic mechanism of exciton dissociation in OPV materials. Here we explore the role of static molecular disorder in mediating this charge dissociation process. Using a simple lattice model of exciton dynamics we demonstrate that random spatial variations in the energetic landscape can mitigate the effects of the exciton binding energy by lowering the free energy barrier. By considering the competition between this thermodynamic effect and the disorder-induced slowing of dissociation kinetics we demonstrate that exciton dissociation yields are expected to depend non-monotonically on the degree of static disorder. We conclude that a certain amount of molecular-scale disorder is desirable in order to optimize the performance of organic photovoltaic materials.

  20. Impact of the role of senior dual disability coordinator on the perceived self-efficacy and job satisfaction of mental health clinicians.

    Science.gov (United States)

    Hendren, Amanda Jayne; Kendall, Melissa Bianca

    2015-01-01

    This study aimed to evaluate a new service role in mental health services, namely, the senior dual disability coordinator role (SDDC) for its impact on the perceived self-efficacy of mental health clinicians in managing clients with dual disability (mental illness and acquired brain injury and/or intellectual disability) and their job satisfaction. Mental health clinicians from a health service district in Queensland, Australia who contacted the SDDC for clinical consultation and liaison between July 2011 and July 2013 were asked to complete a questionnaire assessing perceived self-efficacy in working with clients with dual disability as well as their job satisfaction, prior to (T1) and following (T2) their contact with the SDDC. Twenty-five clinicians completed and returned pre- and post-measure questionnaires. Self-reported knowledge of dual disability, clinical skills in dual disability, service knowledge in dual disability as well as perceived self-efficacy, and job satisfaction increased significantly from T1 to T2. There were no significant differences across professional discipline or years of service. The delivery of a clinical consultation liaison service as part of the role of SDDC may assist mental health clinicians with self-efficacy and job satisfaction, regardless of the number of years they have worked in the service or their professional discipline. Mental health clinicians with improved self-efficacy for working with clients with dual disability may be more likely to consider the client suitable for services through mental health and follow-up with treatment and linking the client with other identified suitable services. Implications for Rehabilitation Dual disability (mental illness and acquired brain injury and/or intellectual disability) presents specific challenges for mental health services Specific strategies are needed to build capacity among mental health practitioners in order to meet the needs of people with dual disability and provide

  1. Role of Dependence in Chance-constrained and Robust Programming

    Czech Academy of Sciences Publication Activity Database

    Houda, Michal

    2007-01-01

    Roč. 15, č. 4 (2007), s. 111-120 ISSN 0572-3043 R&D Projects: GA ČR GD402/03/H057; GA ČR GA402/07/1113 Institutional research plan: CEZ:AV0Z10750506 Keywords : stochastic programming * robust programming * weak dependence Subject RIV: AH - Economics

  2. The Role of Student Publications Depends on Healing Process.

    Science.gov (United States)

    Zibluk, Jack

    1999-01-01

    Notes two very different reactions to school shootings--Westside Middle School has no memorials and no media coverage of the four classmates and a teacher who were killed, whereas Columbine High School has erected memorials and is subject to ongoing media coverage. Concludes that the student media's role in covering tragic events is unique to each…

  3. The dual effects of leading for safety: The mediating role of employee regulatory focus.

    Science.gov (United States)

    Kark, Ronit; Katz-Navon, Tal; Delegach, Marianna

    2015-09-01

    This study examined the underlying mechanisms through which transformational and transactional leadership influence employee safety behaviors. Linking leadership theory with self-regulatory focus (SRF) theory, we examined a model of dual effects of leadership on safety initiative and safety compliance behaviors as mediated by promotion and prevention self-regulations. We conducted an experimental study (N = 107), an online study (N = 99) and a field study (N = 798 employees and 49 managers). Results demonstrated that followers' situational promotion focus mediated the positive relationship between transformational leadership and safety initiative behaviors. Through all 3 studies, transactional active leadership was positively associated with followers' situational prevention focus, however, the association between followers' prevention focus and safety compliance behaviors was inconsistent, showing the expected mediation relationships in the experimental setting, but not in the online and field studies. We discuss theoretical and practical implications of the findings. (c) 2015 APA, all rights reserved).

  4. [Role of the nurse in the prevention of dependence].

    Science.gov (United States)

    Bouchon, Laure; Lagourdette, Christine; Pedra, Maryse; Chassaigne, Marie-Christine; Vellas, Bruno; Berbon, Caroline

    2016-01-01

    Preventing frailty in elderly people to delay their dependency is one of the main missions of the Gérontopôle, a centre of expertise for gerontology, in Toulouse. The proposed actions are simple to put in place and the nurses are autonomous in carrying out assessments. Nursing expertise has also been developed within the centre. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Optimizing Parkinson's disease diagnosis: the role of a dual nuclear imaging algorithm.

    Science.gov (United States)

    Langston, J William; Wiley, Jesse C; Tagliati, Michele

    2018-01-01

    The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine 123 I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency. There is evidence to support an algorithm utilizing a dual neuroimaging strategy combining 123 I-ioflupane SPECT and the noradrenergic receptor ligand 123 I-metaiodobenzylguanidine (MIBG), which assesses the post-ganglion peripheral autonomic nervous system. Evolving concepts regarding the synucleinopathy affecting the central and peripheral autonomic nervous systems as part of a multisystem disease are reviewed to sustain such strategy. Data are presented to show how MIBG deficits are a common feature of multisystem Lewy body disease and can be used as a unique feature to distinguish PD from atypical parkinsonisms. We propose that the combination of cardiac (MIBG) and cerebral 123 I-ioflupane SPECT could satisfy one of the most significant unmet needs of current PD diagnosis and management, namely the early and accurate diagnosis of patients with typical Lewy body PD. Exemplary case scenarios will be described, highlighting how dual neuroimaging strategy can maximize diagnostic accuracy for patient care, clinical trials, pre-symptomatic PD screening, and special cases provided by specific genetic mutations associated with PD.

  6. Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

    Directory of Open Access Journals (Sweden)

    Manasi Das

    Full Text Available Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined and single or dual drug loaded nanoparticles (unconjugated/folate conjugated. The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

  7. On the dual and paradoxical role of media: Messengers of the dominant ideology and vehicles of disruptive speech

    Directory of Open Access Journals (Sweden)

    José Rebelo

    2014-11-01

    Full Text Available This article aims to evaluate the dual function exercised by traditional media - TV, radio and press – as a place of ideological production, assuming the power of communication as a method of naturalization, and as a place of confrontation, giving voice to alternative projects. First, the function of ideological production, in regards to the national and international media coverage of the financial crisis in Portugal, warrants consideration. Furthermore, the role of media confrontation is illuminated by the coverage of protests in Portugal and Brazil. Concluding, if traditional media convey dominant norms and hierarchies, notwithstanding the pressure on social networks, this mode indicates a deviation, thus contributing, even if indirectly, to a redefinition of people and culture.

  8. Outcome of alcohol dependence: The role of continued care

    Directory of Open Access Journals (Sweden)

    Murthy Pratima

    2009-01-01

    Full Text Available Aims: This study attempted to determine the effects of continued care on subjects with alcohol dependence. Materials and Methods: Study patients were recruited from a slum in Bangalore. The control group comprised individuals from a lower socio-economic status. Both groups received identical treatment from a specialised de-addiction facility. The study group also received weekly continued care in the community, either at a clinic located within the slum or through home visits. Those patients without stable jobs were referred for employment. The control group was given routine hospital follow-up visits. Both groups were evaluated on the Alcohol Problem Questionnaire and quantity/frequency of drinking at baseline and every 3 month interval for one year after discharge. Results: Both groups showed improvement in terms of reduction of drinking at 3 months, with the study group showing a 64% improvement with respect to the number of non drinking days and the control group showed a 50% improvement. However, at 6 months, 9 months, and 12 months, the study group continued to maintain these gains while the control group showed a downward slide (differences significant at P < 0.05. At the end of 12 months, the study group maintained a 53% improvement with respect to the number of non drinking days as compared with baseline, while the control group had an improvement of only 28%. Conclusions: Follow-up support and continued care appear to significantly improve longer-term recovery in alcohol dependents.

  9. Implementation science: a role for parallel dual processing models of reasoning?

    Directory of Open Access Journals (Sweden)

    Phillips Paddy A

    2006-05-01

    Full Text Available Abstract Background A better theoretical base for understanding professional behaviour change is needed to support evidence-based changes in medical practice. Traditionally strategies to encourage changes in clinical practices have been guided empirically, without explicit consideration of underlying theoretical rationales for such strategies. This paper considers a theoretical framework for reasoning from within psychology for identifying individual differences in cognitive processing between doctors that could moderate the decision to incorporate new evidence into their clinical decision-making. Discussion Parallel dual processing models of reasoning posit two cognitive modes of information processing that are in constant operation as humans reason. One mode has been described as experiential, fast and heuristic; the other as rational, conscious and rule based. Within such models, the uptake of new research evidence can be represented by the latter mode; it is reflective, explicit and intentional. On the other hand, well practiced clinical judgments can be positioned in the experiential mode, being automatic, reflexive and swift. Research suggests that individual differences between people in both cognitive capacity (e.g., intelligence and cognitive processing (e.g., thinking styles influence how both reasoning modes interact. This being so, it is proposed that these same differences between doctors may moderate the uptake of new research evidence. Such dispositional characteristics have largely been ignored in research investigating effective strategies in implementing research evidence. Whilst medical decision-making occurs in a complex social environment with multiple influences and decision makers, it remains true that an individual doctor's judgment still retains a key position in terms of diagnostic and treatment decisions for individual patients. This paper argues therefore, that individual differences between doctors in terms of

  10. Implementation science: a role for parallel dual processing models of reasoning?

    Science.gov (United States)

    Sladek, Ruth M; Phillips, Paddy A; Bond, Malcolm J

    2006-05-25

    A better theoretical base for understanding professional behaviour change is needed to support evidence-based changes in medical practice. Traditionally strategies to encourage changes in clinical practices have been guided empirically, without explicit consideration of underlying theoretical rationales for such strategies. This paper considers a theoretical framework for reasoning from within psychology for identifying individual differences in cognitive processing between doctors that could moderate the decision to incorporate new evidence into their clinical decision-making. Parallel dual processing models of reasoning posit two cognitive modes of information processing that are in constant operation as humans reason. One mode has been described as experiential, fast and heuristic; the other as rational, conscious and rule based. Within such models, the uptake of new research evidence can be represented by the latter mode; it is reflective, explicit and intentional. On the other hand, well practiced clinical judgments can be positioned in the experiential mode, being automatic, reflexive and swift. Research suggests that individual differences between people in both cognitive capacity (e.g., intelligence) and cognitive processing (e.g., thinking styles) influence how both reasoning modes interact. This being so, it is proposed that these same differences between doctors may moderate the uptake of new research evidence. Such dispositional characteristics have largely been ignored in research investigating effective strategies in implementing research evidence. Whilst medical decision-making occurs in a complex social environment with multiple influences and decision makers, it remains true that an individual doctor's judgment still retains a key position in terms of diagnostic and treatment decisions for individual patients. This paper argues therefore, that individual differences between doctors in terms of reasoning are important considerations in any

  11. Kidneys at Higher Risk of Discard: Expanding the Role of Dual Kidney Transplantation

    Science.gov (United States)

    Tanriover, B.; Mohan, S.; Cohen, D. J.; Radhakrishnan, J.; Nickolas, T. L.; Stone, P. W.; Tsapepas, D. S.; Crew, R. J.; Dube, G. K.; Sandoval, P. R.; Samstein, B.; Dogan, E.; Gaston, R. S.; Tanriover, J. N.; Ratner, L. E.; Hardy, M. A.

    2014-01-01

    Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI) >85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (90%). Kidneys with KDPI >90% were associated with increased odds of discard (OR = 1.99, 95% CI 1.74–2.29) compared to ones with KDPI 90% were associated with lower overall allograft failure (HR = 0.74, 95% CI 0.62–0.89) and better patient survival (HR = 0.79, 95% CI 0.64–0.98) compared to single ECD kidneys with KDPI >90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile. PMID:24472195

  12. Cystatin C Has a Dual Role in Post-Traumatic Brain Injury Recovery

    Directory of Open Access Journals (Sweden)

    Marina Martinez-Vargas

    2014-04-01

    Full Text Available Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage.

  13. Internet Dependence in an Undergraduate Population: The Roles of Coping with Stress, Self-Efficacy Beliefs, and Sex Role Orientation

    Science.gov (United States)

    Odaci, Hatice; Çelik, Çigdem B.

    2017-01-01

    This study examined the relationship between Internet dependence in university students and forms of coping with stress and self-efficacy and investigated whether Internet dependence varies according to such variables as sex roles, gender, and duration of Internet use. The study was performed with 632 university students. The Internet Addiction…

  14. The Different Role of Working Memory in Open-Ended versus Closed-Ended Creative Problem Solving: A Dual-Process Theory Account

    Science.gov (United States)

    Lin, Wei-Lun; Lien, Yunn-Wen

    2013-01-01

    This study examined how working memory plays different roles in open-ended versus closed-ended creative problem-solving processes, as represented by divergent thinking tests and insight problem-solving tasks. With respect to the analysis of different task demands and the framework of dual-process theories, the hypothesis was that the idea…

  15. Dosage-dependent role of Rac1 in podocyte injury

    Science.gov (United States)

    Wan, Xiaoyang; Lee, Mi-Sun

    2016-01-01

    Activation of small GTPase Rac1 in podocytes is associated with rodent models of kidney injury and familial nephrotic syndrome. Induced Rac1 activation in podocytes in transgenic mice results in rapid transient proteinuria and foot process effacement, but not glomerular sclerosis. Thus it remains an open question whether abnormal activation of Rac1 in podocytes is sufficient to cause permanent podocyte damage. Using a number of transgenic zebrafish models, we showed that moderate elevation of Rac1 activity in podocytes did not impair the glomerular filtration barrier but aggravated metronidazole-induced podocyte injury, while inhibition of Rac1 activity ameliorated metronidazole-induced podocyte injury. Furthermore, a further increase in Rac1 activity in podocytes was sufficient to cause proteinuria and foot process effacement, which resulted in edema and lethality in juvenile zebrafish. We also found that activation of Rac1 in podocytes significantly downregulated the expression of nephrin and podocin, suggesting an adverse effect of Rac1 on slit diaphragm protein expression. Taken together, our data have demonstrated a causal link between excessive Rac1 activity and podocyte injury in a dosage-dependent manner, and transgenic zebrafish of variable Rac1 activities in podocytes may serve as useful animal models for the study of Rac1-related podocytopathy. PMID:26792065

  16. Dual Role of Interleukin-23 in Epicutaneously-Sensitized Asthma in Mice

    Directory of Open Access Journals (Sweden)

    Katsunori Masaki

    2014-01-01

    Conclusions: IL-23 expressed in the skin during the sensitization phase plays an essential role in the development of allergic phenotypes, whereas IL-23 in the airways during the challenge phase suppresses airway hy- perresponsiveness.

  17. The dual role of local sites in assisting firms with developing technological capabilities: Evidence from China

    DEFF Research Database (Denmark)

    Wang, Yuandi; Zhou, Zhao

    2013-01-01

    .g., knowledge, human capital) and the role of motivating multinational companies (MNCs) to upgrade their local operations in developing countries so as to perform more innovation activities. Few articles are presented that examine the role of local sites in the learning and technological-capability building......, and the collaborations with local industrial community firms positively influence the relationship between firms' international inward technology licensing and technological capabilities. (C) 2012 Elsevier Ltd. All rights reserved....

  18. Endogenous opioids: role in prostaglandin-dependent and -independent fever.

    Science.gov (United States)

    Fraga, Daniel; Machado, Renes R; Fernandes, Luíz C; Souza, Glória E P; Zampronio, Aleksander R

    2008-02-01

    This study evaluated the participation of mu-opioid-receptor activation in body temperature (T(b)) during normal and febrile conditions (including activation of heat conservation mechanisms) and in different pathways of LPS-induced fever. The intracerebroventricular treatment of male Wistar rats with the selective opioid mu-receptor-antagonist cyclic d-Phe-Cys-Try-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP; 0.1-1.0 microg) reduced fever induced by LPS (5.0 microg/kg) but did not change T(b) at ambient temperatures of either 20 degrees C or 28 degrees C. The subcutaneous, intracerebroventricular, and intrahypothalamic injection of morphine (1.0-10.0 mg/kg, 3.0-30.0 microg, and 1-100 ng, respectively) produced a dose-dependent increase in T(b). Intracerebroventricular morphine also produced a peripheral vasoconstriction. Both effects were abolished by CTAP. CTAP (1.0 microg icv) reduced the fever induced by intracerebroventricular administration of TNF-alpha (250 ng), IL-6 (300 ng), CRF (2.5 microg), endothelin-1 (1.0 pmol), and macrophage inflammatory protein (500 pg) and the first phase of the fever induced by PGF(2alpha) (500.0 ng) but not the fever induced by IL-1beta (3.12 ng) or PGE(2) (125.0 ng) or the second phase of the fever induced by PGF(2alpha). Morphine-induced fever was not modified by the cyclooxygenase (COX) inhibitor indomethacin (2.0 mg/kg). In addition, morphine injection did not induce the expression of COX-2 in the hypothalamus, and CTAP did not modify PGE(2) levels in cerebrospinal fluid or COX-2 expression in the hypothalamus after LPS injection. In conclusion, our results suggest that LPS and endogenous pyrogens (except IL-1beta and prostaglandins) recruit the opioid system to cause a mu-receptor-mediated fever.

  19. Assessing the roles of impulsivity, food-related cognitions, BMI, and demographics in the dual pathway model of binge eating among men and women.

    Science.gov (United States)

    Mason, Tyler B; Lewis, Robin J

    2015-08-01

    The dual pathway model is a widely accepted model of binge eating that focuses on the role of sociocultural factors, negative affect, and dietary restraint. However, less is known about demographic (e.g., gender and ethnicity) differences in the model and the role of other variables in the model. To further our understanding of the dual pathway model of binge eating, the current study examined the role of demographics (i.e., gender, race, BMI, parental education and obesity), impulsivity, and food-related cognitions in the dual pathway model. A sample of college students completed a battery of measures. Multi-group structural equation modeling was used to evaluate the dual pathway model separately for men and women. Results supported the dual pathway model of binge eating among men and women, and also supported food-related cognitions as an important variable prior to binge eating. In other words, body shame was associated with more dietary restraint and negative affect, and in turn, dietary restraint and negative affect were associated with increased negative food-related cognitions. Then, food-related cognitions predicted binge eating. Additionally impulsivity was related to body shame, negative affect, and food-related cognitions, but was unrelated to binge eating after controlling for the other variables. Racial differences existed among women in BMI and body shame, but there were no racial differences among men. Our results suggest that the dual pathway model adequately explains binge eating among men and women, but that food-related cognitions may be an imporant anteceden to binge eating. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Role of digital tomosynthesis and dual energy subtraction digital radiography in detecting pulmonary nodules

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Sarvana G. [Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 160012 (India); Garg, Mandeep Kumar, E-mail: gargmandeep01@gmail.com [Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 160012 (India); Khandelwal, Niranjan; Gupta, Pankaj [Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 160012 (India); Gupta, Dheeraj; Aggarwal, Ashutosh Nath [Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 160012 (India); Bansal, Subash Chand [Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh 160012 (India)

    2015-07-15

    Highlights: • Accuracy of digital tomosynthesis for nodule detection is substantially higher. • Improvement in diagnostic accuracy is most pronounced for nodules <10 mm. • There is five times increase in radiation dose compared to DR. - Abstract: Objective: Digital tomosynthesis (DT) and dual-energy subtraction digital radiography (DES-DR) are known to perform better than conventional radiography in the detection of pulmonary nodules. Yet the comparative diagnostic performances of DT, DES-DR and digital radiography (DR) is not known. The present study compares the diagnostic performances of DT, DES-DR and DR in detecting pulmonary nodules. Subjects and methods: The institutional Review Board approved the study and informed written consent was obtained. Fifty-five patients (30 with pulmonary nodules, 25 with non-nodular focal chest pathology) were included in the study. DT and DES-DR were performed within14 days of MDCT. Composite images acquired at high kVp as part of DES-DR were used as DR images. Images were analyzed for presence of nodules and calcification in nodules. Interpretations were assigned confidence levels from 1 to 5 according to Five-Point rating scale. Areas under the receiver operating characteristic curves were compared using Z test. Results: A total of 110 (88 non-calcified, 22 calcified) nodules were identified on MDCT. For detection of nodules, DR showed cumulative sensitivity and specificity of 25.45% and 67.97%, respectively. DT showed a cumulative sensitivity and specificity of 60.9% and 85.07%, respectively. The performance was significantly better than DR (p < 0.003). DES-DR showed sensitivity and specificity of 27.75% and 82.64%, not statistically different from those of DR (p—0.92). In detection of calcification, there was no statistically significant difference between DT, DES-DR and DR. Conclusions: DT performs significantly better than DES-DR and DR at the cost of moderate increase in radiation dose.

  1. BETWEEN SOCIAL HUMANISM AND SOCIAL MOBILIZATION: The Dual Role of Madrasah in the Landscape of Indonesian Islamic Education

    Directory of Open Access Journals (Sweden)

    Sunhaji Sunhaji

    2017-07-01

    Full Text Available This article analyzes the dual as well as overlapping role of madrasah in the history of Indonesian Islamic education. It argues that madrasah has long been playing the double roles at once; on the one hand it has served as the enlightening process of Indonesian Islam by giving a sense of moderation. It also has paved the way for the accommodation of non-religious subjects within its existing religious ones. In this sense, madrasah has played its social humanism. Madrasah, however, has been an effective means of power struggle as well as social mobilization among Muslims into the center of socio-political spheres. As Indonesian Muslims have long been marginalized by non-Islamic schooling system, madrasah has helped them struggle from their marginality through the emancipation and participation programs launched by madrasah. Muslims have been incessantly fought for their equality in terms of madrasah’s legal status and demanded more equal treatment from the state. In effect, the enactment of the Law No. 2/1989 marks a radical shift in the direction of Islamic education in Indonesia which is celebrated by the community of madrasah as a new era for their autonomy and equal status before the state.

  2. Preoperative evaluation of hyperparathyroidism. The role of dual-phase parathyroid scintigraphy and ultrasound imaging

    International Nuclear Information System (INIS)

    Sukan, A.; Reyhan, M.; Aydin, M.; Yapar, A.F.; Aktas, A.; Sert, Y.; Canpolat, T.

    2008-01-01

    The aim of this study was to evaluate the efficacy of dual-phase 99mTc-methoxyisobutylnitrile (MIBI) parathyroid scintigraphy (PS) and ultrasound (US) in primary (pHPT) and secondary (sHPT) hyperparathyroidism. A total of 69 patients (mean age 47±16; age range 14-79 years), including 19 patients with sHPT were enrolled in this study. Preoperative serum intact parathyroid hormone (iPTH) levels, calcium (Ca), phosphate (P), alkaline phosphatase, and 24-h urinary-free Ca measurements were obtained. Concomitant thyroid pathology was also recorded. Histopathology revealed 30 solitary adenomas and 71 hyperplastic glands in 55 patients. The remaining patients' histopathology revealed normal parathyroid, thyroid, or lymph nodes. The sensitivities of MIBI and US in pUPT were 70% and 60%, respectively. It was 60% for both procedures in sHPT. The overall sensitivity of combined US+MIBI in pHPT and sHPT was 81% and 71%, respectively. The overall specificity of MIBI and US was 87% and 91%; positive predictive value (PPV) was 94% and 92%, respectively. MIBI and US identified the parathyroid pathology in 92% and 85% of patients in the non-concomitant thyroid disease group, and in 53% and 47% of patients in the concomitant thyroid disease group, respectively. The weight of the gland between primary and secondary hyperparathyroidism did not reveal a significant difference (P=0.4). Significant differences were found with respect to age, PTH, Ca, and P levels between the pHPT and sHPT (P<0.001). Intact PTH levels showed significant differences between MIBI positive and negative patients (P=0.013), and also US positive and negative patients (P=0.012). A significant negative correlation was found between iPTH and Ca at sHPT (P<0.001). The concomitancy of thyroid disease greatly influences scintigraphic and ultrasonographic detection of parathyroid pathology in pHPT and sHPT. The combination of MIBI and US appears promising for localizing parathyroid pathology in patients with both

  3. Dual roles of heparanase in vascular calcification associated with human carotid atherosclerosis

    DEFF Research Database (Denmark)

    Aldi, S.; Eriksson, L.; Kronqvist, M.

    2017-01-01

    Vascular intimal calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of heparanase in osteogenesis and bone remodeling...

  4. The dual role of fragments in fragment-assembly methods for de novo protein structure prediction

    Science.gov (United States)

    Handl, Julia; Knowles, Joshua; Vernon, Robert; Baker, David; Lovell, Simon C.

    2013-01-01

    In fragment-assembly techniques for protein structure prediction, models of protein structure are assembled from fragments of known protein structures. This process is typically guided by a knowledge-based energy function and uses a heuristic optimization method. The fragments play two important roles in this process: they define the set of structural parameters available, and they also assume the role of the main variation operators that are used by the optimiser. Previous analysis has typically focused on the first of these roles. In particular, the relationship between local amino acid sequence and local protein structure has been studied by a range of authors. The correlation between the two has been shown to vary with the window length considered, and the results of these analyses have informed directly the choice of fragment length in state-of-the-art prediction techniques. Here, we focus on the second role of fragments and aim to determine the effect of fragment length from an optimization perspective. We use theoretical analyses to reveal how the size and structure of the search space changes as a function of insertion length. Furthermore, empirical analyses are used to explore additional ways in which the size of the fragment insertion influences the search both in a simulation model and for the fragment-assembly technique, Rosetta. PMID:22095594

  5. The dual role of local residents in the management of natural protected areas in Mexico

    Science.gov (United States)

    Gustavo Perez-Verdin; Martha E. Lee; Deborah J. Chavez

    2008-01-01

    In many developing countries, local residents play an important role in the management of protected areas because they represent potential users of natural protected areas (NPA) resources, they receive the benefits (or costs) of developing naturebased recreation, and they are the group most closely interested in the management of an area located near them. In this...

  6. Role development of nurses for technology-dependent children attending mainstream schools in Japan.

    Science.gov (United States)

    Shimizu, Fumie; Suzuki, Machiko

    2015-04-01

    To describe the role development of nurses caring for medical technology-dependent children attending Japanese mainstream schools. Semi-structured interviews with 21 nurses caring for technology-dependent children were conducted and analyzed using the modified grounded theory approach. Nurses developed roles centered on maintaining technology-dependent children's physical health to support children's learning with each other, through building relationships, learning how to interact with children, understanding the children and the school community, and realizing the meaning of supporting technology-dependent children. These findings support nurses to build relationships of mutual trust with teachers and children, and learn on the job in mainstream schools. © 2015, Wiley Periodicals, Inc.

  7. Temporal dependence of the enhancement of material removal in femtosecond-nanosecond dual-pulse laser-induced breakdown spectroscopy

    International Nuclear Information System (INIS)

    Scaffidi, Jon; Pearman, William; Carter, J. Chance; Colston, Bill W. Jr.; Angel, S. Michael

    2004-01-01

    Despite the large neutral atomic and ionic emission enhancements that have been noted in collinear and orthogonal dual-pulse laser-induced breakdown spectroscopy, the source or sources of these significant signal and signal-to-noise ratio improvements have yet to be explained. In the research reported herein, the combination of a femtosecond preablative air spark and a nanosecond ablative pulse yields eightfold and tenfold material removal improvement for brass and aluminum, respectively, but neutral atomic emission is enhanced by only a factor of 3-4. Additionally, temporal correlation between enhancement of material removal and of atomic emission is quite poor, suggesting that the atomic-emission enhancements noted in the femtosecond-nanosecond pulse configuration result in large part from some source other than simple improvement in material removal

  8. Prediction of life stress on athletes’ burnout: the dual role of perceived stress

    OpenAIRE

    Chyi, Theresa; Lu, Frank Jing-Horng; Wang, Erica T.W.; Hsu, Ya-Wen; Chang, Ko-Hsin

    2018-01-01

    Although many studies adopted Smith’s (1986) cognitive–affective model of athletic burnout in examining stress–burnout relationship, very few studies examined the mediating/moderating role of perceived stress on the stress–burnout relationship. We sampled 195 college student-athletes and assessed their life stress, perceived stress, and burnout. Correlation analyses found all study variables correlated. Two separate hierarchical regression analyses found that the “distress” component of perce...

  9. A new look at immune privilege of the eye: dual role for the vision-related molecule retinoic acid.

    Science.gov (United States)

    Zhou, Ru; Horai, Reiko; Mattapallil, Mary J; Caspi, Rachel R

    2011-10-15

    The eye is an immunologically privileged and profoundly immunosuppressive environment. Early studies reported inhibition of T cell proliferation, IFN-γ production, and generation of regulatory T cells (Tregs) by aqueous humor (AH) and identified TGF-β as a critical factor. However, T cell subsets including Foxp3(+) Treg and Th17 were unknown at that time, as was the role of retinoic acid (RA) in Treg induction. Consequently, the effect of the ocular microenvironment on T cell lineage commitment and function, and the role of RA in this process, had not been explored. We now use gene-manipulated mice and highly purified T cell populations to demonstrate that AH suppresses lineage commitment and acquisition of Th1 and Th17 effector function of naive T cells, manifested as reduction of lineage-specific transcription factors and cytokines. Instead, AH promoted its massive conversion to Foxp3(+) Tregs that expressed CD25, GITR, CTLA-4, and CD103 and were functionally suppressive. TGF-β and RA were both needed and synergized for Treg conversion by AH, with TGF-β-enhancing T cell expression of RA receptor α. Newly converted Foxp3(+) Tregs were unstable, but were stabilized upon continued exposure to AH or by the DNA demethylating agent 5-aza-2'-deoxycytidine. In contrast, T cells already committed to effector function were resistant to the suppressive and Treg-inducing effects of AH. We conclude that RA in the eye plays a dual role: in vision and in immune privilege. Nevertheless, primed effector T cells are relatively insensitive to AH, helping to explain their ability to induce uveitis despite an inhibitory ocular microenvironment.

  10. The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

    Directory of Open Access Journals (Sweden)

    Mami Shimizu

    Full Text Available Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C. In addition, injection of high-dose poly(I: C to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

  11. Understanding College-Student Roles: Perspectives of Participants in a High School/Community College Dual-Enrollment Program

    Science.gov (United States)

    Lile, Joy R.; Ottusch, Timothy M.; Jones, Terese; Richards, Leslie N.

    2018-01-01

    Dual-enrollment programs have been proposed as a useful way to ease students' transition from high school to community college. Several studies have shown that dual enrollment produces positive effects for students, but less is known about the mechanisms these programs use to support student success. Symbolic interactionism suggests that clarity…

  12. The New Generation of Auditors Meeting Praxis: Dual Learning's Role in Audit Students' Professional Development

    Science.gov (United States)

    Agevall, Lena; Broberg, Pernilla; Umans, Timurs

    2018-01-01

    This paper explores whether and in what way "dual learning" can develop understanding of the relationship between structure/judgement and explores audit student's perceptions of the audit profession. The Work Integrated Learning (WIL) module, serving as a tool of enabling dual learning, represents the context for this exploration. The…

  13. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

    Science.gov (United States)

    Nakamuta, Shinichi; Yang, Yu-Ting; Wang, Chia-Lin; Gallo, Nicholas B; Yu, Jia-Ray; Tai, Yilin; Van Aelst, Linda

    2017-12-04

    Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. © 2017 Nakamuta et al.

  14. Dual Roles of Endogenous Platelet-activating Factor Acetylhydrolase in a Murine Model of Necrotizing Enterocolitis

    Science.gov (United States)

    Lu, Jing; Pierce, Marissa; Franklin, Andrew; Jilling, Tamas; Stafforini, Diana M.; Caplan, Michael

    2010-01-01

    Human preterm infants with necrotizing enterocolitis (NEC) have increased circulating and luminal levels of platelet-activating factor (PAF) and decreased serum PAF-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF. Formula supplemented with recombinant PAF-AH decreases NEC in a neonatal rat model. We hypothesized that endogenous PAF-AH contributes to neonatal intestinal homeostasis, and therefore developed PAF-AH−/− mice using standard approaches to study the role of this enzyme in the neonatal NEC model. Following exposure to a well-established NEC model, intestinal tissues were evaluated for histology, pro-inflammatory cytokine mRNA synthesis, and death using standard techniques. We found that mortality rates were significantly lower in PAF-AH−/− pups compared to wild-type controls before 24 hours of life but surviving PAF-AH−/− animals were more susceptible to NEC development compared to wild-type controls. Increased NEC incidence was associated with prominent inflammation characterized by elevated intestinal mRNA expression of sPLA2, iNOS and CXCL1. In conclusion, the data support a protective role for endogenous PAF-AH in the development of NEC, and since preterm neonates have endogenous PAF-AH deficiency, this may place them at increased risk for disease. PMID:20531249

  15. TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor

    Directory of Open Access Journals (Sweden)

    Danilo Swann Matassa

    2018-04-01

    Full Text Available Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to tumor outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1 is a molecular chaperone involved in the regulation of energetic metabolism in cancer cells. This protein is highly expressed in several cancers, such as glioblastoma, colon, breast, prostate and lung cancers and is often associated with drug resistance. However, TRAP1 is also downregulated in specific tumors, such as ovarian, bladder and renal cancers, where its lower expression is correlated with the worst prognoses and chemoresistance. TRAP1 is the only mitochondrial member of the Heat Shock Protein 90 (HSP90 family that directly interacts with respiratory complexes, contributing to their stability and activity but it is still unclear if such interactions lead to reduced or increased respiratory capacity. The role of TRAP1 is to enhance or suppress oxidative phosphorylation; the effects of such regulation on tumor development and progression are controversial. These observations encourage the study of the mechanisms responsible for the dualist role of TRAP1 as an oncogene or oncosuppressor in specific tumor types. In this review, TRAP1 puzzling functions were recapitulated with a special focus on the correlation between metabolic reprogramming and tumor outcome. We wanted to investigate whether metabolism-targeting drugs can efficiently interfere with tumor progression and whether they might be combined with chemotherapeutics or molecular-targeted agents to counteract drug resistance and reduce therapeutic failure.

  16. On Attributes, Roles, and Dependencies in Description Logics and the Ackermann Case of the Decision Problem

    DEFF Research Database (Denmark)

    Toman, David; Weddel, Grant Edwin

    2001-01-01

    We present a decision procedure for the logical implication problem of a boolean complete DL dialect that includes attributes roles inverse roles and a new concept constructor that is capable of expressing a variety of equality and order generating dependencies The procedure underlies a mapping o...

  17. Bacillus sp. Acting as Dual Role for Corrosion Induction and Corrosion Inhibition with Carbon Steel (CS

    Directory of Open Access Journals (Sweden)

    Santosh K. Karn

    2017-10-01

    Full Text Available Present work investigated the role of five different bacteria species as a corrosion inducer as well as corrosion inhibitor with carbon steel (CS. We observed the ability of different bacteria species on the metal surface attachment, biofilm formation, and determined Peroxidase, Catalase enzyme activity in the detached biofilm from the CS surface. We found that each strain has diverse conduct for surface attachment like DS1 3.3, DS2 2.5, DS3 4.3, DS4 4.0, and DS5 4.71 log cfu/cm2 and for biofilm 8.3 log cfu/cm2. The enzyme Peroxidase, Catalase was found in huge concentration inside the biofilm Peroxidase was maximum for DS4 36.0 U/ml and least for DS3 19.54 U/ml. Whereas, Catalase was highest for DS4, DS5 70.14 U/ml and least 57.2 U/ml for DS2. Scanning electron microscopy (SEM was conducted to examine the biofilm and electrochemical impedance spectroscopy (EIS were utilized to observe corrosion in the presence of bacteria. The electrochemical results confirmed that DS1, DS3, DS4, and DS5 strains have statistically significant MIC-factors (Microbially Influenced Corrosion of 5.46, 8.51, 2.36, and 1.04, while DS2 protective effect factor of 0.89. Weight reduction results with carbon steel likewise supports that corrosion was initiated by DS1 and DS3, while DS2 and DS5 have no any impact though with DS4 we watched less weight reduction however assumed no role in the corrosion. We established the relation of Peroxidase enzyme activity of the isolates. DS1, DS3 and having Peroxidase in the range 22.18, 19.54 U/ml which induce the corrosion whereas DS2 and DS5 having 28.57 and 27.0 U/ml has no any effect and DS4 36 U/ml has inhibitory effect, increasing concentration inhibiting the corrosion. For Catalase DS1, DS3 have 67.28, 61.57 U/ml which induce corrosion while DS2 and DS5 57.71 and 59.14 U/ml also has no effect whereas DS4 70.14 U/ml can inhibit corrosion. Results clearly express that in a specific range both enzymes can induce the corrosion

  18. A dual role of extracellular DNA during biofilm formation of Neisseria meningitidis

    DEFF Research Database (Denmark)

    Lappann, M.; Claus, H.; van Alen, T.

    2010-01-01

    formation, whereas biofilm formation of cc with low point prevalence (ST-8 cc and ST-11 cc) was eDNA-independent. For initial biofilm formation, a ST-32 cc type strain, but not a ST-11 type strain, utilized eDNA. The release of eDNA was mediated by lytic transglycosylase and cytoplasmic N......-acetylmuramyl-l-alanine amidase genes. In late biofilms, outer membrane phospholipase A-dependent autolysis, which was observed in most cc, but not in ST-8 and ST-11 strains, was required for shear force resistance of microcolonies. Taken together, N. meningitidis evolved two different biofilm formation strategies, an e....... On the contrary, spreaders (ST-11 and ST-8 cc) are unable to use eDNA for biofilm formation and might compensate for poor colonization properties by high transmission rates....

  19. Time perspectives and convenience food consumption among teenagers in Vietnam: The dual role of hedonic and healthy eating values.

    Science.gov (United States)

    Olsen, Svein Ottar; Tuu, Ho Huy

    2017-09-01

    This study uses the subscales of Consideration of Future Consequences (CFC) to explore the effects of future (CFC-future) and immediate (CFC-immediate) on convenience food consumption among teenagers in Vietnam. Furthermore, we investigate the mediating and dual role of hedonic and healthy eating values in the relationships between CFCs and convenience food consumption. Survey data from 451 teenagers in Central Vietnam and structural equation modelling were used to test the relationships in a proposed theoretical model. The results indicate that while CFC-immediate and hedonic eating value has a positive direct effect, CFC-future and healthy eating value has a negative direct effect on convenience food consumption. The findings also reveal that both CFC-immediate and CFC-future have positive effects on hedonic and healthy eating values. However, this study argues and tests the relative importance of the direct (asymmetric) effects of time perspectives on eating values, and finds that while CFC-future dominate in explaining healthy eating values, CFC-immediate dominate in explaining hedonic eating values. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.

    Science.gov (United States)

    Morales, Julio C; Richard, Patricia; Rommel, Amy; Fattah, Farjana J; Motea, Edward A; Patidar, Praveen L; Xiao, Ling; Leskov, Konstantin; Wu, Shwu-Yuan; Hittelman, Walter N; Chiang, Cheng-Ming; Manley, James L; Boothman, David A

    2014-04-01

    Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the human homolog of the yeast transcription termination factor Rtt103, remain undefined. Here, we show that K-H has functions in both transcription termination and DNA double-strand break (DSB) repair. K-H forms distinct protein complexes with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate transcription (e.g. RNA polymerase II). K-H loss resulted in increased basal R-loop levels, DSBs, activated DNA-damage responses and enhanced genomic instability. Significantly lowered Artemis protein levels were detected in K-H knockdown cells, which were restored with specific K-H cDNA re-expression. K-H deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable to reseal complex DSB ends, and showed significantly delayed γ-H2AX and 53BP1 repair-related foci regression. Artemis re-expression in K-H-deficient cells restored DNA-repair function and resistance to DSB-inducing agents. However, R loops persisted consistent with dual roles of K-H in transcription termination and DSB repair.

  1. Role of Fluorine-18-Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients. Experience with Dual Head Coincidence Imaging.

    Science.gov (United States)

    Santiago, Jonas F.; Jana, Suman; Gilbert, Holly M.; Salem, Shahenda; Bellman, Paul Curtis; Hsu, Ricky K.S.; Naddaf, Sleiman; Abdel-Dayem, Hussein M.

    1999-11-01

    OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner.

  2. Dual roles for CoAA and its counterbalancing isoform CoAM in human kidney cell tumorigenesis

    Science.gov (United States)

    Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y.; Tsai, Ming-Jer; W. O’Malley, Bert

    2008-01-01

    Co-Activator Activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein we show that CoAA is a dual-function coregulator that inhibits G1/S transition in human kidney cells and suppresses anchorage independent growth and xenograft tumor formation. Suppression occurs in part by downregulating c-myc and its downstream effectors ccnd1 and skp2, and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene, c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, Coactivator Modulator (CoAM), antagonizes CoAA-induced G1/S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma as compared to normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice-isoform. This is so far the only example of a nuclear receptor coregulator involved in suppression of kidney cancer, and suggests potentially significant new roles for coregulators in renal cancer biology. PMID:18829545

  3. Role of renewable energy policies in energy dependency in Finland: System dynamics approach

    International Nuclear Information System (INIS)

    Aslani, Alireza; Helo, Petri; Naaranoja, Marja

    2014-01-01

    Highlights: • A system dynamics model for evaluating renewable energy policies on dependency is proposed. • The model considers the role of diversification on dependency and security of energy supply in Finland. • Dependency on imported sources will decrease depends on the defined scenarios in Finland. - Abstract: Objective: We discuss the role of diversification on dependency and security of energy supply. A system dynamics model with especial focus on the role of renewable energy resources (as a portfolio) on Finland’s energy dependency is developed. The purpose is also to cover a part of research gap exists in the system dynamics modeling of energy security investigations. Methods: A causal loops diagram and a system dynamics model evaluate Finnish scenarios of renewable energy policies. The analysis describes the relationship between dynamic factors such as RE encouragement packages, dependency, and energy demand. Results: A causal loops diagram and a system dynamics model evaluate three different Finnish scenarios of renewable energy policies by 2020. Conclusion: Analysis shows that despite 7% electricity/heat consumption growth by 2020 in Finland, dependency on imported sources will decrease between 1% and 7% depend on the defined scenarios. Practice Implications: The proposed model not only helps decision makers to test their scenarios related to renewable energy polices, it can be implemented by other countries

  4. Role of digital tomosynthesis and dual energy subtraction digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Sharma, Madhurima; Sandhu, Manavjit Singh; Gorsi, Ujjwal; Gupta, Dheeraj; Khandelwal, Niranjan

    2015-01-01

    Highlights: • Digital tomosynthesis and dual energy subtraction digital radiography are modifications of digital radiography. • These modalities perform better than digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis. • Digital tomosynthesis has a sensitivity of 100% in detection of cavities. • Centrilobular nodules seen on CT in active pulmonary tuberculosis, were also demonstrated on digital tomosynthesis in our study. • Digital tomosynthesis can be used for diagnosis and follow up of patients in pulmonary tuberculosis, thereby reducing the number of CT examinations. - Abstract: Objective: To assess the role of digital tomosynthesis (DTS) and dual energy subtraction digital radiography (DES-DR) in detection of parenchymal lesions in active pulmonary tuberculosis (TB) and to compare them with digital radiography (DR). Materials and methods: This prospective study was approved by our institutional review committee. DTS and DES-DR were performed in 62 patients with active pulmonary TB within one week of multidetector computed tomography (MDCT) study. Findings of active pulmonary TB, that is consolidation, cavitation and nodules were noted on digital radiography (DR), DTS and DES-DR in all patients. Sensitivity, specificity, positive and negative predictive values of all 3 modalities was calculated with MDCT as reference standard. In addition presence of centrilobular nodules was also noted on DTS. Results: Our study comprised of 62 patients (33 males, 29 females with age range 18–82 years). Sensitivity and specificity of DTS for detection of nodules and cavitation was better than DR and DES-DR. Sensitivity and specificity of DTS for detection of consolidation was comparable to DR and DES-DR. DES-DR performed better than DR in detection of nodules and cavitation. DTS was also able to detect centrilobular nodules with sensitivity and specificity of 57.4% and 86.5% respectively. Conclusion: DTS and DES-DR perform better

  5. Role of digital tomosynthesis and dual energy subtraction digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Madhurima, E-mail: madhurimashrm88@gmail.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India); Sandhu, Manavjit Singh, E-mail: manavjitsandhu@yahoo.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India); Gorsi, Ujjwal, E-mail: ujjwalgorsi@gmail.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India); Gupta, Dheeraj, E-mail: dheeraj1910@gmail.com [Department of Pulmonary Medicine, PGIMER, Chandigarh 160012 (India); Khandelwal, Niranjan, E-mail: khandelwaln@hotmail.com [Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh 160012 (India)

    2015-09-15

    Highlights: • Digital tomosynthesis and dual energy subtraction digital radiography are modifications of digital radiography. • These modalities perform better than digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis. • Digital tomosynthesis has a sensitivity of 100% in detection of cavities. • Centrilobular nodules seen on CT in active pulmonary tuberculosis, were also demonstrated on digital tomosynthesis in our study. • Digital tomosynthesis can be used for diagnosis and follow up of patients in pulmonary tuberculosis, thereby reducing the number of CT examinations. - Abstract: Objective: To assess the role of digital tomosynthesis (DTS) and dual energy subtraction digital radiography (DES-DR) in detection of parenchymal lesions in active pulmonary tuberculosis (TB) and to compare them with digital radiography (DR). Materials and methods: This prospective study was approved by our institutional review committee. DTS and DES-DR were performed in 62 patients with active pulmonary TB within one week of multidetector computed tomography (MDCT) study. Findings of active pulmonary TB, that is consolidation, cavitation and nodules were noted on digital radiography (DR), DTS and DES-DR in all patients. Sensitivity, specificity, positive and negative predictive values of all 3 modalities was calculated with MDCT as reference standard. In addition presence of centrilobular nodules was also noted on DTS. Results: Our study comprised of 62 patients (33 males, 29 females with age range 18–82 years). Sensitivity and specificity of DTS for detection of nodules and cavitation was better than DR and DES-DR. Sensitivity and specificity of DTS for detection of consolidation was comparable to DR and DES-DR. DES-DR performed better than DR in detection of nodules and cavitation. DTS was also able to detect centrilobular nodules with sensitivity and specificity of 57.4% and 86.5% respectively. Conclusion: DTS and DES-DR perform better

  6. Dual roles of an algal farming damselfish as a cultivator and opportunistic browser of an invasive seaweed.

    Directory of Open Access Journals (Sweden)

    Kimberly A Peyton

    Full Text Available Herbivory is a fundamental process determining reef resilience, and while algal farming damselfishes can help shape benthic assemblages, an understanding of their contribution to areas outside of defended territories is relatively unexplored. Here, we demonstrate how the farming damselfish Stegastes marginatus plays a dual role in benthic structuring by 1 contributing to persistence of the invasive macroalga Acanthophora spicifera within a Hawaiian marine protected area, where the macroalga occurred exclusively inside Stegastes territories, and 2 behaving as an opportunistic browser of the exotic alga outside their territorial borders. Greater than 50% of the biomass of tethered A. spicifera was consumed within one-hour when placed outside Stegastes territories, compared to <5% lost from tethers within territories or herbivore exclusion cages. In situ remote video revealed that tethered A. spicifera located outside territories was grazed primarily by the surgeonfish Acanthurus nigrofuscus (∼68% of total bites and, surprisingly, by S. marginatus (∼27% of total bites that left their territories to feed on this resource on 107 occasions during 400 min of filming. Further, for over half of those occurrences where S. marginatus grazed on the tethered macroalga outside of territories, they fed alongside conspecifics and other species, displaying little of the aggressiveness that characterizes this damselfish. These results show that S. marginatus plays a wider role in determining benthic assemblages than previously recognized, acting both as cultivators of a canopy-forming invasive macroalga within their territories, and as opportunistic browsers in neighboring sites. Consequently, S. marginatus can affect benthic species composition across their territory borders. These results provide a rare example of interspecific facilitation of an exotic alga by an indigenous marine fish. Accounting for fish behaviors more broadly is important to further our

  7. The role of domain-general frontal systems in language comprehension: evidence from dual-task interference and semantic ambiguity.

    Science.gov (United States)

    Rodd, Jennifer M; Johnsrude, Ingrid S; Davis, Matthew H

    2010-12-01

    Neuroimaging studies have shown that the left inferior frontal gyrus (LIFG) plays a critical role in semantic and syntactic aspects of speech comprehension. It appears to be recruited when listeners are required to select the appropriate meaning or syntactic role for words within a sentence. However, this region is also recruited during tasks not involving sentence materials, suggesting that the systems involved in processing ambiguous words within sentences are also recruited for more domain-general tasks that involve the selection of task-relevant information. We use a novel dual-task methodology to assess whether the cognitive system(s) that are engaged in selecting word meanings are also involved in non-sentential tasks. In Experiment 1, listeners were slower to decide whether a visually presented letter is in upper or lower case when the sentence that they are simultaneously listening to contains words with multiple meanings (homophones), compared to closely matched sentences without homophones. Experiment 2 indicates that this interference effect is not tied to the occurrence of the homophone itself, but rather occurs when listeners must reinterpret a sentence that was initially misparsed. These results suggest some overlap between the cognitive system involved in semantic disambiguation and the domain-general process of response selection required for the case-judgement task. This cognitive overlap may reflect neural overlap in the networks supporting these processes, and is consistent with the proposal that domain-general selection processes in inferior frontal regions are critical for language comprehension. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Dual role of BMP signaling in the regulation of Drosophila intestinal stem cell self-renewal.

    Science.gov (United States)

    Tian, Aiguo; Jiang, Jin

    2017-10-02

    Many adult organs including Drosophila adult midguts rely on resident stem cells to replenish damaged cells during tissue homeostasis and regeneration. Previous studies have shown that, upon injury, intestinal stem cells (ISCs) in the midguts can increase proliferation and lineage differentiation to meet the demand for tissue repair. Our recent study has demonstrated that, in response to certain injury, midguts can expand ISC population size as an additional regenerative mechanism. We found that injury elicited by bleomycin feeding or bacterial infection increased the production of two BMP ligands (Dpp and Gbb) in enterocytes (ECs), leading to elevated BMP signaling in progenitor cells that drove an expansion of ISCs by promoting their symmetric self-renewing division. Interestingly, we also found that BMP signaling in ECs inhibits the production of Dpp and Gbb, and that this negative feedback mechanism is required to reset ISC pool size to the homeostatic state. Our findings suggest that BMP signaling exerts two opposing influences on stem cell activity depending on where it acts: BMP signaling in progenitor cells promotes ISC self-renewal while BMP signaling in ECs restricts ISC self-renewal by preventing excessive production of BMP ligands. Our results further suggest that transient expansion of ISC population in conjunction with increasing ISC proliferation provides a more effective strategy for tissue regeneration.

  9. A Dual Role of P53 in Regulating Colistin-Induced Autophagy in PC-12 Cells

    Directory of Open Access Journals (Sweden)

    Ziyin Lu

    2017-10-01

    Full Text Available This study aimed to investigate the mechanism of p53 in regulating colistin-induced autophagy in PC-12 cells. Importantly, cells were treated with 125 μg/ml colistin for 12 and 24 h after transfection with p53 siRNA or recombinant plasmid. The hallmarks of autophagy and apoptosis were examined by real-time PCR and western blot, fluorescence/immunofluorescence microscopy, and electron microscopy. The results showed that silencing of p53 leads to down-regulation of Atg5 and beclin1 for 12 h while up-regulation at 24 h and up-regulation of p62 noted. The ratio of LC3-II/I and autophagic vacuoles were significantly increased at 24 h, but autophagy flux was blocked. The cleavage of caspase3 and PARP (poly ADP-ribose polymerase were enhanced, while PC-12-sip53 cells exposed to 3-MA showed down-regulation of apoptosis. By contrast, the expression of autophagy-related genes and protein reduced in p53 overexpressing cells following a time dependent manner. Meanwhile, there was an increase in the expression of activated caspase3 and PARP, condensed and fragmented nuclei were evident. Conclusively, the data supported that silencing of p53 promotes impaired autophagy, which acts as a pro-apoptotic induction factor in PC-12 cells treated with colistin for 24 h, and overexpression of p53 inhibits autophagy and accelerates apoptosis. Hence, it has been suggested that p53 could not act as a neuro-protective target in colistin-induced neurotoxicity.

  10. Dual role of interleukin-17 in pannus growth and osteoclastogenesis in rheumatoid arthritis.

    Science.gov (United States)

    Ito, Hiroshi; Yamada, Hidehiro; Shibata, Toshiko N; Mitomi, Hirofumi; Nomoto, So; Ozaki, Shoichi

    2011-02-04

    In a murine model, interleukin (IL)-17 plays a critical role in the pathogenesis of arthritis. There are controversies, however, regarding whether IL-17 is a proinflammatory mediator in rheumatoid arthritis (RA). We previously established an ex vivo cellular model using synovial tissue (ST)-derived inflammatory cells, which reproduced pannus-like tissue growth and osteoclastic activity in vitro. Using this model, we investigated the effects of IL-17 on pannus growth and osteoclastogenesis in RA. Inflammatory cells that infiltrated synovial tissue from patients with RA were collected without enzyme digestion and designated as ST-derived inflammatory cells. ST-derived inflammatory cells were cultured in the presence or absence of IL-17 or indomethacin, and the morphologic changes were observed for 4 weeks. Cytokines produced in the culture supernatants were measured by using enzyme-linked immunosorbent assay kits. Osteoclastic activity was assessed by the development of resorption pits in calcium phosphate-coated slides. Exogenous addition of IL-17 dramatically enhanced the spontaneous production of IL-6 and prostaglandin E₂ (PGE₂) by the ST-derived inflammatory cells, while it had no effect on the production of tumor necrosis factor (TNF)-α and macrophage colony-stimulating factor (M-CSF). Furthermore, IL-17 did not affect the spontaneous development of pannus-like tissue growth and osteoclastic activity by the ST-derived inflammatory cells. On the other hand, IL-17 enhanced pannus-like tissue growth, the production of TNF-α and M-CSF and the development of osteoclastic activity in the presence of indomethacin, an inhibitor of endogenous prostanoid production, while exogenous addition of PGE₁ suppressed their activities. The present study suggests that IL-17 induces negative feedback regulation through the induction of PGE₂, while it stimulates proinflammatory pathways such as inflammatory cytokine production, pannus growth and osteoclastogenesis in RA.

  11. Dependence on Supplier, Supplier Trust and Green Supplier Integration: The Moderating Role of Contract Management Difficulty

    Directory of Open Access Journals (Sweden)

    Xuesong Zhao

    2018-05-01

    Full Text Available This study aims to investigate the impacts of dependence on supplier and supplier trust on green supplier integration, and the moderating role of contract management difficulty. In this study, we develop a dependence-trust-integration model based on resource dependence theory, social capital theory and transaction cost theory. We examine the hypothesized relationships using hierarchical regression analyses based on data collected from 187 Chinese firms. Our findings suggest that dependence on supplier has positive impacts on green supplier integration and supplier trust. Supplier trust partially mediates the relationship between dependence on supplier and green supplier integration. In addition, contract management difficulty negatively moderates the relationship between supplier trust and green supplier integration. This research contributes to the literature by offering empirical evidence concerning the indirect relationship between dependence on supplier and green supplier integration via supplier trust, and the trust-integration link depends on the level of contract management difficulty.

  12. The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Markus Schosserer

    2017-11-01

    situations and signals, which induce senescence. Among them, oncogene-induced senescence and stress-induced premature senescence are prominent. New findings about the role of senescence in tumor biology are critically reviewed with respect to new suggestions for cancer therapy leveraging genetic and pharmacological methods to prevent senescence or to selectively kill senescent cells in tumors.

  13. Evidence of the immunomodulatory role of dual PI3K/mTOR inhibitors in transplantation: an experimental study in mice.

    Science.gov (United States)

    Vilchez, Valery; Turcios, Lilia; Butterfield, David A; Mitov, Mihail I; Coquillard, Cristin L; Brandon, Ja Anthony; Cornea, Virgilius; Gedaly, Roberto; Marti, Francesc

    2017-10-01

    The PI3K/mTOR signaling cascade is fundamental in T-cell activation and fate decisions. We showed the distinct regulation of PI3K/mTOR in regulatory and effector T-cells and proposed the potential therapeutic benefit of targeting this pathway to control the balance between effector and regulatory T-cell activities. Substantial adverse effects in long-term clinical usage of rapamycin suggest the use of alternative treatments in restraining effector T-cell function in transplant patients. We hypothesize that dual PI3K/mTOR inhibitors may represent an immunosuppressant alternative. Here we show that dual PI3K/mTOR PI-103 and PKI-587 inhibitors interfered IL-2-dependent responses in T-cells. However, in contrast to the inhibitory effects in non-Treg T-cell proliferation and effector functions, dual inhibitors increased the differentiation, preferential expansion, and suppressor activity of iTregs. Rapamycin, PI-103, and PKI-587 targeted different signaling events and induced different metabolic patterns in primary T-cells. Similar to rapamycin, in vivo administration of PI-103 and PKI-587 controlled effectively the immunological response against allogeneic skin graft. These results characterize specific regulatory mechanisms of dual PI3K/mTOR inhibitors in T-cells and support their potential as a novel therapeutic option in transplantation. © 2017 Steunstichting ESOT.

  14. Rate dependent direct inverse hysteresis compensation of piezoelectric micro-actuator used in dual-stage hard disk drive head positioning system.

    Science.gov (United States)

    Rahman, Md Arifur; Al Mamun, Abdullah; Yao, Kui

    2015-08-01

    The head positioning servo system in hard disk drive is implemented nowadays using a dual-stage actuator—the primary stage consisting of a voice coil motor actuator providing long range motion and the secondary stage controlling the position of the read/write head with fine resolution. Piezoelectric micro-actuator made of lead zirconate titanate (PZT) has been a popular choice for the secondary stage. However, PZT micro-actuator exhibits hysteresis—an inherent nonlinear characteristic of piezoelectric material. The advantage expected from using the secondary micro-actuator is somewhat lost by the hysteresis of the micro-actuator that contributes to tracking error. Hysteresis nonlinearity adversely affects the performance and, if not compensated, may cause inaccuracy and oscillation in the response. Compensation of hysteresis is therefore an important aspect for designing head-positioning servo system. This paper presents a new rate dependent model of hysteresis along with rigorous analysis and identification of the model. Parameters of the model are found using particle swarm optimization. Direct inverse of the proposed rate-dependent generalized Prandtl-Ishlinskii model is used as the hysteresis compensator. Effectiveness of the overall solution is underscored through experimental results.

  15. Dual inhibition of γ-oryzanol on cellular melanogenesis: inhibition of tyrosinase activity and reduction of melanogenic gene expression by a protein kinase A-dependent mechanism.

    Science.gov (United States)

    Jun, Hee-jin; Lee, Ji Hae; Cho, Bo-Ram; Seo, Woo-Duck; Kang, Hang-Won; Kim, Dong-Woo; Cho, Kang-Jin; Lee, Sung-Joon

    2012-10-26

    The in vitro effects on melanogenesis of γ-oryzanol (1), a rice bran-derived phytosterol, were investigated. The melanin content in B16F1 cells was significantly and dose-dependently reduced (-13% and -28% at 3 and 30 μM, respectively). Tyrosinase enzyme activity was inhibited by 1 both in a cell-free assay and when analyzed based on the measurement of cellular tyrosinase activity. Transcriptome analysis was performed to investigate the biological pathways altered by 1, and it was found that gene expression involving protein kinase A (PKA) signaling was markedly altered. Subsequent analyses revealed that 1 stimulation in B16 cells reduced cytosolic cAMP concentrations, PKA activity (-13% for cAMP levels and -40% for PKA activity), and phosphorylation of the cAMP-response element binding protein (-57%), which, in turn, downregulated the expression of microphthalmia-associated transcription factor (MITF; -59% for mRNA and -64% for protein), a key melanogenic gene transcription factor. Accordingly, tyrosinase-related protein 1 (TRP-1; -69% for mRNA and -82% for protein) and dopachrome tautomerase (-51% for mRNA and -92% for protein) in 1-stimulated B16F1 cells were also downregulated. These results suggest that 1 has dual inhibitory activities for cellular melanogenesis by inhibiting tyrosinase enzyme activity and reducing MITF and target genes in the PKA-dependent pathway.

  16. The role of Rashba spin-orbit coupling in valley-dependent transport of Dirac fermions

    Energy Technology Data Exchange (ETDEWEB)

    Hasanirok, Kobra; Mohammadpour, Hakimeh

    2017-01-01

    At this work, spin- and valley-dependent electron transport through graphene and silicene layers are studied in the presence of Rashba spin- orbit coupling. We find that the transport properties of the related ferromagnetic/normal/ferromagnetic structure depend on the relevant parameters. A fully valley- and spin- polarized current is obtained. As another result, Rashba spin-orbit interaction plays important role in controlling the transmission characteristics.

  17. Dual role of miR-21 in CD4+ T-cells: activation-induced miR-21 supports survival of memory T-cells and regulates CCR7 expression in naive T-cells.

    Directory of Open Access Journals (Sweden)

    Katarzyna Smigielska-Czepiel

    Full Text Available Immune cell-type specific miRNA expression patterns have been described but the detailed role of single miRNAs in the function of T-cells remains largely unknown. We investigated the role of miR-21 in the function of primary human CD4+ T-cells. MiR-21 is substantially expressed in T-cells with a memory phenotype, and is robustly upregulated upon αCD3/CD28 activation of both naive and memory T-cells. By inhibiting the endogenous miR-21 function in activated naive and memory T-cells, we showed that miR-21 regulates fundamentally different aspects of T-cell biology, depending on the differentiation status of the T-cell. Stable inhibition of miR-21 function in activated memory T-cells led to growth disadvantage and apoptosis, indicating that the survival of memory T-cells depends on miR-21 function. In contrast, stable inhibition of miR-21 function in activated naive T-cells did not result in growth disadvantage, but led to a significant induction of CCR7 protein expression. Direct interaction between CCR7 and miR-21 was confirmed in a dual luciferase reporter assay. Our data provide evidence for a dual role of miR-21 in CD4+ T cells; Regulation of T-cell survival is confined to activated memory T-cells, while modulation of potential homing properties, through downregulation of CCR7 protein expression, is observed in activated naive T-cells.

  18. Dual role of protein tyrosine phosphatase 1B in the progression and reversion of non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Águeda González-Rodríguez

    2018-01-01

    Full Text Available Objectives: Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease in Western countries. Protein tyrosine phosphatase 1B (PTP1B, a negative modulator of insulin and cytokine signaling, is a therapeutic target for type 2 diabetes and obesity. We investigated the impact of PTP1B deficiency during NAFLD, particularly in non-alcoholic steatohepatitis (NASH. Methods: NASH features were evaluated in livers from wild-type (PTP1BWT and PTP1B-deficient (PTP1BKO mice fed methionine/choline-deficient diet (MCD for 8 weeks. A recovery model was established by replacing MCD to chow diet (CHD for 2–7 days. Non-parenchymal liver cells (NPCs were analyzed by flow cytometry. Oval cells markers were measured in human and mouse livers with NASH, and in oval cells from PTP1BWT and PTP1BKO mice. Results: PTP1BWT mice fed MCD for 8 weeks exhibited NASH, NPCs infiltration, and elevated Fgf21, Il6 and Il1b mRNAs. These parameters decreased after switching to CHD. PTP1B deficiency accelerated MCD-induced NASH. Conversely, after switching to CHD, PTP1BKO mice rapidly reverted NASH compared to PTP1BWT mice in parallel to the normalization of serum triglycerides (TG levels. Among NPCs, a drop in cytotoxic natural killer T (NKT subpopulation was detected in PTP1BKO livers during recovery, and in these conditions M2 macrophage markers were up-regulated. Oval cells markers (EpCAM and cytokeratin 19 significantly increased during NASH only in PTP1B-deficient livers. HGF-mediated signaling and proliferative capacity were enhanced in PTP1BKO oval cells. In NASH patients, oval cells markers were also elevated. Conclusions: PTP1B elicits a dual role in NASH progression and reversion. Additionally, our results support a new role for PTP1B in oval cell proliferation during NAFLD. Keywords: PTP1B, Steatosis, Steatohepatitis, Inflammation, Oval cells

  19. A physician role typology: colleague and client dependence in an HMO.

    Science.gov (United States)

    Barr, J K; Steinberg, M K

    1985-01-01

    This paper reports on physicians' role definitions in one prepaid group practice, a health maintenance organization (HMO). Colleague and client dependence are reviewed and analyzed as separable dimensions of physician role definitions. Data are derived from documents, interviews, and staff questionnaires collected in 1979-1980. The evidence reported suggests widespread colleague dependence in the HMO. Physicians consulted with one another about patient care and engaged in informal referral and review, developing practice standards; and some of these physicians relied on colleagues for handling their patient visits when needed. In relation to their patients, some physicians viewed themselves as bureaucratic officials relatively dependent on client approval in carrying out their health care activities, while others saw themselves as trusted medical experts in a setting free of nonmedical constraints in patient care. The relationship of organizational structure to these different role definitions is discussed. Classifying these HMO physicians according to a fourfold typology of professional dependence shows that most are Organizational Physicians (Type I), who are both colleague and client dependent. Collegial Physicians (Type II) are colleague dependent and, at the same time, do not perceive clients as demanding. Implications for quality of care and physician satisfaction and turnover are considered.

  20. Dual effect of fetal bovine serum on early development depends on stage-specific reactive oxygen species demands in pigs.

    Directory of Open Access Journals (Sweden)

    Seong-Eun Mun

    Full Text Available Despite the application of numerous supplements to improve in vitro culture (IVC conditions of mammalian cells, studies regarding the effect of fetal bovine serum (FBS on mammalian early embryogenesis, particularly in relation to redox homeostasis, are lacking. Herein, we demonstrated that early development of in vitro-produced (IVP porcine embryos highly depends on the combination of FBS supplementation timing and embryonic reactive oxygen species (ROS requirements. Interestingly, FBS significantly reduced intracellular ROS levels in parthenogenetically activated (PA embryos regardless of the developmental stage. However, the beneficial effect of FBS on early embryogenesis was found only during the late phase (IVC 4-6 days treatment group. In particular, developmental competence parameters, such as blastocyst formation rate, cellular survival, total cell number and trophectoderm proportion, were markedly increased by FBS supplementation during the late IVC phase. In addition, treatment with FBS elevated antioxidant transcript levels during the late IVC phase. In contrast, supplementation with FBS during the entire period (1-6 days or during the early IVC phase (1-2 days greatly impaired the developmental parameters. Consistent with the results from PA embryos, the developmental competence of in vitro fertilization (IVF or somatic cell nuclear transfer (SCNT embryos were markedly improved by treatment with FBS during the late IVC phase. Moreover, the embryonic stage-specific effects of FBS were reversed by the addition of an oxidant and were mimicked by treatment with an antioxidant. These findings may increase our understanding of redox-dependent early embryogenesis and contribute to the large-scale production of high-quality IVP embryos.

  1. A role for adhesion molecules in contact-dependent T help for B cells

    DEFF Research Database (Denmark)

    Owens, T

    1991-01-01

    The role of cell contact in T-dependent B cell activation was examined. Small resting B cells from C57BL/6 mice were cultured with CBA-derived, non-alloreactive cloned T helper cells in anti-T cell receptor V beta 8-coated microwells. This induced polyclonal B cell activation to enter cell cycle...... that continued cell contact involving adhesion/accessory molecules induces B cells to proliferate and to respond to T cell lymphokines. A signaling role for cell interaction molecules on B cells is proposed, similar to the role of these and analogous molecules on T cells....

  2. Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity

    International Nuclear Information System (INIS)

    Toyooka, Tatsushi; Shinmen, Takuya; Aarts, Jac M.M.J.G.; Ibuki, Yuko

    2012-01-01

    A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock‐down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. -- Highlights: ► NAC augmented the cytotoxicity of 9,10-PQ in skin cell lines. ► 9,10-PQ-induced DSBs accompanying γ-H2AX were also augmented by NAC. ► NAC suppressed the cyto- and genotoxicity of 9,10-PQ in adenocarcinoma cell lines. ► The dual effects of NAC on toxicity of 9,10-PQ were dependent on NQO1 activity.

  3. Osteocalcin: The extra-skeletal role of a vitamin K-dependent protein in glucose metabolism

    Directory of Open Access Journals (Sweden)

    Eibhlís M. O'Connor

    2017-03-01

    Full Text Available The role of vitamin K in the body has long been associated with blood clotting and coagulation. In more recent times, its role in a range of physiological processes has been described including the regulation of bone and soft tissue calcification, cell growth and proliferation, cognition, inflammation, various oxidative processes and fertility, where osteocalcin is thought to up-regulate the synthesis of the enzymes needed for the biosynthesis of testosterone thereby increasing male fertility. Vitamin K dependent proteins (VKDP contain γ-carboxyglutamic acid residues which require post-translational, gamma-glutamyl carboxylation by the vitamin K-dependent (VKD gamma-glutamyl carboxylase enzyme for full functionality. These proteins are present both hepatically and extrahepatically. The role of bone-derived osteocalcin has many physiological roles including, maintenance of bone mass with more recent links to energy metabolism due to the role of the skeleton as an endocrine organ. It has been proposed that insulin binds to bone forming cells (osteoblasts promoting osteocalcin production which in turn promotes β-cell proliferation, insulin secretion and glucose control. However much of this research has been conducted in animal models with equivocal findings in human studies. This review will discuss the role of osteocalcin in relation to its role in human health, focusing specifically on glucose metabolism.

  4. The role of DNA dependent protein kinase in synapsis of DNA ends

    NARCIS (Netherlands)

    E.P.W.C. Weterings (Eric); N.S. Verkaik (Nicole); H.T. Brüggenwirth (Hennie); D.C. van Gent (Dik); J.H.J. Hoeijmakers (Jan)

    2003-01-01

    textabstractDNA dependent protein kinase (DNA-PK) plays a central role in the non-homologous end-joining pathway of DNA double strand break repair. Its catalytic subunit (DNA-PK(CS)) functions as a serine/threonine protein kinase. We show that DNA-PK forms a stable complex at DNA termini that blocks

  5. An Exploratory Study of the Role of Task Dependence on Team Captains' Leadership Development

    Science.gov (United States)

    Grandzol, Christian J.

    2011-01-01

    While there is evidence that team captainship in intercollegiate sports can lead to leadership development, there is little evidence about the role that task dependence may play on that effect. The individual or team nature of sports may offer different leadership experiences for team captains, leading to differential outcomes. In this exploratory…

  6. Medium dependent dual turn on/turn off fluorescence sensing for Cu2 + ions using AMI/SDS assemblies

    Science.gov (United States)

    Gujar, Varsha B.; Ottoor, Divya

    2017-02-01

    Behavior of Amiloride (AMI) as a metal ion sensor in anionic surfactant assemblies of varying concentrations at different pH is depicted in this work. From a non-sensor fluorophore, AMI has been transformed in to a tunable fluorosensor for Cu2 + ions in various SDS concentrations. At premicellar concentration of SDS, ion-pair complex is expected to be formed between AMI and SDS due to electrostatic interactions between them. However at CMC concentrations of SDS, fluorescence intensity of AMI is greatly enhanced with red shift in emission, due to the incorporation of AMI molecule in the hydrophobic micellar interface. The behavior of metal sensing by AMI-SDS assemblies gives rise to several interesting observations. Micellation of SDS has been greatly enhanced by increasing copper ion concentrations, as these counter ions screens the charge on monomers of SDS which lead to the aggregation at premicellar concentrations only. Concentrations and pH dependent discrete trends of interactions between SDS-AMI and SDS-Cu2 + ions, have given tunable fluorescence responses (fluorescence turn on/turn off) of AMI for added Cu2 + ions. The electrostatic interaction between the metal cations and the anionic surfactants is the driving force for bringing the metal ions near to the vicinity of micelle where AMI resides. Thus, a comprehensive understanding of the mechanism related to the 'turn on-turn off' fluorescence response of AMI with respect to pH and SDS concentration for effective Cu2 + ion sensing is illustrated in this work.

  7. The role of age, gender, mood states and exercise frequency on exercise dependence.

    Science.gov (United States)

    Costa, Sebastiano; Hausenblas, Heather A; Oliva, Patrizia; Cuzzocrea, Francesca; Larcan, Rosalba

    2013-12-01

    The purpose of our study was to explore the prevalence, and the role of mood, exercise frequency, age, and gender differences of exercise dependence. Regular exercisers (N = 409) completed a socio-demographic questionnaire, the Exercise Dependence Scale, and the Profile of Mood States. For data analyses, the participants were stratified for sex and age (age ranges = young adults: 18-24 years, adults: 25-44 years, and middle-aged adults: 45-64 years). We found that: (a) 4.4% of the participants were classified as at-risk for exercise dependence; (b) the men and the two younger groups (i.e., young adults and adults) had higher exercise dependence scores; and (c) age, gender, exercise frequency, and mood state were related to exercise dependence. Our results support previous research on the prevalence of exercise dependence and reveal that adulthood may be the critical age for developing exercise dependence. These findings have practical implication for identifying individuals at-risk for exercise dependence symptoms, and may aid in targeting and guiding the implementation of prevention program for adults.

  8. Microstructure and Strain Rate-Dependent Tensile Deformation Behavior of Fiber Laser-Welded Butt Joints of Dual-Phase Steels

    Science.gov (United States)

    Liu, Yang; Dong, Danyang; Han, Zhiqiang; Yang, Zhibin; Wang, Lu; Dong, Qingwei

    2018-05-01

    The microstructure and tensile deformation behavior of the fiber laser-welded similar and dissimilar dual-phase (DP) steel joints over a wide range of strain rates from 10-3 to 103 s-1 were investigated for the further applications on the lightweight design of vehicles. The high strain rate dynamic tensile deformation process and full-field strain distribution of the base metals and welded joints were examined using the digital image correlation method and high-speed photography. The strain rate effects on the stress-strain responses, tensile properties, deformation, and fracture behavior of the investigated materials were analyzed. The yield stress (YS) and ultimate tensile strength (UTS) of the dissimilar DP780/DP980 welded joints were lying in-between those of the DP780 and DP980 base metals, and all materials exhibited positive strain rate dependence on the YS and UTS. Owing to the microstructure heterogeneity, the welded joints showed relatively lower ductility in terms of total elongation (TE) than those of the corresponding base metals. The strain localization started before the maximum load was reached, and the strain localization occurred earlier during the whole deformation process with increasing strain rate. As for the dissimilar welded joint, the strain localization tended to occur in the vicinity of the lowest hardness value across the welded joint, which was in the subcritical HAZ at the DP780 side. As the strain rate increased, the typical ductile failure characteristic of the investigated materials did not change.

  9. Microstructure and Strain Rate-Dependent Tensile Deformation Behavior of Fiber Laser-Welded Butt Joints of Dual-Phase Steels

    Science.gov (United States)

    Liu, Yang; Dong, Danyang; Han, Zhiqiang; Yang, Zhibin; Wang, Lu; Dong, Qingwei

    2018-04-01

    The microstructure and tensile deformation behavior of the fiber laser-welded similar and dissimilar dual-phase (DP) steel joints over a wide range of strain rates from 10-3 to 103 s-1 were investigated for the further applications on the lightweight design of vehicles. The high strain rate dynamic tensile deformation process and full-field strain distribution of the base metals and welded joints were examined using the digital image correlation method and high-speed photography. The strain rate effects on the stress-strain responses, tensile properties, deformation, and fracture behavior of the investigated materials were analyzed. The yield stress (YS) and ultimate tensile strength (UTS) of the dissimilar DP780/DP980 welded joints were lying in-between those of the DP780 and DP980 base metals, and all materials exhibited positive strain rate dependence on the YS and UTS. Owing to the microstructure heterogeneity, the welded joints showed relatively lower ductility in terms of total elongation (TE) than those of the corresponding base metals. The strain localization started before the maximum load was reached, and the strain localization occurred earlier during the whole deformation process with increasing strain rate. As for the dissimilar welded joint, the strain localization tended to occur in the vicinity of the lowest hardness value across the welded joint, which was in the subcritical HAZ at the DP780 side. As the strain rate increased, the typical ductile failure characteristic of the investigated materials did not change.

  10. Understanding the role of low reactivity fuel stratification in a dual fuel RCCI engine – A simulation study

    NARCIS (Netherlands)

    Mikulski, M.; Bekdemir, C.

    2017-01-01

    Natural gas - diesel, Reactivity Controlled Compression Ignition (RCCI) is currently one of the most promising combustion strategies for the next generation heavy-duty engines. A major issue to be addressed for this dual fuel concept to become practically applicable is its low combustion efficiency

  11. Performance effects of cognitive heterogeneity in dual leadership structures in the arts: the role of selection system orientations

    NARCIS (Netherlands)

    Bhansing, P.V.; Leenders, M.A.A.M.; Wijnberg, N.M.

    2012-01-01

    A dual executive leadership structure aspires to shape an executive constellation where both executives have different orientations that they use to assess the world around them, process information to make decisions, and evaluate outcomes. By separating the executive position into two functionally

  12. Salting-out-enhanced ionic liquid microextraction with a dual-role solvent for simultaneous determination of trace pollutants with a wide polarity range in aqueous samples.

    Science.gov (United States)

    Gao, Man; Qu, Jingang; Chen, Kai; Jin, Lide; Dahlgren, Randy Alan; Wang, Huili; Tan, Chengxia; Wang, Xuedong

    2017-11-01

    In real aquatic environments, many occupational pollutants with a wide range of polarities coexist at nanogram to milligram per liter levels. Most reported microextraction methods focus on extracting compounds with similar properties (e.g., polarity or specific functional groups). Herein, we developed a salting-out-enhanced ionic liquid microextraction based on a dual-role solvent (SILM-DS) for simultaneous detection of tetracycline, doxycycline, bisphenol A, triclosan, and methyltriclosan, with log K ow ranging from -1.32 to 5.40 in complex milk and environmental water matrices. The disperser in the ionic-liquid-based dispersive liquid-liquid microextraction was converted to the extraction solvent in the subsequent salting-out-assisted microextraction procedures, and thus a single solvent performed a dual role as both extractant and disperser in the SILM-DS process. Acetonitrile was selected as the dual-role solvent because of its strong affinity for both ionic liquids and water, as well as the extractant in the salting-out step. Optimized experimental conditions were 115 μL [C 8 MIM][PF 6 ] as extractor, 1200 μL acetonitrile as dual-role solvent, pH 2.0, 5.0 min ultrasound extraction time, 3.0 g Na 2 SO 4 , and 3.0 min vortex extraction time. Under optimized conditions, the recoveries of the five pollutants ranged from 74.5 to 106.9%, and their LODs were 0.12-0.75 μg kg -1 in milk samples and 0.11-0.79 μg L -1 in environmental waters. Experimental precision based on relative standard deviation was 1.4-6.4% for intraday and 2.3-6.5% for interday analyses. Compared with previous methods, the prominent advantages of the newly developed method are simultaneous determination of pollutants with a wide range of polarities and a substantially reduced workload for ordinary environmental monitoring and food tests. Therefore, the new method has great application potential for simultaneous determination of trace pollutants with strongly contrasting polarities in several

  13. Combined role of childhood maltreatment, family history, and gender in the risk for alcohol dependence.

    Science.gov (United States)

    Fenton, M C; Geier, T; Keyes, K; Skodol, A E; Grant, B F; Hasin, D S

    2013-05-01

    Studies of the relationship between childhood maltreatment and alcohol dependence have not controlled comprehensively for potential confounding by co-occurring maltreatments and other childhood trauma, or determined whether parental history of alcohol disorders operates synergistically with gender and maltreatment to produce alcohol dependence. We addressed these issues using national data. Method Face-to-face surveys of 27 712 adult participants in a national survey. Childhood physical, emotional and sexual abuse, and physical neglect were associated with alcohol dependence (prelationships for physical abuse in the entire sample, and for sexual abuse and emotional neglect in women (APs, 0.21, 0.31, 0.26 respectively), indicating that the odds of alcohol dependence given both parental history and these maltreatments were significantly higher than the additive effect of each alone (pdependence. Importantly, results suggest a synergistic role of parental alcoholism: the effect of physical abuse on alcohol dependence may depend on parental history, while the effects of sexual abuse and emotional neglect may depend on parental history among women. Findings underscore the importance of early identification and prevention, particularly among those with a family history, and could guide genetic research and intervention development, e.g. programs to reduce the burden of childhood maltreatment may benefit from addressing the negative long-term effects of maltreatments, including potential alcohol problems, across a broad range of childhood environments.

  14. Localization Decisions of Entrepreneurs: The Role of Path Dependency and Market Forces

    Science.gov (United States)

    Pylak, Korneliusz; Majerek, Dariusz

    2017-10-01

    The purpose of this research is to determine the role of path dependency and market forces in the localization decisions of entrepreneurs from different industries. We hypothesize that most industries develop new entities based on the number of companies from the same industry that already exist in a region. We also hypothesize that entrepreneurs create new entities based on related industries operating within the same knowledge pool. To test these hypotheses, we used the machine learning decision tree method. The input variables are the number of companies from 86 industries located in 2,531 communities in Poland in 2009. The target values are the number of new companies from these industries created in the years 2009-2015. The principal results show that localization decisions are mostly based on demand and supply industries, in which manufacturing industries play crucial role. Path dependency appears in less than half of the industries’ models and thus is not the main factor influencing decisions regarding the creation of new companies. The highest share of path-dependent industries is in manufacturing sector, but the degree of the dependence is lower than in the service sector. The service sector seems to be the least path-dependent, as services usually serve other industries. Competition in industries is a rare factor in new company creation; however, if it appears, it usually shrinks the industry.

  15. ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition

    Directory of Open Access Journals (Sweden)

    Alexandra Lusser

    2011-10-01

    Full Text Available ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.

  16. The Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases

    Science.gov (United States)

    Tan, Hor-Yue; Li, Sha; Hong, Ming; Wang, Xuanbin

    2016-01-01

    High heterogeneity of macrophage is associated with its functions in polarization to different functional phenotypes depending on environmental cues. Macrophages remain in balanced state in healthy subject and thus macrophage polarization may be crucial in determining the tissue fate. The two distinct populations, classically M1 and alternatively M2 activated, representing the opposing ends of the full activation spectrum, have been extensively studied for their associations with several disease progressions. Accumulating evidences have postulated that the redox signalling has implication in macrophage polarization and the key roles of M1 and M2 macrophages in tissue environment have provided the clue for the reasons of ROS abundance in certain phenotype. M1 macrophages majorly clearing the pathogens and ROS may be crucial for the regulation of M1 phenotype, whereas M2 macrophages resolve inflammation which favours oxidative metabolism. Therefore how ROS play its role in maintaining the homeostatic functions of macrophage and in particular macrophage polarization will be reviewed here. We also review the biology of macrophage polarization and the disturbance of M1/M2 balance in human diseases. The potential therapeutic opportunities targeting ROS will also be discussed, hoping to provide insights for development of target-specific delivery system or immunomodulatory antioxidant for the treatment of ROS-related diseases. PMID:27143992

  17. Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis.

    Science.gov (United States)

    Zeng, Chong; Xing, Rui; Liu, Jing; Xing, Feiyue

    2016-01-01

    Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of the Notch signaling pathway downstream genes in the nucleus. It shows that CSL-dependent signaling regulates the cell apoptosis through Hes-1-PTEN-AKT-mTOR signaling, but rather the CSL-independent signaling mediates the cell apoptosis possibly via NIC-mTORC2-AKT-mTOR signaling, providing a new insight into apoptotic mechanisms.

  18. Statistical mechanical lattice model of the dual-peak electrocaloric effect in ferroelectric relaxors and the role of pressure

    International Nuclear Information System (INIS)

    Dunne, Lawrence J; Axelsson, Anna-Karin; Alford, Neil McN; Valant, Matjaz; Manos, George

    2011-01-01

    Despite considerable effort, the microscopic origin of the electrocaloric (EC) effect in ferroelectric relaxors is still intensely discussed. Ferroelectric relaxors typically display a dual-peak EC effect, whose origin is uncertain. Here we present an exact statistical mechanical matrix treatment of a lattice model of polar nanoregions forming in a neutral background and use this approach to study the characteristics of the EC effect in ferroelectric relaxors under varying electric field and pressure. The dual peaks seen in the EC properties of ferroelectric relaxors are due to the formation and ordering of polar nanoregions. The model predicts significant enhancement of the EC temperature rise with pressure which may have some contribution to the giant EC effect.

  19. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney

    OpenAIRE

    Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V.; Park, Kwon Moo

    2008-01-01

    Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expressio...

  20. Evidence of long range dependence in Asian equity markets: the role of liquidity and market restrictions

    Science.gov (United States)

    Cajueiro, Daniel O.; Tabak, Benjamin M.

    2004-11-01

    In this paper, the efficient market hypothesis is tested for China, Hong Kong and Singapore by means of the long memory dependence approach. We find evidence suggesting that Hong Kong is the most efficient market followed by Chinese A type shares and Singapore and finally by Chinese B type shares, which suggests that liquidity and capital restrictions may play a role in explaining results of market efficiency tests.

  1. Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

    Science.gov (United States)

    2016-12-01

    the extent of injury to determine if variable severity of injury might account for these conflicting responses. Our work on this project has...of phrenic motor output post-CSC; we are currently determining if variability in injury severity can account for these conflicting findings. These...Award Number: W81XWH-13-1-0410 TITLE: Respiratory Plasticity Following Spinal Injury: Role of Chloride-Dependent Inhibitory Neurotransmission

  2. Role of state-dependent learning in the cognitive effects of caffeine in mice

    OpenAIRE

    Sanday, Leandro [UNIFESP; Zanin, Karina Agustini [UNIFESP; Patti, Camilla de Lima [UNIFESP; Fernandes-Santos, Luciano [UNIFESP; Oliveira, Larissa C. [UNIFESP; Longo, Beatriz Monteiro [UNIFESP; Andersen, Monica Levy [UNIFESP; Tufik, Sergio [UNIFESP; Frussa-Filho, Roberto [UNIFESP

    2013-01-01

    Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine be...

  3. Pulmonary imaging using dual-energy CT, a role of the assessment of iodine and air distribution

    Energy Technology Data Exchange (ETDEWEB)

    Ferda, Jiri, E-mail: e-mail@fnplzen.cz [Radiodiagnostic Clinic, Charles University Teaching Hospital Plzen, Alej Svobody 80, 30640 Plzen (Czech Republic); Ferdova, Eva; Mirka, Hynek; Baxa, Jan; Bednarova, Alena [Radiodiagnostic Clinic, Charles University Teaching Hospital Plzen, Alej Svobody 80, 30640 Plzen (Czech Republic); Flohr, Thomas; Schmidt, Bernhard [Siemens Healthcare, Computed Tomography, 91301 Siemensstr. 1, Forchheim (Germany); Matejovic, Martin [1st Internal Department, Charles University Teaching Hospital Plzen, Alej Svobody 80, 30640 Plzen (Czech Republic); Kreuzberg, Boris [Radiodiagnostic Clinic, Charles University Teaching Hospital Plzen, Alej Svobody 80, 30640 Plzen (Czech Republic)

    2011-02-15

    Aim: The aim of the study is to present the feasibility of using dual-energy CT and the evaluation of iodine and air distribution in differentiation of pathological conditions. Material and method: We used the data of 50 CT examinations performed due to suspected pulmonary embolism with any pathological finding except consolidation of the parenchyma. The patients underwent CT angiography of the pulmonary arteries on a dual-source CT (DSCT), with the two tubes independently operated at 140 and 80 kV. By exploiting the dual-energy information, iodine distribution maps were obtained in addition to the conventional CT images which served as a marker of pulmonary perfusion. Minimum intensity projections (MinIP) were used as a marker of air content. Results: By comparing the iodine distribution maps and MinIP images, it was possible to differentiate between the following templates of lung parenchyma: A - normal iodine and air distribution; B - iodine content deficit with minimal or with no redistribution of air; C - reduced iodine content and increased content of air; D - deficit of iodine content and increased content of air; E - increased iodine content and normal content of air; F - increased iodine content and reduced content of air; G - reduced perfusion and reduced content of air. The type A (five cases) was typical for the pulmonary embolism with preserved normal conditions of perfusion and ventilation. Type B (18 cases) occurred in pulmonary embolism; type C was found in case of inflammation of small respiratory airways (five cases); emphysema was typical for type D (nine cases); increased perfusion was observed in the parenchyma preserved from emphysema or preserved from embolism in cases of emphysema or pulmonary embolism; type F occurred in pulmonary interstitial edema (four cases) both with pulmonary infection; finally type G was found in interstitial lung diseases (five cases). Conclusion: Imaging of the pulmonary circulation by means of dual-energy CT opens

  4. assessment of the clinical role of simultaneous 99mTc-MIBI and 201Tl dual-isotopic myocardial perfusion SPECT imaging in the patients wit hypertension

    International Nuclear Information System (INIS)

    Xie Wenhui; Zhang Lihua; Hu Shilong; Yang Shunfang; Zeng Jun

    2004-01-01

    Objective: To study the clinical role of Simultaneous rest technetium-99m sestamibi ( 99m Tc-MIBI) and stress thallium-201 (201Tl) Dual-isotopic myocardial perfusion SPECT imaging in the patients with hypertension. Methods: 116 patients with high blood pressure underwent simultaneous dual-isotopic myocardial perfusion SPECT imaging with 99m Tc-MIBI and 201Tl. 99m Tc-MIBI was injected at rest, 15 min later dobutamine was instilled into vein begin with 5 mg/kg/min, before and after instilling the base ECG, blood pressure, heart rate was recorded. when the maximal dose of Dobutamine was achieved, thallium-201 was injected, the dual-isotopic simultaneously SPECT imagine was performed. The stress and rest imagine was obtained. After tomographic reconstruction, the images were interpreted by two experienced observers without previous knowledge of results of other studies. Coronary angiography was performed in two weeks. All of 116 patients were found normal. Results: (1) All of 116 patients with high blood pressure were divided as three group by the course of disease: A group ( 20 year), 15. The heart/lung ratios of A, B, C group were 2.651±0.246, 2.546±0.231, 2.490±0.36 (mean±SD)respectively, no significant difference was noted among three group. Normal heart/lung ratios is 2.50±0.28 among of control group of 20. (2) The overall sensitivity for the dual-isotopic simultaneously myocardial SPECT imagine of high blood pressure was 46.55%(54/116). (3) Anterior, lateral, inferior, apex, interventricular septal segment were regarded as a whole segment, 111 segments display abnormal 201Tl uptake. 63, 30, 18 segments were in A, B, C group respectively, and no significant difference was noted among three group. 4 85 segments reveal reduced stressing 201Tl uptake and no typical redistribution was observed in the delay 201Tl imagines. 20, 24, 14, 12, 15 segments were in anterior, lateral, inferior, apex, interventricular septal segment respectively. 26 segments display

  5. Dual Regression

    OpenAIRE

    Spady, Richard; Stouli, Sami

    2012-01-01

    We propose dual regression as an alternative to the quantile regression process for the global estimation of conditional distribution functions under minimal assumptions. Dual regression provides all the interpretational power of the quantile regression process while avoiding the need for repairing the intersecting conditional quantile surfaces that quantile regression often produces in practice. Our approach introduces a mathematical programming characterization of conditional distribution f...

  6. Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

    Science.gov (United States)

    Bhattacharya, Palash; Budnick, Isadore; Singh, Medha; Thiruppathi, Muthusamy; Alharshawi, Khaled; Elshabrawy, Hatem; Holterman, Mark J.

    2015-01-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them “tolerogenic,” which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility. PMID:25803788

  7. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues

    International Nuclear Information System (INIS)

    Firth, R.G.; Bell, P.M.; Marsh, H.M.; Hansen, I.; Rizza, R.A.

    1986-01-01

    Patients with noninsulin-dependent diabetes mellitus (NIDDM) have both preprandial and postprandial hyperglycemia. To determine the mechanism responsible for the postprandial hyperglycemia, insulin secretion, insulin action, and the pattern of carbohydrate metabolism after glucose ingestion were assessed in patients with NIDDM and in matched nondiabetic subjects using the dual isotope and forearm catheterization techniques. Prior to meal ingestion, hepatic glucose release was increased (P less than 0.001) in the diabetic patients measured using [2- 3 H] or [3- 3 H] glucose. After meal ingestion, patients with NIDDM had excessive rates of systemic glucose entry (1,316 +/- 56 vs. 1,018 +/- 65 mg/kg X 7 h, P less than 0.01), primarily owing to a failure to suppress adequately endogenous glucose release (680 +/- 50 vs. 470 +/- 32 mg/kg X 7 h, P less than 0.01) from its high preprandial level. Despite impaired suppression of endogenous glucose production during a hyperinsulinemic glucose clamp (P less than 0.001) and decreased postprandial C-peptide response (P less than 0.05) in NIDDM, percent suppression of hepatic glucose release after oral glucose was comparable in the diabetic and nondiabetic subjects (45 +/- 3 vs. 39 +/- 2%). Although new glucose formation from meal-derived three-carbon precursors (53 +/- 3 vs. 40 +/- 7 mg/kg X 7 h, P less than 0.05) was greater in the diabetic patients, it accounted for only a minor part of this excessive postprandial hepatic glucose release. Postprandial hyperglycemia was exacerbated by the lack of an appropriate increase in glucose uptake whether measured isotopically or by forearm glucose uptake. Thus excessive hepatic glucose release and impaired glucose uptake are involved in the pathogenesis of postprandial hyperglycemia in patients with NIDDM

  8. Exploring the role of experiential avoidance from the perspective of attachment theory and the dual process model.

    Science.gov (United States)

    Shear, M Katherine

    2010-01-01

    Avoidance can be adaptive and facilitate the healing process of acute grief or it can be maladaptive and hinder this same process. Maladaptive cognitive or behavioral avoidance comprises the central feature of the condition of complicated grief. This article explores the concept of experiential avoidance as it applies to bereavement, including when it is adaptive when it is problematic. Adaptive avoidance is framed using an attachment theory perspective and incorporates insights from the dual process model (DPM). An approach to clinical management of experiential avoidance in the syndrome of complicated grief is included.

  9. Role of NPR1 dependent and NPR1 independent genes in response to Salicylic acid

    Directory of Open Access Journals (Sweden)

    Neha Agarwal

    2017-10-01

    Full Text Available NPR1 (Nonexpressor of pathogenesis-related gene is a transcription coactivator and central regulator of systemic acquired resistance (SAR pathway. It controls wide range of pathogenesis related genes involved in various defense responses, acts by sensing SAR signal molecule, Salicylic acid (SA. Mutation in NPR1 results in increased susceptibility to pathogen infection and less expression of pathogenesis related genes. The present study aimed to identify the role of NPR1 in gene expression after the Salicylic acid induction. For this RNA-seq was performed in Arabidopsis thaliana Col-0 and npr1-1 in response to Salicylic acid. RNA-seq analysis revealed a total of 3811 differentially expressed gene in which 2109 genes are up-regulated and 1702 genes are down-regulated. We have divided these genes in 6 categories SA induced (SI, SA repressed (SR, NPR1 dependent SI (ND-SI, NPR1 dependent SR (ND-SR, NPR1 independent SI (NI-SI, NPR1 independent SR (NI-SR. Further, Gene ontology and MapMan pathway analysis of differentially expressed genes suggested variety of biological processes and metabolic pathways that are enriched during SAR defense pathway. These results contribute to shed light on importance of both NPR1-dependent (ND and NPR1-independent (NI gene acting downstream to Salicylic acid induction in SAR pathway. The present study aimed to identify the role of NPR1 in gene expression after the Salicylic acid induction.

  10. The Effect of Dual Role Woman Performance as a Civil Servant in the Level of Government Tomohon

    OpenAIRE

    Mekel, Peggy Adeline; Mait, Swingli

    2014-01-01

    Today, woman in Indonesia their role as a housewife has been divided with role as an employee to meet the family needs because of unfavorable economic conditions. However having to simultaneously act for two roles is not easy. This situation will result in a very significant achievement for business establishments, which is affected their performance in the office. This study aimed to determine the influence of role as a housewife and role as an employee to the employee performance as a civil...

  11. Is empathy one of the Big Three? Identifying its role in a dual-process model of ideology and blatant and subtle prejudice

    Science.gov (United States)

    2018-01-01

    In the field of the social psychology of prejudice, John Duckitt's Dual-Process Cognitive-Motivational Model of Ideology and Prejudice has gained a firm grounding over the past decade and a half, while empathy has become one of the most powerful predictors of prejudice, alongside right-wing authoritarianism and social dominance orientation. This study integrates empathy into the dual-process model, exploring the effects of this variable, along with the impact of personality and ideological attitudes, on prejudice in both its blatant and subtle forms. A cross-sectional research design was used to collect data from 260 university students by self-report measures. Despite its cross-sectional nature, a pattern of causal relationships was hypothesized according to experimental and longitudinal findings from previous studies. The path analysis results show that in the model fitted to the data, empathy does not have any direct impact on prejudice, although it plays a significant role in the prediction of prejudice towards a particular immigrant group. On the other hand, the dual-process model is confirmed in the explanation of blatant prejudice and, in a weaker and indirect way, of subtle prejudice; sustaining the distinctive nature of these constructs on some differential predictors and paths. In the discussion, this study proposes that when ideological and personality-based variables are both included in the model, general empathy is not so robust in the explanation of prejudice, since some of the empathetic components might become diluted among other covariates. But even so, its indirect effectiveness through personality and ideological attitudes remains relevant. PMID:29621307

  12. Is empathy one of the Big Three? Identifying its role in a dual-process model of ideology and blatant and subtle prejudice.

    Science.gov (United States)

    Álvarez-Castillo, José Luis; Fernández-Caminero, Gemma; González-González, Hugo

    2018-01-01

    In the field of the social psychology of prejudice, John Duckitt's Dual-Process Cognitive-Motivational Model of Ideology and Prejudice has gained a firm grounding over the past decade and a half, while empathy has become one of the most powerful predictors of prejudice, alongside right-wing authoritarianism and social dominance orientation. This study integrates empathy into the dual-process model, exploring the effects of this variable, along with the impact of personality and ideological attitudes, on prejudice in both its blatant and subtle forms. A cross-sectional research design was used to collect data from 260 university students by self-report measures. Despite its cross-sectional nature, a pattern of causal relationships was hypothesized according to experimental and longitudinal findings from previous studies. The path analysis results show that in the model fitted to the data, empathy does not have any direct impact on prejudice, although it plays a significant role in the prediction of prejudice towards a particular immigrant group. On the other hand, the dual-process model is confirmed in the explanation of blatant prejudice and, in a weaker and indirect way, of subtle prejudice; sustaining the distinctive nature of these constructs on some differential predictors and paths. In the discussion, this study proposes that when ideological and personality-based variables are both included in the model, general empathy is not so robust in the explanation of prejudice, since some of the empathetic components might become diluted among other covariates. But even so, its indirect effectiveness through personality and ideological attitudes remains relevant.

  13. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance

    Science.gov (United States)

    Azam, Mohammad; Nardi, Valentina; Shakespeare, William C.; Metcalf, Chester A.; Bohacek, Regine S.; Wang, Yihan; Sundaramoorthi, Raji; Sliz, Piotr; Veach, Darren R.; Bornmann, William G.; Clarkson, Bayard; Dalgarno, David C.; Sawyer, Tomi K.; Daley, George Q.

    2006-01-01

    Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance in patients with chronic myelogenous leukemia. Many mutations favor active kinase conformations that preclude imatinib binding. Because the active forms of ABL and SRC resemble one another, we tested two dual SRC-ABL kinase inhibitors, AP23464 and PD166326, against 58 imatinib-resistant (IMR) BCR/ABL kinase variants. Both compounds potently inhibit most IMR variants, and in vitro drug selection demonstrates that active (AP23464) and open (PD166326) conformation-specific compounds are less susceptible to resistance than imatinib. Combinations of inhibitors suppressed essentially all resistance mutations, with the notable exception of T315I. Guided by mutagenesis studies and molecular modeling, we designed a series of AP23464 analogues to target T315I. The analogue AP23846 inhibited both native and T315I variants of BCR/ABL with submicromolar potency but showed nonspecific cellular toxicity. Our data illustrate how conformational dynamics of the ABL kinase accounts for the activity of dual SRC-ABL inhibitors against IMR-mutants and provides a rationale for combining conformation specific inhibitors to suppress resistance. PMID:16754879

  14. Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism.

    Science.gov (United States)

    Koh, Ho-Jin; Lee, Su-Min; Son, Byung-Gap; Lee, Soh-Hyun; Ryoo, Zae Young; Chang, Kyu-Tae; Park, Jeen-Woo; Park, Dong-Chan; Song, Byoung J; Veech, Richard L; Song, Hebok; Huh, Tae-Lin

    2004-09-17

    NADPH is an essential cofactor for many enzymatic reactions including glutathione metabolism and fat and cholesterol biosynthesis. We have reported recently an important role for mitochondrial NADP(+)-dependent isocitrate dehydrogenase in cellular defense against oxidative damage by providing NADPH needed for the regeneration of reduced glutathione. However, the role of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is still unclear. We report here for the first time that IDPc plays a critical role in fat and cholesterol biosynthesis. During differentiation of 3T3-L1 adipocytes, both IDPc enzyme activity and its protein content were increased in parallel in a time-dependent manner. Increased expression of IDPc by stable transfection of IDPc cDNA positively correlated with adipogenesis of 3T3-L1 cells, whereas decreased IDPc expression by an antisense IDPc vector retarded adipogenesis. Furthermore, transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia, and obesity. In the epididymal fat pads of the transgenic mice, the expressions of adipocyte-specific genes including peroxisome proliferator-activated receptor gamma were markedly elevated. The hepatic and epididymal fat pad contents of acetyl-CoA and malonyl-CoA in the transgenic mice were significantly lower, whereas the total triglyceride and cholesterol contents were markedly higher in the liver and serum of transgenic mice compared with those measured in wild type mice, suggesting that the consumption rate of those lipogenic precursors needed for fat biosynthesis must be increased by elevated IDPc activity. Taken together, our findings strongly indicate that IDPc would be a major NADPH producer required for fat and cholesterol synthesis.

  15. The role of HSP70 in mediating age-dependent mortality in sepsis

    Science.gov (United States)

    McConnell, Kevin W.; Fox, Amy C.; Clark, Andrew T.; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A.; Farris, Alton B.; Buchman, Timothy G.; Hunt, Clayton R.; Coopersmith, Craig M.

    2011-01-01

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6–12week old) and aged (16–17 month old) HSP70−/− and wild type (WT) mice to determine if HSP70 modulated outcome in an age-dependent fashion. Young HSP70−/− and WT mice subjected to cecal ligation and puncture (CLP), Pseudomonas aeruginosa pneumonia or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70−/− mice than aged WT mice subjected to CLP (p=0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared to WT mice, aged septic HSP70−/− mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70−/−mice had increased systemic levels of TNF-α, IL-6, IL-10 and IL-1β compared to WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation. PMID:21296977

  16. The role of heat shock protein 70 in mediating age-dependent mortality in sepsis.

    Science.gov (United States)

    McConnell, Kevin W; Fox, Amy C; Clark, Andrew T; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A; Farris, Alton B; Buchman, Timothy G; Hunt, Clayton R; Coopersmith, Craig M

    2011-03-15

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70(-/-) and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70(-/-) and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70(-/-) mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70(-/-) mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70(-/-) mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.

  17. The role of inelastic processes in the temperature dependence of hall induced resistance oscillations

    International Nuclear Information System (INIS)

    Kunold, Alejandro; Torres, Manuel

    2013-01-01

    We develop a model of magnetoresistance oscillations induced by the Hall field in order to study the temperature dependence observed in recent experiments in two dimensional electron systems. The model is based on the solution of the von Neumann equation incorporating the exact dynamics of two-dimensional damped electrons in the presence of arbitrarily strong magnetic and dc electric fields, while the effects of randomly distributed neutral and charged impurities are perturbatively added. Both the effects of elastic impurity scattering as well as those related to inelastic processes play an important role. The theoretical predictions correctly reproduce the experimentally observed oscillations amplitude, provided that the quantum inelastic scattering rate obeys a T 2 temperature dependence, consistent with electron–electron interaction effects

  18. Role of state-dependent learning in the cognitive effects of caffeine in mice.

    Science.gov (United States)

    Sanday, Leandro; Zanin, Karina A; Patti, Camilla L; Fernandes-Santos, Luciano; Oliveira, Larissa C; Longo, Beatriz M; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

    2013-08-01

    Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.

  19. Lexicons, contexts, events, and images: commentary on Elman (2009) from the perspective of dual coding theory.

    Science.gov (United States)

    Paivio, Allan; Sadoski, Mark

    2011-01-01

    Elman (2009) proposed that the traditional role of the mental lexicon in language processing can largely be replaced by a theoretical model of schematic event knowledge founded on dynamic context-dependent variables. We evaluate Elman's approach and propose an alternative view, based on dual coding theory and evidence that modality-specific cognitive representations contribute strongly to word meaning and language performance across diverse contexts which also have effects predictable from dual coding theory. Copyright © 2010 Cognitive Science Society, Inc.

  20. Dual role of Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice

    Directory of Open Access Journals (Sweden)

    Alexia Anne Belperron

    2014-06-01

    Full Text Available Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ-/- mice harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88-/- mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ-/-MyD88-/- mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC, Xcr1 (Gpr5, IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi

  1. A Dual Role for the Bacillus anthracis Master Virulence Regulator AtxA: Control of Sporulation and Anthrax Toxin Production.

    Science.gov (United States)

    Dale, Jennifer L; Raynor, Malik J; Ty, Maureen C; Hadjifrangiskou, Maria; Koehler, Theresa M

    2018-01-01

    Bacillus anthracis is an endemic soil bacterium that exhibits two different lifestyles. In the soil environment, B. anthracis undergoes a cycle of saprophytic growth, sporulation, and germination. In mammalian hosts, the pathogenic lifestyle of B. anthracis is spore germination followed by vegetative cell replication, but cells do not sporulate. During infection, and in specific culture conditions, transcription of the structural genes for the anthrax toxin proteins and the biosynthetic operon for capsule synthesis is positively controlled by the regulatory protein AtxA. A critical role for the atxA gene in B. anthracis virulence has been established. Here we report an inverse relationship between toxin production and sporulation that is linked to AtxA levels. During culture in conditions favoring sporulation, B. anthracis produces little to no AtxA. When B. anthracis is cultured in conditions favoring toxin gene expression, AtxA is expressed at relatively high levels and sporulation rate and efficiency are reduced. We found that a mutation within the atxA promoter region resulting in AtxA over-expression leads to a marked sporulation defect. The sporulation phenotype of the mutant is dependent upon pXO2-0075 , an atxA -regulated open reading frame located on virulence plasmid pXO2. The predicted amino acid sequence of the pXO2-0075 protein has similarity to the sensor domain of sporulation sensor histidine kinases. It was shown previously that pXO2-0075 overexpression suppresses sporulation. We have designated pXO2-0075 " skiA " for "sporulation kinase inhibitor." Our results indicate that in addition to serving as a positive regulator of virulence gene expression, AtxA modulates B. anthracis development.

  2. Matrix metalloproteases as maestros for the dual role of LPS- and IL-10-stimulated macrophages in cancer cell behaviour

    International Nuclear Information System (INIS)

    Cardoso, Ana P.; Pinto, Marta L.; Pinto, Ana T.; Pinto, Marta T.; Monteiro, Cátia; Oliveira, Marta I.; Santos, Susana G.; Relvas, João B.; Seruca, Raquel; Mantovani, Alberto; Mareel, Marc; Barbosa, Mário A.; Oliveira, Maria J.

    2015-01-01

    The interactions established between macrophages and cancer cells are largely dependent on instructions from the tumour microenvironment. Macrophages may differentiate into populations with distinct inflammatory profiles, but knowledge on their role on cancer cell activities is still very scarce. In this work, we investigated the influence of pro-inflammatory (LPS-stimulated) and anti-inflammatory (IL-10-stimulated) macrophages on gastric and colorectal cancer cell invasion, motility/migration, angiogenesis and proteolysis, and the associated molecular mechanisms. Following exposure of gastric and colon cancer cell lines to LPS- and IL-10-stimulated human macrophages, either by indirect contact or conditioned media, we analyzed the effect of the different macrophage populations on cancer cell invasion, migration, motility and phosphorylation status of EGFR and several interacting partners. Cancer-cell induced angiogenesis upon the influence of conditioned media from both macrophage populations was assessed using the chick embryo chorioallantoic membrane assay. MMP activities were evaluated by gelatin zymograhy. Our results show that IL-10-stimulated macrophages are more efficient in promoting in vitro cancer cell invasion and migration. In addition, soluble factors produced by these macrophages enhanced in vivo cancer cell-induced angiogenesis, as opposed to their LPS-stimulated counterparts. We further demonstrate that differences in the ability of these macrophage populations to stimulate invasion or angiogenesis cannot be explained by the EGFR-mediated signalling, since both LPS- and IL-10-stimulated macrophages similarly induce the phosphorylation of cancer cell EGFR, c-Src, Akt, ERK1/2, and p38. Interestingly, both populations exert distinct proteolytic activities, being the IL-10-stimulated macrophages the most efficient in inducing matrix metalloprotease (MMP)-2 and MMP-9 activities. Using a broad-spectrum MMP inhibitor, we demonstrated that proteolysis was

  3. Torn between dual roles: the experiences of nurse-family members when a loved one is hospitalised in a critical condition.

    Science.gov (United States)

    Giles, Tracey M; Williamson, Victoria

    2015-11-01

    To understand and interpret the experiences of nurse-family members when a family member or loved one is hospitalised in a critical condition. Having a family member hospitalised with a critical illness is a traumatic stressor, often with long-term sequelae. Providing holistic care for family members who are also nurses makes the provision of care more complex because of their professional expertise; yet few studies have explored this issue. In this descriptive study, qualitative data were collected using a questionnaire and analysed using van Manen's (Researching Lived Experience: Human Science for an Action Sensitive Pedagogy, 1990, State University of New York Press, London, ON) six-step approach. Twenty nurse-family members completed an online questionnaire in June 2013. Qualitative findings from 19 participants were included in the analysis. The phenomenological analysis approach described by van Manen (Researching Lived Experience: Human Science for an Action Sensitive Pedagogy, 1990, State University of New York Press, London, ON) was used to describe and interpret nurse-family member experiences. Nurse-family members experience significant dual role conflicts between their personal and professional personas due to their specialised knowledge, need for watchfulness and competing expectations. Our findings describe how dual role conflicts developed and were managed, and reveal the resultant emotional toll and psychological distress as nurse-family members struggled to resolve these conflicts. Nurse-family members require a different type of care than general public family members, yet their unique needs are often unmet, leading to increased anxiety and distress that could potentially be minimised. An increased awareness and emphasis on the nurse-family member experience can ensure health care professionals are better placed to provide appropriate and targeted care to minimise distressing dual role conflicts. There is a need for targeted and specialised

  4. Dual role of delta-like 1 homolog (DLK1) in skeletal muscle development and adult muscle regeneration

    DEFF Research Database (Denmark)

    Andersen, Ditte Caroline; Laborda, Jorge; Baladron, Victoriano

    2013-01-01

    skeletal muscle regeneration by substantial enhancement of the myogenic program and muscle function, possibly by means of an increased number of available myogenic precursor cells. By contrast, Dlk1 fails to alter the adipogenic commitment of muscle-derived progenitors in vitro, as well as intramuscular......Muscle development and regeneration is tightly orchestrated by a specific set of myogenic transcription factors. However, factors that regulate these essential myogenic inducers remain poorly described. Here, we show that delta-like 1 homolog (Dlk1), an imprinted gene best known for its ability...... fat deposition during in vivo regeneration. Collectively, our results suggest a novel and surprising dual biological function of DLK1 as an enhancer of muscle development, but as an inhibitor of adult muscle regeneration....

  5. P53-dependent upregulation of neutral sphingomyelinase-2: role in doxorubicin-induced growth arrest.

    Science.gov (United States)

    Shamseddine, A A; Clarke, C J; Carroll, B; Airola, M V; Mohammed, S; Rella, A; Obeid, L M; Hannun, Y A

    2015-10-29

    Neutral sphingomyelinase-2 (nSMase2) is a ceramide-generating enzyme that has been implicated in growth arrest, apoptosis and exosome secretion. Although previous studies have reported transcriptional upregulation of nSMase2 in response to daunorubicin, through Sp1 and Sp3 transcription factors, the role of the DNA damage pathway in regulating nSMase2 remains unclear. In this study, we show that doxorubicin induces a dose-dependent induction of nSMase2 mRNA and protein with concomitant increases in nSMase activity and ceramide levels. Upregulation of nSMase2 was dependent on ATR, Chk1 and p53, thus placing it downstream of the DNA damage pathway. Moreover, overexpression of p53 was sufficient to transcriptionally induce nSMase2, without the need for DNA damage. DNA-binding mutants as well as acetylation mutants of p53 were unable to induce nSMase2, suggesting a role of nSMase2 in growth arrest. Moreover, knockdown of nSMase2 prevented doxorubicin-induced growth arrest. Finally, p53-induced nSMase2 upregulation appears to occur via a novel transcription start site upstream of exon 3. These results identify nSMase2 as a novel p53 target gene, regulated by the DNA damage pathway to induce cell growth arrest.

  6. The role of the cannabinoid system in the pathogenesis and treatment of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Bogusława Pietrzak

    2011-09-01

    Full Text Available The lack of satisfactory results of alcohol dependence treatment force us to search for new directions of research. Recent studies concentrate on endocannabinoid transmission. The results show an interplay between the endocannabinoid and dopaminergic signaling in activation of the limbic reward system. The mechanisms leading to development of dependence are very complex and poorly recognized. Endogenous cannabinoids seem to have an important role in the functioning of this system, both directly and indirectly affecting the level of different neurotransmitters. The effect of alcohol on the endocannabinoid system is also complex and involves changes at the molecular level. Experimental studies have demonstrated an important role of the CB1 receptors in the neurochemical mechanism of alcohol consumption and its regulation. SR141716 (rimonabant, a CB1 receptor antagonist, significantly lowers voluntary alcohol intake and motivation for its consumption in various experimental studies. Very encouraging results of preclinical studies were not completely confirmed in the clinical studies. However, further clinical studies are still necessary.

  7. dsRNA-Dependent Protein Kinase PKR and its Role in Stress, Signaling and HCV Infection

    Directory of Open Access Journals (Sweden)

    Eliane F. Meurs

    2012-10-01

    Full Text Available The double-stranded RNA-dependent protein kinase PKR plays multiple roles in cells, in response to different stress situations. As a member of the interferon (IFN‑Stimulated Genes, PKR was initially recognized as an actor in the antiviral action of IFN, due to its ability to control translation, through phosphorylation, of the alpha subunit of eukaryotic initiation factor 2 (eIF2a. As such, PKR participates in the generation of stress granules, or autophagy and a number of viruses have designed strategies to inhibit its action. However, PKR deficient mice resist most viral infections, indicating that PKR may play other roles in the cell other than just acting as an antiviral agent. Indeed, PKR regulates several signaling pathways, either as an adapter protein and/or using its kinase activity. Here we review the role of PKR as an eIF2a kinase, its participation in the regulation of the NF-kB, p38MAPK and insulin pathways, and we focus on its role during infection with the hepatitis C virus (HCV. PKR binds the HCV IRES RNA, cooperates with some functions of the HCV core protein and may represent a target for NS5A or E2. Novel data points out for a role of PKR as a pro-HCV agent, both as an adapter protein and as an eIF2a-kinase, and in cooperation with the di-ubiquitin-like protein ISG15. Developing pharmaceutical inhibitors of PKR may help in resolving some viral infections as well as stress-related damages.

  8. The Complex Subtype-Dependent Role of Connexin 43 (GJA1 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mélanie Busby

    2018-02-01

    Full Text Available Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43 in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

  9. Communication: Modeling of concentration dependent water diffusivity in ionic solutions: Role of intermolecular charge transfer

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yi; Berkowitz, Max L., E-mail: maxb@unc.edu, E-mail: ykanai@unc.edu; Kanai, Yosuke, E-mail: maxb@unc.edu, E-mail: ykanai@unc.edu [Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 (United States)

    2015-12-28

    The translational diffusivity of water in solutions of alkali halide salts depends on the identity of ions, exhibiting dramatically different behavior even in solutions of similar salts of NaCl and KCl. The water diffusion coefficient decreases as the salt concentration increases in NaCl. Yet, in KCl solution, it slightly increases and remains above bulk value as salt concentration increases. Previous classical molecular dynamics simulations have failed to describe this important behavior even when polarizable models were used. Here, we show that inclusion of dynamical charge transfer among water molecules produces results in a quantitative agreement with experiments. Our results indicate that the concentration-dependent diffusivity reflects the importance of many-body effects among the water molecules in aqueous ionic solutions. Comparison with quantum mechanical calculations shows that a heterogeneous and extended distribution of charges on water molecules around the ions due to ion-water and also water-water charge transfer plays a very important role in controlling water diffusivity. Explicit inclusion of the charge transfer allows us to model accurately the difference in the concentration-dependent water diffusivity between Na{sup +} and K{sup +} ions in simulations, and it is likely to impact modeling of a wide range of systems for medical and technological applications.

  10. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

    Directory of Open Access Journals (Sweden)

    Alejo Efeyan

    Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

  11. The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

    Science.gov (United States)

    Busby, Mélanie; Hallett, Michael T.; Plante, Isabelle

    2018-01-01

    Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. PMID:29495625

  12. Dual role of boron in improving electrical performance and device stability of low temperature solution processed ZnO thin film transistors

    Energy Technology Data Exchange (ETDEWEB)

    Gandla, Srinivas; Gollu, Sankara Rao; Sharma, Ramakant; Sarangi, Venkateshwarlu; Gupta, Dipti, E-mail: diptig@iitb.ac.in [Plastic Electronics and Energy Laboratory (PEEL), Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Powai, Mumbai-400076 (India)

    2015-10-12

    In this paper, we have demonstrated the dual role of boron doping in enhancing the device performance parameters as well as the device stability in low temperatures (200 °C) sol-gel processed ZnO thin film transistors (TFTs). Our studies suggest that boron is able to act as a carrier generator and oxygen vacancy suppressor simultaneously. Boron-doped ZnO TFTs with 8 mol. % of boron concentration demonstrated field-effect mobility value of 1.2 cm{sup 2} V{sup −1} s{sup −1} and threshold voltage of 6.2 V, respectively. Further, these devices showed lower shift in threshold voltage during the hysteresis and bias stress measurements as compared to undoped ZnO TFTs.

  13. Context dependence of students' views about the role of equations in understanding biology.

    Science.gov (United States)

    Watkins, Jessica; Elby, Andrew

    2013-06-01

    Students' epistemological views about biology--their ideas about what "counts" as learning and understanding biology--play a role in how they approach their courses and respond to reforms. As introductory biology courses incorporate more physics and quantitative reasoning, student attitudes about the role of equations in biology become especially relevant. However, as documented in research in physics education, students' epistemologies are not always stable and fixed entities; they can be dynamic and context-dependent. In this paper, we examine an interview with an introductory student in which she discusses the use of equations in her reformed biology course. In one part of the interview, she expresses what sounds like an entrenched negative stance toward the role equations can play in understanding biology. However, later in the interview, when discussing a different biology topic, she takes a more positive stance toward the value of equations. These results highlight how a given student can have diverse ways of thinking about the value of bringing physics and math into biology. By highlighting how attitudes can shift in response to different tasks, instructional environments, and contextual cues, we emphasize the need to attend to these factors, rather than treating students' beliefs as fixed and stable.

  14. Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence.

    Science.gov (United States)

    Masuyer, Geoffrey; Yates, Christopher J; Sturrock, Edward D; Acharya, K Ravi

    2014-10-01

    Somatic angiotensin-I converting enzyme (sACE) has an essential role in the regulation of blood pressure and electrolyte fluid homeostasis. It is a zinc protease that cleaves angiotensin-I (AngI), bradykinin, and a broad range of other signalling peptides. The enzyme activity is provided by two homologous domains (N- and C-), which display clear differences in substrate specificities and chloride activation. The presence of chloride ions in sACE and its unusual role in activity was identified early on in the characterisation of the enzyme. The molecular mechanisms of chloride activation have been investigated thoroughly through mutagenesis studies and shown to be substrate-dependent. Recent results from X-ray crystallography structural analysis have provided the basis for the intricate interactions between ACE, its substrate and chloride ions. Here we describe the role of chloride ions in human ACE and its physiological consequences. Insights into the chloride activation of the N- and C-domains could impact the design of improved domain-specific ACE inhibitors.

  15. Dual Criteria Decisions

    DEFF Research Database (Denmark)

    Andersen, Steffen; Harrison, Glenn W.; Lau, Morten Igel

    2014-01-01

    The most popular models of decision making use a single criterion to evaluate projects or lotteries. However, decision makers may actually consider multiple criteria when evaluating projects. We consider a dual criteria model from psychology. This model integrates the familiar tradeoffs between...... to the clear role that income thresholds play in such decision making, but does not rule out a role for tradeoffs between risk and utility or probability weighting....

  16. The Explicit Determinations Of Dual Plane Curves And Dual Helices In Terms Of Its Dual Curvature And Dual Torsion

    OpenAIRE

    Lee Jae Won; Choi Jin Ho; Jin Dae Ho

    2014-01-01

    In this paper, we give the explicit determinations of dual plane curves, general dual helices and dual slant helices in terms of its dual curvature and dual torsion as a fundamental theory of dual curves in a dual 3-space

  17. Role of the pH in state-dependent blockade of hERG currents

    Science.gov (United States)

    Wang, Yibo; Guo, Jiqing; Perissinotti, Laura L.; Lees-Miller, James; Teng, Guoqi; Durdagi, Serdar; Duff, Henry J.; Noskov, Sergei Yu.

    2016-10-01

    Mutations that reduce inactivation of the voltage-gated Kv11.1 potassium channel (hERG) reduce binding for a number of blockers. State specific block of the inactivated state of hERG block may increase risks of drug-induced Torsade de pointes. In this study, molecular simulations of dofetilide binding to the previously developed and experimentally validated models of the hERG channel in open and open-inactivated states were combined with voltage-clamp experiments to unravel the mechanism(s) of state-dependent blockade. The computations of the free energy profiles associated with the drug block to its binding pocket in the intra-cavitary site display startling differences in the open and open-inactivated states of the channel. It was also found that drug ionization may play a crucial role in preferential targeting to the open-inactivated state of the pore domain. pH-dependent hERG blockade by dofetilie was studied with patch-clamp recordings. The results show that low pH increases the extent and speed of drug-induced block. Both experimental and computational findings indicate that binding to the open-inactivated state is of key importance to our understanding of the dofetilide’s mode of action.

  18. Is There Still Any Role for Oxidative Stress in Mitochondrial DNA-Dependent Aging?

    Directory of Open Access Journals (Sweden)

    Gábor Zsurka

    2018-03-01

    Full Text Available Recent deep sequencing data has provided compelling evidence that the spectrum of somatic point mutations in mitochondrial DNA (mtDNA in aging tissues lacks G > T transversion mutations. This fact cannot, however, be used as an argument for the missing contribution of reactive oxygen species (ROS to mitochondria-related aging because it is probably caused by the nucleotide selectivity of mitochondrial DNA polymerase γ (POLG. In contrast to point mutations, the age-dependent accumulation of mitochondrial DNA deletions is, in light of recent experimental data, still explainable by the segregation of mutant molecules generated by the direct mutagenic effects of ROS (in particular, of HO· radicals formed from H2O2 by a Fenton reaction. The source of ROS remains controversial, because the mitochondrial contribution to tissue ROS production is probably lower than previously thought. Importantly, in the discussion about the potential role of oxidative stress in mitochondria-dependent aging, ROS generated by inflammation-linked processes and the distribution of free iron also require careful consideration.

  19. Board leadership structure and firm performance: An examination of resource dependence role

    Directory of Open Access Journals (Sweden)

    Afzalur Rashid

    2011-01-01

    Full Text Available This study examines if the CEO duality influence the firm economic performance in Bangladesh and the moderating effects of board composition in the form of outside independent directors. While doing so, it examines the relationship between CEO duality and firm performance during the pre appointment of outside independent directors and post appointment of outside independent directors (the role of other corporate governance mechanism as moderating variable. The finding is that there is there is a negative (non-significant relationship between CEO duality and firm performance before appointment of outside independent directors in the board. However, independent leadership structure and firm performance is found to be positively related following the acquisition of resource (outside independent directors in the board supporting the ’resource dependence theory’. The findings of this study partially support the ’agency theory’ and ’resource dependence theory’ but do not support the stewardship theory. This study contributes to the literature on CEO duality in the context of less a developed country.

  20. Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs.

    Science.gov (United States)

    Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A; Goosens, Ki Ann; Bendor, Daniel

    2016-01-01

    The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1-2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.

  1. The role of emotions for moral judgments depends on the type of emotion and moral scenario.

    Science.gov (United States)

    Ugazio, Giuseppe; Lamm, Claus; Singer, Tania

    2012-06-01

    Emotions seem to play a critical role in moral judgment. However, the way in which emotions exert their influence on moral judgments is still poorly understood. This study proposes a novel theoretical approach suggesting that emotions influence moral judgments based on their motivational dimension. We tested the effects of two types of induced emotions with equal valence but with different motivational implications (anger and disgust), and four types of moral scenarios (disgust-related, impersonal, personal, and beliefs) on moral judgments. We hypothesized and found that approach motivation associated with anger would make moral judgments more permissible, while disgust, associated with withdrawal motivation, would make them less permissible. Moreover, these effects varied as a function of the type of scenario: the induced emotions only affected moral judgments concerning impersonal and personal scenarios, while we observed no effects for the other scenarios. These findings suggest that emotions can play an important role in moral judgment, but that their specific effects depend upon the type of emotion induced. Furthermore, induced emotion effects were more prevalent for moral decisions in personal and impersonal scenarios, possibly because these require the performance of an action rather than making an abstract judgment. We conclude that the effects of induced emotions on moral judgments can be predicted by taking their motivational dimension into account. This finding has important implications for moral psychology, as it points toward a previously overlooked mechanism linking emotions to moral judgments.

  2. Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure.

    Science.gov (United States)

    Dong, Changsheng; Yang, Shanshan; Fan, Ruiwen; Ji, Kaiyuan; Zhang, Junzhen; Liu, Xuexian; Hu, Shuaipeng; Xie, Jianshan; Liu, Yu; Gao, Wenjun; Wang, Haidong; Yao, Jianbo; Smith, George W; Herrid, Muren

    2017-10-23

    The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of MITF and PAX3. Cdk5 knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (K10) resulting from Cdk5 knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of Cdk5 in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system.

  3. Alcohol and Masculinity: A Review and Reformulaton of the Sex Role, Dependency, and Power Theories of Alcoholism.

    Science.gov (United States)

    Lemle, Russell

    This review examines three theories of alcohol abuse by American males: (1) the sex role theory which states that men drink heavily because American culture accepts and encourages that activity in males; (2) the dependency theory, which interprets drinking as a means by which men secretly gratify their dependency needs while manifesting an…

  4. The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

    Directory of Open Access Journals (Sweden)

    Vafaei A.L.

    2008-03-01

    Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

  5. The role of diversification strategies in the economic development for oil-depended countries: - The case of UAE

    OpenAIRE

    Ahmed Zain Elabdin Ahmed

    2015-01-01

    Diversification strategies adopted by oil-depended economies' played an important role in the economic development in these countries, which rely heavily on oil exports. UAE as an oil-dependency economy has the type of strategy to diversify the sources of its national income and reduce its dependence on oil to counter the instability in global oil prices. This paper seek to investigate whether the diversification strategies adopted by (UAE) is adequate to manage its economic development. T...

  6. P2-16: Dual-Bound Model and the Role of Time Bound in Perceptual Decision Making

    Directory of Open Access Journals (Sweden)

    Daeseob Lim

    2012-10-01

    Full Text Available The diffusion model (DM encapsulates the dynamics of perceptual decision within a ‘diffusion field’ that is defined by a basis with sensory-evidence (SE and time vectors. At the core of the DM, it assumes that a decision is not made until an evidence particle drifts in the diffusion field and eventually hits one of the two pre-fixed bounds defined in the SE axis. This assumption dictates when and which choice is made by referring to when and which bound will be hit by the evidence particle. What if urgency pressures the decision system to make a choice even when the evidence particle has yet hit the SE bound? Previous modeling attempts at coping with time pressure, despite differences in detail, all manipulated the coordinate of SE bounds. Here, we offer a novel solution by adopting another bound on the time axis. This ‘dual-bound’ model (DBM posits that decisions can also be made when the evidence particle hits a time bound, which is determined on a trial-by-trial basis by a ‘perceived time interval’ – how long the system can stay in the ‘diffusion’ field. The classic single-bound model (SBM exhibited systematic errors in predicting both the reaction time distributions and the time-varying bias in choice. Those errors were not corrected by previously proposed variants of the SBM until the time bound was introduced. The validity of the DBM was further supported by the strong across-individual correlation between observed precision of interval timing and the predicted trial-by-trial variability of the time bound.

  7. SOCIAL REPRESENTATIONS OF RUSSIAN AND BYELORUSSIANS ABOUT MAN’S ROLES DEPENDING ON COMMUNICATION WITH PSYCHOLOGICAL MEASUREMENTS OF CULTURE

    OpenAIRE

    Brazhnik Julia Vladimirovna; Gritsenko Valentina Vasilevna

    2012-01-01

    Given article is devoted the analysis of social representations of young men about man's roles. On sample of Russian and Byelorussians (334 persons) by means of a scale of cultural values (G.Hofstede) and the modified variant of a technique «Semantic differential» directed on studying of representations of young men about traditional man's roles (the getter, the defender, the professional figure, the head of the family, the husband, the father), social representations about man's roles depend...

  8. Determining Role of the Chain Mechanism in the Temperature Dependence of the Gas-Phase Rate of Combustion Reactions

    Science.gov (United States)

    Azatyan, V. V.; Bolod'yan, I. A.; Kopylov, N. P.; Kopylov, S. N.; Prokopenko, V. M.; Shebeko, Yu. N.

    2018-05-01

    It is shown that the strong dependence of the rate of gas-phase combustion reactions on temperature is determined by the high values of the reaction rate constants of free atoms and radicals. It is established that with a branched chain mechanism, a special role in the reaction rate temperature dependence is played by positive feedback between the concentrations of active intermediate species and the rate of their change. The role of the chemical mechanism in the temperature dependence of the process rate with and without inhibitors is considered.

  9. Shigella IpaD has a dual role: signal transduction from the type III secretion system needle tip and intracellular secretion regulation.

    Science.gov (United States)

    Roehrich, A Dorothea; Guillossou, Enora; Blocker, Ariel J; Martinez-Argudo, Isabel

    2013-02-01

    Type III secretion systems (T3SSs) are protein injection devices essential for the interaction of many Gram-negative bacteria with eukaryotic cells. While Shigella assembles its T3SS when the environmental conditions are appropriate for invasion, secretion is only activated after physical contact with a host cell. First, the translocators are secreted to form a pore in the host cell membrane, followed by effectors which manipulate the host cell. Secretion activation is tightly controlled by conserved T3SS components: the needle tip proteins IpaD and IpaB, the needle itself and the intracellular gatekeeper protein MxiC. To further characterize the role of IpaD during activation, we combined random mutagenesis with a genetic screen to identify ipaD mutant strains unable to respond to host cell contact. Class II mutants have an overall defect in secretion induction. They map to IpaD's C-terminal helix and likely affect activation signal generation or transmission. The Class I mutant secretes translocators prematurely and is specifically defective in IpaD secretion upon activation. A phenotypically equivalent mutant was found in mxiC. We show that IpaD and MxiC act in the same intracellular pathway. In summary, we demonstrate that IpaD has a dual role and acts at two distinct locations during secretion activation. © 2013 Blackwell Publishing Ltd.

  10. Regulation of MntH by a dual Mn(II- and Fe(II-dependent transcriptional repressor (DR2539 in Deinococcus radiodurans.

    Directory of Open Access Journals (Sweden)

    Hongxing Sun

    Full Text Available The high intracellular Mn/Fe ratio observed within the bacteria Deinococcus radiodurans may contribute to its remarkable resistance to environmental stresses. We isolated DR2539, a novel regulator of intracellular Mn/Fe homeostasis in D. radiodurans. Electrophoretic gel mobility shift assays (EMSAs revealed that DR2539 binds specifically to the promoter of the manganese acquisition transporter (MntH gene, and that DR0865, the only Fur homologue in D. radiodurans, cannot bind to the promoter of mntH, but it can bind to the promoter of another manganese acquisition transporter, MntABC. β-galactosidase expression analysis indicated that DR2539 acts as a manganese- and iron-dependent transcriptional repressor. Further sequence alignment analysis revealed that DR2539 has evolved some special characteristics. Site-directed mutagenesis suggested that His98 plays an important role in the activities of DR2539, and further protein-DNA binding activity assays showed that the activity of H98Y mutants decreased dramatically relative to wild type DR2539. Our study suggests that D. radiodurans has evolved a very efficient manganese regulation mechanism that involves its high intracellular Mn/Fe ratio and permits resistance to extreme conditions.

  11. Biogas between renewable energy and bio-economy policies—opportunities and constraints resulting from a dual role

    NARCIS (Netherlands)

    Pfau, S.F.; Hagens, J.E.; Dankbaar, B.

    2017-01-01

    BACKGROUND - Biogas plays a major role in two policy domains: the renewable energy domain and the bio-economy domain. The purpose of this paper is to examine the relationship of current biogas practices with the two policy domains and to identify how biogas can contribute to both. METHODS - The

  12. Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets.

    Directory of Open Access Journals (Sweden)

    Makoto Mizunami

    Full Text Available Ca(2+/calmodulin (CaM-dependent protein kinase II (CaMKII is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca(2+/CaM and cAMP signaling participates in long-term memory (LTM formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM. Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca(2+ influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca(2+ signaling and cAMP signaling for LTM formation, a new role of Ca

  13. Sensory role of actin in auxin-dependent responses of tobacco BY-2.

    Science.gov (United States)

    Huang, Xiang; Maisch, Jan; Nick, Peter

    2017-11-01

    Polar auxin transport depends on the polar localization of auxin-efflux carriers. The cycling of these carriers between cell interior and plasma membrane depends on actin. The dynamic of actin not only affects auxin transport, but also changes the auxin-responsiveness. To study the potential link between auxin responsiveness and actin dynamics, we investigated developmental responses of the non-transformed BY-2 (Nicotiana tabacum L. cv Bright Yellow 2) cell line and the transgenic BY-2 strain GF11 (stably transformed BY-2 cells with a GFP-fimbrin actin-binding domain 2 construct). The developmental process was divided into three distinct stages: cell cycling, cell elongation and file disintegration. Several phenotypes were measured to monitor the cellular responses to different concentrations of exogenous natural auxin (Indole-3-acetic acid, IAA). We found that auxin stimulated and prolonged the mitotic activity, and delayed the exit from the proliferation phase. However, both responses were suppressed in the GF11 line. At the stationary phase of the cultivation cycle, auxin strongly accelerated the cell file disintegration. Interestingly, it was not suppressed but progressed to a more complete disintegration in the GF11 line. During the cultivation cycle, we also followed the organization of actin in the GF11 line and did not detect any significant difference in actin organization from untreated control or exogenous IAA treatment. Therefore, our findings indicate that the specific differences observed in the GF11 line must be linked with a function of actin that is not structural. It means that there is a sensory role of actin for auxin signaling. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

    Directory of Open Access Journals (Sweden)

    Juan Rodríguez-Vita

    Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

  15. QCD Dual

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2009-01-01

    We uncover a novel solution of the 't Hooft anomaly matching conditions for QCD. Interestingly in the perturbative regime the new gauge theory, if interpreted as a possible QCD dual, predicts the critical number of flavors above which QCD in the nonperturbative regime, develops an infrared stable...

  16. Peptidoglycan crosslinking relaxation plays an important role in Staphylococcus aureus WalKR-dependent cell viability.

    Directory of Open Access Journals (Sweden)

    Aurelia Delaune

    Full Text Available The WalKR two-component system is essential for viability of Staphylococcus aureus, a major pathogen. We have shown that WalKR acts as the master controller of peptidoglycan metabolism, yet none of the identified regulon genes explain its requirement for cell viability. Transmission electron micrographs revealed cell wall thickening and aberrant division septa in the absence of WalKR, suggesting its requirement may be linked to its role in coordinating cell wall metabolism and cell division. We therefore tested whether uncoupling autolysin gene expression from WalKR-dependent regulation could compensate for its essential nature. Uncoupled expression of genes encoding lytic transglycosylases or amidases did not restore growth to a WalKR-depleted strain. We identified only two WalKR-regulon genes whose expression restored cell viability in the absence of WalKR: lytM and ssaA. Neither of these two genes are essential under our conditions and a ΔlytM ΔssaA mutant does not present any growth defect. LytM is a glycyl-glycyl endopeptidase, hydrolyzing the pentaglycine interpeptide crossbridge, and SsaA belongs to the CHAP amidase family, members of which such as LysK and LytA have been shown to have D-alanyl-glycyl endopeptidase activity, cleaving between the crossbridge and the stem peptide. Taken together, our results strongly suggest that peptidoglycan crosslinking relaxation through crossbridge hydrolysis plays a crucial role in the essential requirement of the WalKR system for cell viability.

  17. A dual role for the immune response in a mouse model of inflammation-associated lung cancer

    OpenAIRE

    Dougan, Michael; Li, Danan; Neuberg, Donna; Mihm, Martin; Googe, Paul; Wong, Kwok-Kin; Dranoff, Glenn

    2011-01-01

    Lung cancer is the leading cause of cancer death worldwide. Both principal factors known to cause lung cancer, cigarette smoke and asbestos, induce pulmonary inflammation, and pulmonary inflammation has recently been implicated in several murine models of lung cancer. To further investigate the role of inflammation in the development of lung cancer, we generated mice with combined loss of IFN-γ and the β-common cytokines GM-CSF and IL-3. These immunodeficient mice develop chronic pulmonary in...

  18. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase-dependent

  19. The dual role of poly(ADP-ribose) polymerase-1 in modulating parthanatos and autophagy under oxidative stress in rat cochlear marginal cells of the stria vascularis.

    Science.gov (United States)

    Jiang, Hong-Yan; Yang, Yang; Zhang, Yuan-Yuan; Xie, Zhen; Zhao, Xue-Yan; Sun, Yu; Kong, Wei-Jia

    2018-04-01

    Oxidative stress is reported to regulate several apoptotic and necrotic cell death pathways in auditory tissues. Poly(ADP-ribose) polymerase-1 (PARP-1) can be activated under oxidative stress, which is the hallmark of parthanatos. Autophagy, which serves either a pro-survival or pro-death function, can also be stimulated by oxidative stress, but the role of autophagy and its relationship with parthanatos underlying this activation in the inner ear remains unknown. In this study, we established an oxidative stress model in vitro by glucose oxidase/glucose (GO/G), which could continuously generate low concentrations of H 2 O 2 to mimic continuous exposure to H 2 O 2 in physiological conditions, for investigation of oxidative stress-induced cell death mechanisms and the regulatory role of PARP-1 in this process. We observed that GO/G induced stria marginal cells (MCs) death via upregulation of PARP-1 expression, accumulation of polyADP-ribose (PAR) polymers, decline of mitochondrial membrane potential (MMP) and nuclear translocation of apoptosis-inducing factor (AIF), which all are biochemical features of parthanatos. PARP-1 knockdown rescued GO/G-induced MCs death, as well as abrogated downstream molecular events of PARP-1 activation. In addition, we demonstrated that GO/G stimulated autophagy and PARP-1 knockdown suppressed GO/G-induced autophagy in MCs. Interestingly, autophagy suppression by 3-Methyladenine (3-MA) accelerated GO/G-induced parthanatos, indicating a pro-survival function of autophagy in GO/G-induced MCs death. Taken together, these data suggested that PARP-1 played dual roles by modulating parthanatos and autophagy in oxidative stress-induced MCs death, which may be considered as a promising therapeutic target for ameliorating oxidative stress-related hearing disorders. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Role of Primary Care Providers in Tobacco Cessation, Tobacco Dependence Treatment

    Directory of Open Access Journals (Sweden)

    Rohini Ruhil

    2015-03-01

    Full Text Available Background: Tobacco use is very common among Indian society. In fact, tobacco use is responsible for majority of morbidity and mortality in India and worldwide. Tobacco has been identified as “addictive” and tobacco dependence has been defined as a health problem in ICD-10. Aims & Objectives: This review article aims to emphasize the role of primary health care providers in tobacco cessation and to give recommendations after identifying barriers and exploring the present scenario. Material Methods: Several studies, journals and web-based articles have been referred to support the evidence that a brief tobacco cessation advice from physicians could help the patient quit. Result: Studies show that there is lack of participation from primary health care providers for tobacco cessation. Several barriers have been identified in many studies and also there exist some solutions to these barriers. Conclusion: It has been concluded in the article that primary health care providers should be trained and supported with all possible resources so that they can screen tobacco use in patients and could help them quit.

  1. Cyclin-dependent Kinase 5: Novel role of gene variants identified in ADHD.

    Science.gov (United States)

    Maitra, Subhamita; Chatterjee, Mahasweta; Sinha, Swagata; Mukhopadhyay, Kanchan

    2017-07-28

    Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454, rs2069456 and rs2069459, predicted to affect transcription, were found to be bimorphic. Significant difference in rs2069456 "AC" genotype frequency was noticed in the probands, more specifically in the males. Family based analysis revealed over transmission of rs2069454 "C" and rs2069456 "A" to the probands. Quantitative trait analysis exhibited association of haplotypes with inattention, domain specific impulsivity, and behavioral problem, though no significant contribution was noticed on the age of onset of ADHD. Gene variants also showed significant association with cognitive function and co-morbidity. Probands having rs2069459 "TT" showed betterment during follow up. It may be inferred from this pilot study that CDK5 may affect ADHD etiology, possibly by attenuating synaptic neurotransmission and could be a useful target for therapeutic intervention.

  2. A role for NF-κB–dependent gene transactivation in sunburn

    Science.gov (United States)

    Abeyama, Kazuhiro; Eng, William; Jester, James V.; Vink, Arie A.; Edelbaum, Dale; Cockerell, Clay J.; Bergstresser, Paul R.; Takashima, Akira

    2000-01-01

    Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage. PMID:10862790

  3. The role of DNA dependent protein kinase in synapsis of DNA ends.

    Science.gov (United States)

    Weterings, Eric; Verkaik, Nicole S; Brüggenwirth, Hennie T; Hoeijmakers, Jan H J; van Gent, Dik C

    2003-12-15

    DNA dependent protein kinase (DNA-PK) plays a central role in the non-homologous end-joining pathway of DNA double strand break repair. Its catalytic subunit (DNA-PK(CS)) functions as a serine/threonine protein kinase. We show that DNA-PK forms a stable complex at DNA termini that blocks the action of exonucleases and ligases. The DNA termini become accessible after autophosphorylation of DNA-PK(CS), which we demonstrate to require synapsis of DNA ends. Interestingly, the presence of DNA-PK prevents ligation of the two synapsed termini, but allows ligation to another DNA molecule. This alteration of the ligation route is independent of the type of ligase that we used, indicating that the intrinsic architecture of the DNA-PK complex itself is not able to support ligation of the synapsed DNA termini. We present a working model in which DNA-PK creates a stable molecular bridge between two DNA ends that is remodeled after DNA-PK autophosphorylation in such a way that the extreme termini become accessible without disrupting synapsis. We infer that joining of synapsed DNA termini would require an additional protein factor.

  4. Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mark S. Cooper

    2011-01-01

    Full Text Available Electrophysiological conversion of chloride-dependent synapses from inhibitory to excitatory function, as a result of aberrant neuronal chloride homeostasis, is a known mechanism for the genesis of neuropathic pain. This paper examines theoretically how this type of synaptic conversion can disrupt circuit logic in spinal nociceptive circuits. First, a mathematical scaling factor is developed to represent local aberration in chloride electrochemical driving potential. Using this mathematical scaling factor, electrophysiological symbols are developed to represent the magnitude of synaptic conversion within nociceptive circuits. When inserted into a nociceptive circuit diagram, these symbols assist in understanding the generation of neuropathic pain associated with the collapse of transmembrane chloride gradients. A more generalized scaling factor is also derived to represent the interplay of chloride and bicarbonate driving potentials on the function of GABAergic and glycinergic synapses. These mathematical and symbolic representations of synaptic conversion help illustrate the critical role that anion driving potentials play in the transduction of pain. Using these representations, we discuss ramifications of glial-mediated synaptic conversion in the genesis, and treatment, of neuropathic pain.

  5. A Closer Look at Intergroup Threat Within the Dual Process Model Framework: The Mediating Role of Moral Foundations

    Directory of Open Access Journals (Sweden)

    Márton Hadarics

    2017-04-01

    Full Text Available In our study we investigated how right-wing authoritarianism (RWA and social dominance orientation (SDO are related to perceived intergroup threat, and also tested the potential mediating role of individualizing and binding moral foundations within this relationship pattern. According to our results, both RWA and SDO enhanced the perceived threat related to immigration. Furthermore, the effect of SDO was partly mediated by individualizing moral foundations, while the effect of RWA was partly mediated by both kinds of moral foundations. It seems that perceived intergroup threat, at least to some extent, is influenced by personal moral preferences that can be derived from individual dispositions and motivations.

  6. Dual QCD: A review

    International Nuclear Information System (INIS)

    Baker, M.; Ball, J.S.; Zachariasen, F.

    1991-01-01

    We review the attempts to use dual (electric) vector potentials rather than the standard magnetic vector potentials to describe QCD, particularly in the infrared regime. The use of dual potentials is motivated by the fact that in classical electrodynamics, in a medium with a dielectric constant vanishing at small momenta (as is believed to be the case in QCD), electric potentials provide a far more convenient language than do magnetic potentials. To begin with, we outline attempts to construct the QCD Lagrangian in terms of dual potentials and describe the various possibilities, their shortcomings and advantages, which so far exist. We then proceed to use the most attractive (albeit consistent as a field theory only at the tree level) of these Lagrangians in a number of applications. We show that it describes a non-Abelian dual superconductor (so that it automatically confines color), derive the static quark-antiquark potential, and various temperature dependent effects, such as deconfinement and chiral symmetry breaking. (orig.)

  7. Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Jesús Santana-Gálvez

    2017-02-01

    Full Text Available Chlorogenic acid (5-O-caffeoylquinic acid is a phenolic compound from thehydroxycinnamic acid family. This polyphenol possesses many health-promoting properties, mostof them related to the treatment of metabolic syndrome, including anti-oxidant, anti-inflammatory,antilipidemic, antidiabetic, and antihypertensive activities. The first part of this review will discussthe role of chlorogenic acid as a nutraceutical for the prevention and treatment of metabolicsyndrome and associated disorders, including in vivo studies, clinical trials, and mechanisms ofaction. The second part of the review will be dealing with the role of chlorogenic acid as a foodadditive. Chlorogenic acid has shown antimicrobial activity against a wide range of organisms,including bacteria, yeasts, molds, viruses, and amoebas. These antimicrobial properties can beuseful for the food industry in its constant search for new and natural molecules for thepreservation of food products. In addition, chlorogenic acid has antioxidant activity, particularlyagainst lipid oxidation; protective properties against degradation of other bioactive compoundspresent in food, and prebiotic activity. The combination of these properties makes chlorogenic acidan excellent candidate for the formulation of dietary supplements and functional foods.

  8. Dual Entwining Structures and Dual Entwined Modules

    OpenAIRE

    Abuhlail, Jawad Y.

    2003-01-01

    In this note we introduce and investigate the concepts of dual entwining structures and dual entwined modules. This generalizes the concepts of dual Doi-Koppinen structures and dual Doi-Koppinen modules introduced (in the infinite case over rings) by the author is his dissertation.

  9. Paradox of pattern separation and adult neurogenesis: A dual role for new neurons balancing memory resolution and robustness.

    Science.gov (United States)

    Johnston, Stephen T; Shtrahman, Matthew; Parylak, Sarah; Gonçalves, J Tiago; Gage, Fred H

    2016-03-01

    Hippocampal adult neurogenesis is thought to subserve pattern separation, the process by which similar patterns of neuronal inputs are transformed into distinct neuronal representations, permitting the discrimination of highly similar stimuli in hippocampus-dependent tasks. However, the mechanism by which immature adult-born dentate granule neurons cells (abDGCs) perform this function remains unknown. Two theories of abDGC function, one by which abDGCs modulate and sparsify activity in the dentate gyrus and one by which abDGCs act as autonomous coding units, are generally suggested to be mutually exclusive. This review suggests that these two mechanisms work in tandem to dynamically regulate memory resolution while avoiding memory interference and maintaining memory robustness. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The generic nature of the global and non-entropic arrow of time and the dual role of the energy-momentum tensor

    Energy Technology Data Exchange (ETDEWEB)

    Castagnino, Mario [CONICET-Instituto de AstronomIa y FIsica del Espacio, Casilla de Correos 67, Sucursal 28, 1428 Buenos Aires (Argentina); Lombardi, Olimpia [CONICET-Universidad Autonoma de Madrid, Ctra. Colmenar Km 15, 28049 Madrid (Spain)

    2004-04-16

    In this paper we adopt a generic, global and non-entropic approach to the problem of the arrow of time, according to which the arrow of time is a generic, intrinsic and geometrical property of spacetime. We demonstrate that the arrow of time so defined is generic in the sense that any spacetime with physically reasonable properties (e.g. time-orientability and global time) will be endowed with an arrow of time. The only exceptions are very special cases belonging to a subset of zero measure of the set of all possible spacetimes. We also show the dual role played by the energy-momentum tensor in the context of our approach. On one hand, the energy-momentum tensor is the intermediate step that permits us to turn the geometrical time-asymmetry of the universe into a local arrow of time manifested as a time-asymmetric energy flow. On the other hand, the energy-momentum tensor supplies the basis for deducing the time-asymmetry of quantum field theory, posed as an axiom in this theory.

  11. Dual role for the O-acetyltransferase OatA in peptidoglycan modification and control of cell septation in Lactobacillus plantarum.

    Directory of Open Access Journals (Sweden)

    Elvis Bernard

    Full Text Available Until now, peptidoglycan O-acetyl transferases (Oat were only described for their peptidoglycan O-acetylating activity and for their implication in the control of peptidoglycan hydrolases. In this study, we show that a Lactobacillus plantarum mutant lacking OatA is unable to uncouple cell elongation and septation. Wild-type cells showed an elongation arrest during septation while oatA mutant cells continued to elongate at a constant rate without any observable pause during the cell division process. Remarkably, this defect does not result from a default in peptidoglycan O-acetylation, since it can be rescued by wild-type OatA as well as by a catalytic mutant or a truncated variant containing only the transmembrane domain of the protein. Consistent with a potential involvement in division, OatA preferentially localizes at mid-cell before membrane invagination and remains at this position until the end of septation. Overexpression of oatA or its inactive variants induces septation-specific aberrations, including asymmetrical and dual septum formation. Overproduction of the division inhibitors, MinC or MinD, leads to cell filamentation in the wild type while curved and branched cells are observed in the oatA mutant, suggesting that the Min system acts differently on the division process in the absence of OatA. Altogether, the results suggest that OatA plays a key role in the spatio-temporal control of septation, irrespective of its catalytic activity.

  12. SUMO modification through rapamycin-mediated heterodimerization reveals a dual role for Ubc9 in targeting RanGAP1 to nuclear pore complexes

    International Nuclear Information System (INIS)

    Zhu Shanshan; Zhang Hong; Matunis, Michael J.

    2006-01-01

    SUMOs (small ubiquitin-related modifiers) are eukaryotic proteins that are covalently conjugated to other proteins and thereby regulate a wide range of important cellular processes. The molecular mechanisms by which SUMO modification influences the functions of most target proteins and cellular processes, however, remain poorly defined. A major obstacle to investigating the effects of SUMO modification is the availability of a system for selectively inducing the modification or demodification of an individual protein. To address this problem, we have developed a procedure using the rapamycin heterodimerizer system. This procedure involves co-expression of rapamycin-binding domain fusion proteins of SUMO and candidate SUMO substrates in living cells. Treating cells with rapamycin induces a tight association between SUMO and a single SUMO substrate, thereby allowing specific downstream effects to be analyzed. Using RanGAP1 as a model SUMO substrate, the heterodimerizer system was used to investigate the molecular mechanism by which SUMO modification targets RanGAP1 from the cytoplasm to nuclear pore complexes (NPCs). Our results revealed a dual role for Ubc9 in targeting RanGAP1 to NPCs: In addition to conjugating SUMO-1 to RanGAP1, Ubc9 is also required to form a stable ternary complex with SUMO-1 modified RanGAP1 and Nup358. As illustrated by our studies, the rapamycin heterodimerizer system represents a novel tool for studying the molecular effects of SUMO modification

  13. Dual RNA Processing Roles of Pat1b via Cytoplasmic Lsm1-7 and Nuclear Lsm2-8 Complexes

    Directory of Open Access Journals (Sweden)

    Caroline Vindry

    2017-08-01

    Full Text Available Pat1 RNA-binding proteins, enriched in processing bodies (P bodies, are key players in cytoplasmic 5′ to 3′ mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the spliceosomal U6 small nuclear RNA (snRNA. Furthermore, we establish the set of interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6.U5 tri-small nuclear ribonucleoprotein particle (tri-snRNP components in Cajal bodies, the site of snRNP biogenesis. RNA sequencing following Pat1b depletion revealed the preferential upregulation of mRNAs normally found in P bodies and enriched in 3′ UTR AU-rich elements. Changes in >180 alternative splicing events were also observed, characterized by skipping of regulated exons with weak donor sites. Our data demonstrate the dual role of a decapping enhancer in pre-mRNA processing as well as in mRNA decay via distinct nuclear and cytoplasmic Lsm complexes.

  14. An essential role for the K+-dependent Na+/Ca2+-exchanger, NCKX4, in melanocortin-4-receptor-dependent satiety.

    Science.gov (United States)

    Li, Xiao-Fang; Lytton, Jonathan

    2014-09-12

    K(+)-dependent Na(+)/Ca(2+)-exchangers are broadly expressed in various tissues, and particularly enriched in neurons of the brain. The distinct physiological roles for the different members of this Ca(2+) transporter family are, however, not well described. Here we show that gene-targeted mice lacking the K(+)-dependent Na(+)/Ca(2+)-exchanger, NCKX4 (gene slc24a4 or Nckx4), display a remarkable anorexia with severe hypophagia and weight loss. Feeding and satiety are coordinated centrally by melanocortin-4 receptors (MC4R) in neurons of the hypothalamic paraventricular nucleus (PVN). The hypophagic response of Nckx4 knock-out mice is accompanied by hyperactivation of neurons in the PVN, evidenced by high levels of c-Fos expression. The activation of PVN neurons in both fasted Nckx4 knock-out and glucose-injected wild-type animals is blocked by Ca(2+) removal and MC4R antagonists. In cultured hypothalamic neurons, melanocyte stimulating hormone induces an MC4R-dependent and sustained Ca(2+) signal, which requires phospholipase C activity and plasma membrane Ca(2+) entry. The Ca(2+) signal is enhanced in hypothalamic neurons from Nckx4 knock-out animals, and is depressed in cells in which NCKX4 is overexpressed. Finally, MC4R-dependent oxytocin expression in the PVN, a key essential step in satiety, is prevented by blocking phospholipase C activation or Ca(2+) entry. These findings highlight an essential, and to our knowledge previously unknown, role for Ca(2+) signaling in the MC4R pathway that leads to satiety, and a novel non-redundant role for NCKX4-mediated Ca(2+) extrusion in controlling MC4R signaling and feeding behavior. Together, these findings highlight a novel pathway that potentially could be exploited to develop much needed new therapeutics to tackle eating disorders and obesity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Diameter-dependent photoluminescence properties of strong phase-separated dual-wavelength InGaN/GaN nanopillar LEDs

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qiang, E-mail: qwang365@163.com [School of Science, Qilu University of Technology, Jinan, 250353 (China); School of Microelectronics, Shandong University, Jinan, 250100 (China); Ji, Ziwu, E-mail: jiziwu@sdu.edu.cn [School of Microelectronics, Shandong University, Jinan, 250100 (China); Zhou, Yufan; Wang, Xuelin [School of Physics, Shandong University, Jinan, 250100 (China); Liu, Baoli [Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190 (China); Xu, Xiangang [Key Laboratory of Functional Crystal Materials and Device (Ministry of Education), Shandong University, Jinan, 250100 (China); Gao, Xingguo; Leng, Jiancai [School of Science, Qilu University of Technology, Jinan, 250353 (China)

    2017-07-15

    Highlights: • Nanopillar LED with smaller diameter shows a larger strain relaxation in the MQWs. • Nanopillar induced blue shift of green peak is smaller than that of blue peak. • Nanopillar induced blue shift of green/blue peak at 300 K is smaller than at 4 K. • PL intensity decreases with reducing nanopillar diameter with same pillar density. - Abstract: In this paper, strong phase-separated blue/green dual-wavelength InGaN/GaN nanopillar (NP) light emitting diodes (LEDs) with the same NP density and various NP diameters were fabricated using focused ion beam etching. Micro-Raman spectroscopy was used to show the effect of NP diameter on the strain relaxation in the multi-quantum-wells (MQWs). The effect of NP diameter on optical behaviors of the strong phase-separated dual-wavelength InGaN/GaN NP LEDs was investigated for the first time by using micro-photoluminescence (PL) spectroscopy. The blue shifts of PL peak energies of the NP LEDs showed that the NP LED with a smaller diameter exhibited a larger strain relaxation in the MQWs, as confirmed by micro-Raman results. And the blue shift of green emission was smaller than that of blue emission. The total integrated PL intensities from the NP arrays were enhanced compared to the as-grown sample due to the increased recombination rate and light extraction efficiency. The enhancement factor decreased with decreasing the NP diameter in our experiments, which indicated that the loss of active volume was gradually dominant for the luminous efficiency of NP LEDs compared to the increased recombination rate and light extraction efficiency.

  16. Dual roles of glucose in the freeze-tolerant earthworm Dendrobaena octaedra: cryoprotection and fuel for metabolism

    DEFF Research Database (Denmark)

    Calderon, Sofia; Holmstrup, Martin; Westh, Peter

    2009-01-01

    Ectothermic animals inhabiting the subarctic and temperate regions have evolved strategies to deal with periods of continuous frost during winter. The earthworm Dendrobaena octaedra is freeze tolerant and accumulates large concentrations of glucose upon freezing. The present study investigates...... the roles of glucose accumulation for long-term freeze tolerance in worms kept frozen at -2 degrees C for 47 days. During this period, worms were sampled periodically for determination of survival and for measurements of glucose, glycogen, lactate, alanine and succinate. In addition we performed...... increased slightly whereas succinate levels remained constant. However, it is argued that other waste products (particularly propionate) could be the primary end product of a continued anaerobic metabolism. Calorimetric measures of the metabolic rate of frozen worms were in accord with values calculated...

  17. Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects

    Directory of Open Access Journals (Sweden)

    Elena Gammella

    2016-01-01

    Full Text Available Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings.

  18. Noise-driven diamagnetic susceptibility of impurity doped quantum dots: Role of anisotropy, position-dependent effective mass and position-dependent dielectric screening function

    International Nuclear Information System (INIS)

    Bera, Aindrila; Saha, Surajit; Ganguly, Jayanta; Ghosh, Manas

    2016-01-01

    Highlights: • Diamagnetic susceptibility (DMS) of doped quantum dot is studied. • The dot is subjected to Gaussian white noise. • Role of anisotropy, PDEM and PDDSF have been analyzed. • Noise amplifies and suppresses DMS depending on particular condition. • Findings bear significant technological importance. - Abstract: We explore Diamagnetic susceptibility (DMS) of impurity doped quantum dot (QD) in presence of Gaussian white noise introduced to the system additively and multiplicatively. In view of this profiles of DMS have been pursued with variations of geometrical anisotropy and dopant location. We have invoked position-dependent effective mass (PDEM) and position-dependent dielectric screening function (PDDSF) of the system. Presence of noise sometimes suppresses and sometimes amplifies DMS from that of noise-free condition and the extent of suppression/amplification depends on mode of application of noise. It is important to mention that the said suppression/amplification exhibits subtle dependence on use of PDEM, PDDSF and geometrical anisotropy. The study reveals that DMS, or more fundamentally, the effective confinement of LDSS, can be tuned by appropriate mingling of geometrical anisotropy/effective mass/dielectric constant of the system with noise and also on the pathway of application of latter.

  19. Dual Role of the Tyrosine Kinase Syk in Regulation of Toll-Like Receptor Signaling in Plasmacytoid Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Besma Aouar

    Full Text Available Crosslinking of regulatory immunoreceptors (RR, such as BDCA-2 (CD303 or ILT7 (CD85g, of plasmacytoid dendritic cells (pDCs efficiently suppresses production of type-I interferon (IFN-α/β and other cytokines in response to Toll-like receptor (TLR 7/9 ligands. This cytokine-inhibitory pathway is mediated by spleen tyrosine kinase (Syk associated with the ITAM-containing adapter of RR. Here we demonstrate by pharmacological targeting of Syk that in addition to the negative regulation of TLR7/9 signaling via RR, Syk also positively regulates the TLR7/9 pathway in human pDCs. Novel highly specific Syk inhibitor AB8779 suppressed IFN-α, TNF-α and IL-6 production induced by TLR7/9 agonists in primary pDCs and in the pDC cell line GEN2.2. Triggering of TLR9 or RR signaling induced a differential kinetics of phosphorylation at Y352 and Y525/526 of Syk and a differential sensitivity to AB8779. Consistent with the different roles of Syk in TLR7/9 and RR signaling, a concentration of AB8779 insufficient to block TLR7/9 signaling still released the block of IFN-α production triggered via the RR pathway, including that induced by hepatitis B and C viruses. Thus, pharmacological targeting of Syk partially restored the main pDC function-IFN-α production. Opposing roles of Syk in TLR7/9 and RR pathways may regulate the innate immune response to weaken inflammation reaction.

  20. A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16.

    Science.gov (United States)

    Gottschalk, Elinor Y; Meneses, Patricio I

    2015-09-01

    The infectious process of human papillomaviruses (HPVs) has been studied considerably, and many cellular components required for viral entry and trafficking continue to be revealed. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during HPV16 pseudovirion infection of human keratinocytes. We found that Pyk2 is necessary for infection and appears to be involved in the intracellular trafficking of the virus. Small interfering RNA-mediated reduction of Pyk2 resulted in a significant decrease in infection but did not prevent viral entry at the plasma membrane. Pyk2 depletion resulted in altered endolysosomal trafficking of HPV16 and accelerated unfolding of the viral capsid. Furthermore, we observed retention of the HPV16 pseudogenome in the trans-Golgi network (TGN) in Pyk2-depleted cells, suggesting that the kinase could be required for the viral DNA to exit the TGN. While Pyk2 has previously been shown to function during the entry of enveloped viruses at the plasma membrane, the kinase has not yet been implicated in the intracellular trafficking of a nonenveloped virus such as HPV. Additionally, these data enrich the current literature on Pyk2's function in human keratinocytes. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during human papillomavirus (HPV) infection of human skin cells. Infections with high-risk types of HPV such as HPV16 are the leading cause of cervical cancer and a major cause of genital and oropharyngeal cancer. As a nonenveloped virus, HPV enters cells by interacting with cellular receptors and established cellular trafficking routes to ensure that the viral DNA reaches the nucleus for productive infection. This study identified Pyk2 as a cellular component required for the intracellular trafficking of HPV16 during infection. Understanding the infectious pathways of HPVs is critical for developing additional preventive therapies. Furthermore, this study advances our knowledge of

  1. Genetic Dissection of Dual Roles for the Transcription Factor six7 in Photoreceptor Development and Patterning in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Mailin Sotolongo-Lopez

    2016-04-01

    Full Text Available The visual system of a particular species is highly adapted to convey detailed ecological and behavioral information essential for survival. The consequences of structural mutations of opsins upon spectral sensitivity and environmental adaptation have been studied in great detail, but lacking is knowledge of the potential influence of alterations in gene regulatory networks upon the diversity of cone subtypes and the variation in the ratio of rods and cones observed in numerous diurnal and nocturnal species. Exploiting photoreceptor patterning in cone-dominated zebrafish, we uncovered two independent mechanisms by which the sine oculis homeobox homolog 7 (six7 regulates photoreceptor development. In a genetic screen, we isolated the lots-of-rods-junior (ljrp23ahub mutation that resulted in an increased number and uniform distribution of rods in otherwise normal appearing larvae. Sequence analysis, genome editing using TALENs and knockdown strategies confirm ljrp23ahub as a hypomorphic allele of six7, a teleost orthologue of six3, with known roles in forebrain patterning and expression of opsins. Based on the lack of predicted protein-coding changes and a deletion of a conserved element upstream of the transcription start site, a cis-regulatory mutation is proposed as the basis of the reduced expression of six7 in ljrp23ahub. Comparison of the phenotypes of the hypomorphic and knock-out alleles provides evidence of two independent roles in photoreceptor development. EdU and PH3 labeling show that the increase in rod number is associated with extended mitosis of photoreceptor progenitors, and TUNEL suggests that the lack of green-sensitive cones is the result of cell death of the cone precursor. These data add six7 to the small but growing list of essential genes for specification and patterning of photoreceptors in non-mammalian vertebrates, and highlight alterations in transcriptional regulation as a potential source of photoreceptor variation

  2. Context-dependent adaptation of visually-guided arm movements and vestibular eye movements: role of the cerebellum

    Science.gov (United States)

    Lewis, Richard F.

    2003-01-01

    Accurate motor control requires adaptive processes that correct for gradual and rapid perturbations in the properties of the controlled object. The ability to quickly switch between different movement synergies using sensory cues, referred to as context-dependent adaptation, is a subject of considerable interest at present. The potential function of the cerebellum in context-dependent adaptation remains uncertain, but the data reviewed below suggest that it may play a fundamental role in this process.

  3. Thickness dependence of magnetic properties and giant magneto-impedance effect in amorphous Co{sub 73}Si{sub 12}B{sub 15} thin films prepared by Dual-Ion beam assisted deposition

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu [School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); BISSE/BUAA-SPNEE joint Laboratory Magnetism and Sperconducting technology on Spacecraft, Beihang University, Beijing 100191 (China); Wang, San-sheng, E-mail: wangssh@buaa.edu.cn [School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); BISSE/BUAA-SPNEE joint Laboratory Magnetism and Sperconducting technology on Spacecraft, Beihang University, Beijing 100191 (China); Hu, Teng [School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); He, Tong-fu [School of Instrumentation Science and Opto-electronics Engineering, Beihang University, Beijing 100191 (China); Chen, Zi-yu [School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); Yi, Zhong; Meng, Li-Fei [Science and Technology on Reliability and Environmental Engineering Laboratory, Beijing Institute of Spacecraft Environment Engineering, Beijing 100094 (China); BISSE/BUAA-SPNEE joint Laboratory Magnetism and Sperconducting technology on Spacecraft, Beihang University, Beijing 100191 (China)

    2017-03-15

    Dual-Ion Beam Assisted Deposition is a suitable method for the preparation of giant magneto-impedance (GMI) materials. In this paper, Co{sub 73}Si{sub 12}B{sub 15} thin films with different thicknesses were prepared by Dual-Ion Beam Assisted Deposition, and the influences of film thickness on magnetic properties and GMI effect were investigated. It was found that the asymmetric magnetic hysteresis loop in the prepared Co{sub 73}Si{sub 12}B{sub 15} thin films occurs at ambient temperature, and the shift behavior of hysteresis loop associated with film thickness. With the film thickness increasing, the values of shift field and coercive field and other parameters such as remanence and shift ratio appeared complex variation. At a certain frequency, the large GMI effect is only observed in some films, which have good magnetic properties including low coercivity, low remanence ratio and high shift ratio. The results indicated that the thickness dependence of magnetic properties nonlinearly determined the GMI effect in Co{sub 73}Si{sub 12}B{sub 15} thin films. - Highlights: • The relationship between film thickness and ΔZ/Z, ΔR/R, ΔX/X ratio of CoSiB film exhibits a complex behavior as the film thickness increases from 1.33 to 7.34 µm. The maximum value of GMI ratio is observed when the film thickness was 1.56, 2.48, 3.81 or 7.34 µm. • With the increase of film thickness, the peak frequency shifts to lower frequency, but does not decrease following the t-power law. • The above thickness phenomenon is due to the different magnetic properties of thin films. • The Dual-Ion Beam Assisted Deposition is introduced to prepare the GMI materials.

  4. Expression of cytosolic NADP(+)-dependent isocitrate dehydrogenase in melanocytes and its role as an antioxidant.

    Science.gov (United States)

    Kim, Ji Young; Shin, Jae Yong; Kim, Miri; Hann, Seung-Kyung; Oh, Sang Ho

    2012-02-01

    Cytosolic NADP(+)-dependent ICDH (IDPc) has an antioxidant effect as a supplier of NADPH to the cytosol, which is needed for the production of glutathione. To evaluate the expression of IDPc in melanocytes and to elucidate its role as an antioxidant. The knock-down of IDPc expression in immortalized mouse melanocyte cell lines (melan-a) was performed using the short interfering RNA (siRNA)-targeted gene silencing method. After confirming the silencing of IDPc expression with mRNA and protein levels, viability, apoptosis and necrosis, as well as ROS production in IDPc-silenced melanocytes were monitored under conditions of oxidative stress and non-stress. Also, the ratio of oxidized glutathione to total glutathione was examined, and whether the addition of glutathione recovered cell viability, decreased by oxidant stress, was checked. The expression of IDPc in both primary human melanocytes and melan-a cells was confirmed by Western blot and RT-PCR. The silencing of IDPc expression by transfecting IDPc siRNA in melan-a cells was observed by Western blotting and real-time RT-PCR. IDPc knock-down cells showed significantly decreased cell viability and an increased number of cells under apoptosis and necrosis. IDPc siRNA-treated melanocytes demonstrated a higher intensity of DCFDA after the addition of H(2)O(2) compared with scrambled siRNA-treated melanocytes, and a lower ratio of reduced glutathione to oxidized glutathione were observed in IDPc siRNA transfected melanocytes. In addition, the addition of glutathione recovered cell viability, which was previously decreased after incubation with H(2)O(2). This study suggests that decreased IDPc expression renders melanocytes more vulnerable to oxidative stress, and IDPc plays an important antioxidant function in melanocytes. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney.

    Science.gov (United States)

    Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V; Park, Kwon Moo

    2009-03-01

    Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was higher than in the S3 segment, which is much more susceptible to I/R. IDPc protein was also highly expressed in the mitochondrion-rich intercalated cells of the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in various kidney regions. This study identifies that IDPc may be the primary source of NADPH in the kidney. I/R significantly reduced IDPc expression and activity and NADPH production and increased the ratio of oxidized glutathione to total glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell damage, and lipid peroxidation. In LLC-PK(1) cells, upregulation of IDPc by IDPc gene transfer protected the cells against hydrogen peroxide, enhancing NADPH production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid peroxidation. IDPc downregulation by small interference RNA treatment presented results contrasting with the upregulation. In conclusion, these results demonstrate that IDPc is expressed differentially along tubules in patterns that may contribute to differences in susceptibility to injury, is a major enzyme in cytosolic NADPH generation in kidney, and is downregulated with I/R.

  6. Roles of thioredoxin in nitric oxide-dependent preconditioning-induced tolerance against MPTP neurotoxin

    International Nuclear Information System (INIS)

    Chiueh, C.C.; Andoh, Tsugunobu; Chock, P. Boon

    2005-01-01

    Hormesis, a stress tolerance, can be induced by ischemic preconditioning stress. In addition to preconditioning, it may be induced by other means, such as gas anesthetics. Preconditioning mechanisms, which may be mediated by reprogramming survival genes and proteins, are obscure. A known neurotoxicant, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes less neurotoxicity in the mice that are preconditioned. Pharmacological evidences suggest that the signaling pathway of ·NO-cGMP-PKG (protein kinase G) may mediate preconditioning phenomenon. We developed a human SH-SY5Y cell model for investigating · NO-mediated signaling pathway, gene regulation, and protein expression following a sublethal preconditioning stress caused by a brief 2-h serum deprivation. Preconditioned human SH-SY5Y cells are more resistant against severe oxidative stress and apoptosis caused by lethal serum deprivation and 1-mehtyl-4-phenylpyridinium (MPP + ). Both sublethal and lethal oxidative stress caused by serum withdrawal increased neuronal nitric oxide synthase (nNOS/NOS1) expression and · NO levels to a similar extent. In addition to free radical scavengers, inhibition of nNOS, guanylyl cyclase, and PKG blocks hormesis induced by preconditioning. S-nitrosothiols and 6-Br-cGMP produce a cytoprotection mimicking the action of preconditioning tolerance. There are two distinct cGMP-mediated survival pathways: (i) the up-regulation of a redox protein thioredoxin (Trx) for elevating mitochondrial levels of antioxidant protein Mn superoxide dismutase (MnSOD) and antiapoptotic protein Bcl-2, and (ii) the activation of mitochondrial ATP-sensitive potassium channels [K(ATP)]. Preconditioning induction of Trx increased tolerance against MPP + , which was blocked by Trx mRNA antisense oligonucleotide and Trx reductase inhibitor. It is concluded that Trx plays a pivotal role in · NO-dependent preconditioning hormesis against MPTP/MPP +

  7. Layer-dependent role of collagen recruitment during loading of the rat bladder wall.

    Science.gov (United States)

    Cheng, Fangzhou; Birder, Lori A; Kullmann, F Aura; Hornsby, Jack; Watton, Paul N; Watkins, Simon; Thompson, Mark; Robertson, Anne M

    2018-04-01

    In this work, we re-evaluated long-standing conjectures as to the source of the exceptionally large compliance of the bladder wall. Whereas these conjectures were based on indirect measures of loading mechanisms, in this work we take advantage of advances in bioimaging to directly assess collagen fibers and wall architecture during biaxial loading. A custom biaxial mechanical testing system compatible with multiphoton microscopy was used to directly measure the layer-dependent collagen fiber recruitment in bladder tissue from 9 male Fischer rats (4 adult and 5 aged). As for other soft tissues, the bladder loading curve was exponential in shape and could be divided into toe, transition and high stress regimes. The relationship between collagen recruitment and loading curves was evaluated in the context of the inner (lamina propria) and outer (detrusor smooth muscle) layers. The large extensibility of the bladder was found to be possible due to folds in the wall (rugae) that provide a mechanism for low resistance flattening without any discernible recruitment of collagen fibers throughout the toe regime. For more extensible bladders, as the loading extended into the transition regime, a gradual coordinated recruitment of collagen fibers between the lamina propria layer and detrusor smooth muscle layer was found. A second important finding was that wall extensibility could be lost by premature recruitment of collagen in the outer wall that cut short the toe region. This change was correlated with age. This work provides, for the first time, a mechanistic understanding of the role of collagen recruitment in determining bladder extensibility and capacitance.

  8. The Dual Role of Vegetation as a Constraint on Mass and Energy Flux into the Critical Zone and as an Emergent Property of Geophysical Critical Zone Structure

    Science.gov (United States)

    Brooks, P. D.; Swetnam, T. L.; Barnard, H. R.; Singha, K.; Harpold, A.; Litvak, M. E.

    2017-12-01

    Spatial patterns in vegetation long have been used to scale both landsurface-atmosphere exchanges of water and carbon as well as to infer subsurface structure. These pursuits typical proceed in isolation and rarely do inferences gained from one community propagate to related efforts in another. Perhaps more importantly, vegetation often is treated as an emergent property of landscape-climate interactions rather than an active modifier of both critical zone structure and energy fluxes. We posit that vegetation structure and activity are under utilized as a tool towards understanding landscape evolution and present examples that begin to disentangle the role of vegetation as both an emergent property and an active control on critical zone structure and function. As climate change, population growth, and land use changes threaten water resources worldwide, the need for the new insights vegetation can provide becomes not just a basic science priority, but a pressing applied science question with clear societal importance. This presentation will provide an overview of recent efforts to address the dual role of vegetation in both modifying and reflecting critical zone structure in the western North American forests. For example, interactions between topography and stand scale vegetation structure influence both solar radiation and turbulence altering landscape scale partitioning of evaporation vs transpiration with major impacts of surface water supply. Similarly, interactions between topographic shading, lateral redistribution of plant available water, and subsurface storage create a mosaic of drought resistance and resilience across complex terrain. These complex interactions between geophysical and vegetation components of critical zone structure result in predictable patterns in catchment scale hydrologic partitioning within individual watersheds while simultaneously suggesting testable hypotheses for why catchments under similar climate regimes respond so

  9. The Dual Role of Nrf2 in Nonalcoholic Fatty Liver Disease: Regulation of Antioxidant Defenses and Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Sílvia S. Chambel

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a progressive liver disease with ever-growing incidence in the industrialized world. It starts with the simple accumulation of lipids in the hepatocyte and can progress to the more severe nonalcoholic steatohepatitis (NASH, which is associated with inflammation, fibrosis, and cirrhosis. There is increasing awareness that reactive oxygen species and electrophiles are implicated in the pathogenesis of NASH. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2 is a positive regulator of the expression of a battery of genes involved in the protection against oxidative/electrophilic stress. In rodents, Nrf2 is also known to participate in hepatic fatty acid metabolism, as a negative regulator of genes that promote hepatosteatosis. We review relevant evidence in the literature that these two mechanisms may contribute to the protective role of Nrf2 in the development of hepatic steatosis and in the progression to steatohepatitis, particularly in young animals. We propose that age may be a key to explain contradictory findings in the literature. In summary, Nrf2 mediates the crosstalk between lipid metabolism and antioxidant defense mechanisms in experimental models of NAFLD, and the nutritional or pharmacological induction of Nrf2 represents a promising potential new strategy for its prevention and treatment.

  10. Strategies for vitamin B6 biofortification of plants: A dual role as a micronutrient and a stress protectant

    Directory of Open Access Journals (Sweden)

    Hervé eVanderschuren

    2013-05-01

    Full Text Available Vitamin B6 has an essential role in cells as a cofactor for several metabolic enzymes. It has also been shown to function as a potent antioxidant molecule. The recent elucidation of the vitamin B6 biosynthesis pathways in plants provides opportunities for characterizing their importance during developmental processes and exposure to stress. Humans and animals must acquire vitamin B6 with their diet, with plants being a major source, because they cannot biosynthesize it de novo. However, the abundance of the vitamin in the edible portions of the most commonly consumed plants is not sufficient to meet daily requirements. Genetic engineering has proven successful in increasing the vitamin B6 content in the model plant Arabidopsis. The added benefits associated with the enhanced vitamin B6 content, such as higher biomass and resistance to abiotic stress, suggest that increasing this essential micronutrient could be a valuable option to improve the nutritional quality and stress tolerance of crop plants. This review summarizes current achievements in biofortification of vitamin B6 and considers strategies for increasing vitamin B6 levels in crop plants for human health and nutrition.

  11. Dual roles of palladin protein in in vitro myogenesis: inhibition of early induction but promotion of myotube maturation.

    Directory of Open Access Journals (Sweden)

    Ngoc-Uyen-Nhi Nguyen

    Full Text Available Palladin is a microfilament-associated phosphoprotein whose function in skeletal muscle has rarely been studied. Therefore, we investigate whether myogenesis is influenced by the depletion of palladin expression known to interfere with the actin cytoskeleton dynamic required for skeletal muscle differentiation. The inhibition of palladin in C2C12 myoblasts leads to precocious myogenic differentiation with a concomitant reduction in cell apoptosis. This premature myogenesis is caused, in part, by an accelerated induction of p21, myogenin, and myosin heavy chain, suggesting that palladin acts as a negative regulator in early differentiation phases. Paradoxically, palladin-knockdown myoblasts are unable to differentiate terminally, despite their ability to perform some initial steps of differentiation. Cells with attenuated palladin expression form thinner myotubes with fewer myonuclei compared to those of the control. It is noteworthy that a negative regulator of myogenesis, myostatin, is activated in palladin-deficient myotubes, suggesting the palladin-mediated impairment of late-stage myogenesis. Additionally, overexpression of 140-kDa palladin inhibits myoblast differentiation while 200-kDa and 90-kDa palladin-overexpressed cells display an enhanced differentiation rate. Together, our data suggest that palladin might have both positive and negative roles in maintaining the proper skeletal myogenic differentiation in vitro.

  12. The Dual Role of Cerebral Autoregulation and Collateral Flow in the Circle of Willis After Major Vessel Occlusion.

    Science.gov (United States)

    Kennedy McConnell, Flora; Payne, Stephen

    2017-08-01

    Ischaemic stroke is a leading cause of death and disability. Autoregulation and collateral blood flow through the circle of Willis both play a role in preventing tissue infarction. To investigate the interaction of these mechanisms a one-dimensional steady-state model of the cerebral arterial network was created. Structural variants of the circle of Willis that present particular risk of stroke were recreated by using a network model coupled with: 1) a steady-state physiological model of cerebral autoregulation; and 2) one wherein the cerebral vascular bed was modeled as a passive resistance. Simulations were performed in various conditions of internal carotid and vertebral artery occlusion. Collateral flow alone is unable to ensure adequate blood flow ([Formula: see text] normal flow) to the cerebral arteries in several common variants during internal carotid artery occlusion. However, compared to a passive model, cerebral autoregulation is better able to exploit available collateral flow and maintain flows within [Formula: see text] of baseline. This is true for nearly all configurations. Hence, autoregulation is a crucial facilitator of collateral flow through the circle of Willis. Impairment of this response during ischemia will severely impact cerebral blood flows and tissue survival, and hence, autoregulation should be monitored in this situation.

  13. The Dual Self: First and third person categorisations of the self and the role of objective self-awareness

    Directory of Open Access Journals (Sweden)

    Guido Peeters

    2007-10-01

    Full Text Available The classic duality of self-subject and self-object is related to the linguistic duality of self as a pronoun of the first and the third person. The latter duality is related to alternative ways of categorising people either as self versus other (SO categorisation or as objects conceived in the third person (3P categorisation. Research is reviewed showing that these categorisations underlie personalised and depersonalised representations, respectively. Nevertheless, depersonalising 3P categorisation has been found more prominent in self-other comparisons than in comparisons between hypothetical others. In search for an explanation Duval and Wicklund's theory of subjective and objective self-awareness as well as causal attribution theory are discussed. In an experiment it is shown that conditions associated with objective self-awareness (e.g., presence of a mirror, instructions stimulating self-evaluation increase 3P categorisation in self-other comparisons. The results add to our understanding of the role of objective self-awareness in self-other comparisons and in causal attributions from actors' and observers' perspectives.

  14. A dynamic dual role of IL-2 signaling in the two-step differentiation process of adaptive regulatory T cells.

    Science.gov (United States)

    Guo, Zhiyong; Khattar, Mithun; Schroder, Paul M; Miyahara, Yoshihiro; Wang, Guohua; He, Xiaoshung; Chen, Wenhao; Stepkowski, Stanislaw M

    2013-04-01

    The molecular mechanism of the extrathymic generation of adaptive, or inducible, CD4(+)Foxp3(+) regulatory T cells (iTregs) remains incompletely defined. We show that exposure of splenic CD4(+)CD25(+)Foxp3(-) cells to IL-2, but not other common γ-chain cytokines, resulted in Stat5 phosphorylation and induced Foxp3 expression in ∼10% of the cells. Thus, IL-2/Stat5 signaling may be critical for Foxp3 induction in peripheral CD4(+)CD25(+)Foxp3(-) iTreg precursors. In this study, to further define the role of IL-2 in the formation of iTreg precursors as well as their subsequent Foxp3 expression, we designed a two-step iTreg differentiation model. During the initial "conditioning" step, CD4(+)CD25(-)Foxp3(-) naive T cells were activated by TCR stimulation. Inhibition of IL-2 signaling via Jak3-Stat5 was required during this step to generate CD4(+)CD25(+)Foxp3(-) cells containing iTreg precursors. During the subsequent Foxp3-induction step driven by cytokines, IL-2 was the most potent cytokine to induce Foxp3 expression in these iTreg precursors. This two-step method generated a large number of iTregs with relatively stable expression of Foxp3, which were able to prevent CD4(+)CD45RB(high) cell-mediated colitis in Rag1(-/-) mice. In consideration of this information, whereas initial inhibition of IL-2 signaling upon T cell priming generates iTreg precursors, subsequent activation of IL-2 signaling in these precursors induces the expression of Foxp3. These findings advance the understanding of iTreg differentiation and may facilitate the therapeutic use of iTregs in immune disorders.

  15. An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Nonciliated Neurons.

    Science.gov (United States)

    De Stasio, Elizabeth A; Mueller, Katherine P; Bauer, Rosemary J; Hurlburt, Alexander J; Bice, Sophie A; Scholtz, Sophie L; Phirke, Prasad; Sugiaman-Trapman, Debora; Stinson, Loraina A; Olson, Haili B; Vogel, Savannah L; Ek-Vazquez, Zabdiel; Esemen, Yagmur; Korzynski, Jessica; Wolfe, Kelsey; Arbuckle, Bonnie N; Zhang, He; Lombard-Knapp, Gaelen; Piasecki, Brian P; Swoboda, Peter

    2018-03-01

    Regulatory Factor X (RFX) transcription factors (TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans , the sole RFX gene, daf-19 , encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/ daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons, whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is downregulated in the presence of DAF-19, primarily in nonsensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for downregulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform ( tm5562 ) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. Thus, we have identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects that daf-19 exerts on nervous system function. Copyright © 2018 by the Genetics Society of America.

  16. The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease.

    Science.gov (United States)

    Luo, Yin; Friese, Olga V; Runnels, Herbert A; Khandke, Lakshmi; Zlotnick, Gary; Aulabaugh, Ann; Gore, Thomas; Vidunas, Eugene; Raso, Stephen W; Novikova, Elena; Byrne, Emilia; Schlittler, Michael; Stano, Donald; Dufield, Robert L; Kumar, Sandeep; Anderson, Annaliesa S; Jansen, Kathrin U; Rouse, Jason C

    2016-11-01

    Trumenba (bivalent rLP2086) is a vaccine licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B (NmB) in individuals 10-25 years of age in the USA. The vaccine is composed of two factor H binding protein (fHbp) variants that were recombinantly expressed in Escherichia coli as native lipoproteins: rLP2086-A05 and rLP2086-B01. The vaccine was shown to induce potent bactericidal antibodies against a broad range of NmB isolates expressing fHbp that were different in sequence from the fHbp vaccine antigens. Here, we describe the characterization of the vaccine antigens including the elucidation of their structure which is characterized by two distinct motifs, the polypeptide domain and the N-terminal lipid moiety. In the vaccine formulation, the lipoproteins self-associate to form micelles driven by the hydrophobicity of the lipids and limited by the size of the folded polypeptides. The micelles help to increase the structural stability of the lipoproteins in the absence of bacterial cell walls. Analysis of the lipoproteins in Toll-like receptor (TLR) activation assays revealed their TLR2 agonist activity. This activity was lost with removal of the O-linked fatty acids, similar to removal of all lipids, demonstrating that this moiety plays an adjuvant role in immune activation. The thorough understanding of the structure and function of each moiety of the lipoproteins, as well as their relationship, lays the foundation for identifying critical parameters to guide vaccine development and manufacture.

  17. The role of maternal care in borderline personality disorder and dependent life stress.

    Science.gov (United States)

    Ball Cooper, Ericka; Venta, Amanda; Sharp, Carla

    2018-01-01

    Borderline Personality Disorder (BPD) affects 0.9%-3.2% of adolescents, and more than 20% of inpatient adolescents. Life stress has been linked to BPD across the lifespan, and previous research in adults has linked BPD to dependent stress (i.e., stress induced by the individual). However, prior research has not examined dependent stress alongside BPD in adolescents. Additionally, the potential protective effect of maternal care has not been considered in this relation. This study tested a moderation model expecting that (1) BPD would be positively associated with dependent life stress, (2) maternal care would be negatively associated with BPD, and (3) maternal care would moderate the relation between BPD and dependent life stress. The sample consisted of 184 adolescents recruited from an inpatient psychiatric facility serving a diverse population in the Southwestern United States. Dependent life stress, BPD, and maternal care were measured using the UCLA Life Stress Interview, DSM-IV Childhood Interview for BPD, and Kerns Security Scale, respectively. Results supported the first two hypotheses; BPD diagnosis was significantly, positively associated with dependent life stress, and negatively associated with maternal availability and dependability. Contrary to the third hypothesis, no significant evidence that maternal care acts as a buffer in the relation between BPD and dependent life stress was found. Although maternal care was not found to moderate the association between BPD and dependent life stress, results supported previously found relations between BPD, dependent life stress, and maternal care, and did so within a diverse inpatient adolescent sample.

  18. The Mediational Role of Relational Psychological Contract in Belief in a Zero-Sum Game and Work Input Attitude Dependency

    Directory of Open Access Journals (Sweden)

    Adamska Krystyna

    2015-12-01

    Full Text Available The purpose of this study was to investigate the mediational role of relational psychological contract in social beliefs and work input attitude dependency. We analyzed data taken from employees (N = 258 in four different organizations operating in the Pomeranian market.

  19. Thermodynamic-state and kinetic-process dependent dual ferromagnetic states in high-Si content FeMn(PSi) alloys

    International Nuclear Information System (INIS)

    Li, Guijiang; Eriksson, Olle; Johansson, Börje; Vitos, Levente

    2015-01-01

    We have found that thermodynamic state and kinetic process co-determine the dual ferromagnetic (FM) orders in high-Si content FeMnP 1−x Si x (0.25 < x < 0.5). Alloys undergoing high temperature annealing and quenching process prefer a high magnetic moment FM state in a chemically partial disordered structure with low c/a ratio. This mechanism is suggested to be responsible for the often discussed virgin effect as well. A chemically ordered structure obtained by a slow cooling process from a relatively low annealing temperature and the increase in Si content stabilize a metastable lattice with high c/a ratio and FM order with low magnetic moment. The non-simultaneity of the magnetic and structural transitions can be responsible for the occurrence of FM state in the high c/a range. Thus, a c/a ratio that changes from high to low is physically plausible to stabilize the metastable FM order at low temperature. Our theoretical observations indicate that suitable thermodynamic state and kinetic diffusion process is crucial for optimizing magnetocaloric properties and exploring feasible magnetocaloric materials

  20. A dual inhibitor of FAAH and TRPV1 channels shows dose-dependent effect on depression-like behaviour in rats.

    Science.gov (United States)

    Kirkedal, Christian; Wegener, Gregers; Moreira, Fabricio; Joca, Sâmia Regiane Lourenco; Liebenberg, Nico

    2017-12-01

    The cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) are proposed to mediate opposite behavioural responses. Their common denominator is the endocannabinoid ligand anandamide (AEA), which is believed to mediate antidepressant-like effect via CB1-R stimulation and depressive-like effect via TRPV1 activation. This is supposed to explain the bell-shaped dose-response curve for anandamide in preclinical models. We investigated this assumption by administering the dual inhibitor of AEA hydrolysis and TRPV1 activation N-arachidonoyl-serotonin (AA-5HT) into the medial prefrontal cortex of rats. AA-5HT was given in three different doses (0.125, 0.250, 0.500 nmol/0.4 µl/side) and rat behaviour was assessed in the forced swim test. Our results show significant antidepressant-like effect of AA-5HT (0.250 nmol) but no effects of low or high doses. The effect of 0.250 nmol AA-5HT was partially attenuated when coadministering the inverse CB1-agonist rimonabant (1.6 µg). A 0.250 nmol of AA-5HT administration into the medial prefrontal cortex induced a significant antidepressant-like effect that was partially attenuated by locally blocking CB1-receptor.

  1. Impact of beverage consumption, age, and site dependency on dual energy X-ray absorptiometry (DEXA) measurements in perimenopausal women: a prospective study.

    Science.gov (United States)

    Lo, Huan-Chu; Kuo, Duen-Pang; Chen, Yen-Lin

    2017-08-01

    The aim of this study was to determine the best site for bone mineral density (BMD) measurements based on T -scores, age, and beverage consumption. In this prospective study, 271 women stratified by age (average age: 61.9 years) underwent dual energy X-ray absorptiometry (DEXA) scanning of their lumbar spine, hips, and forearms. Osteoporosis was defined as a BMD of 2.5 standard deviations or more below the mean peak bone mass based on a reference population of adult women (translated as a T -score ≤ -2.5), as measured by DEXA. Participants were also evaluated regarding alcohol and caffeine consumption by a semiquantitative questionnaire. A significant discrepancy was observed in the classification of osteoporosis at different locations, with hip and forearm showing the best correlation (Pearson's r = 0.627, p consumption. In the group ≤ 50 years of age, lumbar spine and forearm T -scores were only associated with alcohol consumption. In the group over 50 years of age, hip and forearm T -scores were only associated with caffeine consumption. Bone mineral density measurements at the hip and forearm correlated with caffeine consumption in elderly Taiwanese women. This is an important finding since age and caffeine consumption are known risk factors for osteoporosis.

  2. The risk for persistent adult alcohol and nicotine dependence: the role of childhood maltreatment.

    Science.gov (United States)

    Elliott, Jennifer C; Stohl, Malka; Wall, Melanie M; Keyes, Katherine M; Goodwin, Renee D; Skodol, Andrew E; Krueger, Robert F; Grant, Bridget F; Hasin, Deborah S

    2014-05-01

    Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. Physical, sexual and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over 3 years of follow-up, with and without control for other childhood adversities. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n = 1172) and nicotine dependence (n = 4017). Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment and other adverse childhood experiences (e.g. parental divorce). Controlling for demographics only, physical, sexual and emotional abuse and physical neglect predicted 3-year persistence of alcohol dependence [adjusted odds ratio (AOR) = 1.50-2.99; 95% CI = 1.04-4.68] and nicotine dependence (AOR = 1.37-1.74; 95% CI = 1.13-2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AOR = 1.53-3.02; 95% CI = 1.07-4.71) and nicotine persistence (AOR = 1.35-1.72; 95% CI = 1.11-2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AOR = 1.19-1.36; 95% CI = 1.11-1.56). A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of dependence. © 2014 Society for the Study of Addiction.

  3. On the role of minority carriers in the frequency dependence of organic magnetoresistance

    NARCIS (Netherlands)

    Janssen, Paul; Wagemans, W.; Verhoeven, Wouter; van der Heijden, E.H.M.; Kemerink, M.; Koopmans, B.

    2011-01-01

    In this work we investigate the frequency dependence of organic magnetoresistance (OMAR) both in small molecule-based (Alq3) and polymer (PPV derivative) materials, and investigate its thickness dependence. For all devices, we observed a strong decrease in magnetoconductance (MC) with increasing

  4. The Role Of Early Maladaptive Schemas And Coping Strategies In Substance Dependence

    Directory of Open Access Journals (Sweden)

    Bikem HACIÖMEROĞLU

    2014-11-01

    Full Text Available Objective: The aim of this study was to evaluate the early maladaptive schemas and coping strategies of substance dependents. We hypothesized that substance dependents would have more maladaptive schemas and would use less adaptive coping strategies than healthy controls. Methods: Thirty-two patients diagnosed with substance dependence and 31 control subjects without any psychiatric disorders were evaluated via Young Schema Questionnaire-SF, COPE, and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I. Results: The substance dependents scored significantly higher than the control group in nine out of fourteen early maladaptive schemas. In terms of coping strategies, the substance dependents scored significantly lower than the control group in positive reinterpretation and growth, seeking social support for instrumental reasons, active coping, and seeking social support for emotional reasons, and significantly higher in behavioral disengagement and alcohol-drug disengagement subscales. Moreover, alcohol-drug disengagement type of coping style was significantly predicted by schemas of emotional deprivation, emotional inhibition, enmeshment/dependence, entitlement/ insufficient self-control, abandonment/instability, punitiveness, defectiveness/shame, vulnerability to harm or illness, and unrelenting standards/hypercriticalness. Discussion: Current study showed that the substance dependents had more maladaptive unhealthy core beliefs and ineffective coping strategies than a non-clinical control group. These findings support the importance of early maladaptive schemas which might be the underlying factor for the dependence problem, and might prevent the person to deal with the problem with more active and problem focused coping strategies.

  5. Roles of density-dependent growth and life history evolution in accounting for fisheries-induced trait changes.

    Science.gov (United States)

    Eikeset, Anne Maria; Dunlop, Erin S; Heino, Mikko; Storvik, Geir; Stenseth, Nils C; Dieckmann, Ulf

    2016-12-27

    The relative roles of density dependence and life history evolution in contributing to rapid fisheries-induced trait changes remain debated. In the 1930s, northeast Arctic cod (Gadus morhua), currently the world's largest cod stock, experienced a shift from a traditional spawning-ground fishery to an industrial trawl fishery with elevated exploitation in the stock's feeding grounds. Since then, age and length at maturation have declined dramatically, a trend paralleled in other exploited stocks worldwide. These trends can be explained by demographic truncation of the population's age structure, phenotypic plasticity in maturation arising through density-dependent growth, fisheries-induced evolution favoring faster-growing or earlier-maturing fish, or a combination of these processes. Here, we use a multitrait eco-evolutionary model to assess the capacity of these processes to reproduce 74 y of historical data on age and length at maturation in northeast Arctic cod, while mimicking the stock's historical harvesting regime. Our results show that model predictions critically depend on the assumed density dependence of growth: when this is weak, life history evolution might be necessary to prevent stock collapse, whereas when a stronger density dependence estimated from recent data is used, the role of evolution in explaining fisheries-induced trait changes is diminished. Our integrative analysis of density-dependent growth, multitrait evolution, and stock-specific time series data underscores the importance of jointly considering evolutionary and ecological processes, enabling a more comprehensive perspective on empirically observed stock dynamics than previous studies could provide.

  6. Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

    Directory of Open Access Journals (Sweden)

    Kandiah N

    2017-04-01

    Full Text Available Nagaendran Kandiah,1,2 Ming-Chyi Pai,3,4 Vorapun Senanarong,5 Irene Looi,6,7 Encarnita Ampil,8 Kyung Won Park,9 Ananda Krishna Karanam,10 Stephen Christopher11 1Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 2Duke-NUS, Graduate Medical School, Singapore; 3Division of Behavioral Neurology, Department of Neurology, 4Alzheimer’s Disease Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 5Division of Neurology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 6Clinical Research Centre, 7Department of Medicine, Hospital Seberang Jaya, Penang, Malaysia; 8Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines; 9Department of Neurology and Cognitive Disorders and Dementia Center, Institute of Convergence Bio-Health, Dong-A University College of Medicine, Busan, Republic of Korea; 10Novartis Healthcare Private Limited, Hyderabad, India; 11Novartis (Singapore Pte. Ltd., Singapore Abstract: Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD and Parkinson’s disease dementia (PDD. Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7, rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8 inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual

  7. The rf-power dependences of the deposition rate, the hardness and the corrosion-resistance of the chromium nitride film deposited by using a dual ion beam sputtering system

    International Nuclear Information System (INIS)

    Lim, Jongmin; Lee, Chongmu

    2006-01-01

    The hexavalent chromium used in chromium plating is so toxic that it is very hazardous to human body and possibly causes cancer in humans. Therefore, it is indispensable to develop an alternative deposition technique. Dependences of the deposition rate, the phases, the hardness, the surface roughness and the corrosion-resistance of CrN x deposited on the high speed steel substrate by using a dual ion beam sputtering system on the rf-power were investigated to see the feasibility of sputtering as an alternative technique for chromium plating. The dual ion beam sputtering system used in this study was designed in such a way as the primary argon ion beam and the secondary nitrogen ion beam are injected toward the target and the substrate, respectively so that the chromium atoms at the chromium target surface may not nearly react with nitrogen atoms. The hardness and the surface roughness were measured by a micro-Vicker's hardness tester and an atomic force microscope (AFM), respectively. X-ray diffraction analyses were performed to identify phases in the films. The deposition rate of CrN x depends more strongly upon the rf-power for argon ion beam than that for nitrogen ion beam. The hardness of the CrN x film is highest when the volume percent of the Cr 2 N phase in the film is highest. Amorphous films are obtained when the rf-power for nitrogen ion beam is much higher than that for argon ion beam. The CrN x film deposited by using the sputtering technique under the optimal condition provides corrosion-resistance comparable to that of the electroplated chromium

  8. Structural Insight into the Critical Role of the N-Terminal Region in the Catalytic Activity of Dual-Specificity Phosphatase 26.

    Directory of Open Access Journals (Sweden)

    Eun-Young Won

    Full Text Available Human dual-specificity phosphatase 26 (DUSP26 is a novel target for anticancer therapy because its dephosphorylation of the p53 tumor suppressor regulates the apoptosis of cancer cells. DUSP26 inhibition results in neuroblastoma cell cytotoxicity through p53-mediated apoptosis. Despite the previous structural studies of DUSP26 catalytic domain (residues 61-211, DUSP26-C, the high-resolution structure of its catalytically active form has not been resolved. In this study, we determined the crystal structure of a catalytically active form of DUSP26 (residues 39-211, DUSP26-N with an additional N-terminal region at 2.0 Å resolution. Unlike the C-terminal domain-swapped dimeric structure of DUSP26-C, the DUSP26-N (C152S monomer adopts a fold-back conformation of the C-terminal α8-helix and has an additional α1-helix in the N-terminal region. Consistent with the canonically active conformation of its protein tyrosine phosphate-binding loop (PTP loop observed in the structure, the phosphatase assay results demonstrated that DUSP26-N has significantly higher catalytic activity than DUSP26-C. Furthermore, size exclusion chromatography-multiangle laser scattering (SEC-MALS measurements showed that DUSP26-N (C152S exists as a monomer in solution. Notably, the crystal structure of DUSP26-N (C152S revealed that the N-terminal region of DUSP26-N (C152S serves a scaffolding role by positioning the surrounding α7-α8 loop for interaction with the PTP-loop through formation of an extensive hydrogen bond network, which seems to be critical in making the PTP-loop conformation competent for phosphatase activity. Our study provides the first high-resolution structure of a catalytically active form of DUSP26, which will contribute to the structure-based rational design of novel DUSP26-targeting anticancer therapeutics.

  9. Dual Diagnosis - Multiple Languages

    Science.gov (United States)

    ... National Library of Medicine Comorbidity or dual diagnosis - Opioid addiction, part 9 - English PDF Comorbidity or dual diagnosis - Opioid addiction, part 9 - español (Spanish) PDF Comorbidity or dual ...

  10. Protective role of Delphinium denudatum (Jadwar) against morphine induced tolerance and dependence in mice.

    Science.gov (United States)

    Zafar, S; Ahmad, M A; Siddiqui, T A

    2001-11-01

    Chronic treatment with Delphinium denudatum (Dd) (Jadwar) (family: Ranunculaceae, 200-1600 mg/kg) suppressed morphine withdrawal jumps in a dose-dependent manner, a sign of the development of dependence to opiate as assessed by naloxone (2 mg/kg) precipitation withdrawal on day 10 of testing in mice. Repeated administration of Dd (200-1600 mg/kg) for 9 days attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg), also produces significant change in tail-flick latency from the saline pretreated group in a dose-dependent manner.

  11. Limitations in dual-task performance

    NARCIS (Netherlands)

    Pannebakker, Merel Mathilde

    2009-01-01

    In this thesis, the effect of information-processing overload on working-memory dependent information processing was examined using dual-task paradigms. The experiments described strengthen the importance of a functional explanation for dual-task limitations. First, it showed evidence for a unified

  12. The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis

    Science.gov (United States)

    Jette, Nicholas; Lees-Miller, Susan P.

    2015-01-01

    The DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and the Ku70/80 heterodimer. Over the past two decades, significant progress has been made in elucidating the role of DNA-PK in non-homologous end joining (NHEJ), the major pathway for repair of ionizing radiation-induced DNA double strand breaks in human cells and recently, additional roles for DNA-PK have been reported. In this review, we will describe the biochemistry, structure and function of DNA-PK, its roles in DNA double strand break repair and its newly described roles in mitosis and other cellular processes. PMID:25550082

  13. Discriminant Profile of Young Internet Dependents: The Role of Family Relationships

    Directory of Open Access Journals (Sweden)

    Michele Terres-Trindade

    2015-12-01

    Full Text Available AbstractInternational studies have shown effects of family relations on Internet addiction in young people. This research aimed to outline a discriminant profile of young people classified as dependent and not dependent on the Internet regarding to socio-biodemographic variables to parenting practices, parent-child conflict and interparental conflict. The sample consisted of 200 students (152 girls and 48 boys, between 15 and 24 years of age, 85.5% reside in Rio Grande do Sul and 14.5% in other Brazilian states. Participants responded individually to the protocol available online. The results showed that interparental conflict, parent-child conflict and the educational practice of supervision of paternal behavior discriminate dependents on Internet. The educational practice of maternal emotional support was the only discriminating variable for non-dependents. These national findings corroborate the international context studies and reinforce the importance of including the family in promotion and prevention of mental health of young people.

  14. Dual Stimulus-Dependent Effect of Oenothera paradoxa Extract on the Respiratory Burst in Human Leukocytes: Suppressing for Escherichia coli and Phorbol Myristate Acetate and Stimulating for Formyl-Methionyl-Leucyl-Phenylalanine

    Directory of Open Access Journals (Sweden)

    Izabela Burzynska-Pedziwiatr

    2014-01-01

    Full Text Available Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA, and formyl-methionyl-leucyl-phenylalanine (fMLP. Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05 and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05. Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D-glucose (PGG, the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

  15. Dual stimulus-dependent effect of Oenothera paradoxa extract on the respiratory burst in human leukocytes: suppressing for Escherichia coli and phorbol myristate acetate and stimulating for formyl-methionyl-leucyl-phenylalanine.

    Science.gov (United States)

    Burzynska-Pedziwiatr, Izabela; Bukowiecka-Matusiak, Malgorzata; Wojcik, Marzena; Machala, Waldemar; Bienkiewicz, Malgorzata; Spolnik, Grzegorz; Danikiewicz, Witold; Wozniak, Lucyna Alicja

    2014-01-01

    Although a growing body of evidence suggests that plant polyphenols can modulate human immune responses, their simultaneous action on monocyte and neutrophil oxidative burst is currently poorly understood. Based on the hypothesis that various polyphenols contained in plant extracts might affect the oxidative burst of phagocytes, we evaluated the effects of ethanolic O. paradoxa extract polyphenols on monocyte and neutrophil oxidative burst in vitro activated by different stimuli, including opsonized bacteria E. coli, phorbol 12-myristate 13-acetate (PMA), and formyl-methionyl-leucyl-phenylalanine (fMLP). Samples were analyzed by the dihydrorhodamine flow cytometry assay. Our results showed that the extract repressed significantly and dose-dependently reactive oxygen species production in both cell types stimulated with E. coli and PMA (P < 0.05) and its inhibitory efficiency was stimulus- and cell-type-dependent. Interestingly, there was significant stimulatory effect of the extract on bursting phagocytes induced by fMLP (P < 0.05). Additionally, several flavonoids and phenolic compounds as well as penta-galloyl-β-(D)-glucose (PGG), the representative of hydrolyzable tannins, were identified in the 60% extract by high-performance liquid chromatography (HPLC) coupled to electrospray ionization in negative ion mode. In summary, the ethanolic O. paradoxa extract, rich in flavonoids and phenolic compounds, exhibits dual stimulus-dependent effect on the respiratory burst in human leukocytes; hence, it might affect immune responses in humans.

  16. Role and psychological dependenci arrangement of opioid by type of reseptor opioid

    OpenAIRE

    Arif Nurrochmad, Arif Nurrochmad

    2015-01-01

    Opioid receptor can be classified as p., 8, and K-opioid receptor that widely expressed in the CNS. The development of selective receptor agonist and cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type. This review focuses on the functional interaction among these opioid receptor types that contribute to opioid dependence especially in psychological dependence. Several lines of evidence provide argument...

  17. Chewing gum and context-dependent memory: The independent roles of chewing gum and mint flavour

    OpenAIRE

    Johnson, A.J.; Miles, C.

    2008-01-01

    Two experiments independently investigated the basis of the chewing-gum induced context-dependent memory effect (Baker et al, 2004). At learning and/or recall participants either chewed flavourless gum (Experiment 1) or received mint-flavoured strips (Experiment 2). No context dependent memory effect was found with either flavourless gum or mint-flavoured strips, indicating that independently the contexts were insufficiently salient to induce the effect. This is found despite participants’ su...

  18. The Role of Early Maladaptive Schemas and Coping Strategies in Substance Dependency

    Directory of Open Access Journals (Sweden)

    Bikem Haciomeroglu

    2014-12-01

    Discussion: Current study showed that the substance dependents had more maladaptive unhealthy core beliefs and ineffective coping strategies than a non-clinical control group. These findings support the importance of early maladaptive schemas which might be the underlying factor for the dependency problem, and might prevent the person to deal with the problem with more active and problem focused coping strategies. [JCBPR 2014; 3(3.000: 162-170

  19. Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation.

    Directory of Open Access Journals (Sweden)

    Naadiya Carrim

    Full Text Available We have previously shown the presence of a TRAF4/p47phox/Hic5/Pyk2 complex associated with the platelet collagen receptor, GPVI, consistent with a potential role of this complex in GPVI-dependent ROS formation. In other cell systems, NOX-dependent ROS formation is facilitated by Pyk2, which along with its closely related homologue FAK are known to be activated and phosphorylated downstream of ligand binding to GPVI.To evaluate the relative roles of Pyk2 and FAK in GPVI-dependent ROS formation and to determine their location within the GPVI signaling pathway.Human and mouse washed platelets (from WT or Pyk2 KO mice were pre-treated with pharmacological inhibitors targeting FAK or Pyk2 (PF-228 and Tyrphostin A9, respectively and stimulated with the GPVI-specific agonist, CRP. FAK, but not Pyk2, was found to be essential for GPVI-dependent ROS production and aggregation. Subsequent human platelet studies with PF-228 confirmed FAK is essential for GPVI-mediated phosphatidylserine exposure, α-granule secretion (P-selectin (CD62P surface expression and integrin αIIbβ3 activation. To determine the precise location of FAK within the GPVI pathway, we analyzed the effect of PF-228 inhibition in CRP-stimulated platelets in conjunction with immunoprecipitation and pulldown analysis to show that FAK is downstream of Lyn, Spleen tyrosine kinase (Syk, PI3-K and Bruton's tyrosine kinase (Btk and upstream of Rac1, PLCγ2, Ca2+ release, PKC, Hic-5, NOX1 and αIIbβ3 activation.Overall, these data suggest a novel role for FAK in GPVI-dependent ROS formation and platelet activation and elucidate a proximal signaling role for FAK within the GPVI pathway.

  20. The Role of Dual Tasking in the Assessment of Gait, Cognition and Community Reintegration of Veterans with Mild Traumatic Brain Injury.

    Science.gov (United States)

    Leland, Azadeh; Tavakol, Kamran; Scholten, Joel; Mathis, Debra; Maron, David; Bakhshi, Simin

    2017-12-01

    This study focussed on the effect of dual versus single tasking on balance, gait and cognition in veterans with mild traumatic brain injury (mTBI). We examined the correlation between these parameters, with responses to questions on community reintegration activities. 22 male and female veterans (aged 19-65) walked along a narrow and 6.1-meter long path, both at their self-selected and fastest but safe pace under single and dual tasking conditions. For dual tasking, participants were required to recall and vocalize a 5-digit number at the end of the path. The outcome measures were the accuracy, velocity, cadence, stride length, and number of steps off the path. We calculated the reliability and correlation coefficient values for the walking time compared with the stride length, velocity, and percentage of swing and stance. Under dual task, the participants demonstrated slower gait, recalled shorter digit span and stepped off the path 12.6% more often than under single task. The stride length decreased by about 20% and the stride velocity increased by over 2% in dual compared with single tasking. Dual tasking slows down the gait and reduces the attention span in patients with mTBI, which can negatively impact their community reintegration, at least early after their hospital discharge, hence the need for exercising caution with their community reintegration activities. Dual tasking may have the potential to improve balance, gait and attention span of the patients in the long-term, thus leading to safer community integration, if incorporated in the rehabilitation plans.

  1. Domain architecture of protein-disulfide isomerase facilitates its dual role as an oxidase and an isomerase in Ero1p-mediated disulfide formation

    DEFF Research Database (Denmark)

    Kulp, M. S.; Frickel, E. M.; Ellgaard, Lars

    2006-01-01

    reduction/rearrangement of non-native disulfides is poorly understood. We analyzed the role of individual PDI domains in disulfide bond formation in a reaction driven by their natural oxidant, Ero1p. We found that Ero1p oxidizes the isolated PDI catalytic thioredoxin domains, A and A' at the same rate......Native disulfide bond formation in eukaryotes is dependent on protein-disulfide isomerase (PDI) and its homologs, which contain varying combinations of catalytically active and inactive thioredoxin domains. However, the specific contribution of PDI to the formation of new disulfides versus...... catalytic (A) domain. The specific order of thioredoxin domains in PDI is important in establishing the asymmetry in the rate of oxidation of the two active sites thus allowing A and A', two thioredoxin domains that are similar in sequence and structure, to serve opposing functional roles as a disulfide...

  2. Dual role of interleukin-1β in islet amyloid formation and its β-cell toxicity: Implications for type 2 diabetes and islet transplantation.

    Science.gov (United States)

    Park, Yoo Jin; Warnock, Garth L; Ao, Ziliang; Safikhan, Nooshin; Meloche, Mark; Asadi, Ali; Kieffer, Timothy J; Marzban, Lucy

    2017-05-01

    Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to β-cell failure in type 2 diabetes, cultured and transplanted islets. We previously showed that biosynthetic hIAPP aggregates induce β-cell Fas upregulation and activation of the Fas apoptotic pathway. We used cultured human and hIAPP-expressing mouse islets to investigate: (1) the role of interleukin-1β (IL-1β) in amyloid-induced Fas upregulation; and (2) the effects of IL-1β-induced β-cell dysfunction on pro-islet amyloid polypeptide (proIAPP) processing and amyloid formation. Human and h IAPP -expressing mouse islets were cultured to form amyloid without or with the IL-1 receptor antagonist (IL-1Ra) anakinra, in the presence or absence of recombinant IL-1β. Human islets in which amyloid formation was prevented (amyloid inhibitor or Ad-prohIAPP-siRNA) were cultured similarly. β-cell function, apoptosis, Fas expression, caspase-8 activation, islet IL-1β, β-cell area, β-/α-cell ratio, amyloid formation, and (pro)IAPP forms were assessed. hIAPP aggregates were found to increase IL-1β levels in cultured human islets that correlated with β-cell Fas upregulation, caspase-8 activation and apoptosis, all of which were reduced by IL-1Ra treatment or prevention of amyloid formation. Moreover, IL-1Ra improved culture-induced β-cell dysfunction and restored impaired proIAPP processing, leading to lower amyloid formation. IL-1β treatment potentiated impaired proIAPP processing and increased amyloid formation in cultured human and h IAPP -expressing mouse islets, which were prevented by IL-1Ra. IL-1β plays a dual role by: (1) mediating amyloid-induced Fas upregulation and β-cell apoptosis; (2) inducing impaired proIAPP processing thereby potentiating amyloid formation. Blocking IL-1β may provide a new strategy to preserve β cells in conditions associated with islet amyloid formation. © 2017 John Wiley & Sons Ltd.

  3. The Role of Thought Suppression, Meta-Cognitive Factors and Negative Emotions in Prediction of Substance Dependency Disorder

    Directory of Open Access Journals (Sweden)

    Omid Saed

    2011-08-01

    Full Text Available Introduction: This study investigated the role of thought suppression, meta- cognitive factors, and negative emotions in predicting of substance dependency disorder. Method: Subjects were 70 patients with substance dependence disorder and 70 normal individuals (total 140. Substance dependants were selected of outpatient treatment centers and the normal sample was selected of the general population too. Sampling methods in both samples were convenience sampling. All people were assessed by MCQ-30, White Bear Suppression Inventory, and Beck’s Anxiety and Depression Questionnaires. For data analysis, discriminant analysis were used. Results: Negative meta-cognitive beliefs about worry, depression, and thought suppression were the most significant predictors of substance dependence disorder. Conclusion: Through meta-cognitive beliefs, thought suppression and negative emotion (especially depression, substance dependency disorder can be predicted. Based on this model can be used to take a substance dependency disorder prevention approach and psychotherapy approach (based on cognitive and meta-cognitive therapies. In addition, the findings of this research can be applied in clinical and counseling environments to help substance dependant clients.

  4. Some properties of dual and approximate dual of fusion frames

    OpenAIRE

    Arefijamaal, Ali Akbar; Neyshaburi, Fahimeh Arabyani

    2016-01-01

    In this paper we extend the notion of approximate dual to fusion frames and present some approaches to obtain dual and approximate alternate dual fusion frames. Also, we study the stability of dual and approximate alternate dual fusion frames.

  5. The roles of time and displacement in velocity-dependent volumetric strain of fault zones

    Science.gov (United States)

    Beeler, N.M.; Tullis, T.E.

    1997-01-01

    The relationship between measured friction??A and volumetric strain during frictional sliding was determined using a rate and state variable dependent friction constitutive equation, a common work balance relating friction and volume change, and two types of experimental faults: initially bare surfaces of Westerly granite and rock surfaces separated by a 1 mm layer of derivative of fault normal displacement with respect shear displacement, d??n ld??s. An implication of this relationship is that the rate dependence of d??n ld??s contributes to the rate dependence of ??A. Experiments show changes in sliding velocity lead to changes in both fault strength and volume. Analysis of data with the rate and state equations combined with the work balance relationship preclude the conventional interpretation of the direct effect in the rate and state variable constitutive equations. Consideration of a model bare surface fault consisting of an undeformable indentor sliding on a deformable surface reveals a serious flaw in the work balance relationship if volume change is time-dependent. For the model, at zero slip rate indentation creep under the normal load leads to time-dependent strengthening of the fault surface but, according to the work balance relationship, no work is done because compaction or dilatancy can only be induced by shearing. Additional tests on initially bare surfaces and gouges show that fault normal strain in experiments is time-dependent, consistent with the model. This time-dependent fault normal strain, which is not accounted for in the work balance relationship, explains the inconsistency between the constitutive equations and the work balance. For initially bare surface faults, all rate dependence of volume change is due to time dependence. Similar results are found for gouge. We conclude that ??A reflects the frictional resistance that results in shear heating, and no correction needs to be made for the volume changes. The result that time-dependent

  6. The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis

    OpenAIRE

    Jette, Nicholas; Lees-Miller, Susan P.

    2014-01-01

    The DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase composed of a large catalytic subunit (DNA-PKcs) and the Ku70/80 heterodimer. Over the past two decades, significant progress has been made in elucidating the role of DNA-PK in non-homologous end joining (NHEJ), the major pathway for repair of ionizing radiation-induced DNA double strand breaks in human cells and recently, additional roles for DNA-PK have been reported. In this review, we will describe the biochemi...

  7. Role of the Frontal Cortex in Standing Postural Sway Tasks While Dual-Tasking: A Functional Near-Infrared Spectroscopy Study Examining Working Memory Capacity

    Directory of Open Access Journals (Sweden)

    Hiroyuki Fujita

    2016-01-01

    Full Text Available Posture control during a dual-task involves changing the distribution of attention resources between the cognitive and motor tasks and involves the frontal cortex working memory (WM. The present study aimed to better understand the impact of frontal lobe activity and WM capacity in postural control during a dual-task. High and low WM-span groups were compared using their reading span test scores. High and low WM capacity were compared based on cognitive and balance performance and hemoglobin oxygenation (oxyHb levels during standing during single (S-S, standing during dual (S-D, one leg standing during single (O-S, and one leg standing during dual (O-D tasks. For sway pass length, significant difference in only the O-D task was observed between both groups. oxyHb levels were markedly increased in the right dorsolateral prefrontal cortex and supplementary motor area in the high-span group during a dual-task. Therefore, WM capacity influenced the allocation of attentional resources and motor performance.

  8. Economic dependence and unprotected sex: the role of sexual assertiveness among young urban mothers.

    Science.gov (United States)

    Biello, Katie Brooks; Sipsma, Heather L; Ickovics, Jeannette R; Kershaw, Trace

    2010-05-01

    In the USA, sexual intercourse is the leading route of human immunodeficiency virus transmission among women, primarily through their main partner. Because male condom use is not directly under a woman's control, gender inequalities may help shape this sexual risk behavior. To examine this association, data came from follow-up interviews of young, primarily minority, pregnant women enrolled in a prospective, randomized controlled trial. Specifically, we aimed to determine the relationship between economic dependence on a male partner and condom use, and to establish whether this relationship was mediated by sexual assertiveness. Overall, 28% of women reported being economically dependent on a male partner. Young women dependent on a male partner were 1.6 times more likely to report not using a condom at last sex than women not dependent on their partner (95% confidence interval = 1.11-2.32; p = 0.01). Sexual assertiveness mediated the relationship between economic dependence and condom use (Sobel = 2.05, p = 0.04). Coupled with past research, this study supports the premise that sexual behaviors may be rooted in a complex web of social determinants. Addressing gender inequalities in contextual factors may promote healthier decisions within sexual relationships.

  9. Essential role of RSK2 in c-Fos-dependent osteosarcoma development.

    Science.gov (United States)

    David, Jean-Pierre; Mehic, Denis; Bakiri, Latifa; Schilling, Arndt F; Mandic, Vice; Priemel, Matthias; Idarraga, Maria Helena; Reschke, Markus O; Hoffmann, Oskar; Amling, Michael; Wagner, Erwin F

    2005-03-01

    Inactivation of the growth factor-regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a progressive skeletal disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is associated with decreased expression of Phex, an endopeptidase regulating bone mineralization. This defect is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362 in the C-terminus. However, in the absence of RSK2, c-Fos-dependent osteosarcoma formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos protein levels, which are thought to be responsible for decreased proliferation and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas.

  10. Chewing gum and context-dependent memory: the independent roles of chewing gum and mint flavour.

    Science.gov (United States)

    Johnson, Andrew J; Miles, Christopher

    2008-05-01

    Two experiments independently investigated the basis of the chewing gum induced context-dependent memory effect. At learning and/or recall, participants either chewed flavourless gum (Experiment 1) or received mint-flavoured strips (Experiment 2). No context-dependent memory effect was found with either flavourless gum or mint-flavoured strips, indicating that independently the contexts were insufficiently salient to induce the effect. This is found despite participants' subjective ratings indicating a perceived change in state following administration of flavourless gum or mint-flavoured strips. Additionally, some preliminary evidence for a non-additive facilitative effect of receiving gum or flavour at either learning and/or recall is reported. The findings raise further concerns regarding the robustness of the previously reported context-dependent memory effect with chewing gum.

  11. The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction.

    Science.gov (United States)

    Selya, Arielle S; Dierker, Lisa; Rose, Jennifer S; Hedeker, Donald; Mermelstein, Robin J

    2017-07-07

    E-cigarettes (Electronic Nicotine Delivery Systems, or ENDS) are an increasingly popular tobacco product among youth. Some evidence suggests that e-cigarettes may be effective for harm reduction and smoking cessation, although these claims remain controversial. Little is known about how nicotine dependence may contribute to e-cigarettes' effectiveness in reducing or quitting conventional smoking. A cohort of young adults were surveyed over 4 years (approximately ages 19-23). Varying-coefficient models (VCMs) were used to examine the relationship between e-cigarette use and conventional smoking frequency, and how this relationship varies across users with different nicotine dependence levels. Lifetime, but not recent, e-cigarette use was associated with less frequent concurrent smoking of conventional cigarettes among those with high levels of nicotine dependence. However, nondependent e-cigarette users smoked conventional cigarettes slightly more frequently than those who had never used e-cigarettes. Nearly half of ever e-cigarette users reported using them to quit smoking at the last measurement wave. For those who used e-cigarettes in a cessation attempt, the frequency of e-cigarette use was not associated with reductions in future conventional smoking frequency. These findings offer possible support that e-cigarettes may act as a smoking reduction method among highly nicotine-dependent young adult cigarette smokers. However, the opposite was found in non-dependent smokers, suggesting that e-cigarette use should be discouraged among novice tobacco users. Additionally, although a substantial proportion of young adults used e-cigarettes to help them quit smoking, these self-initiated quit attempts with e-cigarettes were not associated with future smoking reduction or cessation. This study offers potential support for e-cigarettes as a smoking reduction tool among highly nicotine-dependent young adult conventional smokers, although the extent and nature of this

  12. α-Terpineol attenuates morphine-induced physical dependence and tolerance in mice: role of nitric oxide.

    Science.gov (United States)

    Parvardeh, Siavash; Moghimi, Mahsa; Eslami, Pegah; Masoudi, Alireza

    2016-02-01

    Dependence and tolerance to opioid analgesics are major problems limiting their clinical application. α-Terpineol is a monoterpenoid alcohol with neuroprotective effects which is found in several medicinal plants such as Myrtus communis, Laurus nobilis, and Stachys byzantina. It has been shown that some of these medicinal plants such as S. byzantina attenuate dependence and tolerance to morphine. Since α-terpineol is one of the bioactive phytochemical constituent of these medicinal plants, the present study was conducted to investigate the effects of α-terpineol on morphine-induced dependence and tolerance in mice. The mice were rendered dependent or tolerant to morphine by a 3-day administration schedule. The hot-plate test and naloxone-induced withdrawal syndrome were used to evaluate tolerance and dependence on morphine, respectively. To investigate a possible role for nitric oxide (NO) in the protective effect of α-terpineol, the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME) and NO precursor, L-arginine, were used. Administration of α-terpineol (5, 10, and 20 mg/kg, IP) significantly decreased the number of jumps in morphine dependent animals. Moreover, α-terpineol (20 and 40 mg/kg, IP) attenuated tolerance to the analgesic effect of morphine. The inhibitory effects of α-terpineol on morphine-induced dependence and tolerance were enhanced by pretreatment with L-NAME (10 mg/kg, IP). However, L-arginine (300 mg/kg, IP) antagonized the protective effects of α-terpineol on dependence and tolerance to morphine. These findings indicate that α-terpineol prevents the development of dependence and tolerance to morphine probably through the influence on NO production.

  13. Dual action of a dinoflagellate-derived precursor of Pacific ciguatoxins (P-CTX-4B) on voltage-dependent K(+) and Na(+) channels of single myelinated axons.

    Science.gov (United States)

    Schlumberger, Sébastien; Mattei, César; Molgó, Jordi; Benoit, Evelyne

    2010-10-01

    The effects of Pacific ciguatoxin-4B (P-CTX-4B, also named gambiertoxin), extracted from toxic Gambierdiscus dinoflagellates, were assessed on nodal K(+) and Na(+) currents of frog myelinated axons, using a conventional voltage-clamp technique. P-CTX-4B decreased, within a few minutes, both K(+) and Na(+) currents in a dose-dependent manner, without inducing any marked change in current kinetics. The toxin was more effective in blocking K(+) than Na(+) channels. P-CTX-4B shifted the voltage-dependence of Na(+) conductance by about 14 mV towards more negative membrane potentials. This effect was reversed by increasing Ca(2+) in the external solution. A negative shift of about 16 mV in the steady-state Na(+) inactivation-voltage curve was also observed in the presence of the toxin. Unmodified and P-CTX-4B-modified Na(+) currents were similarly affected by the local anaesthetic lidocaine. The decrease of the two currents by lidocaine was dependent on both the concentration and the membrane potential during pre-pulses. In conclusion, P-CTX-4B appears about four times more effective than P-CTX-1B to affect K(+) channels, whereas it is about 50 times less efficient to affect Na(+) channels of axonal membranes. These actions may be related to subtle differences between the two chemical structures of molecules. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. SUPEROXIDE-DEPENDENT IRON UPTAKE: A NEW ROLE FOR ANION EXCHANGE PROTEIN 2

    Science.gov (United States)

    Lung cells import iron across the plasma membrane as ferrous (Fe2+) ion by incompletely understood mechanisms. We tested the hypothesis that human bronchial epithelial (HBE) cells import non-transferrin-bound iron (NTBI) using superoxide-dependent ferri-reductase activity involvi...

  15. The Crucial Role of Postcue Encoding in Directed Forgetting and Context-Dependent Forgetting

    Science.gov (United States)

    Pastotter, Bernhard; Bauml, Karl-Heinz

    2007-01-01

    People can intentionally forget previously studied material if, after study, a forget cue is provided and new material is learned. It has recently been suggested that such list-method directed forgetting arises because the forget cue induces a change in internal context and causes context-dependent forgetting of the studied material (L. Sahakyan &…

  16. The shared role of oxidative stress and inflammation in major depressive disorder and nicotine dependence.

    Science.gov (United States)

    Nunes, Sandra Odebrecht Vargas; Vargas, Heber Odebrecht; Prado, Eduardo; Barbosa, Decio Sabbatini; de Melo, Luiz Picoli; Moylan, Steven; Dodd, Seetal; Berk, Michael

    2013-09-01

    Nicotine dependence is common in people with mood disorders; however the operative pathways are not well understood. This paper reviews the contribution of inflammation and oxidative stress pathways to the co-association of depressive disorder and nicotine dependence, including increased levels of pro-inflammatory cytokines, increased acute phase proteins, decreased levels of antioxidants and increased oxidative stress. These could be some of the potential pathophysiological mechanisms involved in neuroprogression. The shared inflammatory and oxidative stress pathways by which smoking may increase the risk for development of depressive disorders are in part mediated by increased levels of pro-inflammatory cytokines, diverse neurotransmitter systems, activation the hypothalamic-pituitary-adrenal (HPA) axis, microglial activation, increased production of oxidative stress and decreased levels of antioxidants. Depressive disorder and nicotine dependence are additionally linked imbalance between neuroprotective and neurodegenerative metabolites in the kynurenine pathway that contribute to neuroprogression. These pathways provide a mechanistic framework for understanding the interaction between nicotine dependence and depressive disorder. Copyright © 2013. Published by Elsevier Ltd.

  17. Ecological genetics of the Bromus tectorum (Poaceae) - Ustilago Bullata (Ustilaginaceae): A role for frequency dependent selection?

    Science.gov (United States)

    Susan E. Meyer; David L. Nelson; Suzette Clement; Alisa Ramakrishnan

    2010-01-01

    Evolutionary processes that maintain genetic diversity in plants are likely to include selection imposed by pathogens. Negative frequency-dependent selection is a mechanism for maintenance of resistance polymorphism in plant - pathogen interactions. We explored whether such selection operates in the Bromus tectorum - Ustilago bullata pathosystem. Gene-for-gene...

  18. Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories

    Directory of Open Access Journals (Sweden)

    Jesse Daniel Cushman

    2012-02-01

    Full Text Available Postnatal-neurogenesis (PNN contributes neurons to olfactory bulb (OB and dentate gyrus (DG throughout juvenile development, but the quantitative amount, temporal dynamics and functional roles of this contribution have not been defined. By using transgenic mouse models for cell lineage tracing and conditional cell ablation, we found that juvenile neurogenesis gradually increased the total number of granule neurons by approximately 40% in OB, and by 25% in DG, between two weeks and two months of age, and that total numbers remained stable thereafter. These findings indicate that the overwhelming majority of net postnatal neuronal addition in these regions occurs during the juvenile period and that adult neurogenesis contributes primarily to replacement of granule cells in both regions. Behavioral analysis in our conditional cell ablation mouse model showed that complete loss of PNN throughout both the juvenile and adult period produced a specific set of sex-dependent cognitive changes. We observed normal hippocampus-independent delay fear conditioning, but excessive generalization of fear to a novel auditory stimulus, which is consistent with a role for PNN in psychopathology. Standard contextual fear conditioning was intact, however, pre-exposure dependent contextual fear was impaired suggesting a specific role for PNN in incidental contextual learning. Contextual discrimination between two highly similar contexts was enhanced; suggesting either enhanced contextual pattern separation or impaired temporal integration. We also observed a reduced reliance on olfactory cues, consistent with a role for OB PNN in the efficient processing of olfactory information. Thus, juvenile neurogenesis adds substantively to the total numbers of granule neurons in OB and DG during periods of critical juvenile behavioral development, including weaning, early social interactions and sexual maturation, and plays a sex-dependent role in fear memories.

  19. The Moderating Roles of Relationship Quality and Dependency in Retailers’ New Product Adoption Decisions

    NARCIS (Netherlands)

    Y.M. van Everdingen (Yvonne); L.M. Sloot (Laurens); P.C. Verhoef (Peter)

    2008-01-01

    textabstractThis study contributes to the retail adoption literature by explicitly focusing on the role of both profit-related and relationship variables in explaining new product adoption decisions by retailers, instead of considering either one of these groups of variables in isolation as has been

  20. A Presynaptic Role for FMRP during Protein Synthesis-Dependent Long-Term Plasticity in "Aplysia"

    Science.gov (United States)

    Till, Sally M.; Li, Hsiu-Ling; Miniaci, Maria Concetta; Kandel, Eric R.; Choi, Yun-Beom

    2011-01-01

    Loss of the Fragile X mental retardation protein (FMRP) is associated with presumed postsynaptic deficits in mouse models of Fragile X syndrome. However, the possible presynaptic roles of FMRP in learning-related plasticity have received little attention. As a result, the mechanisms whereby FMRP influences synaptic function remain poorly…

  1. A role for NF-KB-dependent gene transactivation in sunburn

    NARCIS (Netherlands)

    Abeyama, K.; Eng, W.; Jester, J.V.; Vink, A.A.; Edelbaum, D.; Cockerell, C.J.; Bergstresser, P.R.; Takashima, A.

    2000-01-01

    Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking

  2. Role of Proteasome-Dependent Protein Degradation in Long-Term Operant Memory in "Aplysia"

    Science.gov (United States)

    Lyons, Lisa C.; Gardner, Jacob S.; Gandour, Catherine E.; Krishnan, Harini C.

    2017-01-01

    We investigated the in vivo role of protein degradation during intermediate (ITM) and long-term memory (LTM) in "Aplysia" using an operant learning paradigm. The proteasome inhibitor MG-132 inhibited the induction and molecular consolidation of LTM with no effect on ITM. Remarkably, maintenance of steady-state protein levels through…

  3. Do best manufacturing practices depend on the plant role in international manufacturing networks?

    DEFF Research Database (Denmark)

    Demeter, Krisztina; Szász, Levente; Boer, Harry

    2014-01-01

    . This paper investigates the relationship between plant roles and the “goodness” of manufacturing practices using the International Manufacturing Strategy Survey. According to our results plants with higher competence (leaders and contributors) have more best practices than less competent plants. Servers can...

  4. The role of diversification strategies in the economic development for oil-depended countries: - The case of UAE

    Directory of Open Access Journals (Sweden)

    Ahmed Zain Elabdin Ahmed

    2015-03-01

    Full Text Available Diversification strategies adopted by oil-depended economies' played an important role in the economic development in these countries, which rely heavily on oil exports. UAE as an oil-dependency economy has the type of strategy to diversify the sources of its national income and reduce its dependence on oil to counter the instability in global oil prices. This paper seek to investigate whether the diversification strategies adopted by (UAE is adequate to manage its economic development. The methodology employed in this study is to examine the contribution of diversified sectors based on the country's GDP especially during and after the global financial crisis (2008-2012 using statistical analysis procedure. The results confirm that investment in different sectors rather than oil would have substantially improved the performance UAE economy.

  5. Analysis of the dual phase lag bio-heat transfer equation with constant and time-dependent heat flux conditions on skin surface

    Directory of Open Access Journals (Sweden)

    Ziaei Poor Hamed

    2016-01-01

    Full Text Available This article focuses on temperature response of skin tissue due to time-dependent surface heat fluxes. Analytical solution is constructed for DPL bio-heat transfer equation with constant, periodic and pulse train heat flux conditions on skin surface. Separation of variables and Duhamel’s theorem for a skin tissue as a finite domain are employed. The transient temperature responses for constant and time-dependent boundary conditions are obtained and discussed. The results show that there is major discrepancy between the predicted temperature of parabolic (Pennes bio-heat transfer, hyperbolic (thermal wave and DPL bio-heat transfer models when high heat flux accidents on the skin surface with a short duration or propagation speed of thermal wave is finite. The results illustrate that the DPL model reduces to the hyperbolic model when τT approaches zero and the classic Fourier model when both thermal relaxations approach zero. However for τq = τT the DPL model anticipates different temperature distribution with that predicted by the Pennes model. Such discrepancy is due to the blood perfusion term in energy equation. It is in contrast to results from the literature for pure conduction material, where the DPL model approaches the Fourier heat conduction model when τq = τT . The burn injury is also investigated.

  6. Personality correlates of caffeine dependence: the role of sensation seeking, impulsivity, and risk taking.

    Science.gov (United States)

    Jones, Heather A; Lejuez, C W

    2005-08-01

    The consumption of caffeine has become a growing concern, partially because of the withdrawal properties of the drug. The current study examined personality correlates of caffeine consumption and dependence in 60 university students. Self-report and behavioral measures of sensation seeking, impulsivity, and risk taking were administered to 2 groups, identified as caffeine dependent-high consuming or caffeine nondependent-low consuming. Scores on self-report measures of sensation seeking and impulsivity were related to group status, and only sensation seeking evidenced a significant relationship with group status when both variables were considered in a regression analysis. Implications of these findings and future directions are discussed. ((c) 2005 APA, all rights reserved).

  7. Reasons for opioid use among patients with dependence on prescription opioids: the role of chronic pain.

    Science.gov (United States)

    Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; McHugh, R Kathryn; Haller, Deborah; Jacobs, Petra; Gardin, John; Fischer, Dan; Rosen, Kristen D

    2014-08-01

    The number of individuals seeking treatment for prescription opioid dependence has increased dramatically, fostering a need for research on this population. The aim of this study was to examine reasons for prescription opioid use among 653 participants with and without chronic pain, enrolled in the Prescription Opioid Addiction Treatment Study, a randomized controlled trial of treatment for prescription opioid dependence. Participants identified initial and current reasons for opioid use. Participants with chronic pain were more likely to report pain as their primary initial reason for use; avoiding withdrawal was rated as the most important reason for current use in both groups. Participants with chronic pain rated using opioids to cope with physical pain as more important, and using opioids in response to social interactions and craving as less important, than those without chronic pain. Results highlight the importance of physical pain as a reason for opioid use among patients with chronic pain. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

    OpenAIRE

    Flavell, Charlotte R.; Lambert, Elliot A.; Winters, Boyer D.; Bredy, Timothy W.

    2013-01-01

    The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session) can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of...

  9. Respiration-Dependent Utilization of Sugars in Yeasts: a Determinant Role for Sugar Transporters

    OpenAIRE

    Goffrini, Paola; Ferrero, Iliana; Donnini, Claudia

    2002-01-01

    In many yeast species, including Kluyveromyces lactis, growth on certain sugars (such as galactose, raffinose, and maltose) occurs only under respiratory conditions. If respiration is blocked by inhibitors, mutation, or anaerobiosis, growth does not take place. This apparent dependence on respiration for the utilization of certain sugars has often been suspected to be associated with the mechanism of the sugar uptake step. We hypothesized that in many yeast species, the permease activities fo...

  10. Role of Erbin in ErbB2-dependent breast tumor growth

    Science.gov (United States)

    Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin

    2014-01-01

    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression. PMID:25288731

  11. Deficient inhibition in alcohol-dependence: let's consider the role of the motor system!

    Science.gov (United States)

    Quoilin, Caroline; Wilhelm, Emmanuelle; Maurage, Pierre; de Timary, Philippe; Duque, Julie

    2018-04-26

    Impaired inhibitory control contributes to the development, maintenance, and relapse of alcohol-dependence, but the neural correlates of this deficit are still unclear. Because inhibitory control has been labeled as an executive function, most studies have focused on prefrontal areas, overlooking the contribution of more "primary" structures, such as the motor system. Yet, appropriate neural inhibition of the motor output pathway has emerged as a central aspect of healthy behavior. Here, we tested the hypothesis that this motor inhibition is altered in alcohol-dependence. Neural inhibitory measures of motor activity were obtained in 20 detoxified alcohol-dependent (AD) patients and 20 matched healthy subjects, using a standard transcranial magnetic stimulation procedure whereby motor-evoked potentials (MEPs) are elicited in a choice reaction time task. Moreover, behavioral inhibition and trait impulsivity were evaluated in all participants. Finally, the relapse status of patients was assessed 1 year after the experiment. As expected, AD patients displayed poorer behavioral inhibition and higher trait impulsivity than controls. More importantly, the MEP data revealed a considerable shortage of neural motor inhibition in AD patients. Interestingly, this neural defect was strongest in the patients who ended up relapsing during the year following the experiment. Our data suggest a strong motor component in the neural correlates of altered inhibitory control in AD patients. They also highlight an intriguing relationship with relapse and the perspective of a new biomarker to follow strategies aiming at reducing relapse in AD patients.

  12. ‘Developmental Delay’ Reconsidered: The Critical Role of Age-Dependent, Co-variant Development

    Directory of Open Access Journals (Sweden)

    Yonata Levy

    2018-04-01

    Full Text Available In memory of Annette Karmiloff-Smith.This paper reviews recent neurobiological research reporting structural co-variance and temporal dependencies in age-dependent gene expression, parameters of cortical maturation, long range connectivity and interaction of the biological network with the environment. This research suggests that age by size trajectories of brain structures relate to functional properties more than absolute sizes. In line with these findings, recent behavioral studies of typically developing children whose language development was delayed reported long term consequences of such delays. As for neurodevelopmental disorders, disrupted developmental timing and slow acquisitional pace are hallmarks of these populations. It is argued that these behavioral and neuro-biological results highlight the need to commit to a developmental model which will reflect the fact that temporal dependencies overseeing structural co-variance among developmental components are major regulatory factors of typical development of the brain/mind network. Consequently, the concept of ‘developmental delay’ in developmental theorizing needs to be reconsidered.

  13. Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning.

    Science.gov (United States)

    Dodson, Mark W; Zhang, Ting; Jiang, Changan; Chen, Shengdi; Guo, Ming

    2012-03-15

    LRRK2 (PARK8) is the most common genetic determinant of Parkinson's disease (PD), with dominant mutations in LRRK2 causing inherited PD and sequence variation at the LRRK2 locus associated with increased risk for sporadic PD. Although LRRK2 has been implicated in diverse cellular processes encompassing almost all cellular compartments, the precise functions of LRRK2 remain unclear. Here, we show that the Drosophila homolog of LRRK2 (Lrrk) localizes to the membranes of late endosomes and lysosomes, physically interacts with the crucial mediator of late endosomal transport Rab7 and negatively regulates rab7-dependent perinuclear localization of lysosomes. We also show that a mutant form of lrrk analogous to the pathogenic LRRK2(G2019S) allele behaves oppositely to wild-type lrrk in that it promotes rather than inhibits rab7-dependent perinuclear lysosome clustering, with these effects of mutant lrrk on lysosome position requiring both microtubules and dynein. These data suggest that LRRK2 normally functions in Rab7-dependent lysosomal positioning, and that this function is disrupted by the most common PD-causing LRRK2 mutation, linking endolysosomal dysfunction to the pathogenesis of LRRK2-mediated PD.

  14. Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure

    OpenAIRE

    Dong, Changsheng; Yang, Shanshan; Fan, Ruiwen; Ji, Kaiyuan; Zhang, Junzhen; Liu, Xuexian; Hu, Shuaipeng; Xie, Jianshan; Liu, Yu; Gao, Wenjun; Wang, Haidong; Yao, Jianbo; Smith, George W; Herrid, Muren

    2017-01-01

    The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report fo...

  15. Replication and extension of the dual pathway model of disordered eating: The role of fear of negative evaluation, suggestibility, rumination, and self-compassion.

    Science.gov (United States)

    Maraldo, Toni M; Zhou, Wanni; Dowling, Jessica; Vander Wal, Jillon S

    2016-12-01

    The dual pathway model, a theoretical model of eating disorder development, suggests that thin ideal internalization leads to body dissatisfaction which leads to disordered eating via the dual pathways of negative affect and dietary restraint. While the dual pathway model has been a valuable guide for eating disorder prevention, greater knowledge of characteristics that predict thin ideal internalization is needed. The present study replicated and extended the dual pathway model by considering the addition of fear of negative evaluation, suggestibility, rumination, and self-compassion in a sample of community women and female university students. Results showed that fear of negative evaluation and suggestibility predicted thin ideal internalization whereas rumination and self-compassion (inversely) predicted body dissatisfaction. Negative affect was predicted by fear of negative evaluation, rumination, and self-compassion (inversely). The extended model fit the data well in both samples. Analogue and longitudinal study of these constructs is warranted in future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Telomere length in alcohol dependence: A role for impulsive choice and childhood maltreatment.

    Science.gov (United States)

    Kang, Jee In; Hwang, Syung Shick; Choi, Jong Rak; Lee, Seung-Tae; Kim, Jieun; Hwang, In Sik; Kim, Hae Won; Kim, Chan-Hyung; Kim, Se Joo

    2017-09-01

    Telomere shortening, a marker of cellular aging, has been considered to be linked with psychosocial stress as well as with chronic alcohol consumption, possibly mediated by oxidative stress and inflammatory response. Recent findings suggested that early life adversity on telomere dynamics may be related to impulsive choice. To further our understanding of the association of impulsive choice and childhood trauma on telomere length, we examined whether delayed discounting and childhood trauma or their interaction is related to leukocyte telomere length, while controlling for multiple potential confounding variables, in patients with alcohol dependence who are considered to have higher impulsive choice and shorter telomere length. We recruited 253 male patients with chronic alcohol dependence. All participants performed the delay discounting task, and the area under curve was used as a measure of delay discounting. Steeper delay discounting represents more impulsive choices. The modified Parent-Child Conflict Tactics Scale was used to measure childhood maltreatment. In addition, confounding factors, including socio-demographic characteristics, the Alcohol Use Disorders Identification Test, the Buss-Perry Aggression Questionnaire, the Resilience Quotient, the Beck Depression Inventory, and the Beck Anxiety Inventory, were also assessed. Hierarchical regression analyses showed a significant main effect of delay discounting (β=0.161, t=2.640, p=0.009), and an interaction effect between delay discounting and childhood maltreatment on leukocyte telomere length (β=0.173, t=2.138, p=0.034). In subsequent analyses stratified by childhood maltreatment, patients with alcohol dependence and high childhood trauma showed a significant relationship between delay discounting and leukocyte telomere length (β=0.279, t=3.183, p=0.002), while those with low trauma showed no association between them. Our findings suggest that higher impulsive choice is associated with shorter telomere

  17. Age-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters

    Directory of Open Access Journals (Sweden)

    Seok Kyu eKang

    2015-05-01

    Full Text Available Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB, with NKCC1 antagonist bumetanide (BTN as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in postnatal day 7, 10 and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.

  18. The role of the axial anomaly in determining spin-dependent parton distributions

    International Nuclear Information System (INIS)

    Carlitz, R.D.; Collins, J.C.; Mueller, A.H.

    1989-01-01

    It is shown that the forward matrix elements of j 5 μ , the flavor singlet axial vector current, do not measure the helicity carried by quarks and anti-quarks but also include a spin-dependent gluonic component due to the anomaly. Detailed phenomenological and field theoretic reasons are given for the necessity of a gluonic component in the matrix element of j 5 μ . The first higher order corrections to the basic box and triangle graphs are discussed and shown not to modify the conclusions drawn in the leading order calculation. We close with a few comments on the possible phenomenological implications of the anomalous contribution. 25 refs., 6 figs

  19. Developmentally dependent and different roles of fatty acids OMEGA-6 and OMEGA-3

    DEFF Research Database (Denmark)

    Mourek, J; Mourek, J

    2011-01-01

    The developmentally-dependent differences in the biological significances and effects of PUFA-OMEGA-6 (namely of arachidonic acid) and PUFA-OMEGA-3 (namely of docosahexaenoic acid) are discussed. The clinical results as well as developmental experiences are indicating a hypothesis of the evolution...... that created mutual relationship between those two substances (with immunological basis and following recuperation). The anti-inflammatory actions of PUFA-OMEGA-3 are the most visible (and significant) contrasts as compared with the large affects of namely arachidonic acid and its metabolites....

  20. Searching for the physiological role of glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Windeløv, Johanne Agerlin; Boer, Geke Aline

    2016-01-01

    metabolism. Unlike the related hormone, GLP-1, GIP stimulates the secretion of glucagon, which in healthy individuals may help to stabilize glucose levels, but in people with type 2 diabetes may contribute to glucose intolerance. A role in lipid metabolism is supported by numerous indirect observations...... and by resistance to diet-induced obesity after deletion of the GIP receptor. However, a clear effect on lipid clearance could not be identified in humans, raising doubt about its importance. The GIP receptor is widely expressed in the body and also appears to be expressed on bone cells, and experimental studies...

  1. How do dual practitioners divide their time? The cases of three African capital cities.

    Science.gov (United States)

    McPake, Barbara; Russo, Giuliano; Tseng, Fu-Min

    2014-12-01

    Health professionals dual practice has received increasing attention, particularly in the context of the universal health coverage movement. This paper explores the determinants of doctors' choices to become a dual practitioner and of dual practitioners' choices to allocate time to the private sector in the capital cities of Mozambique, Guinea Bissau and Cape Verde. The data are drawn from a survey conducted in 2012 among 329 physicians. We use a two-part model to analyse the decision of both public and private practitioners to become dual practitioners, and to allocate time between public and private sectors. We impute potential earnings in public and private practice by using nearest-neighbour propensity score matching. Our results show that hourly wage in the private sector, number of dependents, length of time as a physician, work outside city, and being a specialist with or without technology all have a positive association with the probability of being a dual physician, while number of dependents displays a negative sign. Level of salaries in the public sector are not associated with dual practice engagement, with important implications for attempts aimed at retaining professionals in the public sector through wage increases. As predicted by theory that recognises doctors' role in price setting, earnings rates are not significant predictors of private sector time allocation; personal characteristics of physicians appear more important, such as age, number of dependents, specialist without technology, specialist with technology, and three reasons for not working more hours in the private sector. Answers to questions about the factors that limit working hours in the private sector have significant predictive power, suggesting that type of employment in the private sector may be an underlying determinant of both dual practice engagement and time allocation decisions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Global power production scenarios to 2100 and the dual role of forests: accelerated climate damage or regulating and provisioning ecosystem services?

    DEFF Research Database (Denmark)

    Callesen, Ingeborg

    The worlds' electrical power production is depending on the current energy infrastructure, and future investments in new power supply facilities using renewable and non-renewable energy sources. Continued growth in power production in the 21st century will cause global environmental change (GEC......). GEC with climate change as an important driver will affect the environment and the economy in multiple ways that can be summarized as losses of biodiversity and changing ecosystem services (ES), but with very diverse temporal and spatial impacts. In a simple global growth model for power production......, including non-renewable and renewable energy sources, the potential role of forest biomass is investigated. The demands for forest ecosystem services imposed by the global power production are assessed in the present study. Three global power supply scenarios to 2050 with different emphasis...

  3. Presence of Ca2+-dependent K+ channels in chemosensory cilia support a role in odor transduction.

    Science.gov (United States)

    Delgado, Ricardo; Saavedra, M Veronica; Schmachtenberg, Oliver; Sierralta, Jimena; Bacigalupo, Juan

    2003-09-01

    Olfactory receptor neurons (ORNs) respond to odorants with changes in the action potential firing rate. Excitatory responses, consisting of firing increases, are mediated by a cyclic AMP cascade that leads to the activation of cationic nonselective cyclic nucleotide-gated (CNG) channels and Ca2+-dependent Cl- (ClCa) channels. This process takes place in the olfactory cilia, where all protein components of this cascade are confined. ORNs from various vertebrate species have also been shown to generate inhibitory odor responses, expressed as decreases in action potential discharges. Odor inhibition appears to rely on Ca2+-dependent K+ (KCa) channels, but the underlying transduction mechanism remains unknown. If these channels are involved in odor transduction, they are expected to be present in the olfactory cilia. We found that a specific antibody against a large conductance KCa recognized a protein of approximately 116 kDa in Western blots of purified rat olfactory ciliary membranes. Moreover, the antibody labeled ORN cilia in isolated ORNs from rat and toad (Caudiverbera caudiverbera). In addition, single-channel recordings from inside-out membrane patches excised from toad chemosensory cilia showed the presence of 4 different types of KCa channels, with unitary conductances of 210, 60, 12, and 29 and 60 pS, high K+-selectivity, and Ca2+ sensitivities in the low micromolar range. Our work demonstrates the presence of K+ channels in the ORN cilia and supports their participation in odor transduction.

  4. Alignment dependence in above-threshold ionization of H2+: role of intermediate resonances

    DEFF Research Database (Denmark)

    Hernández, Jorge Fernández; Madsen, Lars Bojer

    2009-01-01

    We report a 3D ab initio investigation of the dependence of above-threshold ionization of the H2+ molecule on the orientation of a linearly polarized intense femtosecond laser pulse with respect to the molecular axis. The calculations were performed in the frozen nuclei approximation for the 2Σ+g(1......sσg) ground and the 2Σ+u(2pσu) first excited electronic states, in laser pulses of seven optical cycles (19 fs) with a wavelength of 800 nm and for different intensities. The numerical procedure combines two different techniques, a grid-based split-step method to propagate the wave packet during...... the pulse, and a bound and scattering states B-spline basis set calculation to extract the information from the former. We show that the orientation dependence of the above-threshold ionization spectra is very sensitive to the intensity of the field and to the final electron energy. For some intensities...

  5. Critical role of SAP in progression and reactivation but not maintenance of T cell-dependent humoral immunity.

    Science.gov (United States)

    Zhong, Ming-Chao; Veillette, André

    2013-03-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. SAP plays a critical role in the initiation of T cell-dependent B cell responses leading to germinal center reaction, the production of high-affinity antibodies, and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. It is important to address this matter not only for mechanistic reasons but also because blockade of the SAP pathway is being contemplated as a means to treat autoimmune diseases in humans. Using an inducibly SAP deficient mouse, we found that SAP was required not only for the initiation but also for the progression of primary T cell-driven B cell responses to haptens. It was also necessary for the reactivation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of the lineage commitment factor Bcl-6 in follicular T helper (T(FH)) cells. However, once memory B cells and long-lived antibody-secreting cells were established, SAP became dispensable for maintaining T cell-dependent B cell responses. Thus, SAP is pivotal for nearly all phases, but not for maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for the treatment of immune disorders by targeting the SAP pathway.

  6. The Crystal Structure of the RNA-Dependent RNA Polymerase from Human Rhinovirus: A Dual Function Target for Common Cold Antiviral Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Love, Robert A.; Maegley, Karen A.; Yu, Xiu; Ferre, RoseAnn; Lingardo, Laura K.; Diehl, Wade; Parge, Hans E.; Dragovich, Peter S.; Fuhrman, Shella A. (Pfizer)

    2010-11-16

    Human rhinoviruses (HRV), the predominant members of the Picornaviridae family of positive-strand RNA viruses, are the major causative agents of the common cold. Given the lack of effective treatments for rhinoviral infections, virally encoded proteins have become attractive therapeutic targets. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) denoted 3D{sup pol}, which is responsible for replicating the viral genome and for synthesizing a protein primer used in the replication. Here the crystal structures for three viral serotypes (1B, 14, and 16) of HRV 3D{sup pol} have been determined. The three structures are very similar to one another, and to the closely related poliovirus (PV) 3D{sup pol} enzyme. Because the reported PV crystal structure shows significant disorder, HRV 3D{sup pol} provides the first complete view of a picornaviral RdRp. The folding topology of HRV 3D{sup pol} also resembles that of RdRps from hepatitis C virus (HCV) and rabbit hemorrhagic disease virus (RHDV) despite very low sequence homology.

  7. Conformational dynamics and role of the acidic pocket in ASIC pH-dependent gating.

    Science.gov (United States)

    Vullo, Sabrina; Bonifacio, Gaetano; Roy, Sophie; Johner, Niklaus; Bernèche, Simon; Kellenberger, Stephan

    2017-04-04

    Acid-sensing ion channels (ASICs) are proton-activated Na + channels expressed in the nervous system, where they are involved in learning, fear behaviors, neurodegeneration, and pain sensation. In this work, we study the role in pH sensing of two regions of the ectodomain enriched in acidic residues: the acidic pocket, which faces the outside of the protein and is the binding site of several animal toxins, and the palm, a central channel domain. Using voltage clamp fluorometry, we find that the acidic pocket undergoes conformational changes during both activation and desensitization. Concurrently, we find that, although proton sensing in the acidic pocket is not required for channel function, it does contribute to both activation and desensitization. Furthermore, protonation-mimicking mutations of acidic residues in the palm induce a dramatic acceleration of desensitization followed by the appearance of a sustained current. In summary, this work describes the roles of potential pH sensors in two extracellular domains, and it proposes a model of acidification-induced conformational changes occurring in the acidic pocket of ASIC1a.

  8. The mediating role of self-criticism and dependency in the association between perceptions of maternal caring and depressive symptoms.

    Science.gov (United States)

    Campos, Rui C; Besser, Avi; Blatt, Sidney J

    2010-12-01

    This study examined a theoretically based mediation model including participants' perceptions of early relationships with their mother, self-criticism, dependency, and current depressive symptoms. We expect that (a) early relationships characterized by low levels of care and high levels of overprotection will be positively associated with both current depressive state and self-criticism and dependency; (b) high levels of self-criticism and dependency will be positively associated with depressive symptoms; and (c) self-criticism and dependency will play a mediating role in the association between participants' perceptions of early relationships characterized by low levels of care and high levels of overprotection and their current depressive symptoms. A nonclinical community sample of 200 Portuguese adults participated in the study. Perceptions of early relationships were measured using the mother scales of the Parental Bonding Instrument (Parker et al. [1979: Br J Med Psychol 52:1-10]), levels of self-criticism and dependency were measured using the Depressive Experiences Questionnaire (Blatt et al. [1976: J Abn Psy 6:383-389]), and depressive symptoms were measured using the Center for the Epidemiological Studies of Depression Scale (Radloff [1977: Appl Psychol Meas 1:385-401]. Structural equation modeling showed that the link between participants' perceptions of early caretaking relationships with their mothers and their current depressive symptoms is mediated by high levels of self-criticism--a personality trait associated with vulnerability to depression--but not Dependency. However, an ancillary analysis indicated that the link between participants' perceptions of early maternal overprotective relationships and their current depressive symptoms is mediated by high levels of Neediness. Findings underscore the role of perceived early relationships in psychological vulnerability to depression among highly self-critical and among highly needy individuals and

  9. Mechanisms governing the reactivation-dependent destabilization of memories and their role in extinction

    Directory of Open Access Journals (Sweden)

    Charlotte Rachael Flavell

    2013-12-01

    Full Text Available The extinction of learned associations has traditionally been considered to involve new learning, which competes with the original memory for control over behaviour. However, a recent resurgence of interest in reactivation-dependent amnesia has revealed that the retrieval of fear-related memory (with what is essentially a brief extinction session can result in it’s destabilization. This review discusses some of the cellular and molecular mechanisms that are involved in the destabilization of a memory following it’s reactivation and/or extinction, and investigates the evidence that extinction may involve both new learning as well as a partial destabilization-induced erasure of the original memory trace.

  10. Context-dependent effect of mood: the regulatory role of personality

    Directory of Open Access Journals (Sweden)

    Zajusz-Gawędzka Dominika

    2015-03-01

    Full Text Available This study explored the influence of the context-dependent effect of mood as well as individual differences in neuroticism and action vs. state/volatility orientation on predecisional processing in a multiattribute choice task. One hundred and twenty participants acquired information about choice options after filling out personality questionnaires. Results showed that participants in a positive mood processed the information longer in enjoy than in done-enough context. In turn, participants in a negative mood processed the information more selectively in enjoy than in done-enough context. It also appeared that this effect is reinforced for participants with low neuroticism and volatility orientation, while it is weakened for those with low neuroticism and action orientation. Results were interpreted in accordance with the differential-processual approach.

  11. Going beyond "it depends:" the role of context in shaping participation in natural resource management

    Directory of Open Access Journals (Sweden)

    Susan Baker

    2018-03-01

    Full Text Available Public participation is increasingly advocated in natural resource management to meet a spectrum of instrumental to normative goals. However, the success of participation in achieving these goals is highly variable, depending on both societal and institutional contexts. Whether participation realises its benefits or succumbs to its pitfalls is shaped by dynamic interactions operating among three contextual dimensions: participatory rationales (instrumental to normative, institutional fit of different levels (types of participation (information delivery to partnership to delegation, and social structures (such as cultural context, social capital, and power distribution. Some levels of participation may support the existing power hierarchy, others benefit organized stakeholder groups and special interests, and still others foster deliberative democratic outcomes. We argue that wise choice of levels of participation in particular contexts shapes the balance of participation's benefits and pitfalls.

  12. CYBER ADDICTION: THE ROLE OF EMOTIONS IN DEPENDENCE ON DIGITAL TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    Jefferson Cabral Azevedo

    2014-12-01

    Full Text Available This research apply concepts from different areas, aiming to provide a multicausal and dialogical perspective on the nosologic process of dependence upon digital technologies and the influences of motivational and emotional mechanisms on learning compulsive behaviors. The data is approached both qualitatively and quantitatively, since its analysis covers the conceptual factors obtained from literature review and the development of statistical results obtained from the questionnaires applied. This brief theoretical research pursues to reveal pathological behaviors in the use of digital technologies, especially in the actions of internet users in online social networks. The parameters of neuropsychology, psychology, psychiatry are combined with descriptions contained in the DSM V, Diagnostic and Statistical Manual of Mental Disorders, and the ICD 10, International Compendium of Diseases.

  13. Context-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation.

    Science.gov (United States)

    Miller, Yury I; Shyy, John Y-J

    2017-02-01

    Oxidized low-density lipoprotein (OxLDL), which contains hundreds of different oxidized lipid molecules, is a hallmark of hyperlipidemia and atherosclerosis. The same oxidized lipids found in OxLDL are also formed in apoptotic cells, and are present in tissues as well as in the circulation under pathological conditions. In many disease contexts, oxidized lipids constitute damage signals, or patterns, that activate pattern-recognition receptors (PRRs) and significantly contribute to inflammation. Here, we review recent discoveries and emerging trends in the field of oxidized lipids and the regulation of inflammation, focusing on oxidation products of polyunsaturated fatty acids esterified into cholesteryl esters (CEs) and phospholipids (PLs). We also highlight context-dependent activation and biased agonism of Toll-like receptor-4 (TLR4) and the NLRP3 inflammasome, among other signaling pathways activated by oxidized lipids. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Cell context-dependent dual effects of EFEMP1 stabilizes subpopulation equilibrium in responding to changes of in vivo growth environment.

    Science.gov (United States)

    Hu, Yuanjie; Ke, Chao; Ru, Ning; Chen, Yumay; Yu, Liping; Siegel, Eric R; Linskey, Mark E; Wang, Ping; Zhou, Yi-Hong

    2015-10-13

    Conflicting functions of EFEMP1 in cancer have been reported. Using two syngeneic glioma cell lines (U251 and U251-NS) carrying two different principal cell subpopulations that express high or low EGFR, and that are able to interconvert via mis-segregation of chromosome 7 (Chr7), we studied EFEMP1's cell-context-dependent functions in regulating subpopulation equilibrium, here defined by the percentage of cells carrying different copies of Chr7. We found that EFEMP1 attenuated levels of EGFR and cellular respiration in high-EGFR-expressing cells, but increased levels of NOTCH1, MMP2, cell invasiveness, and both oxidative phosphorylation and glycolytic respiration in low-EGFR-expressing cells. Consistently, EFEMP1 suppressed intracranial xenograft formation in U251 and promoted its formation in U251-NS. Interestingly, subpopulation equilibria in xenografts of U251-NS without EFEMP1 overexpression were responsive to inoculum size (1, 10 and 100 thousand cells), which may change the tumor-onset environment. It was not observed in xenografts of U251-NS with EFEMP1 overexpression. The anti-EGFR function of EFEMP1 suppressed acceleration of growth of U251-NS, but not the subpopulation equilibrium, when serially passed under a different (serum-containing adherent) culture condition. Overall, the data suggest that the orthotopic environment of the brain tumor supports EFEMP1 in carrying out both its anti-EGFR and pro-invasive/cancer stem cell-transforming functions in the two glioma cell subpopulations during formation of a single tumor, where EFEMP1 stabilizes the subpopulation equilibrium in response to alterations of the growth environment. This finding implies that EFEMP1 may restrain cancer plasticity in coping with ever-changing tumor microenvironments and/or therapeutic-intervention stresses.

  15. Recovery of rhythmic activity in a central pattern generator: analysis of the role of neuromodulator and activity-dependent mechanisms.

    Science.gov (United States)

    Zhang, Yili; Golowasch, Jorge

    2011-11-01

    The pyloric network of decapods crustaceans can undergo dramatic rhythmic activity changes. Under normal conditions the network generates low frequency rhythmic activity that depends obligatorily on the presence of neuromodulatory input from the central nervous system. When this input is removed (decentralization) the rhythmic activity ceases. In the continued absence of this input, periodic activity resumes after a few hours in the form of episodic bursting across the entire network that later turns into stable rhythmic activity that is nearly indistinguishable from control (recovery). It has been proposed that an activity-dependent modification of ionic conductance levels in the pyloric pacemaker neuron drives the process of recovery of activity. Previous modeling attempts have captured some aspects of the temporal changes observed experimentally, but key features could not be reproduced. Here we examined a model in which slow activity-dependent regulation of ionic conductances and slower neuromodulator-dependent regulation of intracellular Ca(2+) concentration reproduce all the temporal features of this recovery. Key aspects of these two regulatory mechanisms are their independence and their different kinetics. We also examined the role of variability (noise) in the activity-dependent regulation pathway and observe that it can help to reduce unrealistic constraints that were otherwise required on the neuromodulator-dependent pathway. We conclude that small variations in intracellular Ca(2+) concentration, a Ca(2+) uptake regulation mechanism that is directly targeted by neuromodulator-activated signaling pathways, and variability in the Ca(2+) concentration sensing signaling pathway can account for the observed changes in neuronal activity. Our conclusions are all amenable to experimental analysis.

  16. The role of study and work in cannabis use and dependence trajectories among young adult frequent cannabis users

    Directory of Open Access Journals (Sweden)

    Nienke eLiebregts

    2013-08-01

    Full Text Available Life course theory considers events in study and work as potential turning points in deviance, including illicit drug use. This qualitative study explores the role of occupational life in cannabis use and dependence in young adults. Two and three years after the initial structured interview, 47 at baseline frequent cannabis users were interviewed in-depth about the dynamics underlying changes in their cannabis use and dependence. Overall, cannabis use and dependence declined, including interviewees who quit using cannabis completely, in particular with students, both during their study and after they got employed. Life course theory appeared to be a useful framework to explore how and why occupational life is related to cannabis use and dependence over time. Our study showed that life events in this realm are rather common in young adults and can have a strong impact on cannabis use. While sometimes changes in use are temporary, turning points can evolve from changes in educational and employment situations; an effect that seems to be related to the consequences of these changes in terms of amount of leisure time and agency (i.e. feelings of being in control.

  17. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.

    Science.gov (United States)

    Cavuoto, Paul; Fenech, Michael F

    2012-10-01

    Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. The role of hypertension in the development of nephropathy in type 1 (insulin-dependent) diabetes mellitus

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Nørgaard, K; Jensen, T

    1990-01-01

    Which comes first when developing clinical diabetic nephropathy, the blood pressure rise or the increasing urinary albumin excretion? This issue is discussed based on recent literature of studies in humans with Type 1 (insulin-dependent) diabetes mellitus. We conclude that hypertension has...... a central role in the progression of diabetic nephropathy and has deleterious effects on the life expectancy of patients who already have signs of diabetic renal disease in terms of elevated urinary albumin excretion. However, blood pressure is preceded by small increments of urinary albumin excretion rates......, an indicator of universally increased vascular leakiness, and thus does not seem to be the cause of diabetic nephropathy....

  19. The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex.

    Science.gov (United States)

    Pulimood, Nisha S; Rodrigues, Wandilson Dos Santos; Atkinson, Devon A; Mooney, Sandra M; Medina, Alexandre E

    2017-07-12

    The transcription factors CREB (cAMP response element binding factor), SRF (serum response factor), and MEF2 (myocyte enhancer factor 2) play critical roles in the mechanisms underlying neuronal plasticity. However, the role of the activation of these transcription factors in the different components of plasticity in vivo is not well known. In this study, we tested the role of CREB, SRF, and MEF2 in ocular dominance plasticity (ODP), a paradigm of activity-dependent neuronal plasticity in the visual cortex. These three proteins bind to the synaptic activity response element (SARE), an enhancer sequence found upstream of many plasticity-related genes (Kawashima et al., 2009; Rodríguez-Tornos et al., 2013), and can act cooperatively to express Arc , a gene required for ODP (McCurry et al., 2010). We used viral-mediated gene transfer to block the transcription function of CREB, SRF, and MEF2 in the visual cortex, and measured visually evoked potentials in awake male and female mice before and after a 7 d monocular deprivation, which allowed us to examine both the depression component (Dc-ODP) and potentiation component (Pc-ODP) of plasticity independently. We found that CREB, SRF, and MEF2 are all required for ODP, but have differential effects on Dc-ODP and Pc-ODP. CREB is necessary for both Dc-ODP and Pc-ODP, whereas SRF and MEF2 are only needed for Dc-ODP. This finding supports previous reports implicating SRF and MEF2 in long-term depression (required for Dc-ODP), and CREB in long-term potentiation (required for Pc-ODP). SIGNIFICANCE STATEMENT Activity-dependent neuronal plasticity is the cellular basis for learning and memory, and it is crucial for the refinement of neuronal circuits during development. Identifying the mechanisms of activity-dependent neuronal plasticity is crucial to finding therapeutic interventions in the myriad of disorders where it is disrupted, such as Fragile X syndrome, Rett syndrome, epilepsy, major depressive disorder, and autism

  20. Barriers to community-based drug dependence treatment: implications for police roles, collaborations and performance indicators

    Science.gov (United States)

    Ma, Yi; Du, Chunhua; Cai, Thomas; Han, Qingfeng; Yuan, Huanhuan; Luo, Tingyan; Ren, Guoliang; Mburu, Gitau; Wang, Bangyuan; Golichenko, Olga; Zhang, Chaoxiong

    2016-01-01

    Introduction Worldwide, people who use drugs (PWUD) are among the populations at highest risk for HIV infection. In China, PWUD are primarily sentenced to compulsory detainment centres, in which access to healthcare, including HIV treatment and prevention services, is limited or non-existent. In 2008, China's 2008 Anti-Drug Law encouraged the development and use of community-based drug dependence rehabilitation, yet there is limited evidence evaluating the efficacy and challenges of this model in China. In this study, we explore these challenges and describe how cooperation between law enforcement and health departments can meet the needs of PWUD. Methods In 2015, we conducted semi-structured, in-depth interviews with all four staff members and 16 clients of the Ping An Centre No. 1 for community-based drug treatment, three local police officers and three officials from the local Centre for Disease Control. Interviews explored obstacles in implementing community-based drug dependence treatment and efforts to resolve these difficulties. Transcripts were coded and analyzed with qualitative data analysis software (MAXQDA 11). Results We identified three challenges to community-based drug treatment at the Ping An Centre No. 1: (1) suboptimal coordination among parties involved, (2) a divergence in attitudes towards PWUD and harm reduction between law enforcement and health officials and (3) conflicting performance targets for police and health officials that undermine the shared goal of treatment. We also identified the take-home methadone maintenance treatment model at the Ping An Centre No. 1 as an example of an early successful collaboration between the police, the health department and PWUD. Conclusions To overcome barriers to effective community-based drug treatment, we recommend aligning the goals of law enforcement and public health agencies towards health-based performance indicators. Furthermore, tensions between PWUD and police need to be addressed and trust

  1. Haptic subjective vertical shows context dependence: task and vision play a role during dynamic tilt stimulation.

    Science.gov (United States)

    Wright, William Geoffrey; Glasauer, Stefan

    2003-10-01

    Perceiving one's vertical is an integral part of efficiently functioning in an environment physically polarized along that dimension. How one determines the direction of gravity is not a task left only to inertial sensors, such as the vestibular organs, rather as numerous studies have shown, this task is influenced visually and somatosensorily. In addition, there is evidence that higher order cognitive effects such as expectancies and context are critical in perception of the vertical. One's ability to integrate these various inputs during normal activity is not generally questioned, one's doubts being satisfied by observing a waiter navigating a crowded restaurant with a tray balanced on one hand, neither tripping or dropping an entree. But how these various sources are integrated is still debated. Most research focuses on subjective vertical perception used visual matching/alignment tasks, verbal reports, or saccadic eye movements as a dependent measure. Although a motor task involving a joystick or indicator to be aligned with gravity without visual feedback is used much less frequently, there is good evidence that individuals easily orient limbs to an external gravity-aligned coordinate axis while being statically tilted. By exposure to a dynamic situation, the central nervous system should be no more challenged by the task of determining the subjective vertical than during static conditions, because our spatial orientation systems were likely selected for just that. In addition, the sensitive calibration between visual and other sensory input also must have been key to its selection. This sensory interaction can be tested by changing the relation between the various sources. With the advent of virtual reality technology, a complex and "natural" visual stimulus is achievable and is easily manipulable. How one tests perception of verticality is also a pertinent question when researching spatial orientation systems. The system's performance may be better

  2. Subcellular distribution of cyclin-dependent kinase-like 5 (CDKL5) is regulated through phosphorylation by dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A).

    Science.gov (United States)

    Oi, Ami; Katayama, Syouichi; Hatano, Naoya; Sugiyama, Yasunori; Kameshita, Isamu; Sueyoshi, Noriyuki

    2017-01-08

    Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase primarily expressed in the central nervous system and is known to cause X-linked neurodevelopmental disorders such as Rett syndrome. However, the mechanisms regulating CDKL5 have not yet been fully clarified. Therefore, in this study, we investigated the protein kinase that directly phosphorylates CDKL5, identifying it as dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), an enzyme binding to and phosphorylating CDKL5. We showed that subcellular distribution of CDKL5 was regulated by its phosphorylation by DYRK1A. In mouse neuroblastoma Neuro2a cells, CDKL5 was localized in both the cytosol and nucleus, whereas DYRK1A showed a typical nuclear localization. When CDKL5 and DYRK1A were co-expressed, the cytosolic localization of CDKL5 was significantly increased. Results of site-directed mutagenesis revealed that the phosphorylation site was Ser-308, in the vicinity of the nuclear localization signal. A mutation mimicking the phosphorylated serine residue by aspartate substitution (S308D) changed CDKL5 localization to the cytosol, whereas the corresponding alanine-substituted analog, CDKL5(S308A), was primarily localized to the nucleus. Taken together, these results strongly suggested that DYRK1A bound to CDKL5 and phosphorylated it on Ser-308, thus interfering with its nuclear localization. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Virtual Monoenergetic Images From a Novel Dual-Layer Spectral Detector Computed Tomography Scanner in Portal Venous Phase: Adjusted Window Settings Depending on Assessment Focus Are Essential for Image Interpretation.

    Science.gov (United States)

    Hickethier, Tilman; Iuga, Andra-Iza; Lennartz, Simon; Hauger, Myriam; Byrtus, Jonathan; Luetkens, Julian A; Haneder, Stefan; Maintz, David; Doerner, Jonas

    We aimed to determine optimal window settings for conventional polyenergetic (PolyE) and virtual monoenergetic images (MonoE) derived from abdominal portal venous phase computed tomography (CT) examinations on a novel dual-layer spectral-detector CT (SDCT). From 50 patients, SDCT data sets MonoE at 40 kiloelectron volt as well as PolyE were reconstructed and best individual window width and level values manually were assessed separately for evaluation of abdominal arteries as well as for liver lesions. Via regression analysis, optimized individual values were mathematically calculated. Subjective image quality parameters, vessel, and liver lesion diameters were measured to determine influences of different W/L settings. Attenuation and contrast-to-noise values were significantly higher in MonoE compared with PolyE. Compared with standard settings, almost all adjusted W/L settings varied significantly and yielded higher subjective scoring. No differences were found between manually adjusted and mathematically calculated W/L settings. PolyE and MonoE from abdominal portal venous phase SDCT examinations require appropriate W/L settings depending on reconstruction technique and assessment focus.

  4. Role of Prion Replication in the Strain-dependent Brain Regional Distribution of Prions.

    Science.gov (United States)

    Hu, Ping Ping; Morales, Rodrigo; Duran-Aniotz, Claudia; Moreno-Gonzalez, Ines; Khan, Uffaf; Soto, Claudio

    2016-06-10

    One intriguing feature of prion diseases is their strain variation. Prion strains are differentiated by the clinical consequences they generate in the host, their biochemical properties, and their potential to infect other animal species. The selective targeting of these agents to specific brain structures have been extensively used to characterize prion strains. However, the molecular basis dictating strain-specific neurotropism are still elusive. In this study, isolated brain structures from animals infected with four hamster prion strains (HY, DY, 139H, and SSLOW) were analyzed for their content of protease-resistant PrP(Sc) Our data show that these strains have different profiles of PrP deposition along the brain. These patterns of accumulation, which were independent of regional PrP(C) production, were not reproduced by in vitro replication when different brain regions were used as substrate for the misfolding-amplification reaction. On the contrary, our results show that in vitro replication efficiency depended exclusively on the amount of PrP(C) present in each part of the brain. Our results suggest that the variable regional distribution of PrP(Sc) in distinct strains is not determined by differences on prion formation, but on other factors or cellular pathways. Our findings may contribute to understand the molecular mechanisms of prion pathogenesis and strain diversity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Role of codeposited impurities during growth. II. Dependence of morphology on binding and barrier energies

    Science.gov (United States)

    Sathiyanarayanan, Rajesh; Hamouda, Ajmi Bh.; Pimpinelli, A.; Einstein, T. L.

    2011-01-01

    In an accompanying article we showed that surface morphologies obtained through codeposition of a small quantity (2%) of impurities with Cu during growth (step-flow mode, θ = 40 ML) significantly depends on the lateral nearest-neighbor binding energy (ENN) to Cu adatom and the diffusion barrier (Ed) of the impurity atom on Cu(0 0 1). Based on these two energy parameters, ENN and Ed, we classify impurity atoms into four sets. We study island nucleation and growth in the presence of codeposited impurities from different sets in the submonolayer (θ⩽ 0.7 ML) regime. Similar to growth in the step-flow mode, we find different nucleation and growth behavior for impurities from different sets. We characterize these differences through variations of the number of islands (Ni) and the average island size with coverage (θ). Further, we compute the critical nucleus size (i) for all of these cases from the distribution of capture-zone areas using the generalized Wigner distribution.

  6. Respiration-dependent utilization of sugars in yeasts: a determinant role for sugar transporters.

    Science.gov (United States)

    Goffrini, Paola; Ferrero, Iliana; Donnini, Claudia

    2002-01-01

    In many yeast species, including Kluyveromyces lactis, growth on certain sugars (such as galactose, raffinose, and maltose) occurs only under respiratory conditions. If respiration is blocked by inhibitors, mutation, or anaerobiosis, growth does not take place. This apparent dependence on respiration for the utilization of certain sugars has often been suspected to be associated with the mechanism of the sugar uptake step. We hypothesized that in many yeast species, the permease activities for these sugars are not sufficient to ensure the high substrate flow that is necessary for fermentative growth. By introducing additional sugar permease genes, we have obtained K. lactis strains that were capable of growing on galactose and raffinose in the absence of respiration. High dosages of both the permease and maltase genes were indeed necessary for K. lactis cells to grow on maltose in the absence of respiration. These results strongly suggest that the sugar uptake step is the major bottleneck in the fermentative assimilation of certain sugars in K. lactis and probably in many other yeasts.

  7. Neurocognitive Mechanisms of Prejudice Formation: The Role of Time-Dependent Memory Consolidation.

    Science.gov (United States)

    Enge, Luke R; Lupo, Amber K; Zárate, Michael A

    2015-07-01

    Prejudice is generally thought to derive from learned, emotion-laden experiences. The mechanisms underlying the formation of prejudice over time, however, remain unknown. In the present research, we proposed and tested hypotheses regarding prejudice formation derived from research on memory consolidation and social perception. We hypothesized that time-dependent memory consolidation would produce better implicit memory for negative out-group information and positive in-group information, compared with negative in-group information and positive out-group information. Fifty undergraduates learned positive and negative information about racial in-group (Latino) and out-group (African American) targets. Participants returned after both a short time delay (2-6 hr after the learning session) and a long time delay (48 hr after the learning session) to complete a lexical decision task. Results demonstrated that participants responded to information consistent with an in-group bias faster after a long time delay than after a short time delay. Our findings have important implications for the study of social perception and memory consolidation. © The Author(s) 2015.

  8. Cell-cycle-dependent regulation of cell motility and determination of the role of Rac1

    DEFF Research Database (Denmark)

    Walmod, Peter S.; Hartmann-Petersen, Rasmus; Prag, S.

    2004-01-01

    comparable to those of control cells in G1. In contrast, transfection with dominant-negative Rac1 reduced cell speed and resulted in cellular displacements, which were identical in G1 and G2. These observations indicate that migration of cultured cells is regulated in a cell-cycle-dependent manner...... for calculation of three key parameters describing cell motility: speed, persistence time and rate of diffusion. All investigated cell lines demonstrated a lower cell displacement in the G2 phase than in the G1/S phases. This was caused by a decrease in speed and/or persistence time. The decrease in motility...... was accompanied by changes in morphology reflecting the larger volume of cells in G2 than in G1. Furthermore, L-cells and HeLa-cells appeared to be less adherent in the G2 phase. Transfection of L-cells with constitutively active Rac1 led to a general increase in the speed and rate of diffusion in G2 to levels...

  9. Assessment Role of Participation in Narcotic Anonymous in Opiate Dependents during Abstinence

    Directory of Open Access Journals (Sweden)

    Hossien Zare

    2012-09-01

    Full Text Available Background: The activity level of Narcotics Anonymous group (NA is expanding in many countries, including Iran. Some research has confessed the benefits of 12-step NA approach compared with similar methods. In the present study, the role of regular participation of opioid addicts in the NA group was studied in terms of abstinence rate and compared with routine program of detoxification centers of the person Welfare Organization and Medical Sciences University. Materials and Methods: All addicts who attempted to quit in self-introducer clinical centers of Medical Sciences University and the Welfare Organization of Rafsanjan were suggested to participate and not to participate in NA, based on even and odd numbers, respectively. Among them, two equal 120-person (NA and control groups were selected, then evaluated every three months and followed up for 12 months. Their status was assessed through questionnaires, interviews, and morphine tests.Results: The purity rate of NA group with 8.49 months was significantly different with normal addicts in 5.19 months (p=0.001. The recurrence rate at 12 months was significantly lower in the NA group compared with the control group, calculated through independent t-test (p=0.001. Quitting history and addiction duration in the NA group was significantly higher than control group.Conclusion: The findings of the research support a better prognosis for participants of NA group. Further researches are recommended to provide useful clinical information for patients and professionals.

  10. Role of excited state solvent fluctuations on time-dependent fluorescence Stokes shift

    Energy Technology Data Exchange (ETDEWEB)

    Li, Tanping, E-mail: tanping@lsu.edu, E-mail: revatik@lsu.edu; Kumar, Revati, E-mail: tanping@lsu.edu, E-mail: revatik@lsu.edu [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States)

    2015-11-07

    We explore the connection between the solvation dynamics of a chromophore upon photon excitation and equilibrium fluctuations of the solvent. Using molecular dynamics simulations, fluorescence Stokes shift for the tryptophan in Staphylococcus nuclease was examined using both nonequilibrium calculations and linear response theory. When the perturbed and unperturbed surfaces exhibit different solvent equilibrium fluctuations, the linear response approach on the former surface shows agreement with the nonequilibrium process. This agreement is excellent when the perturbed surface exhibits Gaussian statistics and qualitative in the case of an isomerization induced non-Gaussian statistics. However, the linear response theory on the unperturbed surface breaks down even in the presence of Gaussian fluctuations. Experiments also provide evidence of the connection between the excited state solvent fluctuations and the total fluorescence shift. These observations indicate that the equilibrium statistics on the excited state surface characterize the relaxation dynamics of the fluorescence Stokes shift. Our studies specifically analyze the Gaussian fluctuations of the solvent in the complex protein environment and further confirm the role of solvent fluctuations on the excited state surface. The results are consistent with previous investigations, found in the literature, of solutes dissolved in liquids.

  11. An integrin-dependent role of pouch endoderm in hyoid cartilage development.

    Directory of Open Access Journals (Sweden)

    Justin Gage Crump

    2004-09-01

    Full Text Available Pharyngeal endoderm is essential for and can reprogram development of the head skeleton. Here we investigate the roles of specific endodermal structures in regulating craniofacial development. We have isolated an integrinalpha5 mutant in zebrafish that has region-specific losses of facial cartilages derived from hyoid neural crest cells. In addition, the cranial muscles that normally attach to the affected cartilage region and their associated nerve are secondarily reduced in integrinalpha5- animals. Earlier in development, integrinalpha5 mutants also have specific defects in the formation of the first pouch, an outpocketing of the pharyngeal endoderm. By fate mapping, we show that the cartilage regions that are lost in integrinalpha5 mutants develop from neural crest cells directly adjacent to the first pouch in wild-type animals. Furthermore, we demonstrate that Integrinalpha5 functions in the endoderm to control pouch formation and cartilage development. Time-lapse recordings suggest that the first pouch promotes region-specific cartilage development by regulating the local compaction and survival of skeletogenic neural crest cells. Thus, our results reveal a hierarchy of tissue interactions, at the top of which is the first endodermal pouch, which locally coordinates the development of multiple tissues in a specific region of the vertebrate face. Lastly, we discuss the implications of a mosaic assembly of the facial skeleton for the evolution of ray-finned fish.

  12. Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally Dependent Memory.

    Science.gov (United States)

    Pearson-Leary, Jiah; McNay, Ewan C

    2016-11-23

    The insulin-regulated glucose transporter-4 (GluT4) is critical for insulin- and contractile-mediated glucose uptake in skeletal muscle. GluT4 is also expressed in some hippocampal neurons, but its functional role in the brain is unclear. Several established molecular modulators of memory processing regulate hippocampal GluT4 trafficking and hippocampal memory formation is limited by both glucose metabolism and insulin signaling. Therefore, we hypothesized that hippocampal GluT4 might be involved in memory processes. Here, we show that, in male rats, hippocampal GluT4 translocates to the plasma membrane after memory training and that acute, selective intrahippocampal inhibition of GluT4-mediated glucose transport impaired memory acquisition, but not memory retrieval. Other studies have shown that prolonged systemic GluT4 blockade causes insulin resistance. Unexpectedly, we found that prolonged hippocampal blockade of glucose transport through GluT4-upregulated markers of hippocampal insulin signaling prevented task-associated depletion of hippocampal glucose and enhanced both working and short-term memory while also impairing long-term memory. These effects were accompanied by increased expression of hippocampal AMPA GluR1 subunits and the neuronal GluT3, but decreased expression of hippocampal brain-derived neurotrophic factor, consistent with impaired ability to form long-term memories. Our findings are the first to show the cognitive impact of brain GluT4 modulation. They identify GluT4 as a key regulator of hippocampal memory processing and also suggest differential regulation of GluT4 in the hippocampus from that in peripheral tissues. The role of insulin-regulated glucose transporter-4 (GluT4) in the brain is unclear. In the current study, we demonstrate that GluT4 is a critical component of hippocampal memory processes. Memory training increased hippocampal GluT4 translocation and memory acquisition was impaired by GluT4 blockade. Unexpectedly, whereas long

  13. The Role of Aquaporins in pH-Dependent Germination of Rhizopus delemar Spores.

    Directory of Open Access Journals (Sweden)

    Tidhar Turgeman

    Full Text Available Rhizopus delemar and associated species attack a wide range of fruit and vegetables after harvest. Host nutrients and acidic pH are required for optimal germination of R. delemar, and we studied how this process is triggered. Glucose induced spore swelling in an acidic environment, expressed by an up to 3-fold increase in spore diameter, whereas spore diameter was smaller in a neutral environment. When suspended in an acidic environment, the spores started to float, indicating a change in their density. Treatment of the spores with HgCl2, an aquaporin blocker, prevented floating and inhibited spore swelling and germ-tube emergence, indicating the importance of water uptake at the early stages of germination. Two putative candidate aquaporin-encoding genes-RdAQP1 and RdAQP2-were identified in the R. delemar genome. Both presented the conserved NPA motif and six-transmembrane domain topology. Expressing RdAQP1 and RdAQP2 in Arabidopsis protoplasts increased the cells' osmotic water permeability coefficient (Pf compared to controls, indicating their role as water channels. A decrease in R. delemar aquaporin activity with increasing external pH suggested pH regulation of these proteins. Substitution of two histidine (His residues, positioned on two loops facing the outer side of the cell, with alanine eliminated the pH sensing resulting in similar Pf values under acidic and basic conditions. Since hydration is critical for spore switching from the resting to activate state, we suggest that pH regulation of the aquaporins can regulate the initial phase of R. delemar spore germination, followed by germ-tube elongation and host-tissue infection.

  14. Ghrelin system in alcohol-dependent subjects: role of plasma ghrelin levels in alcohol drinking and craving.

    Science.gov (United States)

    Leggio, Lorenzo; Ferrulli, Anna; Cardone, Silvia; Nesci, Antonio; Miceli, Antonio; Malandrino, Noemi; Capristo, Esmeralda; Canestrelli, Benedetta; Monteleone, Palmiero; Kenna, George A; Swift, Robert M; Addolorato, Giovanni

    2012-03-01

    Animal studies suggest that the gut-brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics. This investigation consisted of two studies. Study 1 was a 12-week study with alcohol-dependent subjects, where plasma ghrelin determinations were assessed four times (T0-T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case-control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol-dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non-abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol-dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant. This investigation suggests that ghrelin is potentially able to affect alcohol-seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

  15. A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.

    Science.gov (United States)

    Koulouri, Olympia; Steuwe, Andrea; Gillett, Daniel; Hoole, Andrew C; Powlson, Andrew S; Donnelly, Neil A; Burnet, Neil G; Antoun, Nagui M; Cheow, Heok; Mannion, Richard J; Pickard, John D; Gurnell, Mark

    2015-10-01

    We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. (11)C-methionine PET-CT can aid the detection of

  16. Teachers' perceptions of the role of nurses: caring for children who are technology-dependent in mainstream schools.

    Science.gov (United States)

    Shimizu, Fumie; Katsuda, Hitomi

    2015-01-01

    This study explored special education teachers' perceptions of the role of nurses who specialize in providing nursing care to children who are technology-dependent in mainstream schools. Semistructured interviews with 11 teachers were conducted, and data were analyzed using inductive content analysis. The teachers surveyed thought that the most important role of nurses was to maintain good health and safety, as well as to support children's education as members of the educational team. Teachers desired that nurses give advice based on their professional knowledge to maintain the children's good health and safety. In supporting education, nurses were required to support the children's autonomy and education, and to act as members of the educational team. Study findings suggest that, for an optimal relationship with teachers, nurses who provide nursing care for children who are technology-dependent in mainstream schools need not only fulfill medical functions, but also support the education of children as members of the educational team. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

  17. The chaperone role of the pyridoxal 5'-phosphate and its implications for rare diseases involving B6-dependent enzymes.

    Science.gov (United States)

    Cellini, Barbara; Montioli, Riccardo; Oppici, Elisa; Astegno, Alessandra; Voltattorni, Carla Borri

    2014-02-01

    The biologically active form of the B6 vitamers is pyridoxal 5'-phosphate (PLP), which plays a coenzymatic role in several distinct enzymatic activities ranging from the synthesis, interconversion and degradation of amino acids to the replenishment of one-carbon units, synthesis and degradation of biogenic amines, synthesis of tetrapyrrolic compounds and metabolism of amino-sugars. In the catalytic process of PLP-dependent enzymes, the substrate amino acid forms a Schiff base with PLP and the electrophilicity of the PLP pyridine ring plays important roles in the subsequent catalytic steps. While the essential role of PLP in the acquisition of biological activity of many proteins is long recognized, the finding that some PLP-enzymes require the coenzyme for refolding in vitro points to an additional role of PLP as a chaperone in the folding process. Mutations in the genes encoding PLP-enzymes are causative of several rare inherited diseases. Patients affected by some of these diseases (AADC deficiency, cystathionuria, homocystinuria, gyrate atrophy, primary hyperoxaluria type 1, xanthurenic aciduria, X-linked sideroblastic anaemia) can benefit, although at different degrees, from the administration of pyridoxine, a PLP precursor. The effect of the coenzyme is not limited to mutations that affect the enzyme-coenzyme interaction, but also to those that cause folding defects, reinforcing the idea that PLP could play a chaperone role and improve the folding efficiency of misfolded variants. In this review, recent biochemical and cell biology studies highlighting the chaperoning activity of the coenzyme on folding-defective variants of PLP-enzymes associated with rare diseases are presented and discussed. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. Experimental investigation of standing wave effect in dual-frequency capacitively coupled argon discharges: role of a low-frequency source

    Science.gov (United States)

    Zhao, Kai; Liu, Yong-Xin; Kawamura, E.; Wen, De-Qi; Lieberman, M. A.; Wang, You-Nian

    2018-05-01

    It is well known that the plasma non-uniformity caused by the standing wave effect has brought about great challenges for plasma material processing. To improve the plasma uniformity, a low-frequency (LF) power source is introduced into a 100 MHz very-high-frequency (VHF) capacitively coupled argon plasma reactor. The effect of the LF parameters (LF voltage amplitude ϕ L and LF source f L) on the radial profile of plasma density has been investigated by utilizing a hairpin probe. The result at a low pressure (1 Pa) is compared to the one obtained by a 2D fluid-analytical capacitively coupled plasma model, showing good agreement in the plasma density radial profile. The experimental results show that the plasma density profile exhibits different dependences on ϕ L and f L at different gas pressures/electrode driven types (i.e., the two rf sources are applied on one electrode (case I) and separate electrodes (case II)). At low pressures (e.g., 8 Pa), the pronounced standing wave effect revealed in a VHF discharge can be suppressed at a relatively high ϕ L or a low f L in case I, because the HF sheath heating is largely weakened due to strong modulation by the LF source. By contrast, ϕ L and f L play insignificant roles in suppressing the standing wave effect in case II. At high pressures (e.g., 20 Pa), the opposite is true. The plasma density radial profile is more sensitive to ϕ L and f L in case II than in case I. In case II, the standing wave effect is surprisingly enhanced with increasing ϕ L at higher pressures; however, the center-high density profile caused by the standing wave effect can be compensated by increasing f L due to the enhanced electrostatic edge effect dominated by the LF source. In contrast, the density radial profile shows a much weaker dependence on ϕ L and f L in case I at higher pressures. To understand the different roles of ϕ L and f L, the electron excitation dynamics in each case are analyzed based on the measured spatio

  19. Help to perpetuate traditional gender roles: Benevolent sexism increases engagement in dependency-oriented cross-gender helping.

    Science.gov (United States)

    Shnabel, Nurit; Bar-Anan, Yoav; Kende, Anna; Bareket, Orly; Lazar, Yael

    2016-01-01

    Based on theorizing that helping relations may serve as a subtle mechanism to reinforce intergroup inequality, the present research (N = 1,315) examined the relation between benevolent sexism (i.e., a chivalrous yet subtly oppressive view of women) and helping. In cross-gender interactions, the endorsement of (Studies 1, 3, and 4) or exposure to (Study 2) benevolent sexism predicted (a) men's preference to provide women with dependency-oriented help (i.e., direct assistance) rather than tools for autonomous coping, and (b) women's preference to seek dependency-oriented help rather than tools for autonomous coping. Benevolent sexism did not predict men's and women's engagement in dependency-oriented helping relations in same-gender interactions. Studies 1 and 2 examined behavioral intentions in response to a series of hypothetical scenarios; Studies 3 and 4 examined actual behavior in tests of mathematical and logical ability, and pointed to assumed partner's expectations as a potential mediator. The converging evidence supports the hypothesis that benevolent sexism encourages engagement in cross-gender helping relations that perpetuate traditional gender roles. (c) 2016 APA, all rights reserved).

  20. Structural explanation for the role of Mn2+ in the activity of phi6 RNA-dependent RNA polymerase.

    Science.gov (United States)

    Poranen, Minna M; Salgado, Paula S; Koivunen, Minni R L; Wright, Sam; Bamford, Dennis H; Stuart, David I; Grimes, Jonathan M

    2008-11-01

    The biological role of manganese (Mn(2+)) has been a long-standing puzzle, since at low concentrations it activates several polymerases whilst at higher concentrations it inhibits. Viral RNA polymerases possess a common architecture, reminiscent of a closed right hand. The RNA-dependent RNA polymerase (RdRp) of bacteriophage 6 is one of the best understood examples of this important class of polymerases. We have probed the role of Mn(2+) by biochemical, biophysical and structural analyses of the wild-type enzyme and of a mutant form with an altered Mn(2+)-binding site (E491 to Q). The E491Q mutant has much reduced affinity for Mn(2+), reduced RNA binding and a compromised elongation rate. Loss of Mn(2+) binding structurally stabilizes the enzyme. These data and a re-examination of the structures of other viral RNA polymerases clarify the role of manganese in the activation of polymerization: Mn(2+) coordination of a catalytic aspartate is necessary to allow the active site to properly engage with the triphosphates of the incoming NTPs. The structural flexibility caused by Mn(2+) is also important for the enzyme dynamics, explaining the requirement for manganese throughout RNA polymerization.

  1. Dual Youla parameterization

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik

    2003-01-01

    A different aspect of using the parameterisation of all systems stabilised by a given controller, i.e. the dual Youla parameterisation, is considered. The relation between system change and the dual Youla parameter is derived in explicit form. A number of standard uncertain model descriptions...... are considered and the relation with the dual Youla parameter given. Some applications of the dual Youla parameterisation are considered in connection with the design of controllers and model/performance validation....

  2. Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity

    International Nuclear Information System (INIS)

    Kwasnicka-Crawford, Dorota A.; Vincent, Steven R.

    2005-01-01

    Microsomal cytochrome P450 reductase catalyzes the one-electron transfer from NADPH via FAD and FMN to various electron acceptors, such as cytochrome P450s or to some anti-cancer quinone drugs. This results in generation of free radicals and toxic oxygen metabolites, which can contribute to the cytotoxicity of these compounds. Recently, a cytosolic NADPH-dependent flavin reductase, NR1, has been described which is highly homologous to the microsomal cytochrome P450 reductase. In this study, we show that over-expression of NR1 in human embryonic kidney cells enhances the cytotoxic action of the model quinone, menadione. Furthermore, we show that a novel human histidine triad protein DCS-1, which is expressed together with NR1 in many tissues, can significantly reduce menadione-induced cytotoxicity in these cells. We also show that DCS-1 binds NF1 and directly modulates its activity. These results suggest that NR1 may play a role in carcinogenicity and cell death associated with one-electron reductions

  3. Structure–function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination

    Science.gov (United States)

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-01-01

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry’s ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function. PMID:25074915

  4. Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

    Science.gov (United States)

    Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

    2014-08-12

    The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

  5. Dual affine isoperimetric inequalities

    Directory of Open Access Journals (Sweden)

    Bin Xiong

    2006-01-01

    Full Text Available We establish some inequalities for the dual -centroid bodies which are the dual forms of the results by Lutwak, Yang, and Zhang. Further, we establish a Brunn-Minkowski-type inequality for the polar of dual -centroid bodies.

  6. Light-dependent roles of the G-protein α subunit GNA1 of Hypocrea jecorina (anamorph Trichoderma reesei

    Directory of Open Access Journals (Sweden)

    Kubicek Christian P

    2009-09-01

    Full Text Available Abstract Background The filamentous ascomycete Hypocrea jecorina (anamorph Trichoderma reesei is primarily known for its efficient enzymatic machinery that it utilizes to decompose cellulosic substrates. Nevertheless, the nature and transmission of the signals initiating and modulating this machinery are largely unknown. Heterotrimeric G-protein signaling represents one of the best studied signal transduction pathways in fungi. Results Analysis of the regulatory targets of the G-protein α subunit GNA1 in H. jecorina revealed a carbon source and light-dependent role in signal transduction. Deletion of gna1 led to significantly decreased biomass formation in darkness in submersed culture but had only minor effects on morphology and hyphal apical extension rates on solid medium. Cellulase gene transcription was abolished in Δgna1 on cellulose in light and enhanced in darkness. However, analysis of strains expressing a constitutively activated GNA1 revealed that GNA1 does not transmit the essential inducing signal. Instead, it relates a modulating signal with light-dependent significance, since induction still required the presence of an inducer. We show that regulation of transcription and activity of GNA1 involves a carbon source-dependent feedback cycle. Additionally we found a function of GNA1 in hydrophobin regulation as well as effects on conidiation and tolerance of osmotic and oxidative stress. Conclusion We conclude that GNA1 transmits a signal the physiological relevance of which is dependent on both the carbon source as well as the light status. The widespread consequences of mutations in GNA1 indicate a broad function of this Gα subunit in appropriation of intracellular resources to environmental (especially nutritional conditions.

  7. The Clinical Role of Dual-Time-Point {sup 18}F-FDG PET/CT in Differential Diagnosis of the Thyroid Incidentaloma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sinae; Park, Taegyu; Park, Soyeon; Pahk, Kisoo; Rhee, Seunghong; Cho, Jaehyuk; Jeong, Eugene; Kim, Sungeun; Choe, Jae Gol [Korea Univ., Seoul (Korea, Republic of)

    2014-06-15

    Thyroid incidentalomas are common findings during imaging studies including {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) for cancer evaluation. Although the overall incidence of incidental thyroid uptake detected on PET imaging is low, clinical attention should be warranted owing to the high incidence of harboring primary thyroid malignancy.We retrospectively reviewed 2,368 dual-time-point {sup 18}F-FDG PET/CT cases that were undertaken for cancer evaluation from November 2007 to February 2009, to determine the clinical impact of dual-time-point imaging in the differential diagnosis of thyroid incidentalomas. Focal thyroid uptake was identified in 64 PET cases and final diagnosis was clarified with cytology/histology in a total of 27 patients with {sup 18}F-FDG-avid incidental thyroid lesion. The maximum standardized uptake value (SUVmax) of the initial image (SUV1) and SUVmax of the delayed image (SUV2) were determined, and the retention index (RI) was calculated by dividing the difference between SUV2 and SUV1 by SUV1 (i. e., RI=[SUV2-SUV1]/SUV1Χ100). These indices were compared between patient groups that were proven to have pathologically benign or malignant thyroid lesions. There was no statistically significant difference in SUV1 between benign and malignant lesions. SUV2 and RI of the malignant lesions were significantly higher than the benign lesions. The areas under the ROC curves showed that SUV2 and RI have the ability to discriminate between benign and malignant thyroid lesions. The predictability of dual-time-point PET parameters for thyroid malignancy was assessed by ROC curve analyses. When SUV2 of 3.9 was used as cut-off threshold, malignancy on the pathology could be predicted with a sensitivity of 87.5 % and specificity of 75 %. A thyroid lesion that shows RI greater than 12.5 % could be expected to be malignant (sensitivity 88.9 %, specificity 66.3 %). All malignant lesions showed an

  8. Dual antagonists of integrins.

    Science.gov (United States)

    Nadrah, K; Dolenc, M Sollner

    2005-01-01

    The roles of integrins in pathologies have been studied intensively and only partially explained. This has resulted in the development of several nanomolar antagonists to certain integrins. In most cases, the aim was to produce compounds which are highly selective towards specific integrins. This paradigm has recently shifted a little. Targeting two or more integrins with one compound has become a very attractive concept, especially since it has become clear that several severe disorders, such as pathological angiogenesis, cannot be treated just with highly specific integrin antagonists. This review is aimed to elucidate some aspects regarding the design of drugs with dual activity towards integrins. Integrin structure and tissue distribution will first be described, in order to provide the basis for their functions in various pathologies which will follow. Inhibitors of several pairs of integrins will be described.

  9. Pivotal roles of p53 transcription-dependent and -independent pathways in manganese-induced mitochondrial dysfunction and neuronal apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Chunhua [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China); Ma, Xa; Shi, Shangshi [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Zhao, Jianya; Nie, Xiaoke [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Han, Jingling; Xiao, Jing; Wang, Xiaoke [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiang, Shengyang [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China); Jiang, Junkang, E-mail: Jiang_junkang@163.com [Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019 Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226019 Jiangsu (China)

    2014-12-15

    Chronic exposure to excessive manganese (Mn) has been known to lead to neuronal loss and a clinical syndrome resembling idiopathic Parkinson's disease (IPD). p53 plays an integral role in the development of various human diseases, including neurodegenerative disorders. However, the role of p53 in Mn-induced neuronal apoptosis and neurological deficits remains obscure. In the present study, we showed that p53 was critically involved in Mn-induced neuronal apoptosis in rat striatum through both transcription-dependent and -independent mechanisms. Western blot and immunohistochemistrical analyses revealed that p53 was remarkably upregulated in the striatum of rats following Mn exposure. Coincidentally, increased level of cleaved PARP, a hallmark of apoptosis, was observed. Furthermore, using nerve growth factor (NGF)-differentiated PC12 cells as a neuronal cell model, we showed that Mn exposure decreased cell viability and induced apparent apoptosis. Importantly, p53 was progressively upregulated, and accumulated in both the nucleus and the cytoplasm. The cytoplasmic p53 had a remarkable distribution in mitochondria, suggesting an involvement of p53 mitochondrial translocation in Mn-induced neuronal apoptosis. In addition, Mn-induced impairment of mitochondrial membrane potential (ΔΨm) could be partially rescued by pretreatment with inhibitors of p53 transcriptional activity and p53 mitochondrial translocation, Pifithrin-α (PFT-α) and Pifithrin-μ (PFT-μ), respectively. Moreover, blockage of p53 activities with PFT-α and PFT-μ significantly attenuated Mn-induced reactive oxidative stress (ROS) generation and mitochondrial H{sub 2}O{sub 2} production. Finally, we observed that pretreatment with PFT-α and PFT-μ ameliorated Mn-induced apoptosis in PC12 cells. Collectively, these findings implicate that p53 transcription-dependent and -independent pathways may play crucial roles in the regulation of Mn-induced neuronal death. - Highlights: • p53 is

  10. Pivotal roles of p53 transcription-dependent and -independent pathways in manganese-induced mitochondrial dysfunction and neuronal apoptosis

    International Nuclear Information System (INIS)

    Wan, Chunhua; Ma, Xa; Shi, Shangshi; Zhao, Jianya; Nie, Xiaoke; Han, Jingling; Xiao, Jing; Wang, Xiaoke; Jiang, Shengyang; Jiang, Junkang

    2014-01-01

    Chronic exposure to excessive manganese (Mn) has been known to lead to neuronal loss and a clinical syndrome resembling idiopathic Parkinson's disease (IPD). p53 plays an integral role in the development of various human diseases, including neurodegenerative disorders. However, the role of p53 in Mn-induced neuronal apoptosis and neurological deficits remains obscure. In the present study, we showed that p53 was critically involved in Mn-induced neuronal apoptosis in rat striatum through both transcription-dependent and -independent mechanisms. Western blot and immunohistochemistrical analyses revealed that p53 was remarkably upregulated in the striatum of rats following Mn exposure. Coincidentally, increased level of cleaved PARP, a hallmark of apoptosis, was observed. Furthermore, using nerve growth factor (NGF)-differentiated PC12 cells as a neuronal cell model, we showed that Mn exposure decreased cell viability and induced apparent apoptosis. Importantly, p53 was progressively upregulated, and accumulated in both the nucleus and the cytoplasm. The cytoplasmic p53 had a remarkable distribution in mitochondria, suggesting an involvement of p53 mitochondrial translocation in Mn-induced neuronal apoptosis. In addition, Mn-induced impairment of mitochondrial membrane potential (ΔΨm) could be partially rescued by pretreatment with inhibitors of p53 transcriptional activity and p53 mitochondrial translocation, Pifithrin-α (PFT-α) and Pifithrin-μ (PFT-μ), respectively. Moreover, blockage of p53 activities with PFT-α and PFT-μ significantly attenuated Mn-induced reactive oxidative stress (ROS) generation and mitochondrial H 2 O 2 production. Finally, we observed that pretreatment with PFT-α and PFT-μ ameliorated Mn-induced apoptosis in PC12 cells. Collectively, these findings implicate that p53 transcription-dependent and -independent pathways may play crucial roles in the regulation of Mn-induced neuronal death. - Highlights: • p53 is robustly

  11. DUAL TIMELIKE NORMAL AND DUAL TIMELIKE SPHERICAL CURVES IN DUAL MINKOWSKI SPACE

    OpenAIRE

    ÖNDER, Mehmet

    2009-01-01

    Abstract: In this paper, we give characterizations of dual timelike normal and dual timelike spherical curves in the dual Minkowski 3-space and we show that every dual timelike normal curve is also a dual timelike spherical curve. Keywords: Normal curves, Dual Minkowski 3-Space, Dual Timelike curves. Mathematics Subject Classifications (2000): 53C50, 53C40. DUAL MINKOWSKI UZAYINDA DUAL TIMELIKE NORMAL VE DUAL TIMELIKE KÜRESEL EĞRİLER Özet: Bu çalışmada, dual Minkowski 3-...

  12. Limitations in dual-task performance

    OpenAIRE

    Pannebakker, Merel Mathilde

    2009-01-01

    In this thesis, the effect of information-processing overload on working-memory dependent information processing was examined using dual-task paradigms. The experiments described strengthen the importance of a functional explanation for dual-task limitations. First, it showed evidence for a unified coding medium (as put forward in the theory of event coding; Hommel, Müsseler, Aschersleben, & Prinz, 2001) in which features, operations and responses are available and can influence each other. A...

  13. Dual Inflation

    CERN Document Server

    García-Bellido, J

    1998-01-01

    We propose a new model of inflation based on the soft-breaking of N=2 supersymmetric SU(2) Yang-Mills theory. The advantage of such a model is the fact that we can write an exact expression for the effective scalar potential, including non-perturbative effects, which preserves the analyticity and duality properties of the Seiberg-Witten solution. We find that the scalar condensate that plays the role of the inflaton can drive a long period of cosmological expansion, produce the right amount of temperature anisotropies in the microwave background, and end inflation when the monopole acquires a vacuum expectation value. Duality properties relate the weak coupling Higgs region where inflation takes place with the strong coupling monopole region, where reheating occurs, creating particles corresponding to the light degrees of freedom in the true vacuum.

  14. The role of dual energy CT in differentiating between brain haemorrhage and contrast medium after mechanical revascularisation in acute ischaemic stroke

    International Nuclear Information System (INIS)

    Tijssen, M.P.M.; Stadler, A.A.R.; Zwam, W. van; Graaf, R. de; Postma, A.A.; Hofman, P.A.M.; Oostenbrugge, R.J. van; Klotz, E.; Wildberger, J.E.

    2014-01-01

    To assess the feasibility of dual energy computed tomography (DE-CT) in intra-arterially treated acute ischaemic stroke patients to discriminate between contrast extravasation and intracerebral haemorrhage. Thirty consecutive acute ischaemic stroke patients following intra-arterial treatment were examined with DE-CT. Simultaneous imaging at 80 kV and 140 kV was employed with calculation of mixed images. Virtual unenhanced non-contrast (VNC) images and iodine overlay maps (IOM) were calculated using a dedicated brain haemorrhage algorithm. Mixed images alone, as ''conventional CT'', and DE-CT interpretations were evaluated and compared with follow-up CT. Eight patients were excluded owing to a lack of follow-up or loss of data. Mixed images showed intracerebral hyperdense areas in 19/22 patients. Both haemorrhage and residual contrast material were present in 1/22. IOM suggested contrast extravasation in 18/22 patients; in 16/18 patients this was confirmed at follow-up. The positive predictive value (PPV) of mixed imaging alone was 25 %, with a negative predictive value (NPV) of 91 % and accuracy of 63 %. The PPV for detection of haemorrhage with DE-CT was 100 %, with an NPV of 89 % and accuracy improved to 89 %. Dual energy computed tomography improves accuracy and diagnostic confidence in early differentiation between intracranial haemorrhage and contrast medium extravasation in acute stroke patients following intra-arterial revascularisation. (orig.)

  15. Mental Health and Coping Patterns in Jewish Gay Men in Israel: The Role of Dual Identity Conflict, Religious Identity, and Partnership Status.

    Science.gov (United States)

    Zeidner, Moshe; Zevulun, Attara

    2018-01-01

    This study examined the effects of dual-identity conflict, religious identity (religious/spiritual vs. sexual), and partnership status on the coping strategies and mental health of gay Jewish men in modern Israeli society. Participants were 73 religious and 71 secular gay men recruited via e-mail, social networking sites, and online resources targeting sexual minority men. Participants were assessed via measures of identity conflict, mental health, and coping strategies. Jewish gay men who reported more severe identity conflict also reported using less problem-focused and avoidance coping and more emotion-focused coping strategies and reported poorer mental health than their less identity-conflicted counterparts. Furthermore, gay men who self-identified as religious reported poorer mental health as well as less problem-focused coping and more emotion-focused coping compared to secular men. Religious gay men in romantic relationships reported lower intensities of dual-identity conflict and better mental health compared to their nonpartnered counterparts.

  16. The role of dual energy CT in differentiating between brain haemorrhage and contrast medium after mechanical revascularisation in acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Tijssen, M.P.M.; Stadler, A.A.R.; Zwam, W. van; Graaf, R. de; Postma, A.A. [Maastricht University Medical Centre, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Hofman, P.A.M. [Maastricht University Medical Centre, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Maastricht University, MhENS School for Mental Health and Neuroscience, Maastricht (Netherlands); Oostenbrugge, R.J. van [Maastricht University Medical Centre, Department of Neurology, P.O. Box 5800, Maastricht (Netherlands); Maastricht University, CARIM School for Cardiovascular Diseases, P.O. Box 616, Maastricht (Netherlands); Klotz, E. [Siemens Healthcare Sector, Computed Tomography, Forchheim (Germany); Wildberger, J.E. [Maastricht University Medical Centre, Department of Radiology, P.O. Box 5800, Maastricht (Netherlands); Maastricht University, CARIM School for Cardiovascular Diseases, P.O. Box 616, Maastricht (Netherlands)

    2014-04-15

    To assess the feasibility of dual energy computed tomography (DE-CT) in intra-arterially treated acute ischaemic stroke patients to discriminate between contrast extravasation and intracerebral haemorrhage. Thirty consecutive acute ischaemic stroke patients following intra-arterial treatment were examined with DE-CT. Simultaneous imaging at 80 kV and 140 kV was employed with calculation of mixed images. Virtual unenhanced non-contrast (VNC) images and iodine overlay maps (IOM) were calculated using a dedicated brain haemorrhage algorithm. Mixed images alone, as ''conventional CT'', and DE-CT interpretations were evaluated and compared with follow-up CT. Eight patients were excluded owing to a lack of follow-up or loss of data. Mixed images showed intracerebral hyperdense areas in 19/22 patients. Both haemorrhage and residual contrast material were present in 1/22. IOM suggested contrast extravasation in 18/22 patients; in 16/18 patients this was confirmed at follow-up. The positive predictive value (PPV) of mixed imaging alone was 25 %, with a negative predictive value (NPV) of 91 % and accuracy of 63 %. The PPV for detection of haemorrhage with DE-CT was 100 %, with an NPV of 89 % and accuracy improved to 89 %. Dual energy computed tomography improves accuracy and diagnostic confidence in early differentiation between intracranial haemorrhage and contrast medium extravasation in acute stroke patients following intra-arterial revascularisation. (orig.)

  17. Subcellular distribution of cyclin-dependent kinase-like 5 (CDKL5) is regulated through phosphorylation by dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A)

    International Nuclear Information System (INIS)

    Oi, Ami; Katayama, Syouichi; Hatano, Naoya; Sugiyama, Yasunori; Kameshita, Isamu; Sueyoshi, Noriyuki

    2017-01-01

    Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase primarily expressed in the central nervous system and is known to cause X-linked neurodevelopmental disorders such as Rett syndrome. However, the mechanisms regulating CDKL5 have not yet been fully clarified. Therefore, in this study, we investigated the protein kinase that directly phosphorylates CDKL5, identifying it as dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), an enzyme binding to and phosphorylating CDKL5. We showed that subcellular distribution of CDKL5 was regulated by its phosphorylation by DYRK1A. In mouse neuroblastoma Neuro2a cells, CDKL5 was localized in both the cytosol and nucleus, whereas DYRK1A showed a typical nuclear localization. When CDKL5 and DYRK1A were co-expressed, the cytosolic localization of CDKL5 was significantly increased. Results of site-directed mutagenesis revealed that the phosphorylation site was Ser-308, in the vicinity of the nuclear localization signal. A mutation mimicking the phosphorylated serine residue by aspartate substitution (S308D) changed CDKL5 localization to the cytosol, whereas the corresponding alanine-substituted analog, CDKL5(S308A), was primarily localized to the nucleus. Taken together, these results strongly suggested that DYRK1A bound to CDKL5 and phosphorylated it on Ser-308, thus interfering with its nuclear localization. - Highlights: • We investigated the mechanism regulating subcellular localization of CDKL5. • DYRK1A was identified as an enzyme that bound to and phosphorylated CDKL5. • The phosphorylation site of CDKL5 was Ser-308, in the vicinity of the NLS. • When DYRK1A was co-expressed, the cytosolic CDKL5 was significantly increased. • In conclusion, DYRK1A regulates CDKL5 localization via phosphorylation on Ser-308.

  18. Role of microstructure in the mean stress dependence of fatigue strength in Ti-6Al-4V alloy

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, S.G.; Cohen, F.S.; Biederman, R.R.; Sisson, R.D. Jr.

    1999-07-01

    The high cycle fatigue properties of Ti-6Al-4V alloy with six different microstructure/texture combinations were investigated. Only materials with lamellar and fine bimodal microstructures exhibited linear Goodman relationship on the constant fatigue life diagram. Materials with coarse bimodal and equiaxed microstructures had anomalous mean stress dependency, with HCF strength at intermediate mean stresses being significantly lower than predicted by Goodman relationship, regardless of whether material was forged or cross-rolled. The role of microstructure in mean stress sensitivity behavior of Ti-6Al-4V is studied. Cyclic strain tests were conducted for all microstructures, and the results of strain-controlled and stress-controlled cyclic tests are compared and discussed.

  19. Analysis of Context Dependence in Social Interaction Networks of a Massively Multiplayer Online Role-Playing Game

    Science.gov (United States)

    Son, Seokshin; Kang, Ah Reum; Kim, Hyun-chul; Kwon, Taekyoung; Park, Juyong; Kim, Huy Kang

    2012-01-01

    Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs), here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior. PMID:22496771

  20. Diet and the Role of Altered Carbohydrate Absorption in the Treatment of Noninsulin-Dependent Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Thomas MS Wolever

    1996-01-01

    Full Text Available The gastrointestinal tract has no clear role in the pathophysiology of noninsulin-dependent diabetes mellitus (NIDDM, but it may be an appropriate site for therapeutic intervention, specifically changes in diet, meal frequency and medications. Studies suggest that for patients with NIDDM, a calorie-restricted, high carbohydrate diet low in fat and rich in fibre may improve glycemic control, mitigate the risk of atherosclerosis and retard such diabetic complications as nephropathy and retinopathy. Increased meal frequency slows the rate of carbohydrate absorption, flattens blood insulin responses and reduces serum cholesterol. New therapeutic interventions, such as soluble fibre, low glycemic index foods or alpha glucosidase inhibitors, can further slow carbohydrate absorption and thus reduce secondary risks from hyperglycemia and hyperinsulinemia.

  1. Analysis of context dependence in social interaction networks of a massively multiplayer online role-playing game.

    Science.gov (United States)

    Son, Seokshin; Kang, Ah Reum; Kim, Hyun-chul; Kwon, Taekyoung; Park, Juyong; Kim, Huy Kang

    2012-01-01

    Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs), here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior.

  2. Analysis of context dependence in social interaction networks of a massively multiplayer online role-playing game.

    Directory of Open Access Journals (Sweden)

    Seokshin Son

    Full Text Available Rapid advances in modern computing and information technology have enabled millions of people to interact online via various social network and gaming services. The widespread adoption of such online services have made possible analysis of large-scale archival data containing detailed human interactions, presenting a very promising opportunity to understand the rich and complex human behavior. In collaboration with a leading global provider of Massively Multiplayer Online Role-Playing Games (MMORPGs, here we present a network science-based analysis of the interplay between distinct types of user interaction networks in the virtual world. We find that their properties depend critically on the nature of the context-interdependence of the interactions, highlighting the complex and multilayered nature of human interactions, a robust understanding of which we believe may prove instrumental in the designing of more realistic future virtual arenas as well as provide novel insights to the science of collective human behavior.

  3. A role for nuclear translocation of tripeptidyl-peptidase II in reactive oxygen species-dependent DNA damage responses

    Energy Technology Data Exchange (ETDEWEB)

    Preta, Giulio; Klark, Rainier de [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden); Glas, Rickard, E-mail: rickard.glas@ki.se [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden)

    2009-11-27

    Responses to DNA damage are influenced by cellular metabolism through the continuous production of reactive oxygen species (ROS), of which most are by-products of mitochondrial respiration. ROS have a strong influence on signaling pathways during responses to DNA damage, by relatively unclear mechanisms. Previous reports have shown conflicting data on a possible role for tripeptidyl-peptidase II (TPPII), a large cytosolic peptidase, within the DNA damage response. Here we show that TPPII translocated into the nucleus in a p160-ROCK-dependent fashion in response to {gamma}-irradiation, and that nuclear expression of TPPII was present in most {gamma}-irradiated transformed cell lines. We used a panel of nine cell lines of diverse tissue origin, including four lymphoma cell lines (T, B and Hodgkins lymphoma), a melanoma, a sarcoma, a colon and two breast carcinomas, where seven out of nine cell lines showed nuclear TPPII expression after {gamma}-irradiation. Further, this required cellular production of ROS; treatment with either N-acetyl-Cysteine (anti-oxidant) or Rotenone (inhibitor of mitochondrial respiration) inhibited nuclear accumulation of TPPII. The local density of cells was important for nuclear accumulation of TPPII at early time-points following {gamma}-irradiation (at 1-4 h), indicating a bystander effect. Further, we showed that the peptide-based inhibitor Z-Gly-Leu-Ala-OH, but not its analogue Z-Gly-(D)-Leu-Ala-OH, excluded TPPII from the nucleus. This correlated with reduced nuclear expression of p53 as well as caspase-3 and -9 activation in {gamma}-irradiated lymphoma cells. Our data suggest a role for TPPII in ROS-dependent DNA damage responses, through alteration of its localization from the cytosol into the nucleus.

  4. Role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in gastric ulcer healing in mice.

    Science.gov (United States)

    Kawahara, Y; Nakase, Y; Isomoto, Y; Matsuda, N; Amagase, K; Kato, S; Takeuchi, K

    2011-08-01

    We examined the role of macrophage colony-stimulating factor (M-CSF)-dependent macrophages in the healing of gastric ulcers in mice. Male M-CSF-deficient (op/op) and M-CSF-expressing heterozygote (+/?) mice were used. Gastric ulcers were induced by thermal cauterization under ether anesthesia, and healing was observed for 14 days after ulceration. The numbers of macrophages and microvessels in the gastric mucosa were determined immunohistochemically with anti-CD68 and anti-CD31 antibodies, respectively. Expression of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and vascular endothelial growth factor (VEGF) mRNA was determined via real-time reverse transcription-polymerase chain reaction (RT-PCR), and the mucosal content of prostaglandin (PG) E(2) was determined via enzyme immunoassay on day 10 after ulceration. The healing of gastric ulcers was significantly delayed in op/op mice compared with +/? mice. Further, significantly fewer macrophages were observed in the normal gastric mucosa of op/op mice than in +/? mice. Ulcer induction caused a marked accumulation of macrophages around the ulcer base in +/? mice, but this response was attenuated in op/op mice. The mucosal PGE(2) content as well as the expression of COX-2, VEGF, and TNF-α mRNA were all upregulated in the ulcerated area of +/? mice but significantly suppressed in op/op mice. The degree of vascularization in the ulcerated area was significantly lower in op/op mice than in +/? mice. Taken together, these results suggest that M-CSF-dependent macrophages play an important role in the healing of gastric ulcers, and that this action may be associated with angiogenesis promoted by upregulation of COX-2/PGE(2) production.

  5. Role of surface on the size-dependent mechanical properties of copper nanowire under tensile load: A molecular dynamics simulation

    International Nuclear Information System (INIS)

    Liu, Wei-Ting; Hsiao, Chun-I.; Hsu, Wen-Dung

    2014-01-01

    In this study we have used atomistic simulations to investigate the role of surface on the size-dependent mechanical properties of nanowires. In particular, we have performed computational investigation on single crystal face-centered cubic copper nano-wires with diameters ranging from 2 to 20 nm. The wire axis for all the nanowires are considered along the [0 0 1] direction. Characterization of the initial optimized structures revealed clear differences in interatomic spacing, stress, and potential energy in all the nanowires. The mechanical properties with respect to wire diameter are evaluated by applying tension along the [0 0 1] direction until yielding. We have discussed the stress–strain relationships, Young's modulus, and the variation in potential energy from surface to the center of the wire for all the cases. Our results indicate that the mechanical response (including yield strain, Young's modulus, and resilience) is directly related to the proportion of surface to bulk type atoms present in each nanowire. Thus the size-dependent mechanical properties of single crystal copper nanowire within elastic region are attributed to the surface to volume ratio (surface effect). Using the calculated response, we have formulated a mathematical relationship, which predicts the nonlinear correlation between the mechanical properties and the diameter of the wire.

  6. Role of surface on the size-dependent mechanical properties of copper nanowire under tensile load: A molecular dynamics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wei-Ting [Department of Materials Science and Engineering, National Cheng Kung University, Tainan City 70101 Taiwan (China); Hsiao, Chun-I. [Department of Materials Science and Engineering, National Cheng Kung University, Tainan City 70101 Taiwan (China); Promotion Center for Global Materials Research, National Cheng Kung University, Tainan City 70101 Taiwan (China); Hsu, Wen-Dung, E-mail: wendung@mail.ncku.edu.tw [Department of Materials Science and Engineering, National Cheng Kung University, Tainan City 70101 Taiwan (China); Research Center for Energy Technology and Strategy, National Cheng Kung University, Tainan City 70101 Taiwan (China); Promotion Center for Global Materials Research, National Cheng Kung University, Tainan City 70101 Taiwan (China)

    2014-01-15

    In this study we have used atomistic simulations to investigate the role of surface on the size-dependent mechanical properties of nanowires. In particular, we have performed computational investigation on single crystal face-centered cubic copper nano-wires with diameters ranging from 2 to 20 nm. The wire axis for all the nanowires are considered along the [0 0 1] direction. Characterization of the initial optimized structures revealed clear differences in interatomic spacing, stress, and potential energy in all the nanowires. The mechanical properties with respect to wire diameter are evaluated by applying tension along the [0 0 1] direction until yielding. We have discussed the stress–strain relationships, Young's modulus, and the variation in potential energy from surface to the center of the wire for all the cases. Our results indicate that the mechanical response (including yield strain, Young's modulus, and resilience) is directly related to the proportion of surface to bulk type atoms present in each nanowire. Thus the size-dependent mechanical properties of single crystal copper nanowire within elastic region are attributed to the surface to volume ratio (surface effect). Using the calculated response, we have formulated a mathematical relationship, which predicts the nonlinear correlation between the mechanical properties and the diameter of the wire.

  7. The role of GABA in NMDA-dependent long term depression (LTD) of rat medial vestibular nuclei.

    Science.gov (United States)

    Grassi, S; Della Torre, G; Capocchi, G; Zampolini, M; Pettorossi, V E

    1995-11-20

    The role of GABA in NMDA-dependent long term depression (LTD) in the medial vestibular nuclei (MVN) was studied on rat brainstem slices. High frequency stimulation (HFS) of the primary vestibular afferents induces a long lasting reduction of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the MVN. The induction but not the maintenance of this depression was abolished by AP5, a specific blocking agent for glutamate NMDA receptors. The involvement of GABA in mediating the depression was checked by applying the GABAA and GABAB receptor antagonists, bicuculline and saclofen, before and after HFS. Under bicuculline and saclofen perfusion, HFS provoked a slight potentiation of the N2 wave, while the N2 depression clearly emerged after drug wash-out. This indicates that GABA is not involved in inducing the long term effect, but it is necessary for its expression. Similarly, the LTD reversed and a slight potentiation appeared when both drugs were administered after its induction. Most of these effects were due to the bicuculline, suggesting that GABAA receptors contribute to LTD more than GABAB do. According to our results, it is unlikely that the long lasting vestibular depression is the result of a homosynaptic LTD. On the contrary, our findings suggest that the depression is due to an enhancement of the GABA inhibitory effect, caused by an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

  8. Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors

    Science.gov (United States)

    Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

    2014-01-01

    Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

  9. Identification of Toxoplasma gondii cAMP dependent protein kinase and its role in the tachyzoite growth.

    Directory of Open Access Journals (Sweden)

    Hitomi Kurokawa

    Full Text Available cAMP-dependent protein kinase (PKA has been implicated in the asexual stage of the Toxoplasma gondii life cycle through assaying the effect of a PKA-specific inhibitor on its growth rate. Since inhibition of the host cell PKA cannot be ruled out, a more precise evaluation of the role of PKA, as well as characterization of the kinase itself, is necessary.The inhibitory effects of two PKA inhibitors, H89, an ATP-competitive chemical inhibitor, and PKI, a substrate-competitive mammalian natural peptide inhibitor, were estimated. In the in vitro kinase assay, the inhibitory effect of PKI on a recombinant T. gondii PKA catalytic subunit (TgPKA-C was weaker compared to that on mammalian PKA-C. In a tachyzoite growth assay, PKI had little effect on the growth of tachyzoites, whereas H89 strongly inhibited it. Moreover, T. gondii PKA regulatory subunit (TgPKA-R-overexpressing tachyzoites showed a significant growth defect.Our data suggest that PKA plays an important role in the growth of tachyzoites, and the inhibitory effect of substrate-competitive inhibitor PKI on T. gondii PKA was low compared to that of the ATP competitive inhibitor H89.

  10. Elucidation of new condition-dependent roles for fructose-1,6-bisphosphatase linked to cofactor balances.

    Directory of Open Access Journals (Sweden)

    Du Toit W P Schabort

    Full Text Available The cofactor balances in metabolism is of paramount importance in the design of a metabolic engineering strategy and understanding the regulation of metabolism in general. ATP, NAD+ and NADP+ balances are central players linking the various fluxes in central metabolism as well as biomass formation. NADP+ is especially important in the metabolic engineering of yeasts for xylose fermentation, since NADPH is required by most yeasts in the initial step of xylose utilisation, including the fast-growing Kluyveromyces marxianus. In this simulation study of yeast metabolism, the complex interplay between these cofactors was investigated; in particular, how they may affect the possible roles of fructose-1,6-bisphosphatase, the pentose phosphate pathway, glycerol production and the pyruvate dehydrogenase bypass. Using flux balance analysis, it was found that the potential role of fructose-1,6-bisphosphatase was highly dependent on the cofactor specificity of the oxidative pentose phosphate pathway and on the carbon source. Additionally, the excessive production of ATP under certain conditions might be involved in some of the phenomena observed, which may have been overlooked to date. Based on these findings, a strategy is proposed for the metabolic engineering of a future xylose-fermenting yeast for biofuel production.

  11. Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.

    Science.gov (United States)

    Lyons, Lisa C; Gardner, Jacob S; Lentsch, Cassidy T; Gandour, Catherine E; Krishnan, Harini C; Noakes, Eric J

    2017-01-01

    In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    Directory of Open Access Journals (Sweden)

    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  13. Fear extinction can be made state-dependent on peripheral epinephrine: role of norepinephrine in the nucleus tractus solitarius.

    Science.gov (United States)

    Rosa, Jessica; Myskiw, Jociane C; Furini, Cristiane R G; Sapiras, Gerson G; Izquierdo, Ivan

    2014-09-01

    We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS)→locus coeruleus→hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 μg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 μg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 μg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 μg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 μg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS→locus coeruleus→HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. The Differential Role of Symptoms of Anxiety and Social Withdrawal in Chinese Children's Dependency on Their Teachers during the Transition to Nursery Care

    Science.gov (United States)

    Zhang, Xiao

    2015-01-01

    Research Findings: Based on a short-term longitudinal sample of Chinese children, the present study examined the role of symptoms of anxiety and social withdrawal in dependency on teachers during the transition to nursery care. Children's dependency on their teachers was assessed first at 3 months after nursery entry (Time 1) and then at the end…

  15. Strategic role of the ubiquitin-dependent segregase p97 (VCP or Cdc48) in DNA replication.

    Science.gov (United States)

    Ramadan, Kristijan; Halder, Swagata; Wiseman, Katherine; Vaz, Bruno

    2017-02-01

    Genome amplification (DNA synthesis) is one of the most demanding cellular processes in all proliferative cells. The DNA replication machinery (also known as the replisome) orchestrates genome amplification during S-phase of the cell cycle. Genetic material is particularly vulnerable to various events that can challenge the replisome during its assembly, activation (firing), progression (elongation) and disassembly from chromatin (termination). Any disturbance of the replisome leads to stalling of the DNA replication fork and firing of dormant replication origins, a process known as DNA replication stress. DNA replication stress is considered to be one of the main causes of sporadic cancers and other pathologies related to tissue degeneration and ageing. The mechanisms of replisome assembly and elongation during DNA synthesis are well understood. However, once DNA synthesis is complete, the process of replisome disassembly, and its removal from chromatin, remains unclear. In recent years, a growing body of evidence has alluded to a central role in replisome regulation for the ubiquitin-dependent protein segregase p97, also known as valosin-containing protein (VCP) in metazoans and Cdc48 in lower eukaryotes. By orchestrating the spatiotemporal turnover of the replisome, p97 plays an essential role in DNA replication. In this review, we will summarise our current knowledge about how p97 controls the replisome from replication initiation, to elongation and finally termination. We will also further examine the more recent findings concerning the role of p97 and how mutations in p97 cofactors, also known as adaptors, cause DNA replication stress induced genomic instability that leads to cancer and accelerated ageing. To our knowledge, this is the first comprehensive review concerning the mechanisms involved in the regulation of DNA replication by p97.

  16. Age-dependent role for Ras-GRF1 in the late stages of adult neurogenesis in the dentate gyrus.

    Science.gov (United States)

    Darcy, Michael J; Trouche, Stéphanie; Jin, Shan-Xue; Feig, Larry A

    2014-03-01

    The dentate gyrus of the hippocampus plays a pivotal role in pattern separation, a process required for the behavioral task of contextual discrimination. One unique feature of the dentate gyrus that contributes to pattern separation is adult neurogenesis, where newly born neurons play a distinct role in neuronal circuitry. Moreover,the function of neurogenesis in this brain region differs in adolescent and adult mice. The signaling mechanisms that differentially regulate the distinct steps of adult neurogenesis in adolescence and adulthood remain poorly understood. We used mice lacking RASGRF1(GRF1), a calcium-dependent exchange factor that regulates synaptic plasticity and participates in contextual discrimination performed by mice, to test whether GRF1 plays a role in adult neurogenesis.We show Grf1 knockout mice begin to display a defect in neurogenesis at the onset of adulthood (~2 months of age), when wild-type mice first acquire the ability to distinguish between closely related contexts. At this age, young hippocampal neurons in Grf1 knockout mice display severely reduced dendritic arborization. By 3 months of age, new neuron survival is also impaired. BrdU labeling of new neurons in 2-month-old Grf1 knockout mice shows they begin to display reduced survival between 2 and 3 weeks after birth, just as new neurons begin to develop complex dendritic morphology and transition into using glutamatergic excitatory input. Interestingly, GRF1 expression appears in new neurons at the developmental stage when GRF1 loss begins to effect neuronal function. In addition, we induced a similar loss of new hippocampal neurons by knocking down expression of GRF1 solely in new neurons by injecting retrovirus that express shRNA against GRF1 into the dentate gyrus. Together, these findings show that GRF1 expressed in new neurons promotes late stages of adult neurogenesis. Overall our findings show GRF1 to be an age-dependent regulator of adult hippocampal neurogenesis, which

  17. Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation

    NARCIS (Netherlands)

    Vogel, D.Y.S.; Heijnen, D.A.M.; Breur, M.; de Vries, H.E.; Tool, A.T.; Amor, S.; Dijkstra, C.D.

    2014-01-01

    Background: In neuroinflammatory diseases, macrophages can play a dual role in the process of tissue damage, depending on their activation status (M1 / M2). M1 macrophages are considered to exert damaging effects to neurons, whereas M2 macrophages are reported to aid regeneration and repair of

  18. pH Dependence of a Mammalian Polyamine Oxidase: Insights into Substrate Specificity and the Role of Lysine 315†

    Science.gov (United States)

    Pozzi, Michelle Henderson; Gawandi, Vijay; Fitzpatrick, Paul F.

    2009-01-01

    Mammalian polyamine oxidases (PAO) catalyze the oxidation of N1-acetylspermine and N1-acetylspermidine to produce N-acetyl-3-aminopropanaldehyde and spermidine or putrescine. Structurally, PAO is a member of the monoamine oxidase family of flavoproteins. The effects of pH on kinetic parameters of mouse PAO have been determined to provide insight into the protonation state of the polyamine required for catalysis and the roles of ionizable residues in the active site in amine oxidation. For N1-acetylspermine, N1-acetylspermidine, and spermine, the kcat/Kamine-pH profiles are bell-shaped. In each case the profile agrees with that expected if the productive form of the substrate has a single positively charged nitrogen. The pKi-pH profiles for a series of polyamine analogs are most consistent with the nitrogen at the site of oxidation being neutral and one other nitrogen being positively charged in the reactive form of the substrate. With N1-acetylspermine as substrate, the value of kred, the limiting rate constant for flavin reduction, is pH dependent, decreasing below a pKa value of 7.3, again consistent with the requirement for an uncharged nitrogen for substrate oxidation. Lys315 in PAO corresponds to a conserved active site residue found throughout the monoamine oxidase family. Mutation of Lys315 to methionine has no effect on the kcat/Kamine profile for spermine, the kred value with N1-acetylspermine is only 1.8-fold lower in the mutant protein, and the pKa in the kred-pH profile with N1-acetylspermine shifts to 7.8. These results rule out Lys315 as a source of a pKa in the kcat/Kamine or kcat/kred profiles. They also establish that this residue does not play a critical role in amine oxidation by PAO. PMID:19199575

  19. Role of insulin in regulation of Na+-/K+-dependent ATPase activity and pump function in corneal endothelial cells.

    Science.gov (United States)

    Hatou, Shin; Yamada, Masakazu; Akune, Yoko; Mochizuki, Hiroshi; Shiraishi, Atsushi; Joko, Takeshi; Nishida, Teruo; Tsubota, Kazuo

    2010-08-01

    The Na(+)-/K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. The role of insulin in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells was investigated. Confluent monolayers of mouse corneal endothelial cells were exposed to insulin. ATPase activity was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate; Na,K-ATPase activity was defined as the portion of total ATPase activity sensitive to ouabain. Pump function was measured with the use of a Ussing chamber; pump function attributable to Na,K-ATPase activity was defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis and immunocytochemistry were performed to measure the expression of the Na,K-ATPase alpha(1)-subunit. Insulin increased the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were blocked by protein kinase C (PKC) inhibitors and protein phosphatases 1 and 2A inhibitor. Western blot analysis indicated that insulin decreased the ratio of the inactive Na,K-ATPase alpha(1)-subunit. Immunocytochemistry indicated that insulin increased the cell surface expression of the Na,K-ATPase alpha(1)-subunit. These results suggest that insulin increases the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. The effect of insulin is mediated by PKC and presumably results in the activation of PP1, 2A, or both, which are essential for activating Na,K-ATPase by alpha(1)-subunit dephosphorylation.

  20. A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress.

    Directory of Open Access Journals (Sweden)

    Tao Su

    Full Text Available Peroxiredoxin Q (PrxQ that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions. Accordingly, PrxQ-mediated resistance to adverse stresses mainly relied on the degradation of ROS. The physiological roles of PrxQ in resistance to adverse stresses were corroborated by its induced expression under adverse stresses, regulated directly by the stress-responsive ECF-sigma factor SigH. Through catalytical kinetic activity, heterodimer formation, and bacterial two-hybrid analysis, we proved that C. glutamicum PrxQ catalytically eliminated peroxides by exclusively receiving electrons from thioredoxin (Trx/thioredoxin reductase (TrxR system and had a broad range of oxidizing substrates, but a better efficiency for peroxynitrite and cumene hydroperoxide (CHP. Site-directed mutagenesis confirmed that the conserved Cys49 and Cys54 are the peroxide oxidation site and the resolving Cys residue, respectively. It was also discovered that C. glutamicum PrxQ mainly existed in monomer whether under its native state or functional state. Based on these results, a catalytic model of PrxQ is being proposed. Moreover, our result that C. glutamicum PrxQ can prevent the damaging effects of adverse stresses by acting as thioredoxin-dependent monomeric peroxidase could be further applied to improve the survival ability and robustness of the important bacterium during fermentation process.

  1. Dual Income Taxes

    DEFF Research Database (Denmark)

    Sørensen, Peter Birch

    This paper discusses the principles and practices of dual income taxation in the Nordic countries. The first part of the paper explains the rationale and the historical background for the introduction of the dual income tax and describes the current Nordic tax practices. The second part...... of the paper focuses on the problems of taxing income from small businesses and the issue of corporate-personal tax integration under the dual income tax, considering alternative ways of dealing with these challenges. In the third and final part of the paper, I briefly discuss whether introducing a dual income...

  2. Dependency on suppliers as a peril in the acquisition of innovations? The role of buyer attractiveness in mitigating potential negative dependency effects in buyer–supplier relations

    NARCIS (Netherlands)

    Schiele, Holger; Vos, Frederik Guido Sebastiaan

    2015-01-01

    New product development occurs nowadays mostly in joint buyer–supplier projects, which require closer ties between the partners in order to mobilize their resources. One issue arising from this collaborative model is that the buyer tends to become more dependent on the supplier. Multiple cases of

  3. Arabidopsis calcium-dependent protein kinase AtCPK1 plays a positive role in salt/drought-stress response.

    Science.gov (United States)

    Huang, Kui; Peng, Lu; Liu, Yingying; Yao, Rundong; Liu, Zhibin; Li, Xufeng; Yang, Yi; Wang, Jianmei

    2018-03-25

    The calcium-dependent protein kinases (CDPKs) play vital roles in plant response to various environmental stimuli. Here, we investigated the function of Arabidopsis AtCPK1 in response to salt and drought stress. The loss-of-function cpk1 mutant displayed hypersensitive to salt and drought stress, whereas overexpressing AtCPK1 in Arabidopsis plants significantly enhanced the resistance to salt or drought stress. The reduced or elevated tolerance of cpk1 mutant and AtCPK1-overexpressing lines was confirmed by the changes of proline, malondialdehyde (MDA) and H 2 O 2 . Real-time PCR analysis revealed that the expression of several stress-inducible genes (RD29A, COR15A, ZAT10, APX2) down-regulated in cpk1 mutant and up-regulated in AtCPK1-overexpressing plants. These results are likely to indicate that AtCPK1 positively regulates salt and drought stress in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

    Science.gov (United States)

    Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

    2001-01-01

    Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

  5. Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

    Science.gov (United States)

    Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

    2015-07-01

    The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. © The Author (2014). Published by Oxford University Press.

  6. Internal State Dependent Odor Processing and Perception—The Role of Neuromodulation in the Fly Olfactory System

    Directory of Open Access Journals (Sweden)

    Sercan Sayin

    2018-01-01

    Full Text Available Animals rely heavily on their sense of olfaction to perform various vital interactions with an ever-in-flux environment. The turbulent and combinatorial nature of air-borne odorant cues demands the employment of various coding strategies, which allow the animal to attune to its internal needs and past or present experiences. Furthermore, these internal needs can be dependent on internal states such as hunger, reproductive state and sickness. Neuromodulation is a key component providing flexibility under such conditions. Understanding the contributions of neuromodulation, such as sensory neuron sensitization and choice bias requires manipulation of neuronal activity on a local and global scale. With Drosophila's genetic toolset, these manipulations are feasible and even allow a detailed look on the functional role of classical neuromodulators such as dopamine, octopamine and neuropeptides. The past years unraveled various mechanisms adapting chemosensory processing and perception to internal states such as hunger and reproductive state. However, future research should also investigate the mechanisms underlying other internal states including the modulatory influence of endogenous microbiota on Drosophila behavior. Furthermore, sickness induced by pathogenic infection could lead to novel insights as to the neuromodulators of circuits that integrate such a negative postingestive signal within the circuits governing olfactory behavior and learning. The enriched emporium of tools Drosophila provides will help to build a concrete picture of the influence of neuromodulation on olfaction and metabolism, adaptive behavior and our overall understanding of how a brain works.

  7. Curcumin-Induced Apoptosis in Human Hepatocellular Carcinoma J5 Cells: Critical Role of Ca+2-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Wei-Hsun Wang

    2012-01-01

    Full Text Available The antitumor effects of curcumin, a natural biologically active compound extracted from rhizomes of Curcuma longa, have been studied in many cancer cell types including human hepatocellular carcinoma (HCC. Here, we investigated the effects of Ca2+ on curcumin-induced apoptosis in human HCC J5 cells. The abrogation of mitochondrial membrane potential (ΔΨm, the increase of reactive oxygen species (ROS production, and calcium release were demonstrated with flow cytometry as early as 15 minutes after curcumin treatment. In addition, an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation was observed. To verify the role of Ca2+ in curcumin-induced apoptosis, 1,2-bis(o-aminophenoxyethane-N,N,N′,N′-tetraacetic acid (BAPTA, an intracellular calcium chelator, was applied. Cell viability was increased, but ΔΨm, ROS production, activation of caspase 3, and cell death were decreased in J5 cells pretreated with BAPTA for 2 h followed by the treatment of 25 μM curcumin. These results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via mitochondria-dependent pathway and is closely related to the level of intracellular accumulation of calcium.

  8. Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice

    Science.gov (United States)

    Fournier, Emilie M.; Velez, Maria-Gabriela; Leahy, Katelyn; Swanson, Cristina L.; Rubtsov, Anatoly V.; Torres, Raul M.

    2012-01-01

    Rare dual-reactive B cells expressing two types of Ig light or heavy chains have been shown to participate in immune responses and differentiate into IgG+ cells in healthy mice. These cells are generated more often in autoreactive mice, leading us to hypothesize they might be relevant in autoimmunity. Using mice bearing Igk allotypic markers and a wild-type Ig repertoire, we demonstrate that the generation of dual-κ B cells increases with age and disease progression in autoimmune-prone MRL and MRL/lpr mice. These dual-reactive cells express markers of activation and are more frequently autoreactive than single-reactive B cells. Moreover, dual-κ B cells represent up to half of plasmablasts and memory B cells in autoimmune mice, whereas they remain infrequent in healthy mice. Differentiation of dual-κ B cells into plasmablasts is driven by MRL genes, whereas the maintenance of IgG+ cells is partly dependent on Fas inactivation. Furthermore, dual-κ B cells that differentiate into plasmablasts retain the capacity to secrete autoantibodies. Overall, our study indicates that dual-reactive B cells significantly contribute to the plasmablast and memory B cell populations of autoimmune-prone mice suggesting a role in autoimmunity. PMID:22927551

  9. Dual Enrollment Academy Programs

    Science.gov (United States)

    Gonzalez, Nicolas; Chavez, Guadalupe

    2009-01-01

    Dual Enrollment Engineering (DEEA) and Medical Science (DEMSA) Academies are two-year dual enrollment programs for high school students. Students explore engineering and medical careers through college coursework. Students prepare for higher education in engineering and medical fields while completing associate degrees in biology or engineering…

  10. A Dual Egalitarian Solution

    NARCIS (Netherlands)

    Klijn, F.; Slikker, M.; Tijs, S.H.

    2000-01-01

    In this note we introduce an egalitarian solution, called the dual egalitarian solution, that is the natural counterpart of the egalitarian solution of Dutta and Ray (1989).We prove, among others, that for a convex game the egalitarian solution coincides with the dual egalitarian solution for its

  11. Dual Credit Report

    Science.gov (United States)

    Light, Noreen

    2016-01-01

    In 2015, legislation to improve access to dual-credit programs and to reduce disparities in access and completion--particularly for low income and underrepresented students--was enacted. The new law focused on expanding access to College in the High School but acknowledged issues in other dual-credit programs and reinforced the notion that cost…

  12. Localization and Instability in Sheared Granular Materials: Role of Pore Fluids and Non-monotonic Rate Dependent Rheology

    Science.gov (United States)

    Ma, X.; Elbanna, A. E.; Kothari, K.

    2017-12-01

    Fault zone dynamics hold the key to resolving many outstanding geophysical problems including the heat flow paradox, discrepancy between fault static and dynamic strength, and energy partitioning. Most fault zones that generate tectonic events are gouge filled and fluid saturated posing the need for formulating gouge-specific constitutive models that capture spatially heterogeneous compaction and dilation, non-monotonic rate dependence, and transition between localized and distributed deformation. In this presentation, we focus primarily on elucidating microscopic underpinnings for shear banding and stick-slip instabilities in sheared saturated granular materials and explore their implications for earthquake dynamics. We use a non-equilibrium thermodynamics model, the Shear Transformation Zone theory, to investigate the dynamics of strain localization and its connection to stability of sliding in the presence and absence of pore fluids. We also consider the possible influence of self-induced mechanical vibrations as well as the role of external acoustic vibrations as analogue for triggering by a distant event. For the dry case, our results suggest that at low and intermediate strain rates, persistent shear bands develop only in the absence of vibrations. Vibrations tend to fluidize the granular network and de-localize slip at these rates. Stick-slip is only observed for rough grains and it is confined to the shear band. At high strain rates, stick-slip disappears and the different systems exhibit similar stress-slip response. Changing the vibration intensity, duration or time of application alters the system response and may cause long-lasting rheological changes. The presence of pore fluids modifies the stick slip pattern and may lead to both loss and development of slip instability depending on the value of the confining pressure, imposed strain rate and hydraulic parameters. We analyze these observations in terms of possible transitions between rate

  13. Interactive toxicity of chlorpyrifos and parathion in neonatal rats: Role of esterases in exposure sequence-dependent toxicity

    International Nuclear Information System (INIS)

    Kacham, R.; Karanth, S.; Baireddy, P.; Liu, J.; Pope, C.

    2006-01-01

    capable than adults at detoxifying many organophosphorus insecticides including chlorpyrifos and parathion, toxicant-selective differences in detoxification play a role in sequence-dependent toxicity in both neonatal and adult rats with these two insecticides

  14. The role of CD1d-restricted NKT cells in the clearance of Pseudomonas aeruginosa from the lung is dependent on the host genetic background.

    Science.gov (United States)

    Benoit, Patrick; Sigounas, Vaia Yioula; Thompson, Jenna L; van Rooijen, Nico; Poynter, Matthew E; Wargo, Matthew J; Boyson, Jonathan E

    2015-06-01

    Pseudomonas aeruginosa is an important human opportunistic pathogen, accounting for a significant fraction of hospital-acquired lung infections. CD1d-restricted NKT cells comprise an unusual innate-like T cell subset that plays important roles in both bacterial and viral infections. Previous reports have differed in their conclusions regarding the role of NKT cells in clearance of P. aeruginosa from the lung. Since there is significant strain-dependent variation in NKT cell number and function among different inbred strains of mice, we investigated whether the role of NKT cells was dependent on the host genetic background. We found that NKT cells did indeed play a critical role in the clearance of P. aeruginosa from the lungs of BALB/c mice but that they played no discernible role in clearance from the lungs of C57BL/6 mice. We found that the strain-dependent role of NKT cells was associated with significant strain-dependent differences in cytokine production by lung NKT cells and that impaired clearance of P. aeruginosa in BALB/c CD1d(-/-) mice was associated with an increase in neutrophil influx to the lung and increased levels of proinflammatory cytokines and chemokines after infection. Finally, we found that the role of alveolar macrophages was also dependent on the genetic background. These data provide further support for a model in which the unusually high level of variability in NKT cell number and function among different genetic backgrounds may be an important contributor to infectious-disease susceptibility and pathology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. School Leadership for Dual Language Education: A Social Justice Approach

    Science.gov (United States)

    DeMatthews, David; Izquierdo, Elena

    2016-01-01

    This article examines how a dual language program can be developed within the framework of social justice leadership. The authors analyzed principal, teacher, and parent interview transcripts as well as field notes and key documents to understand the role of school leadership in creating inclusive dual language programs to close the Latina/o-White…

  16. Role of model ingredients on the directed flow and its disappearance using isospin dependent quantum molecular dynamics model

    International Nuclear Information System (INIS)

    Bansal, R.

    2014-01-01

    We study the effect of different equations of state, momentum dependence of nuclear forces and in-medium nucleon-nucleon cross-sections on the directed flow and its disappearance. Our findings reveal that soft momentum-dependent equation of state along with reduced cross-section shows good agreement with the experimentally observed mass dependence of balance energy. (authors)

  17. Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation.

    Science.gov (United States)

    Soya, Shingo; Shoji, Hirotaka; Hasegawa, Emi; Hondo, Mari; Miyakawa, Tsuyoshi; Yanagisawa, Masashi; Mieda, Michihiro; Sakurai, Takeshi

    2013-09-04

    The noradrenergic (NA) projections arising from the locus ceruleus (LC) to the amygdala and bed nucleus of the stria terminalis have been implicated in the formation of emotional memory. Since NA neurons in the LC (LC-NA neurons) abundantly express orexin receptor-1 (OX1R) and receive prominent innervation by orexin-producing neurons, we hypothesized that an OX1R-mediated pathway is involved in the physiological fear learning process via regulation of LC-NA neurons. To evaluate this hypothesis, we examined the phenotype of Ox1r(-/-) mice in the classic cued and contextual fear-conditioning test. We found that Ox1r(-/-) mice showed impaired freezing responses in both cued and contextual fear-conditioning paradigms. In contrast, Ox2r(-/-) mice showed normal freezing behavior in the cued fear-conditioning test, while they exhibited shorter freezing time in the contextual fear-conditioning test. Double immunolabeling of Fos and tyrosine hydroxylase showed that double-positive LC-NA neurons after test sessions of both cued and contextual stimuli were significantly fewer in Ox1r(-/-) mice. AAV-mediated expression of OX1R in LC-NA neurons in Ox1r(-/-) mice restored the freezing behavior to the auditory cue to a comparable level to that in wild-type mice in the test session. Decreased freezing time during the contextual fear test was not affected by restoring OX1R expression in LC-NA neurons. These observations support the hypothesis that the orexin system modulates the formation and expression of fear memory via OX1R in multiple pathways. Especially, OX1R in LC-NA neurons plays an important role in cue-dependent fear memory formation and/or retrieval.

  18. The MEF2 gene is essential for yeast longevity, with a dual role in cell respiration and maintenance of mitochondrial membrane potential.

    Science.gov (United States)

    Callegari, Sylvie; McKinnon, Ross A; Andrews, Stuart; de Barros Lopes, Miguel A

    2011-04-20

    The Saccharomyces cerevisiae MEF2 gene is a mitochondrial protein translation factor. Formerly believed to catalyze peptide elongation, evidence now suggests its involvement in ribosome recycling. This study confirms the role of the MEF2 gene for cell respiration and further uncovers a slow growth phenotype and reduced chronological lifespan. Furthermore, in comparison with cytoplasmic ρ(0) strains, mef2Δ strains have a marked reduction of the inner mitochondrial membrane potential and mitochondria show a tendency to aggregate, suggesting an additional role for the MEF2 gene in maintenance of mitochondrial health, a role that may also be shared by other mitochondrial protein synthesis factors. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Dual Credit/Dual Enrollment and Data Driven Policy Implementation

    Science.gov (United States)

    Lichtenberger, Eric; Witt, M. Allison; Blankenberger, Bob; Franklin, Doug

    2014-01-01

    The use of dual credit has been expanding rapidly. Dual credit is a college course taken by a high school student for which both college and high school credit is given. Previous studies provided limited quantitative evidence that dual credit/dual enrollment is directly connected to positive student outcomes. In this study, predictive statistics…

  20. A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP expression in glial cells in response to neuroinflammatory stimuli

    Directory of Open Access Journals (Sweden)

    Milner Richard

    2011-06-01

    Full Text Available Abstract Background By neutralizing the effect of the matrix metalloproteinases (MMPs, the tissue inhibitors of matrix metalloproteinases (TIMPs play a critical role in maintaining tissue proteolysis in balance. As the major reactive glial cell types in the central nervous system (CNS, microglia and astrocytes play fundamental roles in mediating tissue breakdown and repair. As such, it is important to define the TIMP expression profile in these cells, as well as the mechanisms of regulation by neuroinflammatory stimuli. Methods Primary mixed glial cultures (MGC, pure microglia, and pure astrocytes were used in this study. To study astrocytes, we employed a recently described pure astrocyte culture system, which has the major advantage of totally lacking microglia. The three different types of culture were treated with lipopolysaccharide (LPS or individual cytokines, and cell culture supernatants assayed for TIMP-1 or TIMP-2 protein expression by western blot. Results LPS induced TIMP-1 expression in MGC, but not in pure astrocyte or microglial cultures. When pure astrocytes were treated with the cytokines IL-1β, IFN-γ, TNF or TGF-β1, only IL-1β induced TIMP-1 expression. Significantly, astrocyte TIMP-1 expression was restored in LPS-treated astrocyte cultures after the addition of microglia, or conditioned medium taken from LPS-activated microglia (MG-CM. Furthermore, this effect was lost after depletion of IL-1β from MG-CM. By contrast, TIMP-2 was constitutively expressed by astrocytes, whereas microglia expressed TIMP-2 only after exposure to serum. Conclusions Taken together, these results demonstrate an important concept in glial interactions, by showing that microglia play a central role in regulating glial cell expression of TIMPs, and identify microglial IL-1β as playing a key role in mediating microglial-astrocyte communication.

  1. Dual thyroid ectopia

    International Nuclear Information System (INIS)

    Al-Akeely, Mohammed H.

    2003-01-01

    Ectopic thyroid gland is a rare embryological fault of thyroid development .Dual ectopic thyroid is more rare and only 8 cases have been reported in the literature. The author presents a case of dual ectopic thyroid in a 16 year old boy with an anterior red neck mass, which is gradually growing in size particularly in last 2 years. The initial diagnosis was thyroglossal duct cyst. Thyroid function test revealed elevated thyroid-stimulating hormone. Ultrasound of the neck did not show thyroid gland in its normal pre tracheal position. Thyroid scan (Technetium 99)revealed the diagnosis of dual thyroid ectopia(lingual and subhyoid). (author)

  2. Dual energy CT

    DEFF Research Database (Denmark)

    Al-Najami, Issam; Drue, Henrik Christian; Steele, Robert

    2017-01-01

    and inaccurate with existing methods. Dual Energy Computed Tomography (DECT) enables qualitative tissue differentiation by simultaneous scanning with different levels of energy. We aimed to assess the feasibility of DECT in quantifying tumor response to neoadjuvant therapy in loco-advanced rectal cancer. METHODS...... to determine the average quantitative parameters; effective-Z, water- and iodine-concentration, Dual Energy Index (DEI), and Dual Energy Ratio (DER). These parameters were compared to the regression in the resection specimen as measured by the pathologist. RESULTS: Changes in the quantitative parameters...

  3. Dual coil ignition system

    Energy Technology Data Exchange (ETDEWEB)

    Huberts, Garlan J.; Qu, Qiuping; Czekala, Michael Damian

    2017-03-28

    A dual coil ignition system is provided. The dual coil ignition system includes a first inductive ignition coil including a first primary winding and a first secondary winding, and a second inductive ignition coil including a second primary winding and a second secondary winding, the second secondary winding connected in series to the first secondary winding. The dual coil ignition system further includes a diode network including a first diode and a second diode connected between the first secondary winding and the second secondary winding.

  4. The role of exercise dependence for the relationship between exercise behavior and eating pathology: mediator or moderator?

    Science.gov (United States)

    Cook, Brian J; Hausenblas, Heather A

    2008-05-01

    Our study examined the potential mediating or moderating effect of exercise dependence on the exercise-eating pathology relationship. Female university students (N = 330) completed Internet-based self-report measures of exercise behavior, exercise dependence, and eating pathology. Exercise dependence served as a mediator for the relationship between exercise and eating pathology. This unidirectional causal model suggests that an individual's pathological motivation or compulsion to exercise is the critical mediating component in the exercise-eating pathology relationship. The best target for removing the link between exercise behavior and eating pathology may be reformulating exercise dependence symptoms.

  5. The structure of dual Grassmann codes

    DEFF Research Database (Denmark)

    Beelen, Peter; Pinero, Fernando

    2016-01-01

    In this article we study the duals of Grassmann codes, certain codes coming from the Grassmannian variety. Exploiting their structure, we are able to count and classify all their minimum weight codewords. In this classification the lines lying on the Grassmannian variety play a central role. Rela...

  6. Redox Balance in Lactobacillus reuteri DSM20016: Roles of Iron-Dependent Alcohol Dehydrogenases in Glucose/ Glycerol Metabolism.

    Directory of Open Access Journals (Sweden)

    Lu Chen

    Full Text Available Lactobacillus reuteri, a heterofermentative bacterium, metabolizes glycerol via a Pdu (propanediol-utilization pathway involving dehydration to 3-hydroxypropionaldehyde (3-HPA followed by reduction to 1,3-propandiol (1,3-PDO with concomitant generation of an oxidized cofactor, NAD+ that is utilized to maintain cofactor balance required for glucose metabolism and even for oxidation of 3-HPA by a Pdu oxidative branch to 3-hydroxypropionic acid (3-HP. The Pdu pathway is operative inside Pdu microcompartment that encapsulates different enzymes and cofactors involved in metabolizing glycerol or 1,2-propanediol, and protects the cells from the toxic effect of the aldehyde intermediate. Since L. reuteri excretes high amounts of 3-HPA outside the microcompartment, the organism is likely to have alternative alcohol dehydrogenase(s in the cytoplasm for transformation of the aldehyde. In this study, diversity of alcohol dehydrogenases in Lactobacillus species was investigated with a focus on L. reuteri. Nine ADH enzymes were found in L. reuteri DSM20016, out of which 3 (PduQ, ADH6 and ADH7 belong to the group of iron-dependent enzymes that are known to transform aldehydes/ketones to alcohols. L. reuteri mutants were generated in which the three ADHs were deleted individually. The lagging growth phenotype of these deletion mutants revealed that limited NAD+/NADH recycling could be restricting their growth in the absence of ADHs. Notably, it was demonstrated that PduQ is more active in generating NAD+ during glycerol metabolism within the microcompartment by resting cells, while ADH7 functions to balance NAD+/NADH by converting 3-HPA to 1,3-PDO outside the microcompartment in the growing cells. Moreover, evaluation of ADH6 deletion mutant showed strong decrease in ethanol level, supporting the role of this bifuctional alcohol/aldehyde dehydrogenase in ethanol production. To the best of our knowledge, this is the first report revealing both internal and

  7. Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice

    International Nuclear Information System (INIS)

    Nakada, Shinichiro

    2016-01-01

    The E3 ubiquitin ligases ring finger protein (RNF) 8 and RNF168 transduce the DNA double-strand break (DSB) response (DDR) signal by ubiquitinating DSB sites. The depletion of RNF8 or RNF168 suppresses the accumulation of DNA-repair regulating factors such as 53BP1 and RAP80 at DSB sites, suggesting roles for RNF8- and RNF168-mediated ubiquitination in DSB repair. This mini-review provides a brief overview of the RNF8- and RNF168-dependent DDR-signaling and DNA-repair pathways. The choice of DNA-repair pathway when RNF8- and RNF168-mediated ubiquitination-dependent DDR signaling is negatively regulated by deubiquitinating enzymes (DUBs) is reviewed to clarify how the opposing roles of RNF8/RNF168 and DUBs regulate ubiquitination-dependent DDR signaling and the choice of DNA-repair pathway

  8. The ATPase and protease domains of yeast mitochondrial Lon : Roles in proteolysis and respiration-dependent growth

    NARCIS (Netherlands)

    van Dijl, JM; Kutejova, E; Suda, K; Perecko, D; Schatz, G; Suzuki, CK

    1998-01-01

    The ATP-dependent Lon protease of Saccharomyces cerevisiae mitochondria is required for selective proteolysis in the matrix, maintenance of mitochondrial DNA, and respiration-dependent growth. Lon may also possess a chaperone-like function that facilitates protein degradation and protein-complex

  9. Physical and mental health and social functioning in older alcohol-dependent inpatients: the role of age of onset

    NARCIS (Netherlands)

    van den Berg, Julia F.; Hermes, Jolanda S. J.; van den Brink, Wim; Blanken, Peter; Kist, Nicolien; Kok, Rob M.

    2014-01-01

    Age of onset is an important criterion to distinguish subgroups of alcohol-dependent patients. This study investigated physical and mental health and social functioning of older inpatients with early (age <25), late (25-44), and very late (≥45) onset of alcohol dependence. In a specialized

  10. The dual role of Candida glabrata Drug:H+ Antiporter CgAqr1 (ORF CAGL0J09944g in antifungal drug and acetic acid resistance

    Directory of Open Access Journals (Sweden)

    Catarina eCosta

    2013-06-01

    Full Text Available Opportunistic Candida species often have to cope with inhibitory concentrations of acetic acid, in the acidic environment of the vaginal mucosa. Given that the ability of these yeast species to tolerate stress induced by weak acids and antifungal drugs appears to be a key factor in their persistence and virulence, it is crucial to understand the underlying mechanisms.In this study, the Drug:H+ Antiporter CgAqr1 (ORF CAGL0J09944g, from Candida glabrata, was identified as a determinant of resistance to acetic acid, and also to the antifungal agents flucytosine and, less significantly, clotrimazole. These antifungals were found to act synergistically with acetic acid against this pathogen. The action of CgAqr1 in this phenomenon was analyzed. Using a GFP fusion, CgAqr1 was found to localize to the plasma membrane and to membrane vesicles when expressed in C. glabrata or, heterologously, in Saccharomyces cerevisiae. Given its ability to complement the susceptibility phenotype of its S. cerevisiae homolog, ScAqr1, CgAqr1 was proposed to play a similar role in mediating the extrusion of chemical compounds. Significantly, the expression of this gene was found to reduce the intracellular accumulation of 3H-flucytosine and, to a moderate extent, of 3H-clotrimazole, consistent with a direct role in antifungal drug efflux. Interestingly, no effect of CgAQR1 deletion could be found on the intracellular accumulation of 14C-acetic acid, suggesting that its role in acetic acid resistance may be indirect, presumably through the transport of a still unidentified physiological substrate. Although neither of the tested chemicals induces changes in CgAQR1 expression, pre-exposure to flucytosine or clotrimazole was found to make C. glabrata cells more sensitive to acetic acid stress. Results from this study show that CgAqr1 is an antifungal drug resistance determinant and raise the hypothesis that it may play a role in C. glabrata persistent colonization and

  11. Dual Dynamic Programming - DDP

    International Nuclear Information System (INIS)

    Velasquez Bermudez, Jesus M

    1998-01-01

    Objections are presented to the mathematical formulation of the denominated Dual Dynamic programming-PDD that is the theoretical base of several computational model available for the optimal formulation of interconnected hydrothermal systems

  12. Dual Enrollment, Structural Reform, and the Completion Agenda

    Science.gov (United States)

    Karp, Melinda Mechur

    2015-01-01

    This chapter contextualizes and extends the previous chapters by addressing the intertwined issues of structural systems reform and college completion, as well as the role dual enrollment can play in ensuring equitable postsecondary outcomes for underrepresented students.

  13. Animal Modeling and Neurocircuitry of Dual Diagnosis

    Science.gov (United States)

    Chambers, R. Andrew

    2010-01-01

    Dual diagnosis is a problem of tremendous depth and scope, spanning many classes of mental disorders and addictive drugs. Animal models of psychiatric disorders studied in addiction paradigms suggest a unitary nature of mental illness and addiction vulnerability both on the neurocircuit and clinical-behavioral levels. These models provide platforms for exploring the interactive roles of biological, environmental and developmental factors on neurocircuits commonly involved in psychiatric and addiction diseases. While suggestive of the artifice of segregated research, training, and clinical cultures between psychiatric and addiction fields, this research may lead to more parsimonious, integrative and preventative treatments for dual diagnosis. PMID:20585464

  14. miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell function.

    Science.gov (United States)

    Lim, Shok Ping; Ioannou, Nikolaos; Ramsay, Alan G; Darling, David; Gäken, Joop; Mufti, Ghulam J

    2018-05-01

    MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have showed that miR-181c regulates BRK1 by translational inhibition. Given the importance of miR-181 in T cell function and the potential role of BRK1 in the involvement of WAVE2 complex and actin polymerization in T cells, we therefore investigated the influence of miR-181c-BRK1 axis in T cell function. Stimulation of PBMC derived CD3 + T cells resulted in reduced miR-181c expression and up-regulation of BRK1 protein expression, suggesting that miR-181c-BRK1 axis is important in T cell activation. We further showed that overexpression of miR-181c or suppression of BRK1 resulted in inhibition of T cell activation and actin polymerization coupled with defective lamellipodia generation and immunological synapse formation. Additionally, we found that BRK1 silencing led to reduced expressions of other proteins in the WAVE2 complex, suggesting that the impairment of T cell actin dynamics was a result of the instability of the WAVE2 complex following BRK1 depletion. Collectively, we demonstrated that miR-181c reduces BRK1 protein expression level and highlighted the important role of miR-181c-BRK1 axis in T cell activation and actin polymerization-mediated T cell functions. ©2018 Society for Leukocyte Biology.

  15. Work Stress and Depressive Symptoms in Fishermen With a Smoking Habit: A Mediator Role of Nicotine Dependence and Possible Moderator Role of Expressive Suppression and Cognitive Reappraisal.

    Science.gov (United States)

    Jiang, Hongjuan; Li, Sailan; Yang, Juan

    2018-01-01

    This study examined pathways of influence between work stress, depressive symptoms, nicotine dependence, expressive suppression, and cognitive reappraisal in fishermen with smoking habits in Qionghai, Hainan province, China (N = 1068). These fishermen responded to multiple assessments a week before leaving on a deep-sea fishing trip, including a Mental Stressor Investigation Questionnaire (MSIQ), the Center for Epidemiological Studies Depression Scale (CES-D), the Russell Reason for Smoking Questionnaire (RRSQ), and an Emotion Regulation Questionnaire (ERQ). Structural equation modeling (SEM) analyses of the collected data in Mplus 7 showed that work stress and nicotine dependence were independent predictors of depressive symptoms. The relationship between work stress and depressive symptoms was found to be partially mediated by nicotine dependence and be moderated by cognitive reappraisal. The evidence suggests it advantageous to examine the need of work stress, nicotine dependence, and cognitive reappraisal when attempting to understand depressive symptoms in fishermen with a smoking habit. These findings suggest that improving nicotine dependence through work stress management and training in cognitive reappraisal could be utilized as effective modalities for improving depressive symptoms.

  16. Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 in the surface expression of malaria parasite var proteins

    DEFF Research Database (Denmark)

    Goel, Suchi; Valiyaveettil, Manojkumar; Achur, Rajeshwara N

    2010-01-01

    adherence. However, how CLAG9 influences this process remains unknown. In this study, we show that CLAG9 interacts with VAR2CSA, a PfEMP1 that mediates IRBC adherence to chondroitin 4-sulfate in the placenta. Importantly, our results show that the adherent parasites synthesize CLAG9 at two stages--the early......Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate the adherence of parasite-infected red blood cells (IRBCs) to various host receptors. A previous study has shown that the parasite protein, cytoadherence-linked asexual gene 9 (CLAG9), is also essential for IRBC...... within the parasite. Based on these findings, we propose that CLAG9 plays a critical role in the trafficking of PfEMP1s onto the IRBC surface. These results have important implications for the development of therapeutics for cerebral, placental, and other cytoadherence-associated malaria illnesses....

  17. Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Tusharkanti; Gupta, Pritha; Ghosh, Rupsa; Kabir, Syed N; Roy, Avishek

    2016-12-01

    The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

  18. Dual Role for Hsc70 in the Biogenesis and Regulation of the Heme-Regulated Kinase of the α Subunit of Eukaryotic Translation Initiation Factor 2

    Science.gov (United States)

    Uma, Sheri; Thulasiraman, Vanitha; Matts, Robert L.

    1999-01-01

    The heme-regulated kinase of the α subunit of eukaryotic initiation factor 2 (HRI) is activated in rabbit reticulocyte lysate (RRL) in response to a number of environmental conditions, including heme deficiency, heat shock, and oxidative stress. Activation of HRI causes an arrest of initiation of protein synthesis. Recently, we have demonstrated that the heat shock cognate protein Hsc70 negatively modulates the activation of HRI in RRL in response to these environmental conditions. Hsc70 is also known to be a critical component of the Hsp90 chaperone machinery in RRL, which plays an obligatory role for HRI to acquire and maintain a conformation that is competent to activate. Using de novo-synthesized HRI in synchronized pulse-chase translations, we have examined the role of Hsc70 in the regulation of HRI biogenesis and activation. Like Hsp90, Hsc70 interacted with nascent HRI and HRI that was matured to a state which was competent to undergo stimulus-induced activation (mature-competent HRI). Interaction of HRI with Hsc70 was required for the transformation of HRI, as the Hsc70 antagonist clofibric acid inhibited the folding of HRI into a mature-competent conformation. Unlike Hsp90, Hsc70 also interacted with transformed HRI. Clofibric acid disrupted the interaction of Hsc70 with transformed HRI that had been matured and transformed in the absence of the drug. Disruption of Hsc70 interaction with transformed HRI in heme-deficient RRL resulted in its hyperactivation. Furthermore, activation of HRI in response to heat shock or denatured proteins also resulted in a similar blockage of Hsc70 interaction with transformed HRI. These results indicate that Hsc70 is required for the folding and transformation of HRI into an active kinase but is subsequently required to negatively attenuate the activation of transformed HRI. PMID:10454533

  19. Reduced frontal brain volume in non-treatment-seeking cocaine-dependent individuals: exploring the role of impulsivity, depression, and smoking.

    Science.gov (United States)

    Crunelle, Cleo L; Kaag, Anne Marije; van Wingen, Guido; van den Munkhof, Hanna E; Homberg, Judith R; Reneman, Liesbeth; van den Brink, Wim

    2014-01-01

    In cocaine-dependent patients, gray matter (GM) volume reductions have been observed in the frontal lobes that are associated with the duration of cocaine use. Studies are mostly restricted to treatment-seekers and studies in non-treatment-seeking cocaine abusers are sparse. Here, we assessed GM volume differences between 30 non-treatment-seeking cocaine-dependent individuals and 33 non-drug using controls using voxel-based morphometry. Additionally, within the group of non-treatment-seeking cocaine-dependent individuals, we explored the role of frequently co-occurring features such as trait impulsivity (Barratt Impulsivity Scale, BIS), smoking, and depressive symptoms (Beck Depression Inventory), as well as the role of cocaine use duration, on frontal GM volume. Smaller GM volumes in non-treatment-seeking cocaine-dependent individuals were observed in the left middle frontal gyrus. Moreover, within the group of cocaine users, trait impulsivity was associated with reduced GM volume in the right orbitofrontal cortex, the left precentral gyrus, and the right superior frontal gyrus, whereas no effect of smoking severity, depressive symptoms, or duration of cocaine use was observed on regional GM volumes. Our data show an important association between trait impulsivity and frontal GM volumes in cocaine-dependent individuals. In contrast to previous studies with treatment-seeking cocaine-dependent patients, no significant effects of smoking severity, depressive symptoms, or duration of cocaine use on frontal GM volume were observed. Reduced frontal GM volumes in non-treatment-seeking cocaine-dependent subjects are associated with trait impulsivity and are not associated with co-occurring nicotine dependence or depression.

  20. A Role for the DRD4 Exon III VNTR in Modifying the Association Between Nicotine Dependence and Neuroticism

    NARCIS (Netherlands)

    Ellis, J.A.; Olssen, C.A.; Moore, E.; Greenwood, P.A.; Ven, M.O.M. van de; Patton, G.C.

    2011-01-01

    Introduction: Neurotic psychopathology has been extensively examined as a risk factor for nicotine dependence (ND). Genetic stratification may partially explain variability in risk estimates. Genetic variants that compromise dopaminergic neurotransmission may motivate exposure to

  1. Dual Active Galactic Nuclei in Nearby Galaxies

    Science.gov (United States)

    Das, Mousumi; Rubinur, Khatun; Karb, Preeti; Varghese, Ashlin; Novakkuni, Navyasree; James, Atul

    2018-04-01

    Galaxy mergers play a crucial role in the formation of massive galaxies and the buildup of their bulges. An important aspect of the merging process is the in-spiral of the supermassive black-holes (SMBHs) to the centre of the merger remnant and the eventual formation of a SMBH binary. If both the SMBHs are accreting they will form a dual or binary active galactic nucleus (DAGN). The final merger remnant is usually very bright and shows enhanced star formation. In this paper we summarise the current sample of DAGN from previous studies and describe methods that can be used to identify strong DAGN candidates from optical and spectroscopic surveys. These methods depend on the Doppler separation of the double peaked AGN emission lines, the nuclear velocity dispersion of the galaxies and their optical/UV colours. We describe two high resolution, radio observations of DAGN candidates that have been selected based on their double peaked optical emission lines (DPAGN). We also examine whether DAGN host galaxies have higher star formation rates (SFRs) compared to merging galaxies that do not appear to have DAGN. We find that the SFR is not higher for DAGN host galaxies. This suggests that the SFRs in DAGN host galaxies is due to the merging process itself and not related to the presence of two AGN in the system.

  2. The Experience of Dual Career through Slovak Athletes’ Eyes

    Directory of Open Access Journals (Sweden)

    Geraniosova Kristina

    2015-06-01

    Full Text Available The purpose of this study was to examine how Slovak athletes experience dual career (the combination of an athletic career with education and/or work. The study strived to gain an understanding of the athletes’ attitudes towards education as well as perceived difficulties and supporting elements in pursuing dual career. Five athletes were interviewed once for approx. 105 min. The interviews and data analysis were based on Intepretative Phenomenological Analysis (IPA and the interviews were focused on their experience in combining an athletic career with education or work. The athletes experienced dual career as manageable as long as they were assisted by at least simple supportive structures and provided flexible arrangements. Peers had played an important role in athletes’ decision-making concerning dual career and in providing social support when facing challenges within dual career. The teachers’ prejudice against the athletes based on their athletic role and the lack of dual career structures appeared to be significant deficiencies in dual career support. Finally, the analysis revealed the negative perception of athletes and sport science students by educational representatives. This perception may be a hurdle to be overcome in future dual career development.

  3. A Tale of Two Entangled Instabilities—The Dual Role of δ-O in HgBa2Can-1CunO2(n+1+δ

    Directory of Open Access Journals (Sweden)

    Itai Panas

    2015-10-01

    Full Text Available Low-energy instabilities in the hole-doped cuprates include, besides short range antiferromagnetic fluctuations and superconductivity, also ubiquitous translational and rotational symmetry breakings. The overwhelming majority of interpretations of these possibly related properties rely on mappings onto three bands spanned by the three atomic orbitals Cu3d(x2−y2(σ, O2px(σ, and O2py(σ, these three local orbitals spanning the Zhang–Rice band (ZRB, the lower Hubbard bands (LHB and the upper Hubbard bands (UHB, respectively. Here we demonstrate by means of supercell Density Functional Theory (DFT (a how oxygen intercalation affects the structures of the buffer layers, and (b how the attenuated crystal field pulls two additional oxygen bands in the CuO2 plane to the Fermi level. The self-consistent changes in electronic structure reflected in the corresponding changes in external potential comprise formal properties of the Hohenberg–Kohn theorems. Validation of present days’ approximate exchange-correlation potentials to capture these qualitative effects by means of supercell DFT is made by comparing computed doping dependent structural shifts to corresponding experimentally observed correlations. The simplest generalization of Bardeen–Cooper–Schrieffer (BCS theory is offered to articulate high-critical temperature superconductivity (HTS from a normal state where crystal field causes states related to two non-hybridizing bands to coalesce at EF.

  4. Surface cleaning and adsorbate layer formation: Dual role of alkylamines in the formation of self-assembled monolayers on cuprate superconductors

    International Nuclear Information System (INIS)

    Ritchie, J.E.; Murray, W.R.; Kershan, K.; Diaz, V.; Tran, L.; McDevitt, J.T.

    1999-01-01

    The development of monolayer adsorption chemistry for superconductor surfaces is particularly important for a number of practical and fundamental reasons. As high-T c superconductors begin to approach the marketplace in areas of communications, power industries, medical applications, and scientific instrumentation, the development of new soft chemistry approaches for the surface modification of these technologically relevant electronic materials becomes increasingly important. Monolayer adsorption chemistry has been developed extensively for electronic materials such as metals, semiconductors, and insulators. These methodologies have been expanded recently to include a variety of high-temperature superconductors (HTSCs). The authors describe a series of new X-ray photoelectron spectroscopy (XPS), four-point conductivity, critical current, atomic absorption spectroscopy (AAS), grazing angle infrared spectroscopy, and GE--MS experiments, which lead the suggestion that an entirely different mechanism is involved in the formation of HTSC-localized monolayers. According to the new model, the amine reagents serve two chemically distinct roles. In the initial phase, the degraded superconductor exteriors is etched away with the help of the amine compounds. The etching process proceeds to the point where fresh YBa 2 Cu 3 O 7 is exposed, and only at this point do the amines adsorb and remain at the YBa 2 Cu 3 O 7 surface. As the adsorption process continues, there is an accumulation of an organized monolayer at the surface, which prevents further etching of the YBa 2 Cu 3 O 7 material

  5. Gas Flows in Dual Active Galactic Nuclei

    Science.gov (United States)

    Mueller Sanchez, Francisco; Comerford, Julia M.; Davies, Richard; Treister, Ezequiel; Privon, George C.; Nevin, Becky

    2018-06-01

    Dual Active Galactic Nuclei (AGN) are the Rosetta stone to understand the role of galaxy mergers in triggering nuclear activity and regulating black hole (BH) and galaxy growth. But very little is known about the physical processes required to effectively trigger AGN activity and regulate the growth of the two BHs. The work I will present here characterizes for the first time the properties of the stars, gas (molecular, ionized, and highly-ionized) and dust in all the confirmed dual AGN at z prototypical merger system NGC 6240: vigorous star formation, two AGNs, outflowing winds of ionized gas, rippling dust and gas lanes, and tidal tails. In this galaxy, we observe for the first time a dual outflow of different species of gas: an AGN-driven outflow of highly-ionized gas to the northeast and a starburst-driven outflow of ionized hydrogen to the northwest. This shows that stellar feedback and supermassive black hole feedback can work in tandem to regulate the stellar growth of a galaxy after a merger event. These results open a new door to studies of dual AGN and AGN pairs in general, and enable dual AGN to be used, for the first time, for studies of galaxy evolution.

  6. Continuous mutual improvement of macromolecular structure models in the PDB and of X-ray crystallographic software: the dual role of deposited experimental data.

    Science.gov (United States)

    Terwilliger, Thomas C; Bricogne, Gerard

    2014-10-01

    Accurate crystal structures of macromolecules are of high importance in the biological and biomedical fields. Models of crystal structures in the Protein Data Bank (PDB) are in general of very high quality as deposited. However, methods for obtaining the best model of a macromolecular structure from a given set of experimental X-ray data continue to progress at a rapid pace, making it possible to improve most PDB entries after their deposition by re-analyzing the original deposited data with more recent software. This possibility represents a very significant departure from the situation that prevailed when the PDB was created, when it was envisioned as a cumulative repository of static contents. A radical paradigm shift for the PDB is therefore proposed, away from the static archive model towards a much more dynamic body of continuously improving results in symbiosis with continuously improving methods and software. These simultaneous improvements in methods and final results are made possible by the current deposition of processed crystallographic data (structure-factor amplitudes) and will be supported further by the deposition of raw data (diffraction images). It is argued that it is both desirable and feasible to carry out small-scale and large-scale efforts to make this paradigm shift a reality. Small-scale efforts would focus on optimizing structures that are of interest to specific investigators. Large-scale efforts would undertake a systematic re-optimization of all of the structures in the PDB, or alternatively the redetermination of groups of structures that are either related to or focused on specific questions. All of the resulting structures should be made generally available, along with the precursor entries, with various views of the structures being made available depending on the types of questions that users are interested in answering.

  7. Sil: a Streptococcus iniae bacteriocin with dual role as an antimicrobial and an immunomodulator that inhibits innate immune response and promotes S. iniae infection.

    Directory of Open Access Journals (Sweden)

    Mo-fei Li

    Full Text Available Streptococcus iniae is a Gram-positive bacterium and a severe pathogen to a wide range of economically important fish species. In addition, S. iniae is also a zoonotic pathogen and can cause serious infections in humans. In this study, we identified from a pathogenic S. iniae strain a putative bacteriocin, Sil, and examined its biological activity. Sil is composed of 101 amino acid residues and shares 35.6% overall sequence identity with the lactococcin 972 of Lactococcus lactis. Immunoblot analysis showed that Sil was secreted by S. iniae into the extracellular milieu. Purified recombinant Sil (rSil exhibited a dose-dependent inhibitory effect on the growth of Bacillus subtilis but had no impact on the growths of other 16 Gram-positive bacteria and 10 Gram-negative bacteria representing 23 different bacterial species. Treatment of rSil by heating at 50°C abolished the activity of rSil. rSil bound to the surface of B. subtilis but induced no killing of the target cells. Cellular study revealed that rSil interacted with turbot (Scophthalmus maximus head kidney monocytes and inhibited the innate immune response of the cells, which led to enhanced cellular infection of S. iniae. Antibody blocking of the extracellular Sil produced by S. iniae significantly attenuated the infectivity of S. iniae. Consistent with these in vitro observations, in vivo study showed that administration of turbot with rSil prior to S. iniae infection significantly increased bacterial dissemination and colonization in fish tissues. Taken together, these results indicate that Sil is a novel virulence-associated bacteriostatic and an immunoregulator that promotes S. iniae infection by impairing the immune defense of host fish.

  8. The novel and taxonomically restricted Ah24 gene from grain amaranth (Amaranthus hypochondriacus has a dual role in development and defense

    Directory of Open Access Journals (Sweden)

    Julio Armando Massange-Sanchez

    2015-08-01

    Full Text Available Grain amaranths tolerate stress and produce highly nutritious seeds. We have identified several (abiotic stress-responsive genes of unknown function in Amaranthus hypochondriacus, including the so-called Ah24 gene. Ah24 was expressed in young or developing tissues; it was also strongly induced by mechanical damage, insect herbivory and methyl jasmonate and in meristems and newly emerging leaves of severely defoliated plants. Interestingly, an in silico analysis of its 1304 bp promoter region showed a predominance of regulatory boxes involved in development, but not in defense. The Ah24 cDNA encodes a predicted cytosolic protein of 164 amino acids, the localization of which was confirmed by confocal microscopy. Additional in silico analysis identified several other Ah24 homologs, present almost exclusively in plants belonging to the Caryophyllales. The possible function of this gene in planta was examined in transgenic Ah24 overexpressing Arabidopsis thaliana and Nicotiana tabacum plants. Transformed Arabidopsis showed enhanced vegetative growth and increased leaf number with no penalty in one fitness component, such as seed yield, in experimental conditions. Transgenic tobacco plants, which grew and reproduced normally, had increased insect herbivory resistance. Modified vegetative growth in transgenic Arabidopsis coincided with significant changes in the expression of genes controlling phytohormone synthesis or signaling, whereas increased resistance to insect herbivory in transgenic tobacco coincided with higher jasmonic acid and proteinase inhibitor activity levels, plus the accumulation of nicotine and several other putative defense-related metabolites. It is proposed that the primary role of the Ah24 gene in A. hypochondriacus is to contribute to a rapid recovery post-wounding or defoliation, although its participation in defense against insect herbivory is also plausible.

  9. Reconstitution of proapoptotic BAK function in liposomes reveals a dual role for mitochondrial lipids in the BAK-driven membrane permeabilization process.

    Science.gov (United States)

    Landeta, Olatz; Landajuela, Ane; Gil, David; Taneva, Stefka; Di Primo, Carmelo; Sot, Begoña; Valle, Mikel; Frolov, Vadim A; Basañez, Gorka

    2011-03-11

    BAK is a key effector of mitochondrial outer membrane permeabilization (MOMP) whose molecular mechanism of action remains to be fully dissected in intact cells, mainly due to the inherent complexity of the intracellular apoptotic machinery. Here we show that the core features of the BAK-driven MOMP pathway can be reproduced in a highly simplified in vitro system consisting of recombinant human BAK lacking the carboxyl-terminal 21 residues (BAKΔC) and tBID in combination with liposomes bearing an appropriate lipid environment. Using this minimalist reconstituted system we established that tBID suffices to trigger BAKΔC membrane insertion, oligomerization, and pore formation. Furthermore, we demonstrate that tBID-activated BAKΔC permeabilizes the membrane by forming structurally dynamic pores rather than a large proteinaceous channel of fixed size. We also identified two distinct roles played by mitochondrial lipids along the molecular pathway of BAKΔC-induced membrane permeabilization. First, using several independent approaches, we showed that cardiolipin directly interacts with BAKΔC, leading to a localized structural rearrangement in the protein that "primes" BAKΔC for interaction with tBID. Second, we provide evidence that selected curvature-inducing lipids present in mitochondrial membranes specifically modulate the energetic expenditure required to create the BAKΔC pore. Collectively, our results support the notion that BAK functions as a direct effector of MOMP akin to BAX and also adds significantly to the growing evidence indicating that mitochondrial membrane lipids are actively implicated in BCL-2 protein family function.

  10. The role of emotional and behavioral disorders in the development of drug dependence in patients with medication-induced headache (review

    Directory of Open Access Journals (Sweden)

    A. E. Shagbazyan

    2016-01-01

    Full Text Available Medication-induced headache (MIH is a variety of chronic daily headache (HA. MIH belongs to secondary (symptomatic HA, develops as a complication of pre-existing primary cephalgia, and is caused by the overuse of drugs to relieve HA. The role of drug dependence syndrome and behavioral and emotional disorders in the development of MIH, which may be associated with dysfunction of certain brain systems that control these functions, has been recently discussed. The paper reviews the literature dealing with studies of the role of behavioral and emotional disorders and orbitofrontal cortical dysfunction in the development of drug dependence syndrome in patients with MIH. The importance of analyzing these aspects of MIH is determined by the prospects for applying alternative approaches to managing these patients.

  11. Continuous mutual improvement of macromolecular structure models in the PDB and of X-ray crystallographic software: the dual role of deposited experimental data

    International Nuclear Information System (INIS)

    Terwilliger, Thomas C.; Bricogne, Gerard

    2014-01-01

    made generally available, along with the precursor entries, with various views of the structures being made available depending on the types of questions that users are interested in answering

  12. Continuous mutual improvement of macromolecular structure models in the PDB and of X-ray crystallographic software: the dual role of deposited experimental data

    Energy Technology Data Exchange (ETDEWEB)

    Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov [Los Alamos National Laboratory, Mail Stop M888, Los Alamos, NM 87507 (United States); Bricogne, Gerard, E-mail: terwilliger@lanl.gov [Global Phasing Ltd, Sheraton House, Castle Park, Cambridge CB3 0AX (United Kingdom); Los Alamos National Laboratory, Mail Stop M888, Los Alamos, NM 87507 (United States)

    2014-10-01

    made generally available, along with the precursor entries, with various views of the structures being made available depending on the types of questions that users are interested in answering.

  13. The Predictive Role of Difficulties in Emotion Regulation and Self-Control with Susceptibility to Addiction in Drug-Dependent Individuals

    OpenAIRE

    Mahmoud Shirazi; Monavar Janfaza

    2015-01-01

    Objective: The present study aimed to examine the predictive role of difficulties in emotion regulation and self-control in potential for addiction among drug-dependent individuals. Method: This was a correlational study which falls within the category of descriptive studies. The statistical population of the current study included all patients under treatment in outpatient health centers in Bam, among whom 315 individuals were selected through cluster sampling method as the participants of t...

  14. Self-dual Hopf quivers

    International Nuclear Information System (INIS)

    Huang Hualin; Li Libin; Ye Yu

    2004-07-01

    We study pointed graded self-dual Hopf algebras with a help of the dual Gabriel theorem for pointed Hopf algebras. Quivers of such Hopf algebras are said to be self-dual. An explicit classification of self-dual Hopf quivers is obtained. We also prove that finite dimensional coradically graded pointed self-dual Hopf algebras are generated by group-like and skew-primitive elements as associative algebras. This partially justifies a conjecture of Andruskiewitsch and Schneider and may help to classify finite dimensional self-dual pointed Hopf algebras

  15. The role of cAMP-dependent protein kinase A in bile canalicular plasma membrane biogenesis in hepatocytes

    NARCIS (Netherlands)

    Wojtal, Kacper Andrze

    2007-01-01

    cAMP-dependent protein kinase A is one of the most important enzymes in the eukaryotic cell. The function of this protein is strictly in a close relation to the signaling pathways, which trigger the production of intracellular secondary messenger –cAMP. As a consequence of PKA activation numerous

  16. The role of thymus-dependent T cells in hexachlorobenzene-induced inflammatory skin and lung lesions

    NARCIS (Netherlands)

    Michielsen, CCPPC; Bloksma, N; Klatter, FA; Rozing, J; Vos, JG; van Dijk, JE

    1999-01-01

    The involvement of thymus-dependent T cells in the inflammatory skin and lung lesions and spleen effects induced by hexachlorobenzene (HCB) was investigated by using genetically athymic and euthymic WAG/Rij rats and Brown Norway (BN) rats with or without depletion of T cells by adult thymectomy,

  17. Research Paper: Cross State-dependent Learning Interaction Between Scopolamine and Morphine in Mice: The Role of Dorsal Hippocampus