Sample records for subordinate male helpers

  1. Susceptibility or resilience? Prenatal stress predisposes male rats to social subordination, but facilitates adaptation to subordinate status. (United States)

    Scott, Karen A; de Kloet, Annette D; Smeltzer, Michael D; Krause, Eric G; Flak, Jonathan N; Melhorn, Susan J; Foster, Michelle T; Tamashiro, Kellie L K; Sakai, Randall R


    Mood disorders such as major depressive disorder (MDD) affect a significant proportion of the population. Although progress has been made in the development of therapeutics, a large number of individuals do not attain full remission of symptoms and adverse side effects affect treatment compliance for some. In order to develop new therapies, there is a push for new models that better reflect the multiple risk factors that likely contribute to the development of depressive illness. We hypothesized that early life stress would exacerbate the depressive-like phenotype that we have previously observed in socially subordinate (SUB) adult male rats in the visible burrow system (VBS), a semi-natural, ethologically relevant environment in which males in a colony form a dominance hierarchy. Dams were exposed to chronic variable stress (CVS) during the last week of gestation, resulting in a robust and non-habituating glucocorticoid response that did not alter maternal food intake, body weight or litter size and weight. As adults, one prenatal CVS (PCVS) and one non-stressed (NS) male were housed in the VBS with adult females. Although there were no overt differences between PCVS and NS male offspring prior to VBS housing, a greater percentage of PCVS males became SUB. However, the depressive-like phenotype of SUB males was not exacerbated in PCVS males; rather, they appeared to better cope with SUB status than NS SUB males. They had lower basal plasma corticosterone than NS SUB males at the end of VBS housing. In situ hybridization for CRH in the PVN and CeA did not reveal any prenatal treatment or status effects, while NPY expression was higher within the MeA of dominant and subordinate males exposed to the VBS in comparison with controls, but with no effect of prenatal treatment. These data suggest that prenatal chronic variable stress may confer resilience to offspring when exposed to social stress in adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Sociality and oxytocin and vasopressin in the brain of male and female dominant and subordinate mandarin voles. (United States)

    Qiao, Xufeng; Yan, Yating; Wu, Ruiyong; Tai, Fadao; Hao, Ping; Cao, Yan; Wang, Jianli


    The dominant-subordinate hierarchy in animals often needs to be established via agonistic encounters and consequently affects reproduction and survival. Differences in brain neuropeptides and sociality among dominant and subordinate males and females remain poorly understood. Here we explore neuropeptide levels and sociality during agonistic encounter tests in mandarin voles. We found that dominant mandarin voles engaged in higher levels of approaching, investigating, self-grooming and exploring behavior than subordinates. Dominant males habituated better to a stimulus vole than dominant females. Dominant males displayed significantly less oxytocin-immunoreactive neurons in the paraventricular nuclei and more vasopressin-immunoreactive neurons in the paraventricular nuclei, supraoptic nuclei, and the lateral and anterior hypothalamus than subordinates. Dominant females displayed significantly more vasopressin-immunoreactive neurons in the lateral hypothalamus and anterior hypothalamus than subordinates. Sex differences were found in the level of oxytocin and vasopressin. These results indicate that distinct parameters related to central nervous oxytocin and vasopressin are associated with behaviors during agonistic encounters in a sex-specific manner in mandarin voles.

  3. The need for power, need for influence, sense of power, and directiveness in female and male superiors and subordinates

    Directory of Open Access Journals (Sweden)

    Dagna Kocur


    Full Text Available Background The purpose of the study was to examine the phenomenon of power within an organisation from the vantage point of gender, the occupied position, earnings, and the number of subordinates. Participants and procedure The sample group comprised 107 female and 98 male participants. The mean age was 42.14 years (SD = 11.73. The study covered 100 superiors and 105 subordinates. The research tools were: the Need for Power and Influence Questionnaire (Bennett, 1988, the Personal Sense of Power Scale (Anderson, John, & Keltner, 2012, and the Directiveness Scale SD (Ray, 1976. Results The superiors scored significantly higher on the need for power, need for influence, and directiveness. They also scored higher in terms of the need for power in relations with other people, with colleagues, and in superior-subordinate relations. The number of male leaders was conspicuously greater than the number of female leaders. Furthermore, women had fewer subordinates than men and earned less than men. Female participants scored lower on the sense of power and the need for power scales. Conclusions Occupying either an executive or subordinate position differentiates between women and men in terms of sense of power in interpersonal relationships. The findings on sense of power in the professional context may be applied in organisational psychology in order to increase employees’ competence and qualifications.

  4. Chronic subordinate colony housing (CSC as a model of chronic psychosocial stress in male rats.

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    Kewir D Nyuyki

    Full Text Available Chronic subordinate colony housing (CSC is an adequate and reliable mouse model of chronic psychosocial stress, resulting in reduced body weight gain, reduced thymus and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Furthermore, CSC mice show increased corticotrophin (ACTH responsiveness to acute heterotypic stressors, suggesting a general mechanism which allows a chronically-stressed organism to adequately respond to a novel threat. Therefore, the aim of the present study was to extend the CSC model to another rodent species, namely male Wistar rats, and to characterize relevant physiological, immunological, and behavioural consequences; placing particular emphasis on changes in hypothalamo-pituitary-adrenal (HPA axis responsiveness to an acute heterotypic stressor. In line with previous mouse data, exposure of Wistar rats to 19 days of CSC resulted in a decrease in body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in stress-coping behaviour or social preference were seen; again in agreement with the mouse paradigm. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor (open arm, 5 min despite displaying similar basal levels and similar basal and stressor-induced plasma ACTH levels. In contrast to CSC mice, anxiety-related behaviour and absolute, as well as relative adrenal weights remained unchanged in CSC rats. In summary, the CSC paradigm could be established as an adequate model of chronic psychosocial stress in male rats. Our data further support the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed organism to adequately respond to novel challenges.

  5. Brain levels of arginine-vasotocin and isotocin in dominant and subordinate males of a cichlid fish. (United States)

    Almeida, Olinda; Gozdowska, Magdalena; Kulczykowska, Ewa; Oliveira, Rui F


    The nonapeptides arginine-vasotocin (AVT) and isotocin (IT), which are the teleost homologues of arginine-vasopressin and oxytocin in mammals, have well established peripheral effects on osmoregulation and stress response, and central effects on social behavior. However, all studies that have looked so far into the relationship between these nonapeptides and social behavior have used indirect measures of AVT/IT activity (i.e. immunohistochemistry of AVT/IT immunoreactive neurons, or AVT/IT or their receptors mRNA expression with in situ hybridization or qPCR) and therefore direct measures of peptide levels in relation to social behavior are still lacking. Here we use a recently developed high-performance liquid chromatography analysis with fluorescence detection (HPLC-FL) method to quantify the levels of both AVT and IT in macro-dissected brain areas [i.e. olfactory bulbs, telencephalon, diencephalon, optic tectum, cerebellum, and hindbrain (= rhombencephalon minus cerebellum)] and pituitary of dominant and subordinate male cichlid fish (Oreochromis mossambicus). The pituitary shows higher levels of both peptides than any of the brain macroareas, and the olfactory bulbs have the highest AVT among all brain areas. Except for IT in the telencephalon there is a lack of correlations between central levels and pituitary peptide levels, suggesting an independent control of hypophysial and CNS nonapeptide secretion. There were also no correlations between AVT and IT levels either for each brain region or for the pituitary gland, suggesting a decoupled activity of the AVT and IT systems at the CNS level. Subordinate AVT pituitary levels are significantly higher than those of dominants, and dominant hindbrain IT levels are significantly higher than those of subordinates, suggesting a potential involvement of AVT in social stress in subordinate fish and of IT in the regulation of dominant behavior at the level of the hindbrain. Since in this species dominant males use urine

  6. The role of social environment on parental care: offspring benefit more from the presence of female than male helpers. (United States)

    Brouwer, Lyanne; van de Pol, Martijn; Cockburn, Andrew


    Investment in offspring depends on the costs and benefits to the carer, which can vary with sex and social status. Investment also depends on the effort of others by allowing for compensation (load-lightening), with biparental care studies showing that this depends on the state and type of the other carer. By contrast, studies on cooperative breeders have solely focussed on the effects of group size rather than its composition (i.e. social environment). Here we propose and provide the first test of the 'Social Environment' hypothesis, that is, how the characteristics (here the sex) of other helpers present in the group affect parental care and how this in turn affects offspring fitness in cooperatively breeding red-winged fairy-wrens (Malurus elegans). Breeders provisioned nestlings at a higher rate than helpers, but there was no sex difference in provisioning rate. Compensation to increasing group size varied little with sex and status, but strongly depended on social environment. All group members reduced their provisioning rates in response to an increasing number of male (load-lightening), but not female helpers (additive care). As a result, nestlings received more food and grew faster in the presence of female helpers. The increased nestling growth did convey a fitness advantage due to a higher post-fledging survival to adulthood. Our study provides the first evidence that parental care can depend on social environment. This could be an important overlooked aspect to explain variation in parental care in cooperative breeders in general and in particular the enormous variation between the sexes, which we reveal in a literature overview. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

  7. Male and female helper effects on maternal investment and adult survival in red-winged fairy-wrens

    NARCIS (Netherlands)

    Lejeune, Léa; van de Pol, Martijn; Cockburn, Andrew; Louter, Marina; Brouwer, Lyanne


    Despite its importance for the evolution of cooperative breeding, it has proven difficult to determine whether helpers improve their recipients’ fitness. Helpers affect fitness in multiple ways, both positive and negative, but their effects can also be concealed through reduced maternal investment.

  8. Subordination stress: behavioral, brain, and neuroendocrine correlates. (United States)

    Blanchard, D C; Sakai, R R; McEwen, B; Weiss, S M; Blanchard, R J


    In mixed-sex rat groups consistent asymmetries in offensive and defensive behaviors of male dyads are associated with the development of dominance hierarchies. Subordinate males can be differentiated from dominants on the basis of both agonistic and non-agonistic behaviors, wound patterns, weight changes. Their behavior changes suggest chronic defensiveness and are also broadly isomorphic to many of the symptoms of depression; their voluntary alcohol consumption increases, and their life-spans are shortened. Both subordinate and dominant males tend to show organ change compared to non-grouped controls, with adrenal and spleen enlargement and thymus reduction. However, these changes appear to be more marked in subordinates, and only subordinates show reduced testes weights. Basal corticosterone (CORT) levels were sharply higher, and plasma testosterone (T) sharply lower, in subordinates compared to both dominants and controls, and reduced corticosterone binding globulin further enhanced free CORT for subordinates particularly. Many subordinates failed to show a normal CORT response to restraint stress. Subordinates also appear to show widespread changes in serotonin systems, with increased 5-HIAA/5-HT ratios in a number of brain areas, and alterations of 5-HT1A receptor binding at some sites. These changes suggest that subordination, a common and consistent feature of life for many animals living in social groups, may be a particularly relevant model for investigating the behavioral, neural and endocrine correlates of chronic stress.

  9. The subordinate's predicaments. (United States)

    Neilsen, E H; Gypen, J


    How can subordinates improve relations with their superiors? And how can superiors help their subordinates feel comfortable in what is often a tense relationship? These questions have usually been dealt with only indirectly in management circles. Yet the relationship is so threatening to many subordinates that they react in ways that are damaging to themselves and their ogranizations. Drawing heavily on the work of psychologist Erik Erikson, the authors present dilemmas that commonly confront the subordinate. They point out that being aware of these dilemmas can make them more manageable and then offer advice to superiors to aid subordinates in handling such situations.

  10. Attitudes Of Subordinates Toward Women In Leadership Position ...

    African Journals Online (AJOL)

    The t-test of independent sample was used to analyse the research data. The findings revealed that: (a) Male subordinates have negative attitude toward women leader; (b) Subordinates with higher educational qualification have positive attitude towards women leaders; (c) Young subordinates have negative attitudes ...


    Meerschaert, Mark M; Straka, Peter


    The inverse stable subordinator provides a probability model for time-fractional differential equations, and leads to explicit solution formulae. This paper reviews properties of the inverse stable subordinator, and applications to a variety of problems in mathematics and physics. Several different governing equations for the inverse stable subordinator have been proposed in the literature. This paper also shows how these equations can be reconciled.




    The inverse stable subordinator provides a probability model for time-fractional differential equations, and leads to explicit solution formulae. This paper reviews properties of the inverse stable subordinator, and applications to a variety of problems in mathematics and physics. Several different governing equations for the inverse stable subordinator have been proposed in the literature. This paper also shows how these equations can be reconciled. PMID:25045216

  13. Paternity of subordinates raises cooperative effort in cichlids.

    Directory of Open Access Journals (Sweden)

    Rick Bruintjes

    Full Text Available In cooperative breeders, subordinates generally help a dominant breeding pair to raise offspring. Parentage studies have shown that in several species subordinates can participate in reproduction. This suggests an important role of direct fitness benefits for cooperation, particularly where groups contain unrelated subordinates. In this situation parentage should influence levels of cooperation. Here we combine parentage analyses and detailed behavioural observations in the field to study whether in the highly social cichlid Neolamprologus pulcher subordinates participate in reproduction and if so, whether and how this affects their cooperative care, controlling for the effect of kinship.We show that: (i male subordinates gained paternity in 27.8% of all clutches and (ii if they participated in reproduction, they sired on average 11.8% of young. Subordinate males sharing in reproduction showed more defence against experimentally presented egg predators compared to subordinates not participating in reproduction, and they tended to stay closer to the breeding shelter. No effects of relatedness between subordinates and dominants (to mid-parent, dominant female or dominant male were detected on parentage and on helping behaviour.This is the first evidence in a cooperatively breeding fish species that the helping effort of male subordinates may depend on obtained paternity, which stresses the need to consider direct fitness benefits in evolutionary studies of helping behaviour.

  14. Paternity of subordinates raises cooperative effort in cichlids. (United States)

    Bruintjes, Rick; Bonfils, Danielle; Heg, Dik; Taborsky, Michael


    In cooperative breeders, subordinates generally help a dominant breeding pair to raise offspring. Parentage studies have shown that in several species subordinates can participate in reproduction. This suggests an important role of direct fitness benefits for cooperation, particularly where groups contain unrelated subordinates. In this situation parentage should influence levels of cooperation. Here we combine parentage analyses and detailed behavioural observations in the field to study whether in the highly social cichlid Neolamprologus pulcher subordinates participate in reproduction and if so, whether and how this affects their cooperative care, controlling for the effect of kinship. We show that: (i) male subordinates gained paternity in 27.8% of all clutches and (ii) if they participated in reproduction, they sired on average 11.8% of young. Subordinate males sharing in reproduction showed more defence against experimentally presented egg predators compared to subordinates not participating in reproduction, and they tended to stay closer to the breeding shelter. No effects of relatedness between subordinates and dominants (to mid-parent, dominant female or dominant male) were detected on parentage and on helping behaviour. This is the first evidence in a cooperatively breeding fish species that the helping effort of male subordinates may depend on obtained paternity, which stresses the need to consider direct fitness benefits in evolutionary studies of helping behaviour.

  15. Subordinates as Threats to Leaders


    Glazer, Amihai; Segendorff, Björn


    A leader of an organization may view a subordinate as threatening or weakening the leader's position. The threat may increase with the subordinate's ability and reduce the rents the leader wins. In particular, a leader who trains his subordinate reduces the cost to the owner of a firm in replacing the leader, and so reduces the leader's bargaining power. The leader therefore provides inefficiently low training for the subordinate.

  16. Gender, Leadership Style, and Subordinate Satisfaction: An Experiment (United States)

    Kushell, Elliot; Newton, Rae


    Reports on an experiment that analyzed the effects of gender and leadership style on subordinate satisfaction. While subjects were more satisfied in democratically led groups, gender of leader did not significantly affect satisfaction. Female subordinates were more dissatisfied than males in autocratically led groups. (KH)

  17. Analysis of gender stereotypic characteristics in leaders and subordinates

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    María Laura Lupano Perugini


    Full Text Available An investigation was realized to analyze the way leaders and subordinates describe themselves in relation to perceived gender stereotypic characteristics and, to verify if exists differences in these characteristics according position (leader/ subordinate. Participate 612 individuals, 329 male (54% y 283 female (46%, age average = 37,54 years (DE=11,88. 59 % of the participants occupied executive positions and the rest were subordinates. It was utilized and abbreviate version of the Bem Sex Roles (Bem, 1974 to data recollection. The obtained results show that male leaders describe themselves mainly with agentic-masculine attributes (e.g. dominant, compared with subordinates who describe themselves with communal- feminine characteristics (e.g. submission. On the other hand, the female leaders describe themselves mainly with androgyny attributes combining qualities of both genders (e.g. dominant and sensible to the needs of others; however the female subordinates show communal attributes (e.g. submission

  18. Subordination by convex functions

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    Rosihan M. Ali


    Full Text Available For a fixed analytic function g(z=z+∑n=2∞gnzn defined on the open unit disk and γ<1, let Tg(γ denote the class of all analytic functions f(z=z+∑n=2∞anzn satisfying ∑n=2∞|angn|≤1−γ. For functions in Tg(γ, a subordination result is derived involving the convolution with a normalized convex function. Our result includes as special cases several earlier works.


    Directory of Open Access Journals (Sweden)

    Ting-Chi Wei


    Full Text Available The existence of subordinate gaps in Mandarin Chinese casts doubt on analyses built on canonical coordinate gapping. We observe that the minimality of contrastive focus and the type of subordinate clause determine the acceptability of a missing gap in subordinate structure. Along this vein, we propose that a semantic-based deletion account can be used to interpret gapping in Mandarin. Such account relies on two violable constraints, AvoidF and Focus condition on gapping (Schwarzchild 1999, Merchant 2001 to compute the acceptability of a gap.

  20. Why European Subordinates Trust their Managers

    Directory of Open Access Journals (Sweden)

    Andersen Jon Aarum


    Full Text Available This article addresses the problem of why subordinates trust their managers based on the responses from 108 subordinates of seven Slovenian managers and from 138 subordinates of eight Swedish managers. The subordinates of these managers responded to a 20-item instrument tested for reliability and validity. In both samples the managers enjoyed different degrees of trust. The level of trust vested in Slovenian managers was higher than in Swedish ones. The kinds of managers’ actions that enhanced trust were similar amongst Swedish and Slovenian subordinates. Different socio-cultural contexts may theoretically explain why some other kinds of actions had contrasting effects between the samples. On the whole, the actions of managers explain trust in both countries. Subordinates’ trust in managers declines with the increasing hierarchical distance in both national samples. Managers need to show in action that they trust their subordinates, promote their interests, demonstrate appreciation of their subordinates, and solve problems.

  1. Becoming Care Helper

    DEFF Research Database (Denmark)

    Jensen, Anne Winther

    The paper discusses the shaping of students´ identity within a vocational education programme for elderly care in Denmark. The focus is on the correlation between identity construction within the theoretical periods and students´ experiences in the traineeships. In the school setting the future...... care helper is being constructed within the overall term ‘professional’, but students may meet differing ways of being care helper in the traineeships, and the paper points to an ongoing struggle about the definition of ‘being care helper’. The analysis of the identity issues mobilises the concepts...... ‘positioning’ and ‘storyline’, c.f. Bronwyn Davies, and the empirical material consists of interviews and observations in the theoretical periods and in the traineeships. The paper suggests that a shift from identity to subjectivity may help students to deal with the diversity of ‘care helpers’ and thereby...

  2. Relationship Patterns Between Leader-Subordinate Similarity and Subordinate Satisfaction: a Case Study


    Mat Zin, Razali bin; Fahd, King


    The leadership literature is voluminous. This study adopted the contingency model to explain the relationship between the leader-subordinate similarity and subordinate satisfaction. The effects of selected intervening variables namely age, educational level, race and sex were also analyzed. The findings showed that there is a significant relationship between leader-subordinate similarity and subordinates' satisfaction. However, this significance was determined only after accounting for the de...

  3. The moderating role of subordinate political skill on supervisors' impressions of subordinate ingratiation and ratings of subordinate interpersonal facilitation. (United States)

    Treadway, Darren C; Ferris, Gerald R; Duke, Allison B; Adams, Garry L; Thatcher, Jason B


    Nearly 2 decades ago, social influence theorists called for a new stream of research that would investigate why and how influence tactics are effective. The present study proposed that political skill affects the style of execution of influence attempts. It utilized balance theory to explain the moderating effect of employee political skill on the relationships between self- and supervisor-reported ingratiation. Additionally, supervisor reports of subordinate ingratiation were hypothesized to be negatively related to supervisor ratings of subordinate interpersonal facilitation. Results from a combined sample of 2 retail service organizations provided evidence that subordinates with high political skill were less likely than those low in political skill to have their demonstrated ingratiation behavior perceived by targets as a manipulative influence attempt. Also, when subordinates were perceived by their supervisors to engage in more ingratiation behavior, the subordinates were rated lower on interpersonal facilitation. Implications of these findings, limitations, and future research directions are provided. 2007 APA, all rights reserved

  4. Saudi Arabian Woman's Marriage Life in Girls of Riyadh, a Novel by Rajaa Alsanea: Subordination and Struggle




    This article argues that implementation of Pre-Islamic tradition and culture emerges subordination toward woman in Saudi Arabia. They face subordination in many aspects of life. This phenomenon can be found in Girls of Riyadh novel. In this novel, Rajaa Alsanea, a Saudi Arabian woman writer tells how women live under male domination. In analyzing the phenomena, the writer used feminist approach by applying feminism theory which is combined with Islamic references to reveal subordination and s...

  5. Subordination in Cholón

    NARCIS (Netherlands)

    Alexander-Bakkerus, A.; van Gijn, R.; Haude, K.; Muysken, P.


    In Cholón, an indigenous language from northern Peru, subordinate clauses are formed by means of nominalizers or subordinators. Most of these markers attach to reduced verb forms, but some nominalizers are attached to a fully inflected form. Nominalizers can be followed by a case marker or by a

  6. A real helper data scheme

    NARCIS (Netherlands)

    Shao, X.; Veldhuis, Raymond N.J.


    The helper data scheme utilizes a secret key to protect biometric templates. The current helper data scheme requires binary feature representations that introduce quantization error and thus reduce the capacity of biometric channels. For spectral-minutiae based fingerprint recognition systems,

  7. Mycorrhiza helper bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Deveau, Aurelie [French National Insitute for Agricultural Research (INRA); Labbe, Jessy [ORNL


    This chapter focuses on the Mycorrhiza Helper Bacteria (MHB), a generic name given to bacteria which stimulate the formation of mycorrhizal symbiosis. By extension, some bacterial strains that positively impact the functioning of mycorrhizal symbiosis are also called MHB. These bacteria have applicative interests, as they indirectly improve the health and growth of tree seedlings. MHB are not restricted to a specific type of ecosystem, but are rather generalist in the way that they associate with both herbaceous and woody mycorrhizal plants from boreal, temperate, arid and tropical ecosystems. However, understanding the molecular mechanisms and their specificities will help us to know more about the ecology of the MHB. The process of acquisition varies between fungal species; while ectomycorrhizal fungi most probably recurrently acquire them from the environment, the association between bacterial endosymbionts and Glomeromycota probably dates back to very ancient times, and has since been vertically transmitted.

  8. Subordinates' Reactions to Female Leaders. (United States)

    Forsyth, Donelson R.; Forsyth, Nancy M.

    Although recent reviews of the effectiveness of male versus female leaders reveal little evidence of male superiority, evaluative and perceptual biases (beliefs about what constitutes good leadership, and stereotyped beliefs about men and women) among group members persist. To examine attributional biases against female leaders, 85 college…

  9. Superior-subordinate relations as organizational processes

    DEFF Research Database (Denmark)

    Asmuss, Birte; Aggerholm, Helle Kryger; Oshima, Sae

    -subordinate relations and thus for organizing an institution. References Fletcher, C. (2001). Performance appraisal and management: The developing research agenda. Journal of Occupational and Organizational Psychology, 74:473-487. Cooren, F., Taylor, J.R., & Van Every, E.J. (Eds.) (2006). Communication as organizing...... on organizational practices relates closely to an increased focus on communication as being constitutive of the organization in general and the superior-subordinate relationship in specific. The current study aims to contribute to this line of research by investigating micro-practices involved in establishing...... superior-subordinate relations in a specific institutionalized setting: performance appraisal interviews (PAIs). While one main task of PAIs is to manage and integrate organizational and employee performance (Fletcher, 2001:473), PAIs are also organizational practices where superior-subordinate relations...

  10. Meta-Times and Extended Subordination

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole; Pedersen, Jan

    The problem of defining subordination of a homogeneous Lévy basis by a non-negative homogeneous Lévy basis is discussed. An explicit construction, generalizing the usual one-dimensional case, is given. This construction involves certain random meta-time changes.......The problem of defining subordination of a homogeneous Lévy basis by a non-negative homogeneous Lévy basis is discussed. An explicit construction, generalizing the usual one-dimensional case, is given. This construction involves certain random meta-time changes....

  11. Enhancing Supervisor and Subordinate Communication in Diversity ...

    African Journals Online (AJOL)

    provides for the institutionalisation of diversity management by integrating it with the organisation's management practices. This article proposes that communication between supervisors and subordinates in the public service must be strengthened to enhance diversity management. It argues that diversity management is an ...

  12. Matrix subordinators and related Upsilon transformations

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Pérez-Abreu, V.


    A class of upsilon transformations of Lévy measures for matrix subordinators is introduced. Some regularizing properties of these transformations are derived, such as absolute continuity and complete monotonicity. The class of Lévy measures with completely monotone matrix densities is characterized....... Examples of infinitely divisible nonnegative definite random matrices are constructed using an upsilon transformation....

  13. subordination across ghanaian and british newspaper editorials

    African Journals Online (AJOL)

    Empirical research in this area is scanty, though this theoretical argumentation is not without contention, especially cross-culturally. Empirical investigation is therefore ... Frimpong: Subordination Across Ghanaian and British Newspaper Editorials: A Register. Perspective. 78. Figure 1: The Components in a register analysis.

  14. Peer Helpers in Hungary: A Qualitative Analysis (United States)

    Racz, Jozsef; Lacko, Zsuzsa


    Hungary is a country in transition that has no real tradition of peer helping. A qualitative study was carried out involving 13 peer helpers of two kinds (a) age-based peers, and (b) way-of-life-based peers (fellow helpers). The motivations for and the processes of becoming a peer helper were analyzed. Results showed the largest difference being…

  15. Mitochondrial function in the brain links anxiety with social subordination (United States)

    Hollis, Fiona; van der Kooij, Michael A.; Zanoletti, Olivia; Lozano, Laura; Cantó, Carles; Sandi, Carmen


    Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders. PMID:26621716

  16. Managers can drive their subordinates mad. (United States)

    Kets de Vries, M F


    This article explores the phenomenon of "folie à deux"--an aberrant relationship between manager and subordinates that is characterized by shared delusions. Though most visible among public figures like Adolf Hitler, J. Edgar Hoover and Jim Jones, the problem also surfaces among private managers and their associates with dangerous implications for the firm. In folie à deux, the unusual behavior patterns of a manager in an isolated setting become mirrored by dependent subordinates, and the organization loses touch with its original goals and strategies. The author describes the dynamics of this phenomenon and details steps to remedy the situation. Once recognized, he suggests that the manager establish a trusting relationship with the instigator as a prelude to altering the behavior patterns, then transfer the subordinates and reorient the work climate so that independence and responsibility are encouraged. If the instigator is a powerful executive, the author suggests enlisting the support of a countervailing force, such as the government or a union, to guide the organization away from possible self-destructive adventures.

  17. Lebanon in the Middle East Subordinate System. (United States)


    the land of Aram;4 the "people of the sea," became the Philistines ; and the Hebrews created their kingdom under the scepter of King David), the ...legislative. Before sunrise, they were taken to an ancient fort at Rashaya to be . held in separate cells. On the same day, M. Helleu, French delegate...R AD-138 031 LEBANON IN THE MIDDLE EAST SUBORDINATE SYSTEM(U) RRMY 1/3, COMMRAND AND GENERAL STAFF COLL FORT LEAVENWORTH KS N S EID 03 JUN 83 SBI-AD

  18. The mycorrhiza helper bacteria revisited. (United States)

    Frey-Klett, P; Garbaye, J; Tarkka, M


    In natural conditions, mycorrhizal fungi are surrounded by complex microbial communities, which modulate the mycorrhizal symbiosis. Here, the focus is on the so-called mycorrhiza helper bacteria (MHB). This concept is revisited, and the distinction is made between the helper bacteria, which assist mycorrhiza formation, and those that interact positively with the functioning of the symbiosis. After considering some examples of MHB from the literature, the ecological and evolutionary implications of the relationships of MHB with mycorrhizal fungi are discussed. The question of the specificity of the MHB effect is addressed, and an assessment is made of progress in understanding the mechanisms of the MHB effect, which has been made possible through the development of genomics. Finally, clear evidence is presented suggesting that some MHB promote the functioning of the mycorrhizal symbiosis. This is illustrated for three critical functions of practical significance: nutrient mobilization from soil minerals, fixation of atmospheric nitrogen, and protection of plants against root pathogens. The review concludes with discussion of future research priorities regarding the potentially very fruitful concept of MHB.

  19. Adaptive changes in zebrafish brain in dominant-subordinate behavioral context. (United States)

    Pavlidis, Michail; Sundvik, Maria; Chen, Yu-Chia; Panula, Pertti


    Male zebrafish were held in dyadic social stress situation for a period of 5 days, to characterize stress coping styles and to investigate the role of the underlying neuroendocrine mechanisms in establishing dominant-subordinate relationships. A strong consistent dominant-subordinate relationship was formed in ten out of the sixteen pairs of fish (62.5%). Both dominant (DOM) and subordinate (SUB) individuals showed statistically significant higher trunk cortisol concentration than controls. Expression of genes encoding proteins involved in the functioning of the hypothalamus-hypophysis-interrenal axis (corticotropin releasing factor, CRF; glucocorticoid receptor, GR; mineralocorticoid receptor, MR); arginine vasotocin, AVT), in the biosynthesis and catabolism of catecholamines (tyrosine hydroxylase, TH1 and TH2; DOPA decarboxylase, DDC), dopamine β-hydroxylase, DBH; catechol-O-methyl transferase, COMT), in the biosynthesis of histamine (histidine decarboxylase, HDC) and in the general stress response (galanin, GAL; hypocretin/orexin, Hcrt) was examined. The MR/GR ratio was higher in dominant and subordinate fish than in controls (P=0.016). The mRNA levels of TH2 and HDC were up-regulated in DOM, of AVT in SUB, while COMT mRNA levels were down-regulated in both DOM and SUB compared to control fish. In addition, mRNA levels of hypocretin/orexin (Hcrt) were up-regulated in dominant compared to subordinate and control males. There was a statistically significant correlation between mRNA expression levels of TH2, HDC, Hcrt, GR, MR and CRF genes. The obtained results provide new evidences for the use of zebrafish as an animal model to study social stress and allostasis in vertebrates. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Helpful female subordinate cichlids are more likely to reproduce.

    Directory of Open Access Journals (Sweden)

    Dik Heg

    Full Text Available BACKGROUND: In many cooperatively breeding vertebrates, subordinates assist a dominant pair to raise the dominants' offspring. Previously, it has been suggested that subordinates may help in payment for continued residency on the territory (the 'pay-to-stay hypothesis', but payment might also be reciprocated or might allow subordinates access to reproductive opportunities. METHODOLOGY/PRINCIPAL FINDINGS: We measured dominant and subordinate female alloparental brood care and reproductive success in four separate experiments and show that unrelated female dominant and subordinate cichlid fish care for each other's broods (alloparental brood care, but that there is no evidence for reciprocal 'altruism' (no correlation between alloparental care received and given. Instead, subordinate females appear to pay with alloparental care for own direct reproduction. CONCLUSIONS/SIGNIFICANCE: Our results suggest subordinate females pay with alloparental care to ensure access to the breeding substrate and thereby increase their opportunities to lay their own clutches. Subordinates' eggs are laid, on average, five days after the dominant female has produced her first brood. We suggest that immediate reproductive benefits need to be considered in tests of the pay-to-stay hypothesis.

  1. 46 CFR 67.243 - Requirements for instruments subordinating mortgages. (United States)


    ... 46 Shipping 2 2010-10-01 2010-10-01 false Requirements for instruments subordinating mortgages. 67... MEASUREMENT OF VESSELS DOCUMENTATION OF VESSELS Filing and Recording of Instruments-Mortgages, Preferred Mortgages, and Related Instruments § 67.243 Requirements for instruments subordinating mortgages. An...

  2. Leaders' achievement goals and their reactions to subordinates' creative input

    NARCIS (Netherlands)

    Sijbom, R.B.L.; Janssen, O.; van Yperen, N.W.


    The present experimental research examined the impact of leaders' achievement goals on their reactions to creative input provided by their subordinates. In Experiment 1, performance goal leaders were found to be less receptive to subordinates' creative input than mastery goal leaders. In Experiment

  3. 'Bioethics' is subordinate to morality in Japan. (United States)

    Tanida, Noritoshi


    Disputes over brain death and euthanasia are used to illuminate the question whether there really is a Japanese way of thinking in bioethics. In Japanese thought, a person does not exist as an individual but as a member of the family, community or society. I describe these features of Japanese society as 'mutual dependency'. In this society, an act is 'good' and 'right' when it is commonly done, and it is 'bad' and 'wrong' when nobody else does it. Thus, outsiders to this ring of mutual dependency encounter ostracism. One feature of this society is a lack of open discussion which leads to the existence of multiple standards. This Japanese morality even prevails over written laws. In Japan, there is a public stance that euthanasia does not exist. On the other hand, there are certain decisions which have permitted euthanasia. Similarly, organ transplants were performed from brain dead donors, while that procedure was not accepted officially by the medical profession. In this situation, there is a danger that human rights will be neglected. So far bioethical approaches have not helped to work out these problems. This may be because Japanese think that bioethics is subordinate to morality. The current dispute over brain death involves a struggle for the establishment of a rational society in Japan. Overcoming mutual dependency and ostracism is essential to resolve this struggle and to lead Japan into a society of mutual respect where all individuals, families and communities are esteemed.

  4. From Subordinate Marker to Discourse Marker: que in Andean Spanish

    Directory of Open Access Journals (Sweden)

    Anna María Escobar


    Full Text Available This paper proposes an analysis of a redundant use of que ('that' found in Andean Spanish as an expression which has undergone a grammaticalization process. Evidence suggests that the function of que as subordinate marker is much more generalized in this variety than in other dialects of Spanish. que is found to be used as a marker introducing both nominal and adjectival clauses, suggesting that adjectival subordinates behave as nominal subordinates in this variety of Spanish. An intrusive que appears in restricted syntactic and semantic contexts with clauses that have nominal and adjectival functions, and even appears replacing adverbial expressions in some adverbial subordinates (temporal, spatial, and manner. Furthermore, it is found to be sensitive to the degree of the argument’s thematic/semantic function in the subordinate clause. In particular, it seems to occur more often with low-agency arguments in adjectival and nominal contexts, and, in nominal subordinates, tends to appear with a restricted set of epistemic and evidential main verbs (e.g. creer 'to believe', saber 'to know', decir 'to say'. The analysis suggests that que has developed a new function in this variety of Spanish, namely, one of indicating that the information contained in the subordinate clause does not constitute background information (as would be expected in non-contact varieties of Spanish but instead contains information relevant to the discourse.

  5. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder

    Directory of Open Access Journals (Sweden)

    Maria eRazzoli


    Full Text Available Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Methods: Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm. Conclusion: Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food

  6. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder. (United States)

    Razzoli, Maria; Sanghez, Valentina; Bartolomucci, Alessandro

    Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm. Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake.

  7. V2 word order in subordinate clauses in spoken Danish

    DEFF Research Database (Denmark)

    Jensen, Torben Juel; Christensen, Tanya Karoli

    studies of two age cohorts of speakers in Copenhagen, recorded in the 1980s and again in 2005-07, and on recent recordings with two age cohorts of speakers from the western part of Jutland. This makes it possible to study variation and change with respect to word order in subordinate clauses in both real...... and apparent time, as well as geographical variation. The results show that V2 word order in subordinate clauses is much more frequent than commonly assumed. Furthermore, they indicate that the most decisive factors predicting word order in subordinate clauses are the syntactic function of the clause...

  8. Stress coping style does not determine social status, but influences the consequences of social subordination stress. (United States)

    Boersma, Gretha J; Smeltzer, Michael D; Scott, Karen A; Scheurink, Anton J; Tamashiro, Kellie L; Sakai, Randall R


    Chronic stress exposure may have negative consequences for health. One of the most common sources of chronic stress is stress associated with social interaction. In rodents, the effects of social stress can be studied in a naturalistic way using the visual burrow system (VBS). The way an individual copes with stress, their "stress coping style", may influence the consequences of social stress. In the current study we tested the hypothesis that stress coping style may modulate social status and influence the consequences of having a lower social status. We formed 7 VBS colonies, with 1 proactive coping male, 1 passive coping male, and 4 female rats per colony to assess whether a rat's coping style prior to colony formation could predict whether that individual is more likely to become socially dominant. The rats remained in their respective colonies for 14days and the physiological and behavioral consequences of social stress were assessed. Our study shows that stress coping style does not predict social status. However, stress coping style may influence the consequences of having a lower social status. Subordinate passive and proactive rats had distinctly different wound patterns; proactive rats had more wounds on the front of their bodies. Behavioral analysis confirmed that proactive subordinate rats engaged in more offensive interactions. Furthermore, subordinate rats with a proactive stress coping style had larger adrenals, and increased stress responsivity to a novel acute stressor (restraint stress) compared to passive subordinate rats or dominant rats, suggesting that the allostatic load may have been larger in this group. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. On Certain Subclasses of Analytic Functions Defined by Differential Subordination

    Directory of Open Access Journals (Sweden)

    Hesam Mahzoon


    Full Text Available We introduce and study certain subclasses of analytic functions which are defined by differential subordination. Coefficient inequalities, some properties of neighborhoods, distortion and covering theorems, radius of starlikeness, and convexity for these subclasses are given.

  10. Supervisor's HEXACO personality traits and subordinate perceptions of abusive supervision

    NARCIS (Netherlands)

    Breevaart, Kimberley; de Vries, Reinout Everhard


    Abusive supervision is detrimental to both subordinates and organizations. Knowledge about individual differences in personality related to abusive supervision may improve personnel selection and potentially reduce the harmful effects of this type of leadership. Using the HEXACO personality

  11. Rehabilitation Agency Leadership Style: Impact on Subordinates' Job Satisfaction. (United States)

    Packard, Susan H.; Kauppi, Dwight R.


    One hundred five rehabilitation employees were surveyed on the effect of leadership style on subordinates' perceptions of their work environment and on their job satisfaction. Findings suggest that leadership style affects service delivery. (Author/MKA)

  12. Superiors' Argumentativeness and Verbal Agressiveness as Predictors of Subordinates' Satisfaction. (United States)

    Infante, Dominic A.; Gorden, William I.


    Supported the hypothesis that the more employees perceive their supervisors as high in argumentativeness and low in verbal aggressiveness, the more the subordinates also will be argumentative (i.e., assertive) and have job satisfaction. (PD)

  13. 32 CFR 776.54 - Responsibilities of a subordinate attorney. (United States)


    ... part or the duty of a judge advocate to exercise independent professional judgment as to the best interest of an individual client. (3) A subordinate covered attorney does not violate this part if that...

  14. A taxonomy of supervisor–subordinate exchanges across cultures

    Directory of Open Access Journals (Sweden)

    Naresh Khatri


    Full Text Available Major concerns, both theoretical and methodological, have been raised about the adequacy of the leader-member exchange (LMX theory, the existing model on supervisor–subordinate exchanges. This paper seeks to overcome three main theoretical shortcomings of the LMX theory as documented in past research. First, that the LMX theory does not describe the exchange process sufficiently, and second, that it does not capture the cross-cultural influences on supervisor–subordinate exchanges. This paper deals with these weaknesses by providing a comprehensive description of supervisor–subordinate exchanges across cultures using two theoretical frameworks, Fiske’s relational theory and Triandis’s cultural syndromes. A third problem with the LMX theory is that it assumes all close relationships between supervisors and subordinates to be beneficial for the organisation. However, a stream of research has emerged that documents the downside of close relationships between supervisors and their subordinates. Utilising a recent cross-cultural framework on cronyism, this paper sheds light on the dysfunctional organisational consequences of close relationships between supervisors and their subordinates across cultures.

  15. Effects of the job stress education for supervisors on psychological distress and job performance among their immediate subordinates: a supervisor-based randomized controlled trial. (United States)

    Takao, Soshi; Tsutsumi, Akizumi; Nishiuchi, Kyoko; Mineyama, Sachiko; Kawakami, Norito


    As job stress is now one of the biggest health-related problems in the workplace, several education programs for supervisors have been conducted to reduce job stress. We conducted a supervisor-based randomized controlled trial to evaluate the effects of an education program on their subordinates' psychological distress and job performance. The subjects were 301 employees (46 supervisors and 255 subordinates) in a Japanese sake brewery. First, we randomly allocated supervisors to the education group (24 supervisors) and the waiting-list group (22 supervisors). Then, for the allocated supervisors we introduced a single-session, 60-min education program according to the guidelines for employee mental health promotion along with training that provided consulting skills combined with role-playing exercises. We conducted pre- and post-intervention (after 3 months) surveys for all subordinates to examine psychological distress and job performance. We defined the intervention group as those subordinates whose immediate supervisors received the education, and the control group was defined as those subordinates whose supervisors did not. To evaluate the effects, we employed a repeated measures analysis of variance (ANOVA). Overall, the intervention effects (time x group) were not significant for psychological distress or job performance among both male (p=0.456 and 0.252) and female (p=0.714 and 0.106) subordinates. However, young male subordinates engaged in white-collar occupations showed significant intervention effects for psychological distress (p=0.012) and job performance (p=0.029). In conclusion, our study indicated a possible beneficial effect of supervisor education on the psychological distress and job performance of subordinates. This effect may vary according to specific groups.

  16. Chronic social subordination stress modulates glutamic acid decarboxylase (GAD) 67 mRNA expression in central stress circuits (United States)

    Makinson, Ryan; Lundgren, Kerstin H.; Seroogy, Kim B.; Herman, James P.


    Chronic social subordination is a well-known precipitant of numerous psychiatric and physiological health concerns. In this study, we examine the effects of chronic social stress in the visible burrow system (VBS) on the expression of glutamic acid decarboxylase (GAD) 67 and brain-derived neurotropic factor (BDNF) mRNA in forebrain stress circuitry. Male rats in the VBS system form a dominance hierarchy, whereby subordinate males exhibit neuroendocrine and physiological profiles characteristic of chronic exposure to stress. We found that social subordination decreases GAD67 mRNA in the peri-paraventricular nucleus region of the hypothalamus and the interfascicular nucleus of the bed nucleus of the stria terminalis (BNST), and increases in GAD67 mRNA in the hippocampus, medial prefrontal cortex, and dorsal medial hypothalamus. Expression of BDNF mRNA increased in the dorsal region of the BNST, but remained unchanged in all other regions examined. Results from this study indicate that social subordination is associated with several region-specific alterations in GAD67 mRNA expression in central stress circuits, whereas changes in the expression of BDNF mRNA are limited to the BNST. PMID:26066725

  17. The Subordination of Women in Comparative Perspective. (United States)

    Nader, Laura


    The emphasis on motherhood among Latin-American women and the anti-motherhood position of many American feminists are both appropriate adaptations to male dominance. Motherhood in the U.S. has traditionally isolated women and weakened their social position, whereas in Mexico it is the basis of successful female political action. (VM)

  18. Chronic Subordination Stress Induces Hyperphagia and Disrupts Eating Behavior in Mice Modeling Binge-Eating-Like Disorder (United States)

    Razzoli, Maria; Sanghez, Valentina; Bartolomucci, Alessandro


    Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge-eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress-induced hyperphagia associated with the development of obesity. Here, we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Methods: Adult male mice were exposed to a model of chronic subordination stress (CSS) associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol we tested the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair-feeding paradigm. Conclusion: Overall, these results support the validity of our CSS to model BED allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake. PMID:25621284

  19. A fully subordinated linear flow model for hillslope subsurface stormflow (United States)

    Zhang, Yong; Baeumer, Boris; Chen, Li; Reeves, Donald M.; Sun, HongGuang


    Hillslope subsurface stormflow exhibits complex patterns when natural soils with multiscale heterogeneity impart a spatiotemporally nonlocal memory on flow dynamics. To efficiently quantify such nonlocal flow responses, this technical note proposes a fully subordinated flow (FSF) equation where the time- and flow-subordination capture the temporal and spatial memory, respectively. Results show that the time-subordination component of the FSF model captures a wide range of delayed flow response due to various degrees of soil heterogeneity (especially for low-conductivity zones), while the model's flow-subordination term accounts for the rapid flow responses along preferential flow paths. In the FSF model, parameters defining spatiotemporal memory functions may be related to soil properties, while other parameters such as scalar factors controlling the overall advection and diffusion are difficult to predict and can be estimated from subsurface stormflow hydrographs. These parameters can be constants at the hillslope scale because the spatiotemporal subordination, an upscaling technique, can capture the impact of system heterogeneity on flow dynamics, leading to a linear FSF model that might be applicable for various slopes. Valid scale, limitation and extension of the FSF model, and modification of the model for other complex hydrological dynamics are also discussed.

  20. A Subordination Principle on Wright Functions and Regularized Resolvent Families

    Directory of Open Access Journals (Sweden)

    Luciano Abadias


    Full Text Available We obtain a vector-valued subordination principle for gα,gβ-regularized resolvent families which unified and improves various previous results in the literature. As a consequence, we establish new relations between solutions of different fractional Cauchy problems. To do that, we consider scaled Wright functions which are related to Mittag-Leffler functions, the fractional calculus, and stable Lévy processes. We study some interesting properties of these functions such as subordination (in the sense of Bochner, convolution properties, and their Laplace transforms. Finally we present some examples where we apply these results.

  1. Nonverbal Behavior of Helpers in Initial Helping Interactions (United States)

    D'Augelli, Anthony R.


    Several nonverbal behaviors of helpers in a small group were tallied and related to independent judgments of the helper made by observers and the person being helped. The low but significant correlations suggest that nonverbal behaviors are but one set of cues that lead to clients' first impressions of their helpers. (Author)

  2. Patriarchy and the subordination of women among the Abagusii of ...

    African Journals Online (AJOL)

    The paper discusses the role of private patriarchy in the subordination of women among the Abagusii of western Kenya. It identifies customs and practices governing marriage such as the payment of dowry, circumcision, the gender division of labour within the household and polygamy as the main factors contributing to the ...

  3. Supervisors' and subordinates' perception of the Impact of Botswana ...

    African Journals Online (AJOL)

    This study was a descriptive survey, which ascertained supervisors and subordinates perception of the impact of Botswana College of Agriculture training programme on graduates' job behaviour. The study was carried out in the Ministry of Agriculture, Gaborone, Botswana, which is composed of six departments. All BCA ...

  4. Stable Lévy motion with inverse Gaussian subordinator (United States)

    Kumar, A.; Wyłomańska, A.; Gajda, J.


    In this paper we study the stable Lévy motion subordinated by the so-called inverse Gaussian process. This process extends the well known normal inverse Gaussian (NIG) process introduced by Barndorff-Nielsen, which arises by subordinating ordinary Brownian motion (with drift) with inverse Gaussian process. The NIG process found many interesting applications, especially in financial data description. We discuss here the main features of the introduced subordinated process, such as distributional properties, existence of fractional order moments and asymptotic tail behavior. We show the connection of the process with continuous time random walk. Further, the governing fractional partial differential equations for the probability density function is also obtained. Moreover, we discuss the asymptotic distribution of sample mean square displacement, the main tool in detection of anomalous diffusion phenomena (Metzler et al., 2014). In order to apply the stable Lévy motion time-changed by inverse Gaussian subordinator we propose a step-by-step procedure of parameters estimation. At the end, we show how the examined process can be useful to model financial time series.

  5. Health care managers learning by listening to subordinates' dialogue training. (United States)

    Grill, C; Ahlborg, G; Wikström, E


    Middle managers in health care today are expected to continuously and efficiently decide and act in administration, finance, care quality, and work environment, and strategic communication has become paramount. Since dialogical communication is considered to promote a healthy work environment, the purpose of this paper is to investigate the ways in which health care managers experienced observing subordinates' dialogue training. A qualitative study using semi-structured interviews and documents from eight middle managers in a dialogue programme intervention conducted by dialogue trainers. Focus was on fostering and assisting workplace dialogue. Conventional qualitative content analysis was used. Managers' experiences were both enriching and demanding, and consisted of becoming aware of communication, meaning perceiving interaction between subordinates as well as own silent interaction with subordinates and trainer; Discovering communicative actions for leadership, by gaining self-knowledge and recognizing relational leadership models from trainers--such as acting democratically and pedagogically--and converting theory into practice, signifying practising dialogue-promoting conversation behaviour with subordinates, peers, and superiors. Only eight managers participated in the intervention, but data afforded a basis for further research. Findings stressed the importance of listening, and of support from superiors, for well-functioning leadership communication at work. Studies focusing on health care managers' communication and dialogue are few. This study contributes to knowledge about these activities in managerial leadership.

  6. On a differential subordination of some certain subclass of Univalent ...

    African Journals Online (AJOL)

    convex functions using Briot-Bouquet differential subordination method. Journal of the Nigerian Association of Mathematical Physics Vol. 10 2006: pp. 181-184. · AJOL African Journals Online.

  7. Children's Communication of Basic Level and Subordinate Level Semantic Contrasts. (United States)

    Kossan, Nancy E.

    Developmental differences in preschool children's abilities to communicate about basic and subordinate level semantic contrasts were examined in a referential communication situation. Twenty-four three, four, and five-year-old children communicated with children of the same age and adults about pictures' referents. Speakers talked about one…

  8. Helper effects on breeder allocations to direct care. (United States)

    Kushnick, Geoff


    Mothers receive childcare and productive assistance from allomaternal helpers in many societies. Although much effort has been aimed toward showing helper effects on maternal reproductive success, less has been directed toward highlighting the full range of potential effects on breeder behavior. I present a model of optimal maternal care with helpers, and tests of derived hypotheses with data collected among the Karo Batak-a group of Indonesian agriculturalists. To test the model's predictions I compared the effect of women receiving help from patrilateral versus matrilateral kin because those kin may provide help with different maternal responsibilities. The model predicts a decrease in maternal allocation to care that is substitutable with the helper contribution and the helper assists with that type of care; it predicts an increase in care that is nonsubstitutable with the helper contribution or substitutable care when the helper assists with other responsibilities. With the exception of one other, most models have failed to account for an increase. Analyses of time spent carrying children supported the model. With matrilateral helpers, women increased carrying; with patrilateral helpers, they decreased it. Time spent farmworking showed the opposite pattern, suggesting that matrilateral helpers effectively decrease costs, nudging optimal maternal care upward. Patterns of breastfeeding provided little support for the model. The results do, however, suggest potential proximate mechanisms by which helpers influence maternal reproductive success in cooperative breeding societies. Copyright © 2012 Wiley Periodicals, Inc.

  9. Abusive Supervision and Subordinate Performance : Instrumentality Considerations in the Emergence and Consequences of Abusive Supervision

    NARCIS (Netherlands)

    Walter, Frank; Lam, Catherine K.; van der Vegt, Geert; Huang, X.; Miao, Q.

    Drawing from moral exclusion theory, this article examines outcome dependence and interpersonal liking as key boundary conditions for the linkage between perceived subordinate performance and abusive supervision. Moreover, it investigates the role of abusive supervision for subordinates' subsequent,

  10. The Perceived Leader Support Behavior for Subordinate's Creativity: The Moderating Effect of Trust


    Kuo-Hsiung Chen; Jui-Mei Yien; Chien-Jung Huang


    Problem statement: The main goal behind this study tries to figure out whether or not the leaders supportive behavior will influence subordinates creativity and is there any affection of trust between leaders supportive behavior and subordinates creativity? Approach: This study was conducted to examine the relationships between leader support behavior and subordinate creativity and the moderating effect of trust on subordinates' creativity under the leader support behavior...

  11. Cross-Situational Specificity in Managers' Perceptions of Subordinate Performance, Attributions, and Leader Behaviors. (United States)

    James, Lawrence R.; White, John F.


    Examined managers' perceptions of subordinates' performance, causes (attributions) of subordinates' performance, and the leader behaviors they employed toward subordinates from the standpoint of cross-situational consistency versus cross-situational specificity. Empirical results for 377 Navy managers provided strong support for cross-situational…

  12. Cone-Parameter Convolution Semigroups and Their Subordination


    Pedersen, Jan; Sato, Ken-iti


    Convolution semigroups of probability measures with parameter in a cone in a Euclidean space generalize usual convolution semigroups with parameter in $[0,\\infty)$. A characterization of such semigroups is given and examples are studied. Subordination of cone-parameter convolution semigroups by cone-valued cone-parameter convolution semigroups is introduced. Its general description is given and inheritance properties are shown. In the study the distinction between cones with an...

  13. Subordinated diffusion and continuous time random walk asymptotics. (United States)

    Dybiec, Bartłomiej; Gudowska-Nowak, Ewa


    Anomalous transport is usually described either by models of continuous time random walks (CTRWs) or, otherwise, by fractional Fokker-Planck equations (FFPEs). The asymptotic relation between properly scaled CTRW and fractional diffusion process has been worked out via various approaches widely discussed in literature. Here, we focus on a correspondence between CTRWs and time and space fractional diffusion equation stemming from two different methods aimed to accurately approximate anomalous diffusion processes. One of them is the Monte Carlo simulation of uncoupled CTRW with a Lévy α-stable distribution of jumps in space and a one-parameter Mittag-Leffler distribution of waiting times. The other is based on a discretized form of a subordinated Langevin equation in which the physical time defined via the number of subsequent steps of motion is itself a random variable. Both approaches are tested for their numerical performance and verified with known analytical solutions for the Green function of a space-time fractional diffusion equation. The comparison demonstrates a trade off between precision of constructed solutions and computational costs. The method based on the subordinated Langevin equation leads to a higher accuracy of results, while the CTRW framework with a Mittag-Leffler distribution of waiting times provides efficiently an approximate fundamental solution to the FFPE and converges to the probability density function of the subordinated process in a long-time limit. © 2010 American Institute of Physics.

  14. Grandparent helpers : The adaptive significance of older, postdominant helpers in the Seychelles warbler

    NARCIS (Netherlands)

    Richardson, David S.; Burke, Terry; Komdeur, Jan; Wedell, N.


    The possibility that older, often nonreproductive, individuals may engage in kin-directed cooperative behavior has been largely overlooked in the study of cooperative breeding. Here, we describe and investigate the adaptive significance of such "grandparent" helpers in the Seychelles warbler, the

  15. On the Fractional Poisson Process and the Discretized Stable Subordinator

    Directory of Open Access Journals (Sweden)

    Rudolf Gorenflo


    Full Text Available We consider the renewal counting number process N = N(t as a forward march over the non-negative integers with independent identically distributed waiting times. We embed the values of the counting numbers N in a “pseudo-spatial” non-negative half-line x ≥ 0 and observe that for physical time likewise we have t ≥ 0. Thus we apply the Laplace transform with respect to both variables x and t. Applying then a modification of the Montroll-Weiss-Cox formalism of continuous time random walk we obtain the essential characteristics of a renewal process in the transform domain and, if we are lucky, also in the physical domain. The process t = t(N of accumulation of waiting times is inverse to the counting number process, in honour of the Danish mathematician and telecommunication engineer A.K. Erlang we call it the Erlang process. It yields the probability of exactly n renewal events in the interval (0; t]. We apply our Laplace-Laplace formalism to the fractional Poisson process whose waiting times are of Mittag-Leffler type and to a renewal process whose waiting times are of Wright type. The process of Mittag-Leffler type includes as a limiting case the classical Poisson process, the process of Wright type represents the discretized stable subordinator and a re-scaled version of it was used in our method of parametric subordination of time-space fractional diffusion processes. Properly rescaling the counting number process N(t and the Erlang process t(N yields as diffusion limits the inverse stable and the stable subordinator, respectively.

  16. Understanding of subordinate clauses in the language of dysphasic children

    Directory of Open Access Journals (Sweden)

    Lazarević Emilija


    Full Text Available This paper presents the results of the research of peculiarities of syntactic development, as an element of language structure on the grammatical level of children suffering from developmental dysphasia, after the completed speech pathology treatment of many years. Syntactic level at younger school age was studied by assessing language competence in the accomplishment of communicative sentence with subordinate clause. The research was performed on the samples of children at school age in regular primary schools in Belgrade. The sample comprised 160 respondents who were divided in two groups: target and comparative. The target group consisted of 60 respondents (children suffering from developmental dysphasia after the completed speech pathology treatment of many years, and the comparative group consisted of 100 respondents from regular primary school "Gavrilo Princip" in Zemun. Research results show that grammatical development of children suffering from developmental dysphasia takes place at a considerably slower rate and entails substantially more difficulties in accomplishing predication in subordinate clauses. This paper discusses the consequences which the difficulties in grammatical development can have on school achievement.

  17. Does main clause word order affect attention to change in subordinate clauses?

    DEFF Research Database (Denmark)

    Christensen, Marie Herget; Christensen, Tanya Karoli; Jensen, Torben Juel


    is that a subordinate clause with Verb>Adverb word order will attract more attention than a clause with Adverb>Verb word order. To test this, we conducted an experiment under the text change paradigm. 59 students each read 24 constructions twice, each containing a subordinate clause with either Verb>Adverb or Adverb......>Verb word order. Half of the subordinate clauses were governed by a semifactive predicate (open to both word orders) and the other half by a semantically secondary sentence (in itself strongly favoring Verb>Adverb word order). Attention to the subordinate clause was tested by measuring how disinclined...... the participants were to notice change of a word in the subordinate clause when re-reading it. Results showed significantly more attention to Verb>Adverb clauses than to Adverb>Verb clauses under semifactive predicates, and more attention to subordinate clauses under semantically secondary than semifactive...

  18. Subordinate plant species moderate drought effects on earthworms communities in grasslands


    Mariotte Pierre; Le Bayon Renee-Claire; Eisenhauer Nico; Guenat Claire; Buttler Alexandre


    Loss of plant diversity resulting from forecasted drought events is likely to alter soil functioning and affect earthworm communities. Plant soil interactions are expected to play an important role in mediating climate change effects on soil decomposers. In this study we test above belowground linkages after drought by focusing on the effects of subordinate plant species on earthworm communities. Using a combination of subordinate species removal and experimental drought we show that subordin...

  19. Fleet leaders' attitudes about subordinates' use of mental health services. (United States)

    Westphal, Richard J


    Mental disorders are a significant source of medical and occupational morbidity for sailors. Stigma, fear of negative career impact, and subordinates concern about leaders' attitudes are significant barriers to the use of mental health services. Semistructured interviews and military policies were data sources used to analyze the language, knowledge, and attitudes of Navy surface fleet leaders about mental illness and mental health treatment using Foucault's concept of discourse analysis. A discourse is a system of knowledge that influences language, perceptions, values, and social practices. The results showed that leaders' concerns about sailors' mental combat readiness, not mental illness stigma, was the dominant discourse about mental illness and mental health services use. In particular, organizational differences between the surface warfare and the mental health communities may influence leaders' attitudes more than stigma. This study provides an elaborated view of mental health knowledge and power within a Navy community.

  20. Subordination Principle for a Class of Fractional Order Differential Equations

    Directory of Open Access Journals (Sweden)

    Emilia Bazhlekova


    Full Text Available The fractional order differential equation \\(u'(t=Au(t+\\gamma D_t^{\\alpha} Au(t+f(t, \\ t>0\\, \\(u(0=a\\in X\\ is studied, where \\(A\\ is an operator generating a strongly continuous one-parameter semigroup on a Banach space \\(X\\, \\(D_t^{\\alpha}\\ is the Riemann–Liouville fractional derivative of order \\(\\alpha \\in (0,1\\, \\(\\gamma>0\\ and \\(f\\ is an \\(X\\-valued function. Equations of this type appear in the modeling of unidirectional viscoelastic flows. Well-posedness is proven, and a subordination identity is obtained relating the solution operator of the considered problem and the \\(C_{0}\\-semigroup, generated by the operator \\(A\\. As an example, the Rayleigh–Stokes problem for a generalized second-grade fluid is considered.

  1. Socially transmitted diffusion of a novel behavior from subordinate chimpanzees

    DEFF Research Database (Denmark)

    Watson, Stuart K; Reamer, Lisa A; Mareno, Mary Catherine


    Chimpanzees (Pan troglodytes) demonstrate much cultural diversity in the wild, yet a majority of novel behaviors do not become group-wide traditions. Since many such novel behaviors are introduced by low-ranking individuals, a bias toward copying dominant individuals ("rank-bias") has been proposed...... as an explanation for their limited diffusion. Previous experimental work showed that chimpanzees (Pan troglodytes) preferentially copy dominant over low-rank models. We investigated whether low ranking individuals may nevertheless successfully seed a beneficial behavior as a tradition if there are no "competing....... Finally, we report an innovation by a subordinate individual that built cumulatively on existing methods of opening the puzzle-box and was subsequently copied by a dominant observer. These findings illustrate that chimpanzees are motivated to copy rewarding novel behaviors that are demonstrated...

  2. [Effects of T helper 1 cells and T helper 17 cells secreting cytokines on rat models of experimental periodontitis]. (United States)

    Wang, Z X; Yang, L; Tan, J Y; Chen, L L


    Objectvie: To investigate the effects of secreting cytokines interferon-gamma (IFN-γ) and interleukin-17 (IL-17) of T helper 1 cells (Th1) and T helper 17 cells (Th17) on the peripheral blood and alveolar bone destruction, so as to provide a new explanation for cellular immunity-mediated alveolar bone destruction. Methods: Eighteen eight-week-old male Sprague-Dawley rats were divided, randomly and equally, into 3 groups: lipopolysaccharide (LPS) group, ligation group and normal control group. In the LPS group, Escherichia coli LPS was injected into the alveolar mucosa on the buccalmedian site of the left upper first molar, while the right upper first molar was injected with equal volume of physiological saline as self-controls. The injections were performed every other day for four times totally. In the ligation group, the left upper first molars were ligatured with 0.2 mm orthodontic cords, while the right upper first molars were left untreated as self-controls, and supplemented with high-sugar diet to promote the periodontitis status. The rats in normal control group were fed normally. The concentrations of IFN-γ and IL-17 in peripheral blood were measured using enzyme linked immunosorbent assay (ELISA) method at the fourth week after the start of injection and at the eighth week after ligation. The histological of periodontal tissues were observed after hematoxylin-eosin (HE) staining and osteoclast count was performed under light microscope. The histological of osteoclasts were observed after tartrate-resistant acid phosphatase (TRAP) staining. Expression of IFN-γ and IL-17 were detected by immunohistochemical assay. Results: The concentrations of IFN-γ in peripheral blood of LPS group [(185.0±50.7) ng/L] and ligation group [(202.9±60.4) ng/L] were significantly higher than that of normal control group [(106.3±17.2) ng/L]( Pperiodontitis and alveolar bone resorption could be successfully established by means of ligationand LPS injection, respectively

  3. Experimentally induced helper dispersal in colonially breeding cooperative cichlids

    NARCIS (Netherlands)

    Heg, D.; Heg-Bachar, Z.; Brouwer, L.; Taborsky, M.


    The 'benefits of philopatry' hypothesis states that helpers in cooperatively breeding species derive higher benefits from remaining home, instead of dispersing and attempting to breed independently. We tested experimentally whether dispersal options influence dispersal propensity in the

  4. Die posisie van die Helper in die sending

    Directory of Open Access Journals (Sweden)

    I. J. van der Walt


    Full Text Available Gedurende die aanvangsjare van die sending het die helper ’n onmisbare funksie vervul. Hulle het die onherbergsame binnelande geken, waardevolle kontakpunte vir die sendelinge geopen en hulle mense geestelik help voorlig en voorberei.

  5. Die posisie van die Helper in die sending

    Directory of Open Access Journals (Sweden)

    I. J. van der Walt


    Full Text Available Gedurende die aanvangsjare van die sending het die helper ’n onmisbare funksie vervul. Hulle het die onherbergsame binnelande geken, waardevolle kontakpunte vir die sendelinge geopen en hulle mense geestelik help voorlig en voorberei.

  6. Suppression induction in vivo by a T helper clone?

    DEFF Research Database (Denmark)

    Crispe, I N; Owens, T


    We have previously described a helper T cell clone which augments in vivo cytotoxic T cell responses when injected at 10(4) cells per mouse, but not at 10(5) per mouse (Crispe, I. N. et al., Immunology 1984. 52:55). To test whether this dose-response relationship was due to the induction...... of suppression, naive syngeneic mice were injected with 10(5) cloned T helper cells, and their spleen cells were subsequently assayed for suppressive activity in adoptive transfer experiments. Lymphocytes from such mice indeed suppressed an antigen-specific cytotoxic response, but only in the presence...... of the same T helper cell clone freshly added at the time of adoptive transfer. On this basis we argue that the distinction between T helper cell activity and T suppressor-inducer activity corresponds to differences in cell numbers, rather than to two separate cell lineages....

  7. A closer look at the subordinate population within the visible burrow system. (United States)

    Melhorn, Susan J; Elfers, Clinton T; Scott, Karen A; Sakai, Randall R


    The visible burrow system (VBS) utilizes the natural social behavior of rodents to model chronic social stress. Classically, when male and female rats are housed together in the VBS a dominance hierarchy rapidly forms with one dominant (DOM) and three subordinate (SUB) males. SUB animals show signs of chronic social stress, including loss of body weight and elevated basal corticosterone. This study furthered examined differences among the SUB population. Quantitative observations across numerous VBS colonies within the Sakai Lab suggest that there is variability in the effects of stress on the SUB population, specifically that some animals may experience more severe effects of chronic social stress than others. To further examine this observation, SUB animals were classified as OMEGA if they received a disproportionate amount of their colonies' wounds. OMEGA animals received more wounds to their body compared to SUB (PVBS-housed animals (group×time interaction PVBS housing it was determined the OMGEA also lost lean body mass (PVBS colony and represents the variability of the effects of chronic social stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Herpesviruses provide helper functions for avian adeno-associated parvovirus. (United States)

    Bauer, H J; Monreal, G


    The avian herpesviruses infectious laryngotracheitis virus (ILTV) and herpesvirus of turkeys (HVT), as well as the mammalian herpesvirus pseudorabies virus (PRV) were able to provide complete helper activity for the production of infectious avian adeno-associated virus (AAAV) in chicken cells. The presence of AAAV in the infected chicken cell reduced the multiplication of HVT. ILTV or PRV, however, were not affected if used as helper viruses. Infectious AAAV was determined by an indirect immunofluorescence assay and infectious herpesvirus by plaque assays.

  9. 29 CFR 780.202 - Subordination to farming operations is necessary for exemption. (United States)


    ... 29 Labor 3 2010-07-01 2010-07-01 false Subordination to farming operations is necessary for... Operations § 780.202 Subordination to farming operations is necessary for exemption. While section 3(f) speaks of practices performed “in conjunction with” as well as “incident to” farming operations, it would...

  10. Subordinators and Supradialectal Formulas in the Dialectal Inscriptions from Mainland Greece (Excluding Attica) (United States)

    Minamimoto, Toru


    In this dissertation, I investigated the usage of subordinators in Ancient Greek dialectal inscriptions and their interactions with supradialectal formulas, i.e., relatively fixed expressions shared across dialectal borders. Subordinators are grammatical elements and therefore are expected to behave in a systematic manner; supradialectal formulas…

  11. Aspects of Subordination in English Syntax and its Use Among Bette ...

    African Journals Online (AJOL)

    Bette is a language widely spoken in the north-eastern part of Cross River State, Nigeria. The need for this study arises from an observation of serious interference of Bette system of subordination in Bette bilinguals with that of English. I examined subordination in the two systems through a contrastive linguistic analysis to ...

  12. 7 CFR 1717.858 - Lien subordination for rural development investments. (United States)


    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Lien subordination for rural development investments... Lien subordination for rural development investments. (a) Policy. RUS encourages borrowers to consider... financial risks and the revenues and costs of the rural development enterprise from those of the borrower's...

  13. Involuntary Subordination and Its Relation to Personality, Mood, and Submissive Behavior (United States)

    Sturman, Edward D.


    According to social rank theory, involuntary subordination may be adaptive in species that compete for resources as a mechanism to switch off fighting behaviors when loss is imminent (thus saving an organism from injury). In humans, major depression is thought to occur when involuntary subordination becomes prolonged. The present study sought to…

  14. 12 CFR 563.81 - Inclusion of subordinated debt securities and mandatorily redeemable preferred stock as... (United States)


    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Inclusion of subordinated debt securities and... Borrowings § 563.81 Inclusion of subordinated debt securities and mandatorily redeemable preferred stock as..., subpart A seeking OTS approval of, or non-objection to, the inclusion of covered securities in...

  15. Participation with Supervisor and Subordinate Authoritarianism: A Path-Goal Theory Reconciliation (United States)

    Schuler, Randall S.


    Tested the hypothesis that participation would be satisfying to low-authoritarian subordinates regardless of the degree of task repetitiveness but would be satisfying to high-authoritarian subordinates only on tasks with low repetitiveness and that highly repetitive tasks would be less conducive to ego involvement than low-repetitive tasks.…

  16. Charismatic, Ideological, and Pragmatic Leaders' Influence on Subordinate Creative Performance across the Creative Process (United States)

    Lovelace, Jeffrey B.; Hunter, Samuel T.


    Using the charismatic, ideological, and pragmatic (CIP) model of leadership as a framework, 2 primary research questions were examined. First, when engaging in different tasks along the creative process, does leadership style influence the creative performance of subordinates? Second, how does the level of stress, to which subordinates are…

  17. Patriarchal Hierarchies of Power and the Subordination of Women: Real Doll as a Replacement of Woman Figure

    Directory of Open Access Journals (Sweden)

    Natasha Shokri


    Full Text Available The social structure of the family has always been in the state of transformation. In the past centuries, the nuclear family was replaced with a Patriarchal Family which lasted for only two centuries from 16th to the beginning of 18th century. In this new structure of the family, men were privileged to play the role of the master and the women were marginalized and subordinated. Recent years, however, has witnessed a re-adjustment of this order towards a more equal distribution of power relations. These changes in family structure has ever since initiated new conflicts leading to establishment of the physical and psychological bonds between men and dolls. The present study aims to find out the major socio-psychological reasons behind this conflict. In a qualitative library based study, the researchers attempt to analyse the video interview of some of the doll-owners. In the survey conducted in this study, the video of “Guys and Dolls”, BBC Video Documentary, has been shown to 10 participants, five male and five female. Then, a questionnaire was distributed to ask for their opinion based on their gender. The findings of this analysis reveal that women can hardly accept the notion of using dolls as replacement to real partners in comparison with men. On the contrary, the male participants advocated the employment of dolls as sexual replacement for the real woman figure. Keywords: Patriarchy, Real Doll, Oedipus complex, Female Subordination, Family

  18. Relationships between leaders' and subordinates' emotion regulation and satisfaction and affect at work. (United States)

    Kafetsios, Konstantinos; Nezlek, John B; Vassilakou, Thanai


    The study examined relationships between leaders' emotion regulation and leaders' and subordinates' work-related outcomes. Fifty-one school directors and 281 teachers reported on their strategies of emotion regulation (reappraisal, suppression), job satisfaction, and affect at work. For subordinates, suppression was negatively related to job satisfaction and was positively related to negative affect and emotional exhaustion, and reappraisal was positively related to job satisfaction and negatively to negativ affect. In contrast, multilevel analyses found that directors' use of reappraisal was neg atively related to subordinates' job satisfaction, and directors' use of suppression wa positively related to subordinates' positive affect. Leaders' suppression interacted wit group cohesion to predict subordinates' negative affect. This is one of the first studies to find evidence for the possible tension between leaders' emotion regulation competencie and organizational-role interests.

  19. The role of leadership perception as a mediator between managers' self-monitoring and subordinate attitudes. (United States)

    Özalp Türetgen, Ilknur; Unsal, Pinar; Dural, Uzay


    Although the role of social cognition in leadership perception has been emphasized frequently in recent years, research using this approach in an organizational context is rare. This study investigated subordinates' perceptions of their managers as leaders (that is, to what extent they perceive their manager as a leader) as a potential mediating factor explaining the relationship between managers' self-monitoring and their subordinates' attitudes toward their organizations. The study was carried out with middle-level managers (N = 64) and their subordinates (N = 210) from various business organizations in Turkey. Results indicate that subordinates' leadership perceptions of their managers mediate the relationship between managers' self-monitoring and their subordinates' affective and normative organizational commitment. These results provide insight into some of the antecedents and outcomes of leadership perception.

  20. Psychological characteristics of the rules of subordination within the cultural and historical analysis

    Directory of Open Access Journals (Sweden)

    Budyakova T.P.,


    Full Text Available The article examines the psychology of submission. Given psychological characteristic standards of submission historically embodied in the moral codes and legal sources. The subject of analysis are historical regulations XII—XX centuries, the customs, in which the fixed rate of submission, as well as the memoir literature. There are four basic psychological lines of development in the history of the rules of subordination, in particular: a special regulation of the rules of subordination and increasing social importance of the role of subordinate. It is proved that psychological acceptance of a subordinate role and the satisfaction of its implementation includes the requirement of special rules regulating authority and emphasis on the social importance of the role of subordinate. It was established that one of the reasons that the job satisfaction of employees of state structures higher than employees of private companies, a large schema definition of relations with management. Hierarchical role is considered in terms of two components: the role of attributes and rules, rules of conduct. The article focuses on the fact that the individual external signs, locking status subordination, increase the level of self-esteem of subordinate.

  1. Empowerment and performance of managers and subordinates in elderly care: A longitudinal and multilevel study. (United States)

    Hagerman, Heidi; Högberg, Hans; Skytt, Bernice; Wadensten, Barbro; Engström, Maria


    To investigate relationships between first-line managers' ratings of structural and psychological empowerment, and the subordinates' ratings of structural empowerment, as well as their ratings of the managers' leadership-management performance. Work situations in elderly care are complex. To date, few studies have used a longitudinal, correlational and multilevel design to study the working life of subordinates and managers. In five Swedish municipalities, questionnaires were answered twice during 2010-12 by 56 first-line managers and 769 subordinates working in nursing homes or home-help services. First-line managers' empowerment at Time 1 partially predicted subordinate's structural empowerment and ratings of their managers' leadership-management performance at Time 2. Changes over time partially revealed that the more access managers had to structural empowerment, i.e. increase over time, the higher the ratings were for structural empowerment and managerial leadership-management performance among subordinates. Findings strengthen research and theoretical suggestions linking first-line managers' structural empowerment to their subordinates' structural empowerment and ratings of their manager's leadership-management performance. Managers with high access to structural empowerment are more likely to provide subordinates access to structural empowerment. © 2017 The Authors. Journal of Nursing Management Published by John Wiley & Sons Ltd.

  2. Social subordination impairs hypothalamic-pituitary-adrenal function in female rhesus monkeys. (United States)

    Michopoulos, Vasiliki; Reding, Katherine M; Wilson, Mark E; Toufexis, Donna


    Linear dominance hierarchies organize and maintain stability in female rhesus macaque (Macaca mulatta) social groups regardless of group size. As a consequence of their low social status, subordinate females suffer from an array of adverse outcomes including reproductive compromise, impaired immune function, and poor cardiovascular health. However, data that differentiate limbic-hypothalamic-pituitary-adrenal axis (LHPA) parameters between dominant from subordinate female monkeys are inconsistent, bringing into question whether social subordination alters the LHPA axis in female macaques. One difficulty in examining LHPA function in macaques may be the confounding effects of cycling ovarian steroids that are known to modulate LHPA activity. The current study used ovariectomized dominant and subordinate female rhesus monkeys to examine the effect that social subordination has on LHPA function by measuring morning and diurnal serum cortisol levels, dexamethasone (Dex) suppression of cortisol, metabolic clearance of Dex, and ACTH stimulation of adrenal cortisol release and cortisol response following exposure to acute social isolation. Compared to dominant females, subordinate females showed diminished morning peak cortisol secretion, weakened glucocorticoid negative feedback, and decreased adrenal cortisol response to an ACTH challenge as well as a restrained cortisol response following social isolation. However, the metabolism of Dex did not account for differences in Dex suppression between dominant and subordinate females. These results indicate that the ability to mount and limit glucocorticoid release is significantly reduced by psychosocial stress in female rhesus macaques, suggesting a hyporesponsive LHPA phenotype which resembles that observed in several human psychopathologies. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Model checking to assess T-helper cell plasticity

    Directory of Open Access Journals (Sweden)

    Wassim eAbou-Jaoudé


    Full Text Available Computational modeling constitutes a crucial step towards the functional understanding of complex cellular networks.In particular, logical modeling has proven suitable for the dynamical analysis of large signaling and transcriptional regulatory networks.In this context, signaling input components are generally meant to convey external stimuli, or environmental cues.In response to such external signals, cells acquire specific gene expression patterns modeled in terms of attractors ({em e.g.} stable states.The capacity for cells to alter or reprogram their differentiated states upon changes in environmental conditions is referred to as cell plasticity.In this article, we present a multivalued logical framework along with computational methods recently developed to efficiently analyze large models.We mainly focus on a symbolic model checking approach to investigate switches between attractors subsequent to changes of input conditions.As a case study, we consider the cellular network regulating the differentiation of T-helper cells, which orchestrate many physiological and pathological immune responses.To account for novel cellular subtypes, we present an extended version of a published model of T-helper cell differentiation. We then use symbolic model checking to analyze reachability properties between T-helper subtypes upon changes of environmental cues.This allows for the construction of a synthetic view of T-helper cell plasticity in terms of a graph connecting subtypes with arcs labeled by input conditions.Finally, we explore novel strategies enabling specific T-helper cell polarizing or reprograming events.


    Directory of Open Access Journals (Sweden)

    Fatikha Amalina


    Full Text Available This research is aimed to describe the imprisonment of African American people, especially women, in the case of patriarchy and women subordination through Maya Angelou‘s selected poems entitled ―Caged Bird‖, ―Still I Rise‖ and ―Woman Work‖. This research discusses the meaning behind the poems that reflected Maya Angelou‘s life experience relating to women subordination and freedom. Feminism approach is applied to analyze the concept of freedom in women subordination and patriarchy in this research. The paper points to how the concept of gender intertwines with labor, ethnics, kinship and gender domination. Without aiming to paint a detailed picture of feminism, the paper explores how ideas developed in these inquiries question the taken-for-granted assumption about the universality of women‘s subordination and challenge the emancipation prerequisite of feminist agenda.

  5. Genetic sorting of subordinate species in grassland modulated by intraspecific variation in dominant species.

    Directory of Open Access Journals (Sweden)

    Danny J Gustafson

    Full Text Available Genetic variation in a single species can have predictable and heritable effects on associated communities and ecosystem processes, however little is known about how genetic variation of a dominant species affects plant community assembly. We characterized the genetic structure of a dominant grass (Sorghastrum nutans and two subordinate species (Chamaecrista fasciculata, Silphium integrifolium, during the third growing season in grassland communities established with genetically distinct (cultivated varieties or local ecotypes seed sources of the dominant grasses. There were genetic differences between subordinate species growing in the cultivar versus local ecotype communities, indicating that intraspecific genetic variation in the dominant grasses affected the genetic composition of subordinate species during community assembly. A positive association between genetic diversity of S. nutans, C. fasciculata, and S. integrifolium and species diversity established the role of an intraspecific biotic filter during community assembly. Our results show that intraspecific variation in dominant species can significantly modulate the genetic composition of subordinate species.

  6. Olfactory cues are subordinate to visual stimuli in a neotropical generalist weevil.

    Directory of Open Access Journals (Sweden)

    Fernando Otálora-Luna

    Full Text Available The tropical root weevil Diaprepes abbreviatus is a major pest of multiple crops in the Caribbean Islands and has become a serious constraint to citrus production in the United States. Recent work has identified host and conspecific volatiles that mediate host- and mate-finding by D. abbreviatus. The interaction of light, color, and odors has not been studied in this species. The responses of male and female D. abbreviatus to narrow bandwidths of visible light emitted by LEDs offered alone and in combination with olfactory stimuli were studied in a specially-designed multiple choice arena combined with a locomotion compensator. Weevils were more attracted to wavelengths close to green and yellow compared with blue or ultraviolet, but preferred red and darkness over green. Additionally, dim green light was preferred over brighter green. Adult weevils were also attracted to the odor of its citrus host + conspecifics. However, the attractiveness of citrus + conspecific odors disappeared in the presence of a green light. Photic stimulation induced males but not females to increase their speed. In the presence of light emitted by LEDs, turning speed decreased and path straightness increased, indicating that weevils tended to walk less tortuously. Diaprepes abbreviatus showed a hierarchy between chemo- and photo-taxis in the series of experiments presented herein, where the presence of the green light abolished upwind anemotaxis elicited by the pheromone + host plant odor. Insight into the strong responses to visual stimuli of chemically stimulated insects may be provided when the amount of information supplied by vision and olfaction is compared, as the information transmission capacity of compound eyes is estimated to be several orders of magnitude higher compared with the olfactory system. Subordination of olfactory responses by photic stimuli should be considered in the design of strategies aimed at management of such insects.

  7. Olfactory Cues Are Subordinate to Visual Stimuli in a Neotropical Generalist Weevil (United States)

    Otálora-Luna, Fernando; Lapointe, Stephen L.; Dickens, Joseph C.


    The tropical root weevil Diaprepes abbreviatus is a major pest of multiple crops in the Caribbean Islands and has become a serious constraint to citrus production in the United States. Recent work has identified host and conspecific volatiles that mediate host- and mate-finding by D. abbreviatus. The interaction of light, color, and odors has not been studied in this species. The responses of male and female D. abbreviatus to narrow bandwidths of visible light emitted by LEDs offered alone and in combination with olfactory stimuli were studied in a specially-designed multiple choice arena combined with a locomotion compensator. Weevils were more attracted to wavelengths close to green and yellow compared with blue or ultraviolet, but preferred red and darkness over green. Additionally, dim green light was preferred over brighter green. Adult weevils were also attracted to the odor of its citrus host + conspecifics. However, the attractiveness of citrus + conspecific odors disappeared in the presence of a green light. Photic stimulation induced males but not females to increase their speed. In the presence of light emitted by LEDs, turning speed decreased and path straightness increased, indicating that weevils tended to walk less tortuously. Diaprepes abbreviatus showed a hierarchy between chemo- and photo-taxis in the series of experiments presented herein, where the presence of the green light abolished upwind anemotaxis elicited by the pheromone + host plant odor. Insight into the strong responses to visual stimuli of chemically stimulated insects may be provided when the amount of information supplied by vision and olfaction is compared, as the information transmission capacity of compound eyes is estimated to be several orders of magnitude higher compared with the olfactory system. Subordination of olfactory responses by photic stimuli should be considered in the design of strategies aimed at management of such insects. PMID:23341926

  8. Supervising Helpers Who Work with the Trauma of Sexual Abuse (United States)

    Etherington, Kim


    This paper contributes to the ongoing discussion in this journal about counsellors' experiences of vicarious traumatisation (Sexton, 1999; Dunkley & Whelan, 2006a, b). It builds on my previous paper (Etherington, 2000a) that focused on the role of supervision in moderating the potential impact on helpers, and on the helping relationship, of…

  9. Increased expression of T-helper cell activation markers in ...

    African Journals Online (AJOL)


    part, by the actions of eosinophil-active cytokines derived predominantly from activated CD4 T-cells, of which interleukin-5 (IL-5) is uniquely eosinophil- specific 3,4. T-helper cells are a heterogeneous group of cells that can be divided into subpopulations on the basis of the expression of the cell surface markers. The.

  10. A Peer Helper Program for Pregnant and Parenting Teenagers. (United States)

    Canam, Connie J.


    The paper presents a model for developing a special educational program for pregnant and parenting teens, with a rationale for its effectiveness. The curriculum is outlined, and program logistices are covered, including selection of leaders; recruitment, utilization and supervision of peer helpers; and evaluation of the program. (Author/CL)

  11. A better understanding of helper T cell differentiation using mathematical models and bioinformatics

    NARCIS (Netherlands)

    van den Ham, H.J.|info:eu-repo/dai/nl/304837245


    Helper T cells play an important role in determining the outcome of an immune response. Helper T cells of distinct phenotypes induce different immune responses by producing distinct cytokines. The phenotype of a helper T cell and the production of the corresponding cytokine(s) is determined by

  12. Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses.

    Directory of Open Access Journals (Sweden)

    Sandra J van Vliet


    Full Text Available Gonorrhea is one of the most prevalent sexually transmitted diseases in the world. A naturally occurring variation of the terminal carbohydrates on the lipooligosaccharide (LOS molecule correlates with altered disease states. Here, we investigated the interaction of different stable gonoccocal LOS phenotypes with human dendritic cells and demonstrate that each variant targets a different set of receptors on the dendritic cell, including the C-type lectins MGL and DC-SIGN. Neisseria gonorrhoeae LOS phenotype C constitutes the first bacterial ligand to be described for the human C-type lectin receptor MGL. Both MGL and DC-SIGN are locally expressed at the male and female genital area, the primary site of N. gonorrhoeae infection. We show that targeting of different C-type lectins with the N. gonorrhoeae LOS variants results in alterations in dendritic cell cytokine secretion profiles and the induction of distinct adaptive CD4(+ T helper responses. Whereas N. gonorrhoeae variant A with a terminal N-acetylglucosamine on its LOS was recognized by DC-SIGN and induced significantly more IL-10 production, phenotype C, carrying a terminal N-acetylgalactosamine, primarily interacted with MGL and skewed immunity towards the T helper 2 lineage. Together, our results indicate that N. gonorrhoeae LOS variation allows for selective manipulation of dendritic cell function, thereby shifting subsequent immune responses in favor of bacterial survival.

  13. Supervisors' upward exchange relationships and subordinate outcomes: testing the multilevel mediation role of empowerment. (United States)

    Zhou, Le; Wang, Mo; Chen, Gilad; Shi, Junqi


    This study empirically examined the proposition that supervisors' exchange relationships with their own supervisors (i.e., leader-leader exchange, or LLX) are related to their subordinates' work-related outcomes through 3 mechanisms: (a) leaders modeling their LLX to develop and maintain their exchange relationships with their subordinates (i.e., leader-member exchange, or LMX), (b) motivating the team and its members, captured by team and individual empowerment, and (c) facilitating the relationships between LMX and individual outcomes. Analyses of multisource and lagged data from 104 team supervisors and 577 subordinates showed that LMX mediated the positive relationship of LLX on subordinates' individual empowerment. Furthermore, team empowerment and individual empowerment sequentially mediated the positive relationships between LLX and subordinates' job satisfaction and job performance. The authors also found that the indirect relationships of LMX with job satisfaction and job performance via individual empowerment were stronger when LLX was higher. Theoretical and practical implications of these findings are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  14. Leadership predictors of innovation and task performance : Subordinates self-esteem and self-presentation as moderators


    Rank, Johannes; Nelson, Nicole E.; Allen, Tammy D.; Xu, Xian


    This study examined self-related subordinate variables as moderators of relationships between supervisors leadership behaviours (transformational as well as activecorrective transactional leadership) and subordinates innovative behaviour and task performance. Based on behavioural plasticity and self-monitoring theory, we hypothesized that these associations would be moderated by subordinates organization-based self-esteem and by their propensity to modify self-presentation, a major facet o...

  15. Similarity and Dissimilarity between Superiors and Subordinates and Their Implications for Dyadic Relationship Quality

    Directory of Open Access Journals (Sweden)

    Nereida Salette Paulo da Silveira


    Full Text Available Although literature advocates the advantages of work force diversification, studies based on the Similarity- Attraction Paradigm indicate that people are more disposed to feel attraction to those who are similar to them. A field study with the comparative data of 89 dyads investigated the effect of the actual and perceived similarity in the quality of the relationship between superiors and subordinates within the Leader-Member Exchange [LMX] perspective. The investigated characteristics were: gender, age and work-family conflict. The data indicate the influence only of perceived similarity in the quality of the relationship between superiors and subordinates. This effect broadens when the subordinate feels satisfied with the quality and frequency of contact with his/her superior. The methodological procedures included factorial analysis and validation of two scales (EIFT and LMX-7, the correlations analysis and hierarchic regressions. Finally, the implications of some results and directions for future research in diversity are discussed.

  16. Implementation of an Economical Parking Helper Device Using Ultrasound Sensors (United States)

    Jamil, Tariq


    Every motorist dreams of a car that will take the stress out of parking by finding a suitable space and then maneuvers itself into the space with minimal assistance from the driver. This paper describes a parking helper device using ultrasound sensors, mounted on the car, to monitor both sides of the street for a suitable parking space, and when a large enough parking space is detected, the helper instructs the driver to stop the car and guides him/her via a display screen and voice about steering maneuvers which will ultimately result in the car being properly parked in the given parking space. Ultrasound sensors mounted on the front and rear bumpers of the car will ensure that a safe distance is maintained to other vehicles and objects and the driver will need to operate only the accelerator and the brake pedals. A warning signal sounds if the vehicle gets too close to other objects in the parking space.

  17. Maintaining helper wellness and competence in a shared trauma reality. (United States)

    Halpern, James


    As shared trauma reality becomes more common in Israel and other countries, this commentary argues that we need more research to inform how to best assist mental health professionals who are both victims and helpers in the aftermath of traumatic events. Typical remedies for the occupational hazards of working with trauma survivors may not apply for those who are exposed to a prolonged terror threat. Research-informed self-care strategies need to be identified and practiced.

  18. Memory T follicular helper CD4 T cells

    Directory of Open Access Journals (Sweden)

    J. Scott eHale


    Full Text Available T follicular helper (Tfh cells are the subset of CD4 T helper cells that are required for generation and maintenance of germinal center reactions and the generation of long-lived humoral immunity. This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and other molecules. Tfh cells are characterized by their expression of the chemokine receptor CXCR5, expression of the transcriptional repressor Bcl6, and their capacity to migrate to the follicle and promote germinal center B cell responses. Until recently, it remained unclear whether Tfh cells differentiated into memory cells and whether they maintain their Tfh commitment at the memory phase. This review will highlight several recent studies that support the idea of Tfh-committed CD4 T cells at the memory stage of the immune response. The implication of these findings is that memory Tfh cells retain their capacity to recall their Tfh-specific effector functions upon reactivation to provide help for B cell responses and play an important role in prime and boost vaccination or during recall responses to infection. The markers that are useful for distinguishing Tfh effector and memory cells, as well as the limitations of using these markers will be discussed. Tfh effector and memory generation, lineage maintenance, and plasticity relative to other T helper lineages (Th1, Th2, Th17, etc will also be discussed. Ongoing discoveries regarding the maintenance and lineage stability versus plasticity of memory Tfh cells will improve strategies that utilize CD4 T cell memory to modulate antibody responses during prime and boost vaccination.

  19. Ruin Time and Severity for a Lévy Subordinator Claim Process: A Simple Approach

    Directory of Open Access Journals (Sweden)

    Claude Lefèvre


    Full Text Available This paper is concerned with an insurance risk model whose claim process is described by a Lévy subordinator process. Lévy-type risk models have been the object of much research in recent years. Our purpose is to present, in the case of a subordinator, a simple and direct method for determining the finite time (and ultimate ruin probabilities, the distribution of the ruin severity, the reserves prior to ruin, and the Laplace transform of the ruin time. Interestingly, the usual net profit condition will be essentially relaxed. Most results generalize those known for the compound Poisson claim process.

  20. Subject of Subordinate Clause as Object with Verbs of Perception, Thought, and Communication in Old Russian

    Directory of Open Access Journals (Sweden)

    Anna A. Pichkhadze


    Full Text Available This paper describes the Old Russian construction involving verbs of perception, thought, and communication. In this construction, a single semantic argument corresponds to two syntactic constituents: a direct object and a finite subordinate clause, the subject of which is coreferential with the direct object of the main clause. The Old Russian construction is seen as an instantiation of a cross-linguistic option in the argument structure of these verbs (above all, of the perception verbs, that is, to take the subject of the subordinate clause as the direct object.

  1. "Little Helper" - An Autonomous Industrial Mobile Manipulator Concept

    Directory of Open Access Journals (Sweden)

    Mads Hvilshoj


    Full Text Available This paper presents the concept "autonomous industrial mobile manipulation" (AIMM based on the mobile manipulator "Little Helper" - an ongoing research project at Aalborg University, Denmark, concerning the development of an autonomous and flexible manufacturing assistant. The paper focuses on the contextual aspects and the working principles of AIMM. Furthermore, the paper deals with the design principles and overall hardware and software architectures of "Little Helper" from a functional and modular mechatronics point of view, in order to create a generic AIMM platform. The design challenges faced in the project is to integrate commercial off‐the‐shelf (COTS and dedicated highly integrated systems into an autonomous mobile manipulator system with the ability to perform diverse tasks in industrial environments. We propose an action based domain specific communication language for AIMM for routine and task definition, in order to lower the entry barriers for the users of the technology. To demonstrate the "Little Helper" concept a full‐scale prototype has been built and different application examples carried out. Experiences and knowledge gained from this show promising results regarding industrial integration, exploitation and maturation of the AIMM technology.

  2. Supervisor-Subordinate Relationship, Differentiation, and Employee Creativity: A Self-Categorization Perspective (United States)

    Zhao, Hongdan; Kessel, Maura; Kratzer, Jan


    This study seeks to explore the effect of the quality of supervisor-subordinate relationship (i.e., leader-member exchange; LMX) on employee creativity by examining a moderated-mediation model. The model focuses on the mediating role of perceived insider status and the moderating role of perceived LMX differentiation in influencing the mediation.…

  3. Impact of different-sized herbivores on recruiment opportunities for subordinate herbs in grasslands

    NARCIS (Netherlands)

    Bakker, E.S.; Olff, H.


    Potential effects of herbivores on plant species diversity depend on herbivore size, species and density. In this study we examine the effect of different-sized herbivores (cattle and rabbits) on recruitment of subordinate herbs in grasslands. We show that in a grazed floodplain, grassland plant

  4. Impact of different-sized herbivores on recruitment opportunities for subordinate herbs in grasslands

    NARCIS (Netherlands)

    Bakker, Elisabeth S.; Olff, Han


    Potential effects of herbivores on plant species diversity depend on herbivore size, species and density. In this study we examine the effect of different-sized herbivores (cattle and rabbits) on recruitment of subordinate herbs in grasslands. We show that in a grazed floodplain, grassland plant

  5. Analysis of Subordination Errors in Students' Writings: A Study of Selected Teacher Training Colleges in Ghana (United States)

    Adjei, Amma Abrafi


    This study is aimed at examining how students of selected Teacher Training Colleges handle one important aspect of sentence structure, i.e. "subordination". Data were collected from written scripts, and tests responded to by 150 participants from three selected colleges. These were analyzed by identifying both correct and incorrect uses…

  6. Sex of leader, sex of subordinate and leader behaviour type as ...

    African Journals Online (AJOL)

    Sex of leader, sex of subordinate and leader behaviour type as predictors of task performance. Jackson I Osu. Abstract. No Abstract Available African Journal for the Psychological Study of Social Issues Vol.4(2) 1999: 245-258. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL ...

  7. Perceptions of Leadership Style: Superior and Subordinate Descriptions of Decision-Making Behavior (United States)

    Jago, Arthur G.; Vroom, Victor H.


    This research concerns the level of agreement among subordinates reporting to the same leader in their descriptions of his behavior. (Available from the Comparative Administration Research Institute, Graduate School of Business Administration, Kent State University, Kent, OH 44242; $12.00 annually) (Author/MLF)

  8. The subordinate concept ‘marketing’ in the contemporary business English discourse

    Directory of Open Access Journals (Sweden)

    Liudmyla Naumenko


    Full Text Available The paper considers architectonics of the concept ‘marketing’ as a subordinate one to the concept ‘market’ which, alongside with other concepts, organizes the conceptual sphere of the basic concept ‘trade’. The notional, sense (sense centres, and schematic (dynamic frame components are researched, the model of the concept inner structure is developed

  9. On differential subordinations for a class of analytic functions defined by a linear operator

    Directory of Open Access Journals (Sweden)

    V. Ravichandran


    Full Text Available We obtain several results concerning the differential subordination between analytic functions and a linear operator defined for a certain family of analytic functions which are introduced here by means of these linear operators. Also, some special cases are considered.

  10. A Study of Relationship between Leader Behaviors and Subordinate Job Expectancies: A Path-Goal Approach

    Directory of Open Access Journals (Sweden)

    Sikandar Hayyat Malik


    Full Text Available This study investigates relationship between leader behavior (directive, supportive, participative and achievement-oriented of corporate managers and subordinates’ job expectancies using House (1974 Path-goal model of leadership. The results reveal thatleader behavior affects subordinates’ job expectancies. The situational factors (task structure, role ambiguity, stress, need for autonomy, locus of control, need for achievement and perception about abilities affect subordinates’ job expectancies (I&II.While subordinates’ attributes/characteristics (age, gender, qualification, rank, experience and length of service under the current supervisor do not affect job expectancies (I&II except for rank/position and expectancy-II. Path goal theory predicts that directive leader behavior will be more effective for the subordinates with high need for achievement because directive leader through clarifying path guides subordinates. Similarly, participative leader behavior is also effective as heconsults with subordinates in setting, clarifying and achieving goals. The results of this study reveal that there is an inverse relationship between subordinates’ job expectancy (I&II. According to Yukl (2006, for subordinates with high need for autonomy,participative leader behavior will increase the intrinsic valence of work.

  11. Some subordination and superordination results for the generalized hypergeometric functions associated with Ruscheweyh derivative

    Directory of Open Access Journals (Sweden)

    Abdul Rahman S. Juma


    Full Text Available Our purpose in this paper is to define a linear operator  F_{p,q,s}[\\alpha_{1},m], then applying it to obtain some results on subordination and superordination preserving properties of holomorphic multivalent functions in the  open unit disc. And sandwich-type result for these holomorphic multivalent functions is also considered.

  12. The (Biological or Cultural Essence of Essentialism: Implications for Policy Support among Dominant and Subordinated Groups

    Directory of Open Access Journals (Sweden)

    Nur Soylu Yalcinkaya


    Full Text Available Most research links (racial essentialism to negative intergroup outcomes. We propose that this conclusion reflects both a narrow conceptual focus on biological/genetic essence and a narrow research focus from the perspective of racially dominant groups. We distinguished between beliefs in biological and cultural essences, and we investigated the implications of this distinction for support of social justice policies (e.g., affirmative action among people with dominant (White and subordinated (e.g., Black, Latino racial identities in the United States. Whereas, endorsement of biological essentialism may have similarly negative implications for social justice policies across racial categories, we investigated the hypothesis that endorsement of cultural essentialism would have different implications across racial categories. In Studies 1a and 1b, we assessed the properties of a cultural essentialism measure we developed using two samples with different racial/ethnic compositions. In Study 2, we collected data from 170 participants using an online questionnaire to test the implications of essentialist beliefs for policy support. Consistent with previous research, we found that belief in biological essentialism was negatively related to policy support for participants from both dominant and subordinated categories. In contrast, the relationship between cultural essentialism and policy support varied across identity categories in the hypothesized way: negative for participants from the dominant category but positive for participants from subordinated categories. Results suggest that cultural essentialism may provide a way of identification that subordinated communities use to mobilize support for social justice.

  13. Supervisors' Responses to Subordinate Performance: Effect of Personal-Control Orientation and Situational Control. (United States)

    Ashkanasy, Neal M.


    Presents a study extending a model of leadership response based on attribution theories to include measures of locus of control and situational control. Describes a procedure by which subjects responded to descriptions of subordinate performance. Concludes that supervisors with an external locus of control were less sensitive to subordinate…

  14. Task Structure as Moderator of College Principals' Leadership Behavior and Their Subordinates' Outcomes (United States)

    Awan, Riffat-Un-Nisa; Zaidi, Nayyar Raza; Naz, Anjum; Noureen, Ghazala


    This research article intended to investigate the moderating effect of structured task on the relationship of leadership behavior of degree college principals and their subordinates' job satisfaction, job expectancies and acceptance of leader. Data was collected from 640 college faculty members and 170 principals of degree colleges situated in 34…

  15. Leader reliance on subordinates across nations that differ in development and climate

    NARCIS (Netherlands)

    Van de Vliert, E; Smith, P B

    How, where, and why do leaders follow the people they lead? An 84-nation analysis of survey responses from 19,525 managers shows that their reliance on subordinates depends on the level of wealth and development, and the harshness of cold or hot climates. In support of the thermal demands-resources

  16. Peering is not a formal indicator of subordination in bonobos (Pan paniscus)

    NARCIS (Netherlands)

    Stevens, J.M.G.; Vervaecke, H.; Vries, Han de; Elsacker, L. van


    It has been suggested that peering behavior in bonobos is a formal signal acknowledging social dominance status. We investigated whether peering meets the published criteria for a formal signal of subordination in five captive groups of bonobos. The degree of linearity in the set of peering

  17. Leaders' achievement goals and their integrative management of creative ideas voiced by subordinates or superiors

    NARCIS (Netherlands)

    Sijbom, Roy B. L.; Janssen, Onne; Van Yperen, Nico W.


    The purpose of this research was to examine the joint impact of leader achievement goals and hierarchical position of the voicer of creative ideas (subordinate vs. superior) on the extent to which leaders (intent to) integrate these voiced creative ideas with their own ideas (integrative idea

  18. Leaders’ achievement goals and their integrative management of creative ideas voiced by subordinates or superiors

    NARCIS (Netherlands)

    Sijbom, R.B.L.; Janssen, O.; van Yperen, N.W.


    The purpose of this research was to examine the joint impact of leader achievement goals and hierarchical position of the voicer of creative ideas (subordinate vs. superior) on the extent to which leaders (intent to) integrate these voiced creative ideas with their own ideas (integrative idea

  19. Leader motives, charismatic leadership and subordinates' work attitude in the profit and voluntary sector

    NARCIS (Netherlands)

    de Hoogh, A.H.B.; den Hartog, D.N.; Koopman, P.L.; Thierry, Hk.; van den Berg, P.T.; van der Weide, J.G.; Wilderom, C.P.M.


    This multimethod study examined leaders' motives, charismatic leader behavior, and subordinates' work attitude for CEOs (N=73) of small and medium-sized organizations in two sectors, namely, the profit and voluntary sector. Interviews with CEOs were coded for motive imagery. Direct reports rated CEO

  20. Production supervisor impacts on subordinates' safety outcomes: an investigation of leader-member exchange and safety communication (United States)

    Judd H. Michael; Zhen George Guo; Janice K. Wiedenbeck; Charles D. Ray


    Problem: Supervisors are increasingly important to the functioning of manufacturing operations, in large part due to their role as leaders. While supervisors' relations and communication with their subordinates are known to be important in influencing subordinates' behavior, little is known about how these two factors will impact...

  1. T-helper 17 cell polarization in pulmonary arterial hypertension. (United States)

    Hautefort, Aurélie; Girerd, Barbara; Montani, David; Cohen-Kaminsky, Sylvia; Price, Laura; Lambrecht, Bart N; Humbert, Marc; Perros, Frédéric


    Inflammation may contribute to the pathobiology of pulmonary arterial hypertension (PAH). Deciphering the PAH fingerprint on the inflammation orchestrated by dendritic cells (DCs) and T cells, key driver and effector cells, respectively, of the immune system, may allow the identification of immunopathologic approaches to PAH management. Using flow cytometry, we performed immunophenotyping of monocyte-derived DCs (MoDCs) and circulating lymphocytes from patients with idiopathic PAH and control subjects. With the same technique, we performed cytokine profiling of both populations following stimulation, coculture, or both. We tested the immunomodulatory effects of a glucocorticoid (dexamethasone [Dex]) on this immunophenotype and cytokine profile. Using an epigenetic approach, we confirmed the immune polarization in blood DNA of patients with PAH. The profile of membrane costimulatory molecules of PAH MoDCs was similar to that of control subjects. However, PAH MoDCs retained higher levels of the T-cell activating molecules CD86 and CD40 after Dex pretreatment than did control MoDCs. This was associated with an increased expression of IL-12p40 and a reduced migration toward chemokine (C-C motif) ligand 21. Moreover, both with and without Dex, PAH MoDCs induced a higher activation and proliferation of CD4+ T cells, associated with a reduced expression of IL-4 (T helper 2 response) and a higher expression of IL-17 (T helper 17 response). Purified PAH CD4+ T cells expressed a higher level of IL-17 after activation than did those of control subjects. Lastly, there was significant hypomethylation of the IL-17 promoter in the PAH blood DNA as compared with the control blood. We have highlighted T helper 17 cell immune polarization in patients with PAH, as has been previously demonstrated in other chronic inflammatory and autoimmune conditions.

  2. Emerging concepts in T follicular helper cell responses to malaria. (United States)

    Hansen, Diana S; Obeng-Adjei, Nyamekye; Ly, Ann; Ioannidis, Lisa J; Crompton, Peter D


    Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (TFH) cells provide critical help to B cells to generate long-lived antibody responses, they have become the focus of recent studies of Plasmodium-infected mice and humans. The emerging data converge on common themes, namely, that malaria-induced TH1 cytokines are associated with the activation of (i) T-like memory TFH cells with impaired B cell helper function, and (ii) pre-TFH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional TFH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses. Deeper knowledge of TFH cells in malaria could illuminate strategies to improve vaccines through modulating TFH cell responses. This review summarizes emerging concepts in TFH cell responses to malaria. Copyright © 2016. Published by Elsevier Ltd.

  3. Variance in male reproductive success and sexual size dimorphism in pinnipeds: testing an assumption of sexual selection theory


    González-Suárez, M.; Cassini, Marcelo H.


    The theory of evolution by sexual selection for sexual size dimorphism (SSD) postulates that SSD primarily reflects the adaptation of males and females to their different reproductive roles. For example, competition among males for access to females increases male body size because larger males are better able to maintain dominant status than smaller males. Larger dominant males sire most offspring while smaller subordinate males are unsuccessful, leading to skew in reproductive success. Ther...

  4. The influence of leadership style on subordinates' attachment to the leader. (United States)

    Molero, Fernando; Moriano, Juan A; Shaver, Phillip R


    The aim of this research is to explore the extent to which employees establish attachment bonds with their leaders and the effects these bonds have on organizational outcomes. A sample of 225 participants reported on their supervisor's leadership style (transformational, transactional, or passive-avoidant), their attachment bonds to this supervisor (anxious or avoidant), and four organizational variables (subordinate's satisfaction, identification with the organization, extra effort, and perceived leadership effectiveness). Results, analyzed using a Partial Least Squares (PLS) approach, indicated that (a) transformational leadership was negatively associated with employees' insecure (anxious or avoidant) attachment to their leader; (b) passive/avoidant leadership was positively associated with subordinates' insecure attachment to their leader; (c) transactional leadership was positively associated with employee's anxious attachment but not with their avoidant attachment; (d) avoidant, but not anxious, attachment to the leader was negatively associated with employee satisfaction, perceived leader effectiveness, employee's extra effort, and organizational identification.

  5. Principal-subordinate hierarchical multi-objective programming model of initial water rights allocation

    Directory of Open Access Journals (Sweden)

    Dan WU


    Full Text Available The principal-subordinate hierarchical multi-objective programming model of initial water rights allocation was developed based on the principle of coordinated and sustainable development of different regions and water sectors within a basin. With the precondition of strictly controlling maximum emissions rights, initial water rights were allocated between the first and the second levels of the hierarchy in order to promote fair and coordinated development across different regions of the basin and coordinated and efficient water use across different water sectors, realize the maximum comprehensive benefits to the basin, promote the unity of quantity and quality of initial water rights allocation, and eliminate water conflict across different regions and water sectors. According to interactive decision-making theory, a principal-subordinate hierarchical interactive iterative algorithm based on the satisfaction degree was developed and used to solve the initial water rights allocation model. A case study verified the validity of the model.

  6. Context-Specific Dimensions of Trust in Manager, Subordinate and Co-Worker in Organizations

    Directory of Open Access Journals (Sweden)

    Ferda Erdem


    Full Text Available The purpose of this study is to determine the dimensions of trust relationship among managers, subordinates and the co-workers in organizations. Using an original trust questionnaire data has been collected from 550 middle-level managers from organizations operating in different regions of Turkey. Results from both qualitative and quantitative research methods indicate that the dimensions of trust vary in organizational relationships between managers and subordinates and between co-workers and furthermore, that a culture-specific meaning is attributed to its content. This study contributes to trust literature developing three original sub-scales and also it indicates that the meaning of trust in organizational relationships is influenced by cultural context.

  7. Psychosocial predictors of supervisor-, peer-, subordinate-, and service-provider-targeted aggression. (United States)

    Inness, Michelle; Leblanc, Manon Mireille; Barling, Julian


    The authors investigate whether known person predictors (trait anger, trait aggression) and situational predictors (perceived interpersonal mistreatment, perceived organizational sanctions against aggression) of supervisor-targeted aggression also predict employee's aggression toward other workplace targets, namely peers, subordinates, and customers' aggression toward service providers. The authors also investigate the moderating impact of situational factors on the relationship between person factors and aggression. Participants (N = 308) were asked whether they had a conflict with their supervisor, a subordinate, a work peer, and/or a service provider in the past 6 months. Different patterns of main and interaction effects emerged across the 4 targets, suggesting the importance of accounting for the target of aggression in workplace aggression research.

  8. Study on monitoring achievement of performance indicators in the subordinate local companies in Romania

    Directory of Open Access Journals (Sweden)

    Gheorghe Neamţiu


    Full Text Available This paper deals with the pursuit of economic indicators which are calculated in local subordinate companies. These indicators are imposed by the Board employee manager contract term. Accounting provides enough information to calculate them but we put the issue of prevention of the ability to stay within budget, projected revenues and expenses, before closing operations of an accounting period (month, quarter, semester, year.

  9. Manager-subordinate exchange relationships : investigation of a manager behavior model


    Carter, Marta L.


    This field study investigated the relationship among behavioral and perceptual measures of the Leader-Member Exchange (LMX) relationship and organizational outcome variables. The major purposes of this study were to determine: (1) the extent to which the dyad is the appropriate level of analysis for the examination of manager-subordinate relationships, (2) which objectively observed managerr behaviors are important in defining negotiating latitude, the most commonly us...

  10. Calling Where It Counts: Subordinate Pied Babblers Target the Audience of Their Vocal Advertisements. (United States)

    Humphries, David J; Finch, Fiona M; Bell, Matthew B V; Ridley, Amanda R


    For territorial group-living species, opportunities to reproduce on the natal territory can be limited by a number of factors including the availability of resources within a territory, access to unrelated individuals, and monopolies on reproduction by dominant group members. Individuals looking to reproduce are therefore faced with the options of either waiting for a breeding opportunity to arise in the natal territory, or searching for reproductive opportunities in non-natal groups. In the cooperatively breeding Southern pied babbler, Turdoides bicolor, most individuals who achieve reproductive success do so through taking up dominant breeding positions within non-natal groups. For subordinate pied babblers therefore, searching for breeding opportunities in non-natal groups is of primary importance as this represents the major route to reproductive success. However, prospecting (where individuals leave the group to search for reproductive opportunities within other groups) is costly and individuals rapidly lose weight when not part of a group. Here we demonstrate that subordinate pied babblers adopt an alternative strategy for mate attraction by vocal advertisement from within their natal territories. We show that subordinates focus their calling efforts on the edges of their territory, and specifically near boundaries with neighbouring groups that have potential breeding partners (unrelated individuals of the opposite sex). In contrast to prospecting, calling individuals showed no body mass loss associated with this behaviour, suggesting that calling from within the group may provide a 'cheap' advertisement strategy. Additionally, we show that subordinates use information regarding the composition of neighbouring groups to target the greatest number of potential mating partners.

  11. Genome sequence of the mycorrhizal helper bacterium Pseudomonas fluorescens BBc6R8

    Energy Technology Data Exchange (ETDEWEB)

    Deveau, Aurelie [French National Insitute for Agricultural Research (INRA); Grob, Harald [University of Bonn, Germany; Morin, Emmanuelle [INRA, Nancy, France; Karpinets, Tatiana V [ORNL; Utturkar, Sagar M [ORNL; Mehnaz, Samina [University of the Punjab, Pakistan; Kurz, Sven [University of Bonn, Germany; Martin, Francis [INRA, Nancy, France; Frey-Klett, Pascale [INRA, Nancy, France; Labbe, Jessy L [ORNL


    We report the draft genome sequence of the mycorrhiza helper bacterium Pseudomonas fluorescens strain BBc6R8 . Several traits which could be involved in the mycorrhiza helper ability of the bacterial strain such as multiple secretion systems, auxin metabolism and phosphate mobilization were evidenced in the genome.

  12. Extra-territorial movements differ between territory holders and subordinates in a large, monogamous rodent. (United States)

    Mayer, Martin; Zedrosser, Andreas; Rosell, Frank


    Territorial animals carry out extra-territorial movements (forays) to obtain pre-dispersal information or to increase reproductive success via extra-pair copulation. However, little is known about other purposes and spatial movement patterns of forays. In this study, we GPS-tagged 54 Eurasian beavers (Castor fiber), a year-round territorial, monogamous mammal, during the non-mating season. We investigated forays in territory-holding breeders (dominants) and non-breeding (subordinate) family members. Twenty of 46 dominant individuals (44%), and 6 of 10 subordinates (60%) conducted forays. Generally, beavers spent between 0 and 11% of their active time on forays, travelled faster and spend more time in water when on forays compared to intra-territorial movements, suggesting that forays are energetically costly. Further, beavers in smaller territories conducted more forays. Possibly, smaller territories might not have sufficient resources and thus dominant individuals might conduct forays to assess possibilities for territory expansion, and potentially for foraging. Generally, besides territory advertisement (e.g. via scent-marking), forays might serve as an additional mechanism for territory owners to assess neighbours. Subordinates spent more time on forays, moved greater distances and intruded into more territories than dominant individuals did, suggesting that they prospected to gain information on the population density and available mates before dispersal.

  13. Helpers' Self-Assessment Biases Before and after Helping Skills Training

    Directory of Open Access Journals (Sweden)

    Marine Jaeken


    Full Text Available Several studies have shown that therapists are generally biased concerning their performed helping skills, as compared to judges' ratings. As clients' ratings of therapists' performance are better predictors of psychotherapy effectiveness than judges' ratings, this study examined the validity and effectiveness of a helping skills training program at reducing novice helpers' self-enhancement biases concerning their helping skills, in comparison to their clients' ratings. Helping skills were assessed by three objective measures (a knowledge multiple choice test, a video test and a role play, as well as by a self- and peer-reported questionnaire. In addition, some performed helping skills' correlates (relationship quality, session quality, and helpers' therapeutic attitudes were assessed both by helpers and their simulated helpees. Seventy-two sophomores in psychology participated to this study, 37 being assigned to a 12-h helping skills training program, and 35 to a control group. Helpers were expected to assess the aforementioned performed helping skills and correlates as being better than their helpees' assessments at pretest, thus revealing a self-enhancement bias. At posttest, we expected that trained helpers would objectively exhibit better helping skills than untrained helpers while beginning to underestimate their performance, thus indexing a self-diminishment bias. In contrast, we hypothesized that untrained helpers would continue to overestimate their performance. Our hypotheses were only partly confirmed but results reflected a skilled-unaware pattern among trainees. Trained helpers went either from a pretest overestimation to a posttest equivalence (performed helping skills and performed therapeutic attitudes, or from a pretest equivalence to a posttest underestimation (performed session quality and performed therapeutic relationship, as compared to helpees' ratings. Results showed that trained helpers improved on all helping skills

  14. The Paradox of Power Sharing: Participative Charismatic Leaders have Subordinates with more instead of less Need for Leadership

    NARCIS (Netherlands)

    de Vries, R.E.; Pathak, R.D.; Paquin, A.R.


    Although charismatic and participative leaders have been noted for their positive effects on criteria such as performance, job satisfaction, and commitment, few studies have looked at the relations with subordinates' leadership needs. In this study, the relations between charismatic and

  15. File list: His.Bld.05.AllAg.Follicular_helper_T_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Follicular_helper_T_cells mm9 Histone Blood Follicular helper T ce...SRX1143932 ...

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  5. Home ranges and satellite tactics of male green swordtails (Xiphophorus helleri) in nature. (United States)

    Franck, D; Klamroth, B; Taebel-Hellwig, A; Schartl, M


    Dominance relationships were studied between marked or otherwise individually recognizable male green swordtails in a creek at Lake Catemaco and in a tributary of the Rio Atoyac (Veracruz, Mexico). The Atoyac population is unique because of a high degree of polymorphism, including both macromelanophore spotting and a micromelanophore tailspot pattern. During the dry season males living in the same area maintained a linear social hierarchy for periods of many days. The subordinate males settled down either in the same home ranges or in home ranges largely overlapping with that of dominant males. Although dominant males untiringly chased the subordinate males away, they returned persistently and achieved the status of non-tolerated satellites. Females were less stationary and presumably passed through many male home ranges during their feeding activities. The data clearly demonstrate that green swordtails live in complex social systems in which male-male competition and probably also female mate choice are likely to be essential factors for individual reproductive success.

  6. Effects of sustained sleep restriction on mitogen-stimulated cytokines, chemokines and T helper 1/ T helper 2 balance in humans.

    Directory of Open Access Journals (Sweden)

    John Axelsson

    Full Text Available BACKGROUND: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. METHODS: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h followed by 5 days with restricted sleep (03.00-07.00 h. On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α, interleukin (IL -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1 after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA. Also leukocyte numbers, mononuclear cells and cortisol were analysed. RESULTS: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05. A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05. In addition, all variables varied across the 24 h day. CONCLUSIONS: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

  7. Subordinate clause comprehension and tense/agreement inconsistency in children with specific language impairment. (United States)

    Souto, Sofía M; Leonard, Laurence B; Deevy, Patricia; Fey, Marc E; Bredin-Oja, Shelley L


    Several recent studies have suggested that the production errors of children with specific language impairment (SLI) such as The girl singing may be explained by a misinterpretation of grammatical adult input containing a similar structure (e.g., The boy hears the girl singing). Thirteen children with SLI and 13 younger typically developing children with comparable sentence comprehension test scores (TD-COMP) completed a comprehension task to assess their understanding of sentences involving a nonfinite subject-verb sequence in a subordinate clause such as The dad sees the boy running. TD-COMP children were more accurate on subordinate clause items than children with SLI despite similar performance on simple transitive (e.g., The horse sees the cow) and simple progressive (e.g., The cow is eating) items. However, no relationship was found between the SLI group's specific subordinate clause comprehension level and their specific level of auxiliary is production, casting some doubt on this type of structure as a source for inconsistent use of auxiliary is. The reader will learn that children with specific language impairment (SLI): (1) have difficulty understanding complex sentences that include nonfinite subject-verb sequences; (2) that this difficulty is apparent in comparison to younger typically developing peers who have similar scores not only on a sentence comprehension test, but also on simple sentences that correspond to the component parts of the complex sentences; and (3) that this weakness is concurrent with these children's inconsistent use of auxiliary is in production. Although novel verb studies show a clear connection between how children with SLI hear new verbs and how they use them, we do not yet have evidence that this connection is tied to a poor understanding of the input sentences that house the verbs. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Tailored immune responses: novel effector helper T cell subsets in protective immunity. (United States)

    Kara, Ervin E; Comerford, Iain; Fenix, Kevin A; Bastow, Cameron R; Gregor, Carly E; McKenzie, Duncan R; McColl, Shaun R


    Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H)1/T(H)2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  9. Tailored immune responses: novel effector helper T cell subsets in protective immunity.

    Directory of Open Access Journals (Sweden)

    Ervin E Kara


    Full Text Available Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H1/T(H2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  10. Identification of novel helper epitope peptides of Survivin cancer-associated antigen applicable to developing helper/killer-hybrid epitope long peptide cancer vaccine. (United States)

    Ohtake, Junya; Ohkuri, Takayuki; Togashi, Yuji; Kitamura, Hidemitsu; Okuno, Kiyotaka; Nishimura, Takashi


    We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01. The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02. This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4(+) and CD8(+) T cells though it contained both helper and killer epitopes. To enhance the vaccine efficacy, we synthesized a long peptide by conjugating SU18 peptide and another DR53-restricted helper epitope peptide (SU22; 12 amino-acids) using glycine-linker. We designated this artificial 40 amino-acids long peptide containing two helper and three killer epitopes as Survivin-helper/killer-hybrid epitope long peptide (Survivin-H/K-HELP). Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4(+) Th1 cells and CD8(+) Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC). Survivin-H/K-HELP-pulsed Mo-DC pretreated with OK-432 also exhibited sustained antigen-presentation capability of stimulating Survivin-specific Th1 cells compared with Mo-DC pulsed with a mixture of SU18 and SU22 short peptides. Moreover, we demonstrated that Survivin-H/K-HELP induced a complete response in a breast cancer patient with the induction of cellular and humoral immune responses. Thus, we believe that an artificially synthesized Survivin-H/K-HELP will become an innovative cancer vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Discrimination between dominant and subordinate groups: the positive-negative asymmetry effect and normative processes. (United States)

    Amiot, Catherine E; Bourhis, Richard Y


    Research using the minimal group paradigm (MGP) demonstrates that categorization and in-group identification can suffice to foster intergroup discrimination. However, the positive- negative asymmetry effect (PNAE) shows that less discrimination occurs when negative than when positive outcomes are distributed between group members. Combining the polarization paradigm and the MGP, this study investigated the discriminatory behaviour of dominant and subordinate group members ( N = 197) on positive and negative outcome distributions. During private outcome distributions at pre-consensus, dominant groups discriminated more than subordinate groups while the PNAE was not replicated. Positive/negative outcome distributions were sought during intragroup discussion in the consensus phase, while post-consensus involved private outcome distributions. The PNAE emerged in both consensus and post-consensus phases: group members discriminated less on salary cuts than on salary increases, whereas the power effect disappeared in those phases. The emergence of in-group norms during face-to-face discussions at consensus as well as social identity processes help account for the results obtained in this study.

  12. Model checking to assess T-helper cell plasticity. (United States)

    Abou-Jaoudé, Wassim; Monteiro, Pedro T; Naldi, Aurélien; Grandclaudon, Maximilien; Soumelis, Vassili; Chaouiya, Claudine; Thieffry, Denis


    Computational modeling constitutes a crucial step toward the functional understanding of complex cellular networks. In particular, logical modeling has proven suitable for the dynamical analysis of large signaling and transcriptional regulatory networks. In this context, signaling input components are generally meant to convey external stimuli, or environmental cues. In response to such external signals, cells acquire specific gene expression patterns modeled in terms of attractors (e.g., stable states). The capacity for cells to alter or reprogram their differentiated states upon changes in environmental conditions is referred to as cell plasticity. In this article, we present a multivalued logical framework along with computational methods recently developed to efficiently analyze large models. We mainly focus on a symbolic model checking approach to investigate switches between attractors subsequent to changes of input conditions. As a case study, we consider the cellular network regulating the differentiation of T-helper (Th) cells, which orchestrate many physiological and pathological immune responses. To account for novel cellular subtypes, we present an extended version of a published model of Th cell differentiation. We then use symbolic model checking to analyze reachability properties between Th subtypes upon changes of environmental cues. This allows for the construction of a synthetic view of Th cell plasticity in terms of a graph connecting subtypes with arcs labeled by input conditions. Finally, we explore novel strategies enabling specific Th cell polarizing or reprograming events.

  13. Profiling helper T cell subset gene expression in deer mice

    Directory of Open Access Journals (Sweden)

    Hjelle Brian


    Full Text Available Abstract Background Deer mice (Peromyscus maniculatus are the most common mammals in North America and are reservoirs for several zoonotic agents, including Sin Nombre virus (SNV, the principal etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in North America. Unlike human HCPS patients, SNV-infected deer mice show no overt pathological symptoms, despite the presence of virus in the lungs. A neutralizing IgG antibody response occurs, but the virus establishes a persistent infection. Limitations of detailed analysis of deer mouse immune responses to SNV are the lack of reagents and methods for evaluating such responses. Results We developed real-time PCR-based detection assays for several immune-related transcription factor and cytokine genes from deer mice that permit the profiling of CD4+ helper T cells, including markers of Th1 cells (T-bet, STAT4, IFNγ, TNF, LT, Th2 cells (GATA-3, STAT6, IL-4, IL-5 and regulatory T cells (Fox-p3, IL-10, TGFβ1. These assays compare the expression of in vitro antigen-stimulated and unstimulated T cells from individual deer mice. Conclusion We developed molecular methods for profiling immune gene expression in deer mice, including a multiplexed real-time PCR assay for assessing expression of several cytokine and transcription factor genes. These assays should be useful for characterizing the immune responses of experimentally- and naturally-infected deer mice.

  14. In vitro and in vivo characterization of microRNA-targeted alphavirus replicon and helper RNAs. (United States)

    Kamrud, Kurt I; Coffield, V McNeil; Owens, Gary; Goodman, Christin; Alterson, Kim; Custer, Max; Murphy, Michael A; Lewis, Whitney; Timberlake, Sarah; Wansley, Elizabeth K; Berglund, Peter; Smith, Jonathan


    Alphavirus-based replicon vector systems (family Togaviridae) have been developed as expression vectors with demonstrated potential in vaccine development against both infectious diseases and cancer. The single-cycle nature of virus-like replicon particles (VRP), generated by supplying the structural proteins from separate replicable helper RNAs, is an attractive safety component of these systems. MicroRNAs (miRNAs) have emerged as important cellular RNA regulation elements. Recently, miRNAs have been employed as a mechanism to attenuate or restrict cellular tropism of replication-competent viruses, such as oncolytic adenoviruses, vesicular stomatitis virus, and picornaviruses as well as nonreplicating lentiviral and adenoviral vectors. Here, we describe the incorporation of miRNA-specific target sequences into replicable alphavirus helper RNAs that are used in trans to provide the structural proteins required for VRP production. VRP were found to be efficiently produced using miRNA-targeted helper RNAs if miRNA-specific inhibitors were introduced into cells during VRP production. In the absence of such inhibitors, cellular miRNAs were capable of downregulating helper RNA replication in vitro. When miRNA targets were incorporated into a replicon RNA, cellular miRNAs were capable of downregulating replicon RNA replication upon delivery of VRP into animals, demonstrating activity in vivo. These data provide the first example of miRNA-specific repression of alphavirus replicon and helper RNA replication and demonstrate the feasibility of miRNA targeting of expression vector helper functions that are provided in trans.

  15. A novel subset of helper T cells promotes immune responses by secreting GM-CSF (United States)

    Zhang, J; Roberts, A I; Liu, C; Ren, G; Xu, G; Zhang, L; Devadas, S; Shi, Yufang


    Helper T cells are crucial for maintaining proper immune responses. Yet, they have an undefined relationship with one of the most potent immune stimulatory cytokines, granulocyte macrophage-colony-stimulating factor (GM-CSF). By depleting major cytokines during the differentiation of CD4+ T cells in vitro, we derived cells that were found to produce large amounts of GM-CSF, but little of the cytokines produced by other helper T subsets. By their secretion of GM-CSF, this novel subset of helper T cells (which we have termed ThGM cells) promoted the production of cytokines by other T-cell subtypes, including type 1 helper T cell (Th1), type 2 helper T cell (Th2), type 1 cytotoxic T cell (Tc1), type 2 cytotoxic T cell (Tc2), and naive T cells, as evidenced by the fact that antibody neutralization of GM-CSF abolished this effect. ThGM cells were found to be highly prone to activation-induced cell death (AICD). Inhibitors of TRAIL or granzymes could not block AICD in ThGM cells, whereas inhibition of FasL/Fas interaction partially rescued ThGM cells from AICD. Thus, ThGM cells are a novel subpopulation of T helper cells that produce abundant GM-CSF, exhibit exquisite susceptibility to apoptosis, and therefore play a pivotal role in the regulation of the early stages of immune responses. PMID:24076588

  16. Tbet Deficiency Causes T Helper Cell Dependent Airways Eosinophilia and Mucus Hypersecretion in Response to Rhinovirus Infection.

    Directory of Open Access Journals (Sweden)

    Nicholas Glanville


    Full Text Available Current understanding of adaptive immune, particularly T cell, responses to human rhinoviruses (RV is limited. Memory T cells are thought to be of a primarily T helper 1 type, but both T helper 1 and T helper 2 memory cells have been described, and heightened T helper 2/ lessened T helper 1 responses have been associated with increased RV-induced asthma exacerbation severity. We examined the contribution of T helper 1 cells to RV-induced airways inflammation using mice deficient in the transcription factor T-Box Expressed In T Cells (Tbet, a critical controller of T helper 1 cell differentiation. Using flow cytometry we showed that Tbet deficient mice lacked the T helper 1 response of wild type mice and instead developed mixed T helper 2/T helper 17 responses to RV infection, evidenced by increased numbers of GATA binding protein 3 (GATA-3 and RAR-related orphan receptor gamma t (RORγt, and interleukin-13 and interleukin-17A expressing CD4+ T cells in the lung. Forkhead box P3 (FOXP3 and interleukin-10 expressing T cell numbers were unaffected. Tbet deficient mice also displayed deficiencies in lung Natural Killer, Natural Killer T cell and γδT cell responses, and serum neutralising antibody responses. Tbet deficient mice exhibited pronounced airways eosinophilia and mucus production in response to RV infection that, by utilising a CD4+ cell depleting antibody, were found to be T helper cell dependent. RV induction of T helper 2 and T helper 17 responses may therefore have an important role in directly driving features of allergic airways disease such as eosinophilia and mucus hypersecretion during asthma exacerbations.

  17. Fire disturbance disrupts an acacia ant-plant mutualism in favor of a subordinate ant species. (United States)

    Sensenig, Ryan L; Kimuyu, Duncan K; Ruiz Guajardo, Juan C; Veblen, Kari E; Riginos, Corinna; Young, Truman P


    Although disturbance theory has been recognized as a useful framework in examining the stability of ant-plant mutualisms, very few studies have examined the effects of fire disturbance on these mutualisms. In myrmecophyte-dominated savannas, fire and herbivory are key drivers that could influence ant-plant mutualisms by causing complete colony mortality and/or decreasing colony size, which potentially could alter dominance hierarchies if subordinate species are more fire resilient. We used a large-scale, replicated fire experiment to examine long-term effects of fire on acacia-ant community composition. To determine if fire shifted ant occupancy from a competitive dominant to a subordinate ant species, we surveyed the acacia-ant community in 6-7 yr old burn sites and examined how the spatial scale of these burns influenced ant community responses. We then used two short-term fire experiments to explore possible mechanisms for the shifts in community patterns observed. Because survival of ant colonies is largely dependent on their ability to detect and escape an approaching fire, we first tested the evacuation response of all four ant species when exposed to smoke (fire signal). Then to better understand how fire and its interaction with large mammal herbivory affect the density of ants per tree, we quantified ant worker density in small prescribed burns within herbivore exclusion plots. We found clear evidence suggesting that fire disturbance favored the subordinate ant Crematogaster nigriceps more than the dominant and strong mutualist ant C. mimosae, whereby C. nigriceps (1) was the only species to occupy a greater proportion of trees in 6-7 yr old burn sites compared to unburned sites, (2) had higher burn/unburn tree ratios with increasing burn size, and (3) evacuated significantly faster than C. mimosae in the presence of smoke. Fire and herbivory had opposite effects on ant density per meter of branch for both C. nigriceps and C. mimosae, with fire

  18. Differential modulation of T helper type 1 (Th1) and T helper type 2 (Th2) cytokine secretion by prostaglandin E2 critically depends on interleukin-2

    NARCIS (Netherlands)

    Hilkens, C. M.; Vermeulen, H. [=Hans; van Neerven, R. J.; Snijdewint, F. G.; Wierenga, E. A.; Kapsenberg, M. L.


    Prostaglandin E2 (PGE2) favors T helper type 2 (Th2)-like cytokine secretion profiles in murine and human CD4+ T cells by inhibiting the production of the Th1-associated cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and up-regulating the production of the Th2-associated cytokines

  19. Newly identified helper bacteria stimulate ectomycorrhizal formation in Populus

    Directory of Open Access Journals (Sweden)

    Jessy L Labbé


    Full Text Available Mycorrhiza helper bacteria (MHB are known to increase host root colonization by mycorrhizal fungi but the molecular mechanisms and potential tripartite interactions are poorly understood. Through an effort to study Populus microbiome, we isolated 21 Pseudomonas strains from native Populus deltoides roots. These bacterial isolates were characterized and screened for MHB effectiveness on the Populus-Laccaria system. Two additional Pseudomonas strains (i.e., Pf-5 and BBc6R8 from existing collections were included for comparative purposes. We analyzed the effect of co-cultivation of these 23 individual Pseudomonas strains on Laccaria bicolor ‘S238N’ growth rate, mycelial architecture and transcriptional changes. Nineteen of the 23 Pseudomonas strains tested had positive effects on L. bicolor S238N growth, as well as on mycelial architecture, with strains GM41 and GM18 having the most significant effect. Four of seven L. bicolor reporter genes, Tra1, Tectonin2, Gcn5 and Cipc1, thought to be regulated during the interaction with MHB strain BBc6R8, were induced or repressed, while interacting with Pseudomonas strains GM17, GM33, GM41, GM48, Pf-5 and BBc6R8. Strain GM41 promoted the highest roots colonization across three Populus species but most notably in P. deltoides, which is otherwise poorly colonized by L. bicolor. Here we report novel MHB strains isolated from native Populus that improve L. bicolor root colonization on Populus. This tripartite relationship could be exploited for Populus species/genotypes nursery production as a means of improving establishment and survival in marginal lands.

  20. The subjunctive, a marker of 'subordinance'? A comparison between German and Spanish

    Directory of Open Access Journals (Sweden)

    Hans Jörg Busch


    Full Text Available Moods as inflectional paradigms can only have a very general value and function, similar to other verbal categories such as tense and aspect. A comparison with German shows that the subjunctive functions as a marker of subordination and signals that the proposition in which it stands is incomplete and must be interpreted with the help of other contextual elements, for example the meaning of the main or matrix verb, a characteristic that has also been called procedural. Therefore only the indicative can be used to express independent statements. All the communicative functions of the subjunctive, for example to express politeness, will be explained as a result of its procedural character. The article clarifies why the subjunctive is also used with factual propositions, for example after verbs of emotions and ‘aunque’. (37,402 characters with spaces

  1. From Ambiguity to Deceptiveness: the Case of Hybrid since- Subordinates in English

    Directory of Open Access Journals (Sweden)

    Bénédicte GUILLAUME


    Full Text Available Lorsqu’il est utilisé en tant que subordonnant, since peut introduire une subordonnée circonstancielle de temps ou bien de cause. Cet article s’intéresse aux cas dans lesquels une telle polysémie au niveau du subordonnant déclenche une ambiguïté quant à la nature temporelle ou causale de l’utilisation de la subordonnée. En plus du recours au contexte endophorique ou exophorique, nous proposons des critères syntaxiques de désambigüisation, mis au jour grâce à l’étude d’un corpus de près de cinq cent exemples pris dans le British National Corpus, un corpus d’anglais contemporain de cent millions de mots. En dépit de tout cela, une petite minorité d’exemples reste inclassable, remplissant ainsi les conditions pour être considérés comme « hybrides » en fonction de la définition que nous en proposons, à savoir des subordonnées permettant de remettre en cause la division traditionnelle entre les catégories de subordonnées en anglais, dans la mesure où ils possèdent au moins une caractéristique déviante par rapport à la catégorie à laquelle ils semblent appartenir en fonction de tous leurs autres traits. De tels phénomènes rendent nécessaires la prise en compte d’un « reste », selon la terminologie de Jean-Jacques Lecercle, dans la grammaire d’une langue donnée.When since is used as a subordinator,it can introduce either a temporal adverbial clause or a causal one. My purpose in this paper is to study cases in which such a polysemy at the level of the subordinator results in the production of subordinates whose meaning proves to be ambiguous between the categories of time and cause. In addition to the taking into account of the context, whether exophoric or endophoric, I put forward a series of syntactic criteria which should help disambiguate between the two possible interpretations. These are based on the study of the characteristics of nearly five-hundred examples of since- clauses taken

  2. Brownian yet Non-Gaussian Diffusion: From Superstatistics to Subordination of Diffusing Diffusivities

    Directory of Open Access Journals (Sweden)

    Aleksei V. Chechkin


    Full Text Available A growing number of biological, soft, and active matter systems are observed to exhibit normal diffusive dynamics with a linear growth of the mean-squared displacement, yet with a non-Gaussian distribution of increments. Based on the Chubinsky-Slater idea of a diffusing diffusivity, we here establish and analyze a minimal model framework of diffusion processes with fluctuating diffusivity. In particular, we demonstrate the equivalence of the diffusing diffusivity process with a superstatistical approach with a distribution of diffusivities, at times shorter than the diffusivity correlation time. At longer times, a crossover to a Gaussian distribution with an effective diffusivity emerges. Specifically, we establish a subordination picture of Brownian but non-Gaussian diffusion processes, which can be used for a wide class of diffusivity fluctuation statistics. Our results are shown to be in excellent agreement with simulations and numerical evaluations.

  3. Increased frequency of follicular helper T cells in mice viral myocarditis is relevant with anti-ANT antoantibody. (United States)

    Yang, Fan; Mo, Wen-hong; Tan, Bao-ping; Wei, Xiao-mou; Wang, Hong


    Recently, a new subset of CD4(+)T helper cell termed Follicular helper T cells (Tfh), which play a pivotal role in B cell activation and differentiation in lymphoid structures, has been reported to participate in some certain autoimmune diseases. But whether Tfh cells are involved in the pathogenesis of VMC remains unclear. Male BALB/c mice were intraperitoneally (i.p) infected with CVB3 to establish VMC models. Control mice were treated with phosphate-buffered saline i.p. On 0, 1, 2, 3, 4, 6 weeks post injection, frequencies of splenic Tfh cells were determined by flow cytometric analysis, productions of IL-21 and anti-adenine nucleotide translocator(ANT) autoantibody were detected by enzyme-linked immunosorbent assay. To further investigate the effects of Tfh cells, VMC mice were treated with Anti-IL-21 neutralizing antibody. Heart pathology was examined histologically, the frequencies of Tfh cells and the expressions of anti-ANT autoantibody were investigated after anti-IL-21 intervention. Spearman analysis was used to evaluate the relationship between the frequencies of Tfh cells and IL-21 levels with anti-ANT autoantibody. The percentage of Tfh cells significantly increased in VMC mice from 1 W to 6 W, the serum level of IL-21 and ANT autoantibody were also significantly increased in VMC mice. Neutralization of IL-21 with anti-IL-21 can ameliorate the myocardium inflammation, decrease Tfh cells and ANT autoantibody after IL-21 antibody intervention compared with those of the control (P ANT antibody levels (R = 0.758, P ANT autoantibody production. Targeting the Tfh cell and IL-21 may be a new therapeutic target for the treatment of CVB3-induced VMC.

  4. Personal experience in professional narratives: the role of helpers' families in their work with terror victims. (United States)

    Shamai, Michal


    This article describes research on the narratives of social workers who help terror victims, focusing on the relationship between the helpers' families and their work. Qualitative analysis of three training groups of social workers who are responsible for helping in the event of terror attacks in different parts of Israel, and of three debriefing groups for social workers after terror attacks, reveals that the helpers' families play a role in the narratives constructed by the helpers. Two main themes were identified. The first centers on the interaction between work and the family, and shows that in the situation of a terror attack, the conflict between the two disappears and the family often serves as a support system for the helpers. The second theme refers to the family dimension alone, and focuses on the dichotomy between vitality and loss. The way that family life events affect helpers'professional intervention is described. The findings are discussed in light of Conservation of Resources Theory, the fight-flight response to threat, and the concept of the family as a source of safety and risk taking.

  5. 29 CFR 408.6 - Amendments to the Labor Organization Information Report filed by or on behalf of the subordinate... (United States)


    ... 29 Labor 2 2010-07-01 2010-07-01 false Amendments to the Labor Organization Information Report filed by or on behalf of the subordinate labor organization. 408.6 Section 408.6 Labor Regulations... LABOR ORGANIZATION TRUSTEESHIP REPORTS § 408.6 Amendments to the Labor Organization Information Report...

  6. Forum: Interpersonal Communication in Instructional Settings. The Instructor-Student Relationship as an Alternative Form of Superior-Subordinate Relationship (United States)

    Myers, Scott A.


    In this brief forum article, the author suggests studying the instructor-student relationship as a superior-subordinate relationship offers an alternative way to view how student learning occurs in the college classroom, and can provide instructional communication researchers with the opportunity to explore how structural and institutional…

  7. The Development of Subordinate Clauses in German and Swedish as L2s: A Theoretical and Methodological Camparison (United States)

    Baten, Kristof; Håkansson, Gisela


    In this article, we aim to contribute to the debate about the use of subordination as a measure of language proficiency. We compare two theories of SLA--specifically, processability theory (PT; Pienemann, 1998) and dynamic systems theory (DST; de Bot, Lowie, & Verspoor, 2007)--and, more particularly, how they address the development of…

  8. Responses of biotic interactions of dominant and subordinate species to decadal warming and simulated rotational grazing in Tibetan alpine meadow. (United States)

    Li, Xin'e; Zhu, Xiaoxue; Wang, Shiping; Cui, Shujuan; Luo, Caiyun; Zhang, Zhenhua; Zhang, Lirong; Jiang, Lili; Lü, Wangwang


    Warming increases competition among plant species in alpine communities by ameliorating harsh environmental conditions, such as low temperatures. Grazing, as the main human activity, may mitigate the effect of warming, as previously reported. However, it is critical to refine the effects of warming on biotic interactions among species, for example, by taking the competitive ability of species into consideration. Based on a 10-year warming and grazing experiment in a Tibetan alpine meadow, we evaluated interspecific biotic interactions of dominant and subordinate species, using the approach of interspecific spatial associations. Warming significantly increased competition between subordinate and dominant species as well as among subordinate species, but not among dominant species. Moreover, facilitation of dominant-subordinate species also increased under warming. Simulated rotational grazing had similar effects to warming, with increasing interspecific competition. Our results show that, when studying the effects of warming on biotic interactions among species, it is necessary to characterize different species pairs relative to their competitive ability, and that simulated rotational grazing does not mitigate the effects of warming in the long term. Our results also provide evidence that the spatial pattern of species is a critical mechanism in species coexistence.

  9. How to get radical creative ideas into a leader's mind? Leader's achievement goals and subordinates' voice of creative ideas

    NARCIS (Netherlands)

    Sijbom, Roy B.L.; Janssen, Onne; Van Yperen, Nico W.


    In the present research we investigated when and why leaders tend to oppose or adopt radical creative ideas voiced by their subordinates. In a field study (Study 1, N=127) we showed that leaders' performance goals were positively related to their tendency to oppose radical creative ideas, whereas



    Brindusa VARTOLOMEI


    Fundamental legal feature of the labor contract is the subordination of the employee to the employer. This is evidenced, during the execution of the labor contract of the employer rights granted much higher in comparison with those of the employee. Economic dependency is the objective support legal subordination of the employee to the employer.

  11. An intraovarian mechanism that enhances the effect of an FSH surge on recovery of subordinate follicles in heifers. (United States)

    Ginther, O J; Siddiqui, M A R; Baldrighi, J M; Araujo, E R


    The effect of the future dominant follicle (DF), corpus luteum (CL), and side (left ovary [LO] and right ovary [RO]) on FSH-induced recovery (increase in diameter) of regressing subordinate follicles was studied in heifers. The DF of wave 2 and the largest subordinate follicle remained intact (controls, n = 14 heifers) or were ablated (n = 14 heifers) on a mean of 13 d postovulation when the DF was ∼10 mm (hour 0). Concentration of FSH (P < 0.0004) and diameter of subordinate follicles (P < 0.0002) decreased between hours -48 to 0 combined for the control and ablation groups. Thereafter, follicle diameter continued to decrease in the controls. Concentration of FSH increased (P < 0.05) and diameter of subordinates began to increase at hour 12 in the ablation group. Follicle-stimulating hormone increased to hour 24 and then returned to the hour 0 concentration by hour 72, completing the induced FSH surge. Concentration of LH began to increase at hour 0 in each group and at a similar rate between groups. Follicle recovery in the ablation group was compared among 8 subgroups as defined by the 2 sides and 4 intraovarian patterns (DF-CL pattern, both structures in same ovary; DF pattern, DF alone; CL pattern, CL alone; and devoid pattern, both structures absent). Follicle diameter increased (P < 0.05) between hours 24 and 48, and diameter at hours 24, 48, 72, and 96 involved a 3-way interaction (P < 0.0001) of pattern, side, and hour. The interaction was similar when diameter of the DF that originated from a recovered subordinate was either included or excluded in the analysis. Diameter of subordinate follicles in the ablation group at hour 96 was greater (P < 0.05) in the DF-CL/RO and DF/RO subgroups than that in the devoid/LO, devoid/RO, and CL/LO subgroups. The DF-CL/LO and CL/RO subgroups were intermediate. For follicles that decreased in diameter before hour 0, a greater (P < 0.05) percentage increased after hour 0 when the ovary contained a DF and was in

  12. The figure of the helper advisor in cases of sexual abuse against people with intellectual disabilities

    Directory of Open Access Journals (Sweden)



    Full Text Available In this paper we analyse the main barriers that people with intellectual disabilities who have suffered sexual abuse have to face when they access the Justice system. Regarding these barriers, the Victim Support Unit for People with Intellectual Disabilities of the Fundación Carmen Pardo-Valcarce proposes the inclusion in the judicial process of a helper advisor. The entry into force in 2015 of the Law 4/2015, in 27 April, the Statute of the crime victim represents an exemplary opportunity to ensure the incorporation of support proposals involving the insertion of the helper advisor in the judicial process in cases where the victim is a person with intellectual disabilities. In this paper we analyse the impact of the helper advisor, with particular emphasis on cases that have been dismissed under instruction.

  13. Essential competencies for the education of nursing assistants and care helpers in elderly care. (United States)

    Oeseburg, Barth; Hilberts, Rudi; Roodbol, Petrie F


    The Dutch health care system faces huge challenges with regard to the demand on elderly care and the competencies of professionals required to meet this demand. However, a recent study showed that the curricula in vocational education for nursing assistants and care helpers remains inadequate to prepare them for the social and healthcare needs of the elderly. To determine the essential competencies for the initial education of nursing assistants and care helpers in elderly care. First, a draft version of essential competencies for the education of nursing assistants and care helpers in elderly care (N=120) was developed and approved by experts, also members of the project steering committee. Second, a Delphi survey was conducted to determine the essential competencies. The Delphi panel consisted of eleven field experts (teachers/educational developers) working for different vocational education training colleges in the Netherlands. Ten panel members participated in a two-round consensus building process via email. A definitive set of 116 essential competencies for the initial education of nursing assistants and 42 essential competencies for the initial education of care helpers were determined. The competencies in the definitive set are more in line with social and healthcare needs of the elderly like: autonomy, daily functioning prevention of health problems, healthy ageing and wellbeing, involvement of informal care, collaboration between professionals and informal care. The main challenge now is to translate these competencies into educational programmes for vocational education training colleges for care helpers and nursing assistants. Recommendations are made for the implementation of these competencies in the Dutch vocational education training colleges for care helpers and nursing assistants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The Reproduction of Family Life: Perspectives of Male and Female Adolescents. (United States)

    Gaskell, Jane


    Capitalist, patriarchal, and sexist social structures and values affect how working class adolescents plan to allocate responsibility for domestic labor. Interviews with 83 Canadian male and female high school students revealed that they anticipate choosing patterns of domestic labor which perpetuate women's subordinate roles at home and work. (AM)

  15. The Effect of a School-Based Helper Program on Adolescent Self-Image, Attitudes and Behavior. (United States)

    Switzer, Galen E.; And Others


    Examined effects of participation in school-based helper program on adolescents' self-image, attitudes, and behaviors. Seventh-grade students (n=171) were divided into 2 groups, 1 required to engage in volunteer helping activities. Gender-specific results showed that boys in helper program showed positive changes in self-esteem relative to other…

  16. Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect

    DEFF Research Database (Denmark)

    Lund, O; Lund, O S; Gram, G


    transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests...

  17. A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Tamer A Sharafeldin

    Full Text Available Newly emergent turkey arthritis reoviruses (TARV were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O'Neil strain. Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi. Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1-2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV.

  18. Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets. (United States)

    Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Hanning, Uta; Posevitz-Fejfár, Anita; Korsukewitz, Catharina; Schwab, Nicholas; Meuth, Sven G; Wiendl, Heinz; Klotz, Luisa


    Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing TH1 cells or interleukin (IL)-17-producing TH17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of TH17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

  19. Supervisor-subordinate communication relationships, role ambiguity, autonomy and affective commitment for nurses. (United States)

    Brunetto, Yvonne; Farr-Wharton, Rod; Shacklock, Kate


    This paper examine nurses' levels of satisfaction with their supervisor-subordinate communication relationships on their level of role ambiguity (in relation to their supervisors) and their resultant perceptions of autonomy and in turn, affective commitment. A survey of 900 nurses working in private sector hospitals in Australia was used to collect data. The combined effects of supervisor-nurse communication relationships, nurses' role ambiguity in relation to their supervisors plus nurses' resultant perceptions of autonomy, definitely influenced nurses' level of affective commitment. Also, nurses were somewhat dissatisfied with their communication relationships with their supervisors, experienced role ambiguity, reported being only a little autonomous, and were subsequently only somewhat committed to their hospitals. Contribution: The findings contribute to addressing nurse retention challenges by identifying factors affecting nurses' organisational commitment. Not only will nurses be more productive (with less supervisor ambiguity), but high quality Nurse Unit Manager-nurse communication relationships are also likely to enhance perceptions of autonomy and thereby, encourage nurses' commitment to their organisation and intention to remain. These results raise the question as to whether the present management practices are ideal for retaining nurses who are in short supply in many Organisation for Economic Co-operation and Development countries.

  20. [The effects of planning leadership behavior on the subordinates' person perception]. (United States)

    Arima, Y


    According to the two factor theory of leadership, leaders were instructed to behave both gently and strictly. However, how can be achieved such behavior? Here, a solution to this problem is suggested by an analysis of subordinates' person perception. Yamada (1987) analyzed the data of PM leadership surveys, and found three factors; Maintenance [M.] (corresponds to "Consideration" in the Ohio Study) Planning (Initiating Structure), and Pressure (Production Emphasis). It was found that High Planning supported the independence of M. from Pressure. The purpose of this experimental study was to test the effect of Planning behavior on cognitive structure. Sixty-four female subjects performed a maze task using computer simulation. In the high Planning condition, the leader displayed direction signs, whereas no sign was displayed in the low Planning condition. Each condition was further subdivided into two Pressure conditions (High or low) by the amount of linguistic behavior. The result of the survey data was supported. M. cognition decreased by increasing Pressure cognition in the low Planning condition, but no correlation was found between M. and Pressure in the High Planning condition.

  1. Chronic clomipramine treatment reverses core symptom of depression in subordinate tree shrews.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Chronic stress is the major cause of clinical depression. The behavioral signs of depression, including anhedonia, learning and memory deficits, and sleep disruption, result from the damaging effects of stress hormones on specific neural pathways. The Chinese tree shrew (Tupaia belangeri chinensis is an aggressive non-human primate with a hierarchical social structure that has become a well-established model of the behavioral, endocrine, and neurobiological changes associated with stress-induced depression. The tricyclic antidepressant clomipramine treats many of the core symptoms of depression in humans. To further test the validity of the tree shrew model of depression, we examined the effects of clomipramine on depression-like behaviors and physiological stress responses induced by social defeat in subordinate tree shrews. Social defeat led to weight loss, anhedonia (as measured by sucrose preference, unstable fluctuations in locomotor activity, sustained urinary cortisol elevation, irregular cortisol rhythms, and deficient hippocampal long-term potentiation (LTP. Clomipramine ameliorated anhedonia and irregular locomotor activity, and partially rescued the irregular cortisol rhythm. In contrast, weight loss increased, cortisol levels were even higher, and in vitro LTP was still impaired in the clomipramine treatment group. These results demonstrate the unique advantage of the tree shrew social defeat model of depression.

  2. The downside of goal-focused leadership: the role of personality in subordinate exhaustion. (United States)

    Perry, Sara Jansen; Witt, L A; Penney, Lisa M; Atwater, Leanne


    Exhaustion has a significant impact on employees and organizations, and leader behavior may affect it. We applied conservation of resources theory to test propositions regarding the joint effects of goal-focused leadership (GFL) and personality on employee exhaustion. We proposed that the relationship between GFL and exhaustion depends on employees' standing on both conscientiousness and emotional stability. Specifically, we expected that high-conscientiousness subordinates experience greater compatibility with a goal-focused leader because of their predisposition to direct resources toward achievement and goal setting, resulting in lower exhaustion under such a leader than among low-conscientiousness employees. Furthermore, high emotional stability may compensate for GFL incompatibility among low-conscientiousness employees by providing additional resources to manage GFL. In contrast, employees low on both traits likely experience greater exhaustion under a goal-focused leader compared with other employees. Results revealed a 3-way interaction in 2 independent samples and were generally supportive of our predictions. GFL was associated with heightened exhaustion among individuals in the low-emotional-stability, low-conscientiousness group but not among workers having any other trait combination. (c) 2010 APA, all rights reserved.

  3. Chronic subordinate colony housing paradigm: A mouse model to characterize the consequences of insufficient glucocorticoid signalling

    Directory of Open Access Journals (Sweden)

    Dominik eLanggartner


    Full Text Available Chronic, in particular chronic psychosocial, stress is a burden of modern societies and known to be a risk factor for numerous somatic and affective disorders (in detail referenced below. However, based on the limited existence of appropriate, and clinically-relevant, animal models for studying the effects of chronic stress, the detailed behavioural, physiological, neuronal, and immunological mechanisms linking stress and such disorders are insufficiently understood. To date, most chronic stress studies in animals employ intermittent exposure to the same (homotypic or to different (heterotypic stressors of varying duration and intensity. Such models are only of limited value, since they do not adequately reflect the chronic, and continuous, situation that humans typically experience. Furthermore, application of different physical or psychological stimuli renders comparisons to the mainly psychosocial stressors faced by humans, as well as between the different stress studies almost impossible. In contrast, rodent models of chronic psychosocial stress represent situations more akin to those faced by humans and consequently seem to hold more clinical relevance. Our laboratory has developed a model in which mice are exposed to social stress for 19 continuous days, namely the chronic subordinate colony housing (CSC paradigm, which bridges this gap. The main aim of the current review article is to provide a detailed summary of the behavioural, physiological, neuronal and immunological consequences of the CSC paradigm, and wherever possible relate the findings to other stress models and to those from human studies.

  4. Comparison for Chinese subordinates as a motivation approach: Scale Development and Psychometric Properties

    Directory of Open Access Journals (Sweden)

    Jingjing Ge


    Full Text Available Purpose: Chinese people are motivated by social comparison and temporal comparison. Based on this finding, we conceptualized lateral comparison and vertical comparison as two distinct constructs that represent individual self-enhancement toward the nature of social comparison with others and temporal comparison with self over time. We hypothesized that as stable individual psychological difference, lateral comparison and vertical comparison would have differential effects on people’s working behavior in the Chinese organizational context. Design/methodology/approach: Based on a conceptualization approach to Chinese management research, we conducted three studies to develop and validate a two-factor comparison scale which includes three-item lateral comparison and a three-item vertical comparison. Findings: Results from qualitative data in Study 1 provide evidence of convergent and discriminate validity of the scale, while Study 2 demonstrates the scale’s predictive validity. Furthermore, in Study two, a field survey in multiple Chinese organizations showed that lateral comparison and vertical comparison had differential effects on employee task performance and organizational citizenship behavior. Research implications: The theoretical and practical implications of this study are discussed in the working context in Chinese organizations and beyond. Originality/value: This finding integrates insights from previous research in social comparison and temporal comparison into a motivation approach that supervisors use toward subordinates in the Chinese organizational context.

  5. Effect of unlabeled helper probes on detection of an RNA target by bead-based sandwich hybridization

    DEFF Research Database (Denmark)

    Barken, K.B.; Cabig-Ciminska, M.; Holmgren, A.


    Unlabeled helper oligonucleotides assisting a bead-based sandwich hybridization assay were tested for the optimal placement of the capture and detection probes. The target used was a full-length in vitro synthesized mRNA molecule. Helper probes complementary to regions adjacent to the binding site...... of the 5' end attached capture probe were found much more effective than helper probes targeting positions adjacent to the detection probe binding site. The difference is believed to be caused by a disruption of the RNA secondary structure in the area where the capture probe binds, thereby reducing...... structural interference from the bead. The use of additional helpers showed an additive effect. Using helpers, at both sides of the capture and detection probes showed a 15- to 40-fold increase in hybridization efficiency depending on the target, thereby increasing the sensitivity of the hybridization assays...

  6. C-type lectin receptors in the control of T helper cell differentiation

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.


    Pathogen recognition by C-type lectin receptors (CLRs) expressed by dendritic cells is important not only for antigen presentation, but also for the induction of appropriate adaptive immune responses via T helper (TH) cell differentiation. CLRs act either by themselves or in cooperation with other

  7. Type I interferon is required for T helper (Th) 2 induction by dendritic cells

    NARCIS (Netherlands)

    Webb, Lauren M.; Lundie, Rachel J.; Borger, Jessica G.; Brown, Sheila L.; Connor, Lisa M.; Cartwright, Adam N.R.; Dougall, Annette M.; Wilbers, Ruud H.P.; Cook, Peter C.; Jackson-Jones, Lucy H.; Phythian-Adams, Alexander T.; Johansson, Cecilia; Davis, Daniel M.; Dewals, Benjamin G.; Ronchese, Franca; Macdonald, Andrew S.


    Type 2 inflammation is a defining feature of infection with parasitic worms (helminths), as well as being responsible for widespread suffering in allergies. However, the precise mechanisms involved in T helper (Th) 2 polarization by dendritic cells (DCs) are currently unclear. We have identified a

  8. Essential competencies for the education of nursing assistants and care helpers in elderly care

    NARCIS (Netherlands)

    Oeseburg, Barth; Hilberts, Rudi; Roodbol, Petrie F


    BACKGROUND: The Dutch health care system faces huge challenges with regard to the demand on elderly care and the competencies of professionals required to meet this demand. However, a recent study showed that the curricula in vocational education for nursing assistants and care helpers remains

  9. Prevalence and Duties of Collegiate Human Sexuality Peer Helpers: Results of a National Study (United States)

    Butler, Scott M.; Black, David R.


    The purpose of the present study is to assess human sexuality peer helper use among college student health centers nationwide. Results from 358 institutions indicate that 53.9% of centers use peers for educational programming, prevention efforts, and/or counseling initiatives. When adjusting for institutions that sponsor a program (n = 193), the M…

  10. The T Helper 17 Lineage in Pulmonary Diseases : cytokine analysis in local and systemic inflammation

    NARCIS (Netherlands)

    M.S. Paats (Marthe )


    textabstractAlready in 1986, Mosmann and Coffman introduced the concept of separate types of T helper cells, which was based on the distinct cytokine profiles that these key effector cells of the immune system produce when stimulated to differentiate. Cytokines are small proteins that are crucial in

  11. Importance of helper T-cell activation in dendritic cell-based anticancer immunotherapy

    NARCIS (Netherlands)

    Schreibelt, Gerty; Bol, Kalijn F.; Aarntzen, Erik H. J. G.; Gerritsen, Winald R.; Punt, Cornelis J. A.; Figdor, Carl G.; de Vries, I. Jolanda M.


    Dendritic cell-based anticancer immunotherapy is feasible, safe and results in the induction of tumor-specific immune responses, at least in a fraction of vaccinated patients. The concomitant activation of cytotoxic and helper T cells, by loading DCs with peptides or electroporating them with the

  12. Universal tumor-reactive helper peptides from telomerase as new tools for anticancer vaccination. (United States)

    Dosset, Magalie; Vauchy, Charline; Beziaud, Laurent; Adotevi, Olivier; Godet, Yann


    Accumulating evidence demonstrates the importance of CD4+ T cells in antitumor immune responses. Identifying promiscuous MHC class II-binding peptides derived from relevant tumor-associated antigens that specifically target CD4+ helper T cells in vivo represent a powerful approach to fully exploit these cells for anticancer immunotherapy.

  13. Human Rights and International Labour Law issues concerning Migrant Women Working as Domestic Helpers in China

    NARCIS (Netherlands)

    Peng, Q.


    This book addresses the human rights and international labour law issues concerning rural migrant women workers as domestic helpers in China and offers several legislative suggestions to the Chinese government. By describing the current de facto and de jure condition of rural migrant women working

  14. The helper component-proteinase of cowpea aphid-borne mosaic virus

    NARCIS (Netherlands)

    Mlotshwa, S.


    Cowpea aphid-borne mosaic potyvirus causes severe yield losses in cowpea, an important legume crop in semi-arid regions of Africa. We have elucidated the genomic sequence of the virus and subsequently focused our attention on the so-called helper component-proteinase (HC-Pro), a

  15. Leadership behavior changes following a theory-based leadership development intervention: A longitudinal study of subordinates' and leaders' evaluations. (United States)

    Larsson, Gerry; Sandahl, Christer; Söderhjelm, Teresa; Sjövold, Endre; Zander, Ann


    The aim was to evaluate effects of leadership courses based on the developmental leadership model at the leadership behavioral level. A longitudinal design was employed with assessments before, one and six months after the leadership courses. The sample consisted of 59 leaders who made self-ratings and were rated by at least three subordinates on each occasion. Leadership behaviors were measured with the Developmental Leadership Questionnaire (DLQ). A limited increase of favorable leadership behaviors and a significant reduction of unfavorable leadership behaviors were found, particularly according to the subordinates' ratings. A cluster analysis yielded three meaningful leader profiles and showed that this pattern was found in all three profiles, irrespective of how favorably they were rated before the onset of the intervention. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  16. Two types of dominant male cichlid fish: behavioral and hormonal characteristics

    Directory of Open Access Journals (Sweden)

    Rosa M. Alcazar


    Full Text Available Male African cichlid fish, Astatotilapia burtoni, have been classified as dominant or subordinate, each with unique behavioral and endocrine profiles. Here we characterize two distinct subclasses of dominant males based on types of aggressive behavior: (1 males that display escalating levels of aggression and court females while they establish a territory, and (2 males that display a stable level of aggression and delay courting females until they have established a territory. To profile differences in their approach to a challenge, we used an intruder assay. In every case, there was a male-male confrontation between the resident dominant male and the intruder, with the intruder quickly taking a subordinate role. However, we found that dominant males with escalating aggression spent measurably more time attacking subordinates than did dominant males with stable aggression that instead increased their attention toward the females in their tank. There was no difference in the behavior of intruders exposed to either type of dominant male, suggesting that escalating aggression is an intrinsic characteristic of some dominant males and is not elicited by the behavior of their challengers. Male behavior during the first 15 min of establishing a territory predicts their aggressive class. These two types of dominant males also showed distinctive physiological characteristics. After the intruder assay, males with escalating aggression had elevated levels of 11-ketotestosterone (11-KT, testosterone, estradiol, and cortisol, while those with stable aggression did not. These observations show that the same stimulus can elicit different behavioral and endocrine responses among A. burtoni dominant males that characterize them as either escalating or stable aggressive types. Our ability to identify which individuals within a population have escalating levels of aggressive responses versus those which have stable levels of aggressive responses when exposed to

  17. The Paradox of Power Sharing: Participative Charismatic Leaders have Subordinates with more instead of less Need for Leadership


    de Vries, R.E.; Pathak, R.D.; Paquin, A.R.


    Although charismatic and participative leaders have been noted for their positive effects on criteria such as performance, job satisfaction, and commitment, few studies have looked at the relations with subordinates' leadership needs. In this study, the relations between charismatic and participative leadership, team outcomes, and a team's need for leadership were investigated. The sample consisted of South Pacific CEOs and their top-level management teams from Fiji, Tonga, Samoa, Vanuatu, an...

  18. Bed site selection by a subordinate predator: an example with the cougar (Puma concolor) in the Greater Yellowstone Ecosystem. (United States)

    Kusler, Anna; Elbroch, L Mark; Quigley, Howard; Grigione, Melissa


    As technology has improved, our ability to study cryptic animal behavior has increased. Bed site selection is one such example. Among prey species, bed site selection provides thermoregulatory benefits and mitigates predation risk, and may directly influence survival. We conducted research to test whether a subordinate carnivore also selected beds with similar characteristics in an ecosystem supporting a multi-species guild of competing predators. We employed a model comparison approach in which we tested whether cougar (Puma concolor) bed site attributes supported the thermoregulatory versus the predator avoidance hypotheses, or exhibited characteristics supporting both hypotheses. Between 2012-2016, we investigated 599 cougar bed sites in the Greater Yellowstone Ecosystem and examined attributes at two scales: the landscape (second-order, n = 599) and the microsite (fourth order, n = 140). At the landscape scale, cougars selected bed sites in winter that supported both the thermoregulatory and predator avoidance hypotheses: bed sites were on steeper slopes but at lower elevations, closer to the forest edge, away from sagebrush and meadow habitat types, and on southern, eastern, and western-facing slopes. In the summer, bed attributes supported the predator avoidance hypothesis over the thermoregulation hypothesis: beds were closer to forest edges, away from sagebrush and meadow habitat classes, and on steeper slopes. At the microsite scale, cougar bed attributes in both the winter and summer supported both the predator avoidance and thermoregulatory hypotheses: they selected bed sites with high canopy cover, high vegetative concealment, and in a rugged habitat class characterized by cliff bands and talus fields. We found that just like prey species, a subordinate predator selected bed sites that facilitated both thermoregulatory and anti-predator functions. In conclusion, we believe that measuring bed site attributes may provide a novel means of measuring the

  19. Bed site selection by a subordinate predator: an example with the cougar (Puma concolor in the Greater Yellowstone Ecosystem

    Directory of Open Access Journals (Sweden)

    Anna Kusler


    Full Text Available As technology has improved, our ability to study cryptic animal behavior has increased. Bed site selection is one such example. Among prey species, bed site selection provides thermoregulatory benefits and mitigates predation risk, and may directly influence survival. We conducted research to test whether a subordinate carnivore also selected beds with similar characteristics in an ecosystem supporting a multi-species guild of competing predators. We employed a model comparison approach in which we tested whether cougar (Puma concolor bed site attributes supported the thermoregulatory versus the predator avoidance hypotheses, or exhibited characteristics supporting both hypotheses. Between 2012–2016, we investigated 599 cougar bed sites in the Greater Yellowstone Ecosystem and examined attributes at two scales: the landscape (second-order, n = 599 and the microsite (fourth order, n = 140. At the landscape scale, cougars selected bed sites in winter that supported both the thermoregulatory and predator avoidance hypotheses: bed sites were on steeper slopes but at lower elevations, closer to the forest edge, away from sagebrush and meadow habitat types, and on southern, eastern, and western-facing slopes. In the summer, bed attributes supported the predator avoidance hypothesis over the thermoregulation hypothesis: beds were closer to forest edges, away from sagebrush and meadow habitat classes, and on steeper slopes. At the microsite scale, cougar bed attributes in both the winter and summer supported both the predator avoidance and thermoregulatory hypotheses: they selected bed sites with high canopy cover, high vegetative concealment, and in a rugged habitat class characterized by cliff bands and talus fields. We found that just like prey species, a subordinate predator selected bed sites that facilitated both thermoregulatory and anti-predator functions. In conclusion, we believe that measuring bed site attributes may provide a novel

  20. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. (United States)

    Cheng, Xinwei; Lee, Robert J


    Lipid nanoparticles (LNPs) have shown promise as delivery vehicles for therapeutic oligonucleotides, including antisense oligos (ONs), siRNA, and microRNA mimics and inhibitors. In addition to a cationic lipid, LNPs are typically composed of helper lipids that contribute to their stability and delivery efficiency. Helper lipids with cone-shape geometry favoring the formation hexagonal II phase, such as dioleoylphosphatidylethanolamine (DOPE), can promote endosomal release of ONs. Meanwhile, cylindrical-shaped lipid phosphatidylcholine can provide greater bilayer stability, which is important for in vivo application of LNPs. Cholesterol is often included as a helper that improves intracellular delivery as well as LNP stability in vivo. Inclusion of a PEGylating lipid can enhance LNP colloidal stability in vitro and circulation time in vivo but may reduce uptake and inhibit endosomal release at the cellular level. This problem can be addressed by choosing reversible PEGylation in which the PEG moiety is gradually released in blood circulation. pH-sensitive anionic helper lipids, such as fatty acids and cholesteryl hemisuccinate (CHEMS), can trigger low-pH-induced changes in LNP surface charge and destabilization that can facilitate endosomal release of ONs. Generally speaking, there is no correlation between LNP activity in vitro and in vivo because of differences in factors limiting the efficiency of delivery. Designing LNPs requires the striking of a proper balance between the need for particle stability, long systemic circulation time, and the need for LNP destabilization inside the target cell to release the oligonucleotide cargo, which requires the proper selection of both the cationic and helper lipids. Customized design and empirical optimization is needed for specific applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension. (United States)

    Maston, Levi D; Jones, David T; Giermakowska, Wieslawa; Howard, Tamara A; Cannon, Judy L; Wang, Wei; Wei, Yongyi; Xuan, Weimin; Resta, Thomas C; Gonzalez Bosc, Laura V


    Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4+ T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4+ T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1-/-, lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4+, CD8+, or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1-/- mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4+ but not CD8+ T cells restored the hypertensive phenotype in RAG1-/- mice. Interestingly, RAG1-/- mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4+ cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension. Copyright © 2017 the American Physiological Society.

  2. Condoms - male (United States)

    Prophylactics; Rubbers; Male condoms; Contraceptive - condom; Contraception - condom; Barrier method - condom ... The male condom is a thin cover that fits over a man's erect penis . Condoms are made of: Animal ...

  3. Production supervisor impacts on subordinates' safety outcomes: an investigation of leader-member exchange and safety communication. (United States)

    Michael, Judd H; Guo, Zhen George; Wiedenbeck, Janice K; Ray, Charles D


    Supervisors are increasingly important to the functioning of manufacturing operations, in large part due to their role as leaders. While supervisors' relations and communication with their subordinates are known to be important in influencing subordinates' behavior, little is known about how these two factors will impact subordinates' safety. This study investigated how much each factor contributes to safety-related outcomes for blue-collar production employees. Production employees at five Pennsylvania wood manufacturers completed a survey during their work shift. Five hundred and ninety eight employees provided data on leader-member exchange (LMX), safety communication, and safety-related events. Archival data on OSHA recordables were also obtained from the producers' human resources database. Analyses found that the influence of LMX was greater than that of safety communication in predicting safety-related events. Neither LMX nor safety communication was significantly related to OSHA recordables. Results also demonstrated that employee job satisfaction and demographic variables such as gender and age have safety implications. Results from this study further emphasize the importance of production supervisors and illustrate the potential role of leader-member exchange in enhancing workplace safety. Specifically, organizations should foster positive social exchange between their employees and supervisors and enhance the leadership qualities of supervisors to help reduce workplace injuries.

  4. Relationship between nurses and physicians in terms of organizational culture: who is responsible for subordination of nurses? (United States)

    Skela Savic, Brigita; Pagon, Milan


    To investigate how nurses and physicians perceive organizational culture, their integration into the organizational processes, and relations within a health care team. We performed a cross-sectional study that included 106 physicians and 558 nurses from 14 Slovenian hospitals in December 2005. The hospitals were randomly selected. We distributed the questionnaires on the same day to physicians and nurses during a morning shift. The total number of distributed questionnaires represented a 20% of each personnel category at each hospital. The following variables were studied: organizational culture, integration of nurses and physicians in hospital processes, and subordination of nurses to physicians. Physicians and nurses favored a culture of internal focus, stability, and control. Both groups estimated that they had a low level of personal involvement in their organizations and indicated insufficient involvement in work teams, while nurses also felt that they were subordinated (mean+/-standard deviation, 3.6+/-0.9 on a scale from 1 to 5) to physicians (2.7+/-1.0; Porientation correlated positively with the subordination of nurses (PPmarket culture, level of personal involvement, and the level of education. Our research showed that the professional growth of nurses was mainly threatened by organizational factors such as hierarchy, control orientation, a lack of cooperation and team building between physicians and nurses, as well as insufficient inclusion of both physicians and nurses into change implementation activities.

  5. Third-Order Differential Subordination and Superordination Results for Meromorphically Multivalent Functions Associated with the Liu-Srivastava Operator

    Directory of Open Access Journals (Sweden)

    Huo Tang


    Full Text Available There are many articles in the literature dealing with the first-order and the second-order differential subordination and superordination problems for analytic functions in the unit disk, but only a few articles are dealing with the above problems in the third-order case (see, e.g., Antonino and Miller (2011 and Ponnusamy et al. (1992. The concept of the third-order differential subordination in the unit disk was introduced by Antonino and Miller in (2011. Let Ω be a set in the complex plane C. Also let p be analytic in the unit disk U=z:z∈C  and  z<1 and suppose that ψ:C4×U→C. In this paper, we investigate the problem of determining properties of functions p(z that satisfy the following third-order differential superordination: Ω⊂ψpz,zp′z,z2p′′z,z3p′′′z;z:z∈U. As applications, we derive some third-order differential subordination and superordination results for meromorphically multivalent functions, which are defined by a family of convolution operators involving the Liu-Srivastava operator. The results are obtained by considering suitable classes of admissible functions.

  6. Organizational environment factors associated with corporate social responsibility: effects on communication and guanxi relationship between supervisors and subordinates in SMEs

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    Edward WONG SEK KHIN


    Full Text Available Effective communication within an organization as part of CSR benchmarking factor that helps align employee expectations facilitates problem solving, builds cooperative relationships and channels employee efforts to achieve common goals. This paper seeks to determine how CSR benchmarking factors of the organizational environment (such as management style, organizational structure and workplace culture affect the effectiveness of intra-organizational communication and to examine the moderating effect of supervisor – subordinate guanxi. Data for the study was collected using self-administered questionnaires from working respondents in Kuala Lumpur in Selangor State, Malaysia. This study found that a more participative management style, less formalized organizational structure of SMEs and a healthier workplace culture are positively related to intra-organizational communication effectiveness. It was also discovered that the supervisor – subordinate relationship known as guanxi, has a positive moderating effect on all three relationships between management style, organizational structure and workplace culture with intra-organizational communication effectiveness. This study concludes that an organization’s management attitude towards employee participation, formalization of structure and healthiness of culture play important roles in encouraging effective communication and close supervisor – subordinate guanxi and further promotes communication, in addition to the mentioned environmental conditions.

  7. Male Hypogonadism (United States)

    Male hypogonadism Overview Male hypogonadism is a condition in which the body doesn't produce enough testosterone — the hormone that plays a key ... sperm or both. You may be born with male hypogonadism, or it can develop later in life, ...

  8. Systemic frequencies of T helper 1 and T helper 17 cells in patients with age-related macular degeneration: A case-control study

    DEFF Research Database (Denmark)

    Singh, Amardeep; Subhi, Yousif; Nielsen, Marie Krogh


    Age-related macular degeneration (AMD) is a degenerative disease of the retina and a leading cause of irreversible vision loss. We investigated the systemic differences in the frequency of T helper (Th) 1 and Th17 cells in patients with non-exudative and exudative AMD and compared to age...... in patients with exudative AMD. A significant age-dependent decrement in Th1 was observed in controls, but not in non-exudative or exudative AMD. This may be related to the CXCR3+ CD4+ T-cells, which showed similar pattern in controls, but not in non-exudative or exudative AMD. No significant group...

  9. Male Investments in High Quality Sperm Improve Fertilization Success, but May Have Negative Impact on Offspring Fitness in Whitefish (United States)

    Kekäläinen, Jukka; Soler, Carles; Veentaus, Sami; Huuskonen, Hannu


    Many ejaculate traits show remarkable variation in relation to male social status. Males in disfavoured (subordinate) mating positions often invest heavily on sperm motility but may have less available resources on traits (e.g., secondary sexual ornaments) that improve the probability of gaining matings. Although higher investments in sperm motility can increase the relative fertilization success of subordinate males, it is unclear whether status-dependent differences in sperm traits could have any consequences for offspring fitness. We tested this possibility in whitefish (Coregonus lavaretus L.) by experimentally fertilizing the eggs of 24 females with the sperm of either highly-ornamented (large breeding tubercles, dominant) or less-ornamented (small tubercles, subordinate) males (split-clutch breeding design). In comparison to highly-ornamented individuals, less-ornamented males had higher sperm motility, which fertilized the eggs more efficiently, but produced embryos with impaired hatching success. Also offspring size and body condition were lower among less-ornamented males. Furthermore, sperm motility was positively associated with the fertilization success and offspring size, but only in highly-ornamented males. Together our results indicate that male investments on highly motile (fertile) sperm is not necessarily advantageous during later offspring ontogeny and that male status-dependent differences in sperm phenotype may have important effects on offspring fitness in different life-history stages. PMID:26389594

  10. Knowledge and Practices About the Subject Emergency Contraception of the Pharmacists and Their Helpers in the Pharmacies in Manisa

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    Ayten Taspinar


    Full Text Available AIM: The study was carried out as descriptive to determine the knowledge and practices about the subject emergency contraception of the pharmacists and their helpers in the pharmacies in central Manisa. METHOD: The universe of the research was formed by the 113 pharmacies registered to Manisa chamber of pharmacists in the year 2008 and all the pharmacies were included in the study. 47 pharmacists and 88 helpers agreed to join the study. The research which was planned to be descriptive March-to-June 2008. A questionnaire was produced by researchers and filled in during face-to face interviews with the pharmacists and their helpers. RESULTS: The pharmacists and their helpers stated that combined pills (46.8% and 44.5% and condoms (41.5% and 42.7% the most requested family planning methods their pharmacy. It was determined that 48.9% of the pharmacists, 33% of the pharmacist’s helpers gave information to customers about their use of family planning methods, 38.3% of the pharmacists, 23.9 % of the pharmacist’s helpers gave information what to do in case of failure to use/ where to apply to. 91.5% of the pharmacists, 95.5% of the pharmacist’s helpers stated that they had emergency contraception (EC purpose pills in their pharmacies. It was determined that 61.7% of the pharmacists, 28.4% of the pharmacist’s helpers had the knowledge about EC, 61.7% of the pharmacists, 52.3% of the pharmacist’s helpers could consider the EC methods true, 68.1% of the pharmacists, 70.5% of the pharmacist’s helpers gave the correct answers to the question of when the EC – purpose pills would be used. 68.1% of the pharmacists, 45.5% of the pharmacist’s helpers stated that EC methods might have adverse effects, 14.9% of the pharmacists, 25% of the pharmacist’s helpers stated that EC methods were protect agains to STD or not information about it, 12.8% of the pharmacists, 9.1% of the pharmacist’s helpers stated that these pills might be effective after the

  11. Male contraception

    Directory of Open Access Journals (Sweden)

    Vivek Mathew


    Full Text Available Contraception is an accepted route for the control of population explosion in the world. Traditionally hormonal contraceptive methods have focused on women. Male contraception by means of hormonal and non hormonal methods is an attractive alternative. Hormonal methods of contraception using testosterone have shown good results. Non hormonal reversible methods of male contraception like reversible inhibition of sperm under guidanceare very promising. In this article we have reviewed the current available options for male contraception.

  12. Expansion of pathogen-specific T-helper 1 and T-helper 17 cells in pulmonary tuberculosis with coincident type 2 diabetes mellitus. (United States)

    Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V; Jawahar, Mohideen S; Nutman, Thomas B; Babu, Subash


    Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4(+) Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection.

  13. Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus (United States)

    Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash


    Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. PMID:23715661

  14. Pathogen-Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination

    Directory of Open Access Journals (Sweden)

    Tammy Oth


    Full Text Available A coordinated cellular interplay is of crucial importance in both host defense against pathogens and malignantly transformed cells. The various interactions of Dendritic Cells (DC, Natural Killer (NK cells, and T helper (Th cells can be influenced by a variety of pathogen-associated molecular patterns (PAMPs and will lead to enhanced CD8+ effector T cell responses. Specific Pattern Recognition Receptor (PRR triggering during maturation enables DC to enhance Th1 as well as NK helper cell responses. This effect is correlated with the amount of IL-12p70 released by DC. Activated NK cells are able to amplify the proinflammatory cytokine profile of DC via the release of IFN-γ. The knowledge on how PAMP recognition can modulate the DC is of importance for the design and definition of appropriate therapeutic cancer vaccines. In this review we will discuss the potential role of specific PAMP-matured DC in optimizing therapeutic DC-based vaccines, as some of these DC are efficiently activating Th1, NK cells, and cytotoxic T cells. Moreover, to optimize these vaccines, also the inhibitory effects of tumor-derived suppressive factors, for example, on the NK-DC crosstalk, should be taken into account. Finally, the suppressive role of the tumor microenvironment in vaccination efficacy and some proposals to overcome this by using combination therapies will be described.


    Directory of Open Access Journals (Sweden)

    Parmonangan Manurung


    Full Text Available Victoria Park is the largest city park in Hong Kong. This city park is not only known in Hong Kong, but also very well known in Indonesia as a gathering place for Indonesia domestic helpers (TKW in Hong Kong. This research tried to find out some determinant factors that have been affected the public open spac of Victoria Park to be a gathering place for thousands of TKW in Sunday and holidays as their day off. In order to get the results of research, some methodological research had been conducted such as: observation (survey, mapping, interviews and literature studies. The results showed that Victoria Park has a number of factors capable of meeting the needs of domestic help-ers in Hong Kong, these factors consist of internal factors and external factors. Internally, the character and functions held Victoria Park became a very influential factor, while externally, the accessibility and support functions around Victoria Park also has a considerable influence.

  16. General pathologist-helper: The new medical app about general pathology

    Directory of Open Access Journals (Sweden)

    Iván Fernandez-Vega


    Full Text Available Introduction: Smartphone applications (apps have become increasingly prevalent in medicine. Due to most pathologists, pathology trainees, technicians, and medical students use smartphones; apps can be a different way for general pathology education. “General pathologist-helper (GP-HELPER” is a novel app developed as a reference tool in general pathology and especially for general pathologists, developed for Android and iOS platforms. Materials and Methods: “GP-HELPER,” was created using Mobincube website platform. This tool also integrates “FORUM GP-HELPER,” an external website created using Miarroba website ( and “COMMUNITY GP-HELPER” a multichannel chat created using Chatango website platform. Results: The application was released in July 2015, and it is been periodically updated since then. The app has permanent information (offline data about different pathology protocols (TNM latest edition, protocols regarding management of tumors of unknown primary origin, and flowcharts for some of the most difficult tumors to diagnose and a database with more than 5000 immunohistochemistry results from different tumors. Online data have links to more than 1100 reference pathology video lectures, 250 antibodies information, more than 70 pathology association websites, 46 pathology providers, and 78 outstanding pathology journal websites. Besides this information, the app has two interactive places such as “FORUM GP-HELPER” and “COMMUNITY GP-HELPER” that let users to stay in touch everywhere and every time. Expert consult section is also available. Conclusions: “GP-HELPER” pretends to integrate offline and online data about pathology with two interactive external places in order to represent a reference tool for general pathologists and associate members.

  17. Increased Peripheral Proinflammatory T Helper Subsets Contribute to Cardiovascular Complications in Diabetic Patients

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    Ru-xing Zhao


    Full Text Available Background. Coronary atherosclerotic heart disease (CHD is one of the major concerns in type 2 diabetes (T2D. The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. Methods. The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n=42 and 67, resp.. Results. Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. Conclusions. Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.

  18. Rotavirus-specific helper T cell responses in newborns, infants, children, and adults. (United States)

    Offit, P A; Hoffenberg, E J; Pia, E S; Panackal, P A; Hill, N L


    An obstacle to developing a successful rotavirus vaccine has been the inability to consistently correlate the humoral immune response with protection against disease. Transplacental transfer of maternal rotavirus-specific antibodies may obscure the capacity to discriminate an active from a passively acquired humoral immune response in infants. In an attempt to circumvent this problem, an assay was developed to detect rotavirus-specific helper T cells among circulating mononuclear cells. Rotavirus-specific lymphoproliferative responses and rotavirus-specific neutralizing antibody titers in blood were determined in 11 mother/newborn pairs at the time of delivery and in 54 infants, children, and adults ranging in age from 16 days to 40 years. Only 1 of 11 infants tested between 16 days and 6 months of age had detectable rotavirus-specific helper T cell activity whereas 8 of 11 had circulating rotavirus-specific neutralizing antibodies. Acquisition of rotavirus-specific helper T cell activity over the first few years of life correlated with the age at which infants and young children are known to be infected with rotavirus. These findings support the hypothesis that detection of rotavirus-specific lymphoproliferative activity in infants may more accurately determine previous exposure to rotavirus than detection of rotavirus-specific antibodies.

  19. DeltaPhage—a novel helper phage for high-valence pIX phagemid display (United States)

    Nilssen, Nicolay R.; Frigstad, Terje; Pollmann, Sylvie; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger; Løset, Geir Å.


    Phage display has been instrumental in discovery of novel binding peptides and folded domains for the past two decades. We recently reported a novel pIX phagemid display system that is characterized by a strong preference for phagemid packaging combined with low display levels, two key features that support highly efficient affinity selection. However, high diversity in selected repertoires are intimately coupled to high display levels during initial selection rounds. To incorporate this additional feature into the pIX display system, we have developed a novel helper phage termed DeltaPhage that allows for high-valence display on pIX. This was obtained by inserting two amber mutations close to the pIX start codon, but after the pVII translational stop, conditionally inactivating the helper phage encoded pIX. Until now, the general notion has been that display on pIX is dependent on wild-type complementation, making high-valence display unachievable. However, we found that DeltaPhage does facilitate high-valence pIX display when used with a non-suppressor host. Here, we report a side-by-side comparison with pIII display, and we find that this novel helper phage complements existing pIX phagemid display systems to allow both low and high-valence display, making pIX display a complete and efficient alternative to existing pIII phagemid display systems. PMID:22539265

  20. Social cliques in male northern muriquis Brachyteles hypoxanthus

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    Marcos TOKUDA, Jean P. BOUBLI, Patrícia IZAR, Karen B. STRIER


    Full Text Available Analyses of spatial relationships and social interactions provide insights into the social structure of animal societies and the ways in which social preferences among and between dyads affect higher order social relationships. In this paper we describe the patterns of spatial associations and social interactions among adult male northern muriquis in order to evaluate the dynamics of their social networks above the dyadic levels. Systematic observations were made on the 17 adult males present in a multi-male/multi-female group from April 2004 through February 2005, and in July 2005. Analyses of their spatial relationships identified two distinct male cliques; some adult males (called “N” males were more connected to the females and immatures than other adult males (“MU” males, which were more connected to one another. Affiliative interactions were significantly higher among dyads belonging to the same clique than to different cliques. Although frequencies of dyadic agonistic interactions were similarly low among individuals within and between cliques, MU males appeared to be subordinate to N males. Nonetheless, there were no significant differences in the copulation rates estimated for MU males and N males. Mutual benefits of cooperation between MU and N cliques in intergroup encounters might explain their ongoing associations in the same mixed-sex group [Current Zoology 58 (2: 342-352, 2012].

  1. Male Infertility (United States)

    ... or swelling in the testicle area Have a history of testicle, prostate or sexual problems Have had groin, testicle, penis or scrotum surgery Request an Appointment at Mayo Clinic Causes Male fertility is a complex process. To ...

  2. The role of social environment on parental care: offspring benefit more from the presence of female than male helpers

    NARCIS (Netherlands)

    Brouwer, L.; Van de Pol, M.; Cockburn, A.


    1.Investment in offspring depends on the costs and benefits to the carer, which can vary with sex and social status. Investment also depends on the effort of others by allowing for compensation (load-lightening), with biparental care studies showing that this depends on the state and type of the

  3. Male contraception


    Vivek Mathew; Ganapathi Bantwal


    Contraception is an accepted route for the control of population explosion in the world. Traditionally hormonal contraceptive methods have focused on women. Male contraception by means of hormonal and non hormonal methods is an attractive alternative. Hormonal methods of contraception using testosterone have shown good results. Non hormonal reversible methods of male contraception like reversible inhibition of sperm under guidanceare very promising. In this article we have reviewed the curren...

  4. Male Contraception


    Amory, John K.


    Although female contraceptives are very effective at preventing unintended pregnancy, some women cannot use them due to health conditions or side effects, leaving some couples without effective contraceptive options. In addition, many men wish to take active responsibility for family planning. Thus, there is a great need for male contraceptives to prevent unintended pregnancy, of which 80–90 million occur annually. At present, effective male contraceptive options are condoms and vasectomy, wh...

  5. General job performance of first-line supervisors: the role of conscientiousness in determining its effects on subordinate exhaustion. (United States)

    Perry, Sara Jansen; Rubino, Cristina; Witt, L A


    In an integrated test of the job demands-resources model and trait activation theory, we predicted that the general job performance of employees who also hold supervisory roles may act as a demand to subordinates, depending on levels of subordinate conscientiousness. In a sample of 313 customer service call centre employees, we found that high-conscientiousness individuals were more likely to experience emotional exhaustion, and low-conscientiousness individuals were less likely as the general job performance of their supervisor improved. The results were curvilinear, such that high-conscientiousness individuals' exhaustion levelled off with very high supervisor performance (two standard deviations above the mean), and low-conscientiousness individuals' exhaustion levelled off as supervisor performance improved from moderate to high. These findings suggest high-conscientiousness employees may efficiently handle demands presented by a low-performing coworker who is their boss, but when performance expectations are high (i.e. high-performing boss), these achievement-oriented employees may direct their resources (i.e. energy and time) towards performance-related efforts at the expense of their well-being. Conversely, low-conscientiousness employees suffer when paired with a low-performing boss, but benefit from a supervisor who demonstrates at least moderate job performance.

  6. Are all types of expertise created equal? Car experts use different spatial frequency scales for subordinate categorization of cars and faces.

    Directory of Open Access Journals (Sweden)

    Assaf Harel

    Full Text Available A much-debated question in object recognition is whether expertise for faces and expertise for non-face objects utilize common perceptual information. We investigated this issue by assessing the diagnostic information required for different types of expertise. Specifically, we asked whether face categorization and expert car categorization at the subordinate level relies on the same spatial frequency (SF scales. Fifteen car experts and fifteen novices performed a category verification task with spatially filtered images of faces, cars, and airplanes. Images were categorized based on their basic (e.g. "car" and subordinate level (e.g. "Japanese car" identity. The effect of expertise was not evident when objects were categorized at the basic level. However, when the car experts categorized faces and cars at the subordinate level, the two types of expertise required different kinds of SF information. Subordinate categorization of faces relied on low SFs more than on high SFs, whereas subordinate expert car categorization relied on high SFs more than on low SFs. These findings suggest that expertise in the recognition of objects and faces do not utilize the same type of information. Rather, different types of expertise require different types of diagnostic visual information.

  7. Neurotransmitter signalling via NMDA receptors leads to decreased T helper type 1-like and enhanced T helper type 2-like immune balance in humans. (United States)

    Orihara, Kanami; Odemuyiwa, Solomon O; Stefura, William P; Ilarraza, Ramses; HayGlass, Kent T; Moqbel, Redwan


    Given the pivotal roles that CD4 + T cell imbalance plays in human immune disorders, much interest centres on better understanding influences that regulate human helper T-cell subset dominance in vivo. Here, using primary CD4 + T cells and short-term T helper type 1 (Th1) and Th2-like lines, we investigated roles and mechanisms by which neurotransmitter receptors may influence human type 1 versus type 2 immunity. We hypothesized that N-methyl-d-aspartate receptors (NMDA-R), which play key roles in memory and learning, can also regulate human CD4 + T cell function through induction of excitotoxicity. Fresh primary CD4 + T cells from healthy donors express functional NMDA-R that are strongly up-regulated upon T cell receptor (TCR) mediated activation. Synthetic and physiological NMDA-R agonists elicited Ca 2+ flux and led to marked inhibition of type 1 but not type 2 or interleukin-10 cytokine responses. Among CD4 + lines, NMDA and quinolinic acid preferentially reduced cytokine production, Ca 2+ flux, proliferation and survival of Th1-like cells through increased induction of cell death whereas Th2-like cells were largely spared. Collectively, the findings demonstrate that (i) NMDA-R is rapidly up-regulated upon CD4 + T cell activation in humans and (ii) Th1 versus Th2 cell functions such as proliferation, cytokine production and cell survival are differentially affected by NMDA-R agonists. Differential cytokine production and proliferative capacity of Th1 versus Th2 cells is attributable in part to increased physiological cell death among fully committed Th1 versus Th2 cells, leading to increased Th2-like dominance. Hence, excitotoxicity, beyond its roles in neuronal plasticity, may contribute to ongoing modulation of human T cell responses. © 2017 John Wiley & Sons Ltd.

  8. Male baldness. (United States)

    Clarke, Philip


    Male baldness is very common. Its effect on individuals is extremely variable, and in some people it will have a significant adverse effect on their quality of life. The objectives of this article are to help general practitioners (GPs) be aware of potential health problems related to male baldness, to have an approach to assessing hair loss and to be aware of treatment options. Male baldness is, most often, a normal occurrence, but it may have significant effects on a man's health. It may also be a pointer to other potential health issues. The GP is in the ideal position to conduct an initial evaluation, consider other health issues and advise on treatment options.

  9. T-Helper Cytokine Patterns and Related Antibodies in Patients with Gestational Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    A Alavi


    Full Text Available Background: Diabetes mellitus (DM is a group of metabolic disorders such as DM I, DM II, secondary causes of DM and gestational diabetes mellitus characterized by hyperglycemic phonotype. The etiology of gestational diabetes mellitus is unknown. Recent studies address the chronic activity of immune system against infections (not autoimmunity as an important cause of gestational diabetes mellitus. This study aimed to compare T-helper cells 1 and 2 cytokines and associated antibodies in patients with gestational diabetes mellitus and normal pregnant women. Methods: This cross-sectional study was performed on 45 female patients with GDM and 45 healthy pregnant women in Bandar Abbas, Iran, from 2008- 2009. The exclusion criteria were presence of any infectious diseases or autoimmune disorders such as SLE or RA. Present and past medical histories were taken from the participants thorough physical examination. Blood samples (10 mL were drawn and sent to laboratory for measuring serum IgE, IgG1, IgG2, IgG3, IgG4, interleukin-10 (IL-10, interleukin-12 (IL-12, transforming growth factor-beta (TGF1, and interferon-gamma (IFN measurements. T-test and Kolmogorov-Smirnov test were used for data analysis. Results: The mean age of the patients with GDM and healthy pregnant women was 32.5 and 27.9 yrs, respectively. T-helper 1 and 2 associated antibodies and cytokines had no significant differences between the case and control groups. Conclusion: The changes in T-helper 1 and 2 associated antibodies and cytokines are not associated with gestational diabetes mellitus and could not be considered as a predictor for gestational diabetes mellitus.

  10. Shifted T Helper Cell Polarization in a Murine Staphylococcus aureus Mastitis Model. (United States)

    Zhao, Yanqing; Zhou, Ming; Gao, Yang; Liu, Heyuan; Yang, Wenyu; Yue, Jinhua; Chen, Dekun


    Mastitis, one of the most costly diseases in dairy ruminants, is an inflammation of the mammary gland caused by pathogenic infection. The mechanisms of adaptive immunity against pathogens in mastitis have not been fully elucidated. To investigate T helper cell-mediated adaptive immune responses, we established a mastitis model by challenge with an inoculum of 4 × 106 colony-forming units of Staphylococcus aureus in the mammary gland of lactating mice, followed by quantification of bacterial burden and histological analysis. The development of mastitis was accompanied by a significant increase in both Th17 and Th1 cells in the mammary gland. Moreover, the relative expression of genes encoding cytokines and transcription factors involved in the differentiation and function of these T helper cells, including Il17, Rorc, Tgfb, Il1b, Il23, Ifng, Tbx21, and Il12, was greatly elevated in the infected mammary gland. IL-17 is essential for neutrophil recruitment to infected mammary gland via CXC chemokines, whereas the excessive IL-17 production contributes to tissue damage in mastitis. In addition, a shift in T helper cell polarization toward Th2 and Treg cells was observed 5 days post-infection, and the mRNA expression of the anti-inflammatory cytokine Il10 was markedly increased at day 7 post-infection. These results indicate that immune clearance of Staphylococcus aureus in mastitis is facilitated by the enrichment of Th17, Th1 and Th2 cells in the mammary gland mediated by pro-inflammatory cytokine production, which is tightly regulated by Treg cells and the anti-inflammatory cytokine IL-10.

  11. The adjectival subordinate clause in the production of meaning in the text: the prospect of Portuguese textbooks in high school

    Directory of Open Access Journals (Sweden)

    Aliana Lopes Câmara


    Full Text Available This paper studies how Portuguese textbooks of high school, approved by the Programa Nacional do Livro Didático-2015, approach the teaching of adjectival subordinate clause. Several researchers (Bagno, 2011; Neves, 2011; Travaglia, 2009, 2011 address the issue of grammar teaching, questioning the mechanistic and traditional teaching of identification and classification of linguistic units (morphological and syntactic. These authors argue the articulation of grammar with the teaching of reader and writer skills, so that linguistic resources are studied in mobilizing effects of meaning in the textual construction. The choice of textbooks corpus, therefore, was determined by the grammar teaching proposal explicitly stated in the manuals for the teacher (part attached to the textbook, under which linguistic resources are subsidiary to the reading and writing teaching. First we compare the proposal of manuals on the teaching of grammar and what was accomplished in the book of the student, more specifically on the proposals for the teaching of adjectival subordinate clause. Then, from the study on the functional description of the adjectival subordinate clause (Câmara, 2015, which is based on Functional Discourse Grammar (Hengeveld e Mackenzie, 2008, we studied how some descriptive aspects can be subsidiary for the teaching of the adjective clause, aiming at the development of reading and writing skills. The reason for the choice of this theoretical support is the fact that grammar is hierarchically structured in levels and layers of linguistic analysis, and the pragmatic units determine the semantic units, which in turn determine the morphosyntactic units which, in turn, determine the phonological units. The data show that remains, in the educational proposals of the relative clause in high school textbooks, a grammar teaching that focuses primarily in the nomenclature, metalanguage and in the normative grammar rules. There isn’t many

  12. Identification of genomic regions of the herpesvirus of turkeys (HVT) with helper activity for avian adeno-associated virus (AAAV). (United States)

    Bauer, H J; Schüller, S; Monreal, G; Lindenmaier, W


    Herpesvirus of turkeys (HVT) is a potent helper for the defective parvovirus avian adeno-associated virus (AAAV). To study the helper mechanism at the molecular level, we established a complete cosmid library of HVT DNA in a set of seven overlapping clones and transiently cotransfected secondary chicken embryo fibroblast (CEF) cells with AAAV DNA and recombinant cosmids (cBL) (individual as well as in different combinations). Using an AAAV-specific indirect immunofluorescence assay, we identified four regions on the HVT genome, represented by cBL267, cBL27, cBL33, and cBL34, which express helper functions for AAAV. As demonstrated by infection studies with extracts from cotransfected CEF cells, cBL267 promotes productive AAAV growth, while the helper effect induced by cBL27, cBL33, and cBL34 is limited to the synthesis of noninfectious AAAV antigen. In view of the data presented, possible HVT-specific helper mechanisms for AAAV are discussed.

  13. When helping helps: autonomous motivation for prosocial behavior and its influence on well-being for the helper and recipient. (United States)

    Weinstein, Netta; Ryan, Richard M


    Self-determination theory posits that the degree to which a prosocial act is volitional or autonomous predicts its effect on well-being and that psychological need satisfaction mediates this relation. Four studies tested the impact of autonomous and controlled motivation for helping others on well-being and explored effects on other outcomes of helping for both helpers and recipients. Study 1 used a diary method to assess daily relations between prosocial behaviors and helper well-being and tested mediating effects of basic psychological need satisfaction. Study 2 examined the effect of choice on motivation and consequences of autonomous versus controlled helping using an experimental design. Study 3 examined the consequences of autonomous versus controlled helping for both helpers and recipients in a dyadic task. Finally, Study 4 manipulated motivation to predict helper and recipient outcomes. Findings support the idea that autonomous motivation for helping yields benefits for both helper and recipient through greater need satisfaction. Limitations and implications are discussed. Copyright 2009 APA, all rights reserved

  14. Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors. (United States)

    Brunetti-Pierri, N; Ng, P


    Preclinical studies in small and large animal models using helper-dependent adenoviral vectors (HDAds) have generated promising results for the treatment of genetic diseases. However, clinical translation is complicated by the dose-dependent, capsid-mediated acute toxic response following systemic vector injection. With the advancements in vectorology, a better understanding of vector-mediated toxicity, and improved delivery methods, HDAds may emerge as an important vector for gene therapy of genetic diseases and this report highlights recent progress and prospects in this field.

  15. Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines. (United States)

    Pappu, Bhanu P; Angkasekwinai, Pornpimon; Dong, Chen


    Interleukin 17 (IL-17) family consists of six cytokines in mammals. Among them, IL-17 and IL-17F are expressed by a novel subset of CD4+ helper T (Th) cells and play critical function in inflammation and autoimmunity. On the other hand, IL-17E, also called IL-25, has been associated with allergic responses. Here we summarize recent work by us as well as other investigators in understanding the regulation and function of these three cytokines. From these studies, IL-17 family cytokines may serve as novel targets for pharmaceutical intervention of immune and inflammatory diseases.

  16. Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells. (United States)

    Sadtler, Kaitlyn; Estrellas, Kenneth; Allen, Brian W; Wolf, Matthew T; Fan, Hongni; Tam, Ada J; Patel, Chirag H; Luber, Brandon S; Wang, Hao; Wagner, Kathryn R; Powell, Jonathan D; Housseau, Franck; Pardoll, Drew M; Elisseeff, Jennifer H


    Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair. Copyright © 2016, American Association for the Advancement of Science.

  17. Circumcision (Male) (United States)

    ... Pediatrics; 2009:828. Provencio-Vasquez E. Circumcision revisited. Journal for Specialists in Pediatric Nursing. 2009;14:295. Brown-Trask B, et al. Circumcision care. RN. 2009;72:22. Circumcision policy statement. American ... BJU International. 2008;101:65. Task Force on Circumcision. Male ...

  18. A Model of Adding Relations in Multi-levels to a Formal Organization Structure with Two Subordinates (United States)

    Sawada, Kiyoshi; Amano, Kazuyuki


    This paper proposes a model of adding relations in multi-levels to a formal organization structure with two subordinates such that the communication of information between every member in the organization becomes the most efficient. When edges between every pair of nodes with the same depth in L (L = 1, 2, …, H) levels are added to a complete binary tree of height H, an optimal set of depths {N1, N2, …, NL} (H⩾N1>N2> …>NL⩾1) is obtained by maximizing the total shortening path length which is the sum of shortening lengths of shortest paths between every pair of all nodes in the complete binary tree. It is shown that {N1, N2, …, NL}* = {H, H-1, …, H-L+1}.

  19. Aggressiveness and brain amine concentration in dominant and subordinate finishing pigs fed the beta-adrenoreceptor agonist ractopamine. (United States)

    Poletto, R; Cheng, H W; Meisel, R L; Garner, J P; Richert, B T; Marchant-Forde, J N


    Under farm conditions, aggression related to the formation of social hierarchy and competition for resources can be a major problem because of associated injuries, social stress, and carcass losses. Any factor that may affect the regulation and amount of aggression within a farmed system, for instance, feeding the beta-adrenoreceptor agonist ractopamine (RAC), is therefore worthy of investigation. The objectives of this study were to assess the effects of the widely used swine feed additive RAC, considering also the effects of sex and social rank on aggressiveness and concentrations of brain amines, neurotransmitters essential for controlling aggression, in finishing pigs. Thirty-two barrows and 32 gilts (4 pigs/pen by sex) were fed either a control diet or a diet with RAC (Paylean, Elanco Animal Health, Greenfield, IN) added (5 mg/kg for 2 wk, followed by 10 mg/kg for 2 wk). The top dominant and bottom subordinate pigs (16 pigs/sex) in each pen were determined after mixing by a 36-h period of continuous behavioral observation. These pigs were then subjected to resident-intruder tests (maximum 300 s) during the feeding trial to measure aggressiveness. At the end of wk 4, the amygdala, frontal cortex, hypothalamus, and raphe nuclei were dissected and analyzed for concentrations of dopamine (DA); serotonin (5-HT); their metabolites 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA), respectively; norepinephrine; and epinephrine using HPLC. Ractopamine-fed gilts performed more attacks during the first 30 s of testing than pigs in all other subgroups (P dominant control gilts and barrows, and both dominant and subordinate RAC-fed gilts performed the greatest percentage of attacks (P brain 5-HT synthesis) of dominant gilts (P brain monoamine profiling of a deficient serotonergic system in the raphe nuclei, amygdala, and frontal cortex, and enhanced DA metabolism in the amygdala, brain areas vital for aggression

  20. Contrasting patterns of comprehension for superordinate, basic-level, and subordinate names in semantic dementia and aphasic stroke patients. (United States)

    Crutch, Sebastian J; Warrington, Elizabeth K


    It is well established that patients with semantic memory impairment show a relative sparing of general superordinate information as compared with more detailed item-specific information. The objective of the current study was to examine whether or not this superordinate superiority effect is also reliably observed in individuals with stroke. The participants were 3 patients with a diagnosis of semantic dementia (SD) and 4 left middle cerebral artery stroke patients. In the first experiment, participants were administered a series of spoken-word-picture matching tasks, in which picture identity was probed under two conditions: item name (e.g., goose, beetle, shark, hedgehog) and superordinate name (e.g., bird, insect, fish, mammal). The SD patients showed the predicted pattern of performance, identifying stimuli significantly more accurately by their superordinate term than by their specific name. By contrast, the stroke patients showed the reverse pattern of inferior performance in the superordinate condition in all versions of the experimental task. In a second experiment comparing comprehension ofbasic-level names (e.g., dog, bird, fish) and subordinate-level names (e.g., Dalmatian, sparrow, trout), stroke patients also showed a reversal of the normal basic-level effect, showing less accurate comprehension of basic-level names. The pattern of results documented among the stroke patients cannot be accommodated obviously or readily by existing models of conceptual knowledge. These contrasting abilities of SD patients, stroke patients, and normal healthy participants to process subordinate, basic-level, and superordinate names are considered in relation to disorders of executive processing and taxonomic categorization.

  1. Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets. (United States)

    Chen, Z; Lönnberg, T; Lahesmaa, R


    Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions. © 2013 John Wiley & Sons Ltd.

  2. Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect

    DEFF Research Database (Denmark)

    Lund, O; Lund, O S; Gram, G


    This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells...... will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction cells that is initially...... transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests...

  3. Social and emotional wellbeing, natural helpers, critical health literacy and translational research: connecting the dots for positive health outcomes. (United States)

    Drew, Neil


    The tripartite framework for principled practice was developed as part of the Wundargoodie Aboriginal Youth and Community Wellbeing Programme. The programme engages natural helpers to enhance critical health literacy. This paper examines the importance of translational research to enhancing critical health literacy for this group of de facto health workers using the work of the Australian Indigenous HealthInfoNet as an example. Translational research provides workforce support for those who are time poor and overburdened. Connecting these concepts and natural helpers will make a positive difference to Aboriginal health outcomes. There is a need for the development of translational research products that enhance the critical health literacy of natural helpers. The tripartite framework for principled practice supports reflective and accountable practice in the intercultural space to build trust and confidence between Aboriginal and non-Aboriginal people to enhance the opportunity for authentic knowledge production and transfer. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  4. Assessment the Efficiency of the Constructed Minigenome of Rabies Virus using PV Strain as Helper Virus. (United States)

    Ajorloo, Mehdi; Bamdad, Taravat; Gholami, Ali Reza; Azadmanesh, Keyhan


    Rabies is an acute viral disease that causes encephalomyelitis in mammals and human. The only way to prevent this disease is through vaccination before or after exposure. The aim of this study is to evaluate the efficiency of the Pasteur virus (PV) minigenome, using PV strain. Enhanced Green Fluorescent Protein (EGFP) sequence was placed between the designed necessary elements (Hammerhead, HDV ribozyme, 3' Leader, and 5' Trailer sequences), which resemble the rabies virus PV strain (PV2061) genome and anti-genome. These constructs were placed between T7 polymerase promoter and T7 polymerase terminator sequences. The accuracy of the minigenome was confirmed by the expression of EGFP using the helper virus in T7-BHK cell line. The viral necessary elements of positive and negative sense strands were evaluated for the ability of EGFP expression in the presence of the helper virus. While the positive strand showed background results, no EGFP background was observed in the negative strand application. Establishment of minigenome system does not require advanced biosafety levels. Furthermore, using minigenome system eliminates many potential confounding factors that may be present in coding regions of the genome. Use of the minigenome system is easier and more feasible than the full genome rescue of the virus. This study successfully shows the efficiency of the constructed rabies virus minigenome in expression of inserted gene.

  5. Detection of tmRNA molecules on microarrays at low temperatures using helper oligonucleotides

    Directory of Open Access Journals (Sweden)

    Palta Priit


    Full Text Available Abstract Background The hybridization of synthetic Streptococcus pneumoniae tmRNA on a detection microarray is slow at 34°C resulting in low signal intensities. Results We demonstrate that adding specific DNA helper oligonucleotides (chaperones to the hybridization buffer increases the signal strength at a given temperature and thus makes the specific detection of Streptococcus pneumoniae tmRNA more sensitive. No loss of specificity was observed at low temperatures compared to hybridization at 46°C. The effect of the chaperones can be explained by disruption of the strong secondary and tertiary structure of the target RNA by the selective hybridization of helper molecules. The amplification of the hybridization signal strength by chaperones is not necessarily local; we observed increased signal intensities in both local and distant regions of the target molecule. Conclusions The sensitivity of the detection of tmRNA at low temperature can be increased by chaperone oligonucleotides. Due to the complexity of RNA secondary and tertiary structures the effect of any individual chaperone is currently not predictable.

  6. Helicobacter pylori and T Helper Cells: Mechanisms of Immune Escape and Tolerance

    Directory of Open Access Journals (Sweden)

    Tiziana Larussa


    Full Text Available Helicobacter pylori colonizes the gastric mucosa of at least half of the human population, causing a worldwide infection that appears in early childhood and if not treated, it can persist for life. The presence of symptoms and their severity depend on bacterial components, host susceptibility, and environmental factors, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori-driven interactions with the host immune system underlie the persistence of the infection in humans, since the bacterium is able to interfere with the activity of innate and adaptive immune cells, reducing the inflammatory response in its favour. Gastritis due to H. pylori results from a complex interaction between several T cell subsets. In particular, H. pylori is known to induce a T helper (Th1/Th17 cell response-driven gastritis, whose impaired modulation caused by the bacterium is thought to sustain the ongoing inflammatory condition and the unsuccessful clearing of the infection. In this review we discuss the current findings underlying the mechanisms implemented by H. pylori to alter the T helper lymphocyte proliferation, thus facilitating the development of chronic infections and allowing the survival of the bacterium in the human host.

  7. NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors

    Directory of Open Access Journals (Sweden)

    Wei Xu


    Full Text Available Innate lymphoid cells (ILCs are a family of effectors that originate from a common innate lymphoid cell progenitor. However, the transcriptional program that sets the identity of the ILC lineage remains elusive. Here, we show that NFIL3 is a critical regulator of the common helper-like innate lymphoid cell progenitor (CHILP. Cell-intrinsic Nfil3 ablation led to variably impaired development of fetal and adult ILC subsets. Conditional gene targeting demonstrated that NFIL3 exerted its function prior to ILC subset commitment. Accordingly, NFIL3 ablation resulted in loss of ID2+ CHILP and PLZF+ ILC progenitors. Nfil3 expression in lymphoid progenitors was under the control of the mesenchyme-derived hematopoietin IL-7, and NFIL3 exerted its function via direct Id2 regulation in the CHILP. Moreover, ectopic Id2 expression in Nfil3-null precursors rescued defective ILC lineage development in vivo. Our data establish NFIL3 as a key regulator of common helper-like ILC progenitors as they emerge during early lymphopoiesis.

  8. Ties that bind: state policy and migrant female domestic helpers in Singapore. (United States)

    Huang, S; Yeoh, B S


    The introduction to this paper reviews the global economic restructuring that has led to theories of a new international division of labor (NIDL) marked by a global feminization of labor that exploits traditional feminine qualities. The argument is made that the NIDL theory fails to cover international labor migration such as that undertaken by female domestic servants in East and Southeast Asia. After summarizing recent research on international waged domestic labor, it is noted that policies of labor-sending countries have, until recently, reflected concerns with enhancing the flow of remittances home to relieve international debt rather than with the well-being of the workers. The paper goes on to focus on the effect of Singapore's state policies on incoming labor migration. After examining the conditions that created the demand for foreign maids, the paper investigates how state policy facilitated the exploitation of these women and perpetuated the social ideology of housework both as women's work and as non-work. It is shown that the official view that paid or unpaid productive labor belongs to the private domain beyond the purview of the state has detrimental repercussions for foreign domestic helpers. These arguments are bolstered with data from secondary sources and from field work conducted in 1995 involving a survey of 162 matched pairs of foreign domestic helpers and employers and in-depth interviews with 15 workers and 15 employers (13 matched pairs).

  9. Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma. (United States)

    Kumai, Takumi; Ohkuri, Takayuki; Nagato, Toshihiro; Matsuda, Yoshinari; Oikawa, Kensuke; Aoki, Naoko; Kimura, Shoji; Celis, Esteban; Harabuchi, Yasuaki; Kobayashi, Hiroya


    HER-3 expression has been reported to act as an important oncoprotein in head and neck squamous cell carcinoma. This protein is known to control tumor proliferation and acquisition of resistance by tumor cells towards EGFR inhibitors, therefore, development of a HER-3-targeted therapy is desirable. In this study, we found that HER-3 expression on tumor cells was increased after EGFR inhibition. To establish a novel therapeutic approach for HER-3-positive head and neck carcinoma, we identified a HER-3 helper epitope that could elicit effective helper T cell responses to the naturally processed HER-3-derived epitope presented in a HER-3 expressing tumors. This epitope induced potent cytolytic activity of CD4 T cells against such tumor cells. Moreover, pan HER-family tyrosine kinase inhibitor augmented the responses of HER-3-reactive CD4 T cells via upregulation of HLA-DR protein on the surface of tumor cells. Our results supports the validity of CD4 T cell-dependent HER-3-targeted therapy combined with a broad inhibitor of HER-family.

  10. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

    Full Text Available We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis.Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines.Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood.Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  11. Efficient Gene Delivery to Pig Airway Epithelia and Submucosal Glands Using Helper-Dependent Adenoviral Vectors

    Directory of Open Access Journals (Sweden)

    Huibi Cao


    Full Text Available Airway gene delivery is a promising strategy to treat patients with life-threatening lung diseases such as cystic fibrosis (CF. However, this strategy has to be evaluated in large animal preclinical studies in order to translate it to human applications. Because of anatomic and physiological similarities between the human and pig lungs, we utilized pig as a large animal model to examine the safety and efficiency of airway gene delivery with helper-dependent adenoviral vectors. Helper-dependent vectors carrying human CFTR or reporter gene LacZ were aerosolized intratracheally into pigs under bronchoscopic guidance. We found that the LacZ reporter and hCFTR transgene products were efficiently expressed in lung airway epithelial cells. The transgene vectors with this delivery can also reach to submucosal glands. Moreover, the hCFTR transgene protein localized to the apical membrane of both ciliated and nonciliated epithelial cells, mirroring the location of wild-type CF transmembrane conductance regulator (CFTR. Aerosol delivery procedure was well tolerated by pigs without showing systemic toxicity based on the limited number of pigs tested. These results provide important insights into developing clinical strategies for human CF lung gene therapy.

  12. Efficient gene delivery to pig airway epithelia and submucosal glands using helper-dependent adenoviral vectors. (United States)

    Cao, Huibi; Machuca, Tiago N; Yeung, Jonathan C; Wu, Jing; Du, Kai; Duan, Cathleen; Hashimoto, Kohei; Linacre, Virginia; Coates, Allan L; Leung, Kitty; Wang, Jian; Yeger, Herman; Cutz, Ernest; Liu, Mingyao; Keshavjee, Shaf; Hu, Jim


    Airway gene delivery is a promising strategy to treat patients with life-threatening lung diseases such as cystic fibrosis (CF). However, this strategy has to be evaluated in large animal preclinical studies in order to translate it to human applications. Because of anatomic and physiological similarities between the human and pig lungs, we utilized pig as a large animal model to examine the safety and efficiency of airway gene delivery with helper-dependent adenoviral vectors. Helper-dependent vectors carrying human CFTR or reporter gene LacZ were aerosolized intratracheally into pigs under bronchoscopic guidance. We found that the LacZ reporter and hCFTR transgene products were efficiently expressed in lung airway epithelial cells. The transgene vectors with this delivery can also reach to submucosal glands. Moreover, the hCFTR transgene protein localized to the apical membrane of both ciliated and nonciliated epithelial cells, mirroring the location of wild-type CF transmembrane conductance regulator (CFTR). Aerosol delivery procedure was well tolerated by pigs without showing systemic toxicity based on the limited number of pigs tested. These results provide important insights into developing clinical strategies for human CF lung gene therapy.Molecular Therapy-Nucleic Acids (2013) 2, e127; doi:10.1038/mtna.2013.55; published online 8 October 2013.

  13. Definition of herpes simplex virus helper functions for the replication of adeno-associated virus type 5. (United States)

    Stutika, Catrin; Hüser, Daniela; Weger, Stefan; Rutz, Natalja; Heßler, Melanie; Heilbronn, Regine


    Adeno-associated virus (AAV) type 5 represents the genetically most distant AAV serotype and the only one isolated directly from human tissue. Seroepidemiological evidence suggests herpes simplex virus (HSV) as a helper virus for human AAV5 infections, underlining the in vivo relevance of the AAV-herpesvirus relationship. In this study we analysed, for the first time, HSV helper functions for productive AAV5 replication, and compared these to AAV2. Using a combination of HSV strains and plasmids for individual genes, the previously defined HSV helper functions for AAV2 replication were shown to induce AAV5 gene expression, DNA replication and production of infectious progeny. The helper functions comprise the replication genes for ICP8 (UL29), helicase-primase (UL5/8/52), and DNA polymerase (UL30/42). HSV immediate-early genes for ICP0 and ICP4 further enhanced AAV5 replication, mainly by induction of rep gene expression. In the presence of HSV helper functions, AAV5 Rep co-localized with ICP8 in nuclear replication compartments, and HSV alkaline exonuclease (UL12) enhanced AAV5 replication, similarly to AAV2. UL12, in combination with ICP8, was shown to induce DNA strand exchange on partially double-stranded templates to resolve and repair concatemeric HSV replication intermediates. Similarly, concatemeric AAV replication intermediates appeared to be processed to yield AAV unit-length molecules, ready for AAV packaging. Taken together, our findings show that productive AAV5 replication is promoted by the same combination of HSV helper functions as AAV2. © 2015 The Authors.

  14. Important role of phosphoramido linkage in imidazole-based dioleyl helper lipids for liposome stability and primary cell transfection. (United States)

    Mével, Mathieu; Haudebourg, Thomas; Colombani, Thibault; Peuziat, Pauline; Dallet, Laurence; Chatin, Benoît; Lambert, Olivier; Berchel, Mathieu; Montier, Tristan; Jaffrès, Paul-Alain; Lehn, Pierre; Pitard, Bruno


    To optimize synthetic gene delivery systems, there is a need to develop more efficient lipid formulations. Most cationic lipid formulations contain 'helper' neutral lipids because of their ability to increase DNA delivery, in particular by improving endosomal escape of DNA molecules via the pH-buffering effect of protonatable groups and/or fusion with the lipid bilayer of endosomes. We evaluated the influence of the linker structure between the two oleyl chains in the helper lipid on transfection efficiency in cell lines, as well as in primary cells (hepatocytes/cardiomyocytes). We reported the synthesis of two new pH-buffering imidazole helper lipids characterized by a polar headgroup containing one (compound 6) or two (compound 5) imidazole groups and two oleyl chains linked by an amide group. We studied their association with the aminoglycoside lipidic derivative dioleylsuccinylparomomycin (DOSP), which contains two oleyl chains linked to the aminoglycoside polar headgroup via an amide function. We compared the morphology and transfection properties of such binary liposomes of DOSP/5 and DOSP/6 with those of liposomes combining DOSP with another imidazole-based dioleyl helper lipid (MM27) in which a phosphoramido group acts as a linker between the two oleyl chains and imidazole function. The phosphoramido linker in the helper lipid induces a major difference in terms of morphology and resistance to decomplexation at physical pH for DOSP/helper lipid complexes. This hybrid dioleyl linker composition of DOSP/MM27 led to higher transfection efficiency in cell lines and in primary cells compared to complexes with homogeneous dioleyl linker. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Male contraception


    Chao, Jing; Page, Stephanie T.; Anderson, Richard A.


    Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on suppression of gonadotropins and thus of testicular function and spermatogenesis, and has been investigated for several decades. This approach can achieve sufficient suppression of spermatogenesis for effective contraception in most men, but not all; the basis for these men responding insufficiently is unclear. Alternatively, the nonho...



    Oliveira, Lindomar Guimarães; Guimarães, Mara Lucia Rassi


    As a result of population ageing worldwide, osteoporotic fractures are becoming a serious problem in the western world. Osteoporotic fractures are associated with a significant burden in terms of morbidity, mortality, and economic costs. Although less frequent than in women, male osteoporosis is also a relatively common problem. Since bone loss and fragility fractures in men have been recognized as a serious medical condition, over the last two decades several studies have investigated a numb...

  17. Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production

    NARCIS (Netherlands)

    Gringhuis, Sonja I.; Kaptein, Tanja M.; Wevers, Brigitte A.; van der Vlist, Michiel; Klaver, Elsenoor J.; van Die, Irma; Vriend, Lianne E. M.; de Jong, Marein A. W. P.; Geijtenbeek, Teunis B. H.


    Dendritic cells (DCs) orchestrate antibody-mediated responses to combat extracellular pathogens including parasites by initiating T helper cell differentiation. Here we demonstrate that carbohydrate-specific signalling by DC-SIGN drives follicular T helper cell (TFH) differentiation via IL-27

  18. PubstractHelper: A Web-based Text-Mining Tool for Marking Sentences in Abstracts from PubMed Using Multiple User-Defined Keywords. (United States)

    Chen, Chou-Cheng; Ho, Chung-Liang


    While a huge amount of information about biological literature can be obtained by searching the PubMed database, reading through all the titles and abstracts resulting from such a search for useful information is inefficient. Text mining makes it possible to increase this efficiency. Some websites use text mining to gather information from the PubMed database; however, they are database-oriented, using pre-defined search keywords while lacking a query interface for user-defined search inputs. We present the PubMed Abstract Reading Helper (PubstractHelper) website which combines text mining and reading assistance for an efficient PubMed search. PubstractHelper can accept a maximum of ten groups of keywords, within each group containing up to ten keywords. The principle behind the text-mining function of PubstractHelper is that keywords contained in the same sentence are likely to be related. PubstractHelper highlights sentences with co-occurring keywords in different colors. The user can download the PMID and the abstracts with color markings to be reviewed later. The PubstractHelper website can help users to identify relevant publications based on the presence of related keywords, which should be a handy tool for their research. and

  19. Dog Helper's Guide: Dog Project Group Activities Grades 3-12. 4-H Skills for Life Animal Series. National 4-H Curriculum. BU-08169 (United States)

    National 4-H Council, 2005


    This final guide in the series is designed to assist in one's role of helper for youth interested in the dog project. These learn-by-doing activities can be adapted for families, classrooms, dog project meetings, after school programs, camps or other settings. In this Helper's Guide, one will find helpful information about characteristics of…

  20. Dirty Hands Make Dirty Leaders?! The Effects of Touching Dirty Objects on Rewarding Unethical Subordinates as a Function of a Leader’s Self-Interest

    NARCIS (Netherlands)

    Cramwinckel, F.M.; De Cremer, D.; van Dijke, M.


    We studied the role of social dynamics in moral decision-making and behavior by investigating how physical sensations of dirtiness versus cleanliness influence moral behavior in leader–subordinate relationships, and whether a leader’s self-interest functions as a boundary condition to this effect. A

  1. Conceptualizing Military Acceptance of Civilian Control: Ideological Cohesion, Military Responsibilities, and the Military’s Propensity for Subordination in Brazil and Venezuela (United States)


    control. The last of these variables, the military’s propensity for subordination, provides the focal point for the remainder of the paper. After...agreed upon in the Pact of Punto Fijo. They included conciliatory provisions designed to improve state relations between the Catholic Church, business

  2. Dirty Hands Make Dirty Leaders?! The Effects of Touching Dirty Objects on Rewarding Unethical Subordinates as a Function of a Leader's Self-Interest

    NARCIS (Netherlands)

    F.M. Cramwinckel (Florien); D. de Cremer (David); M.H. van Dijke (Marius)


    textabstractWe studied the role of social dynamics in moral decision-making and behavior by investigating how physical sensations of dirtiness versus cleanliness influence moral behavior in leader-subordinate relationships, and whether a leader's self-interest functions as a boundary condition to

  3. Relative contributions of human types 1 and 2 T-helper cell-derived eosinophilotrophic cytokines to development of eosinophilia

    NARCIS (Netherlands)

    Wierenga, E. A.; Backx, B.; Snoek, M.; Koenderman, L.; Kapsenberg, M. L.


    The relative contributions of type 1 and 2 T-helper (Th1 and Th2) cell-derived interleukin (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 were studied in the regulation of sequential events in the development of eosinophilia. Using eosinophils from normal donors and

  4. Examining Live-In Foreign Domestic Helpers as a Coping Resource for Family Caregivers of People With Dementia in Singapore. (United States)

    Basnyat, Iccha; Chang, Leanne


    In Singapore, the responsibility of caring for persons with dementia falls on family members who cope with a long-term caregiver burden, depending on available support resources. Hiring foreign domestic workers to alleviate caregiver burden becomes a prevalent coping strategy that caregivers adopt. This strategy allows caregivers to provide home care as part of fulfilling family obligations while managing the caregiver burden. This study aimed to investigate primary caregivers' relationship with hired support and its impact on coping with caregiver burden. Twenty in-depth interviews were conducted with primary caregivers who hired live-in domestic helpers to take care of their family members with dementia. The findings revealed that caregivers perceived the normative obligations to provide home care to family members with dementia. They sought support from domestic helpers to cope with physical and mental burnout, disruption of normal routines, and avoidance of financial strain. A mutual-support relationship was built between caregivers and domestic helpers through trust and interdependence. The presence of domestic helpers as a coping resource reveals the positive outcomes of problem-, emotional-, and diversion-focused coping. This study illustrates that coping strategies are employed in different ways depending on the needs of caregivers, access to infrastructure, cultural expectations, and available resources.

  5. More Water, Madam? An ESL Curriculum for Service Helpers in Full-Service and Fast-Food Restaurants. (United States)

    Cwach, Marlin Day; Gravely, Mary Liles

    This document, which was developed as a cooperative effort between the business and education communities in Denver, presents an English-as-a-second-language curriculum for service helpers in full-service and fast food restaurants. The curriculum consists of five lessons targeted toward high intermediate to advanced nonnative speakers who work in…

  6. Effects of a Peer Helping Training Program on Helping Skills and Self-Growth of Peer Helpers (United States)

    Aladag, Mine; Tezer, Esin


    The purpose of this study was to develop a peer helping training program for university students in Turkey and to examine its effectiveness in improving the helping skills and self-growth of peer helpers. A pre-test, post-test, follow-up-test experimental design, involving a treatment and control group, was carried out with a total sample of 31…

  7. Increased production of antigen-specific lymphocytes-b during invitro immunization using carrier-specific t-helper hybridomas

    NARCIS (Netherlands)

    Schilizzi, B. M.; Kroesen, B.-J.; The, T. Hauw; de Leij, L.


    An in vitro method to increase the production of hapten-specific antibody-forming B cells (AFC) using a carrier-specific T helper hybridoma and murine splenocytes is described. Naive splenocytes (6 X 10(6)/ml) are cultured in vitro in the presence of a hapten-carrier conjugate (DNP.OVA) and

  8. Bad Influence?--An Investigation into the Purported Negative Influence of Foreign Domestic Helpers on Children's Second Language English Acquisition (United States)

    Leung, Alex Ho-Cheong


    This paper explores the purported negative influence of foreign domestic helpers (FDHs) on child second language acquisition (SLA) by studying Hong Kong Cantonese children's listening ability in second language (L2) English. 31 kindergarten third graders aged 4;6 to 6, and 29 first year secondary students aged 11-14 who have had a Filipino…

  9. T-helper 17 cell cytokines and interferon type I: Partners in crime in systemic lupus erythematosus?

    NARCIS (Netherlands)

    Z. Brkic (Zana); O.B.J. Corneth (Odilia); C.G. van Helden-Meeuwsen; R.J.E.M. Dolhain (Radboud); M. de Maria; S.M.J. Paulissen (Sandra); N. Davelaar (Nadine); J.P. van Hamburg (Jan Piet); P.L.A. van Daele (Paul); V.A.S.H. Dalm (Virgil); P.M. van Hagen (Martin); J.M.W. Hazes (Mieke); M.A. Versnel (Marjan); E.W. Lubberts (Erik)


    textabstractIntroduction: A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and

  10. Translational mini-review series on Th17 cells: development of mouse and human T helper 17 cells

    NARCIS (Netherlands)

    de Jong, E.; Suddason, T.; Lord, G. M.


    There has been a considerable amount of interest in the immunological community about new phenotypic subsets of CD4(+) T cells, particularly cells that produce the cytokine interleukin (IL)-17 [named T helper type 17 (Th17) cells]. While the initial discovery of Th17 cells and the pathways that

  11. The Role of Foreign Domestic Helpers in Hong Kong Chinese Children's English and Chinese Skills: A Longitudinal Study (United States)

    Dulay, Katrina May; Tong, Xiuhong; McBride, Catherine


    We investigated the influence of nonparental caregivers, such as foreign domestic helpers (FDH), on the home language spoken to the child and its implications for vocabulary and word reading development in Cantonese- and English-speaking bilingual children. Using data collected from ages 5 to 9, we analyzed Chinese vocabulary, Chinese character…

  12. Male contraception. (United States)

    Chao, Jing; Page, Stephanie T; Anderson, Richard A


    Clear evidence shows that many men and women would welcome new male methods of contraception, but none have become available. The hormonal approach is based on suppression of gonadotropins and thus of testicular function and spermatogenesis, and has been investigated for several decades. This approach can achieve sufficient suppression of spermatogenesis for effective contraception in most men, but not all; the basis for these men responding insufficiently is unclear. Alternatively, the non-hormonal approach is based on identifying specific processes in sperm development, maturation and function. A range of targets has been identified in animal models, and targeted effectively. This approach, however, remains in the pre-clinical domain at present. There are, therefore, grounds for considering that safe, effective and reversible methods of contraception for men can be developed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection. (United States)

    Chen, Xiaojun; Yang, Xiaowei; Li, Yong; Zhu, Jifeng; Zhou, Sha; Xu, Zhipeng; He, Lei; Xue, Xue; Zhang, Weiwei; Dong, Xiaoxiao; Wu, Henry; Li, Carrie J; Hsu, Hsiang-Ting; Kong, Wenjun; Liu, Feng; Tripathi, Prem B; Yu, Michelle S; Chang, Jason; Zhou, Liang; Su, Chuan


    Following Schistosoma japonicum (S. japonicum) infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.

  14. Challenges and Prospects for Helper-Dependent Adenoviral Vector-Mediated Gene Therapy

    Directory of Open Access Journals (Sweden)

    Pasquale Piccolo


    Full Text Available Helper-dependent adenoviral (HDAd vectors that are devoid of all viral coding sequences are promising non-integrating vectors for gene therapy because they efficiently transduce a variety of cell types in vivo, have a large cloning capacity, and drive long-term transgene expression without chronic toxicity. The main obstacle preventing clinical applications of HDAd vectors is the host innate inflammatory response against the vector capsid proteins that occurs shortly after intravascular vector administration and result in acute toxicity, the severity of which is dose dependent. Intense efforts have been focused on elucidating adenoviral vector–host interactions and the factors involved in the acute toxicity. This review focuses on the recent acquisition of data on such interactions and on strategies investigated to improve the therapeutic index of HDAd vectors.

  15. Gene Therapy with Helper-Dependent Adenoviral Vectors: Current Advances and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Philip Ng


    Full Text Available Recombinant Adenoviral vectors represent one of the best gene transfer platforms due to their ability to efficiently transduce a wide range of quiescent and proliferating cell types from various tissues and species. The activation of an adaptive immune response against the transduced cells is one of the major drawbacks of first generation Adenovirus vectors and has been overcome by the latest generation of recombinant Adenovirus, the Helper-Dependent Adenoviral (HDAd vectors. HDAds have innovative features including the complete absence of viral coding sequences and the ability to mediate high level transgene expression with negligible chronic toxicity. This review summarizes the many aspects of HDAd biology and structure with a major focus on in vivo gene therapy application and with an emphasis on the unsolved issues that these vectors still presents toward clinical application.

  16. IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease. (United States)

    Zepp, Jarod; Wu, Ling; Li, Xiaoxia


    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is widely used to dissect molecular mechanisms of MS and to develop new therapeutic strategies. The T helper 17 (Th17) subset of CD4 T cells plays a crucial role in the development of EAE. IL-17, a cytokine produced by Th17 cells, participates in EAE pathogenesis through induction of inflammatory gene expression in target cells. Recent work has shown that Act1, a U-box E3 ubiquitin ligase, is recruited to IL-17 receptor (IL-17R) upon IL-17 stimulation and is required for IL-17-mediated signaling. Here, we review the molecular and cellular mechanisms by which IL-17 and Act1-mediated signaling contribute to EAE. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. IL-7 and CD4 T Follicular Helper Cells in HIV-1 Infection

    Directory of Open Access Journals (Sweden)

    Francesca Chiodi


    Full Text Available IL-7 was previously shown to upregulate the expression of molecules important for interaction of CD4+ T cells with B cells. It is poorly studied whether IL-7 has a role in the biology of T follicular helper (Tfh cells and whether IL-7 dysregulates the expression of B-cell costimulatory molecules on Tfh cells. We review the literature and provide arguments in favor of IL-7 being involved in the biology of human Tfh cells. The CD127 IL-7 receptor is expressed on circulating Tfh and non-Tfh cells, and we show that IL-7, but not IL-6 or IL-21, upregulates the expression of CD70 and PD-1 on these cells. We conclude that IL-7, a cytokine whose level is elevated during HIV-1 infection, may have a role in increased expression of B cell costimulatory molecules on Tfh cells and lead to abnormal B cell differentiation.

  18. T helper cell 2 immune skewing in pregnancy/early life

    DEFF Research Database (Denmark)

    McFadden, J P; Thyssen, J P; Basketter, D A


    During the last 50 years there has been a significant increase in Western societies of atopic disease and associated allergy. The balance between functional subpopulations of T helper cells (Th) determines the quality of the immune response provoked by antigen. One such subpopulation - Th2 cells...... - is associated with the production of IgE antibody and atopic allergy, whereas, Th1 cells antagonize IgE responses and the development of allergic disease. In seeking to provide a mechanistic basis for this increased prevalence of allergic disease, one proposal has been the 'hygiene hypothesis', which argues...... that in Westernized societies reduced exposure during early childhood to pathogenic microorganisms favours the development of atopic allergy. Pregnancy is normally associated with Th2 skewing, which persists for some months in the neonate before Th1/Th2 realignment occurs. In this review, we consider...

  19. Helper-Dependent Adenoviral Vectors and Their Use for Neuroscience Applications. (United States)

    Montesinos, Mónica S; Satterfield, Rachel; Young, Samuel M


    Neuroscience research has been revolutionized by the use of recombinant viral vector technology from the basic, preclinical and clinical levels. Currently, multiple recombinant viral vector types are employed with each having its strengths and weaknesses depending on the proposed application. Helper-dependent adenoviral vectors (HdAd) are emerging as ideal viral vectors that solve a major need in the neuroscience field: (1) expression of transgenes that are too large to be packaged by other viral vectors and (2) rapid onset of transgene expression in the absence of cytotoxicity. Here, we describe the methods for large-scale production of HdAd viral vectors for in vivo use with neurospecific transgene expression.

  20. High Interleukin-10 Expression in Type 2 T Helper Cells in Septic Patients. (United States)

    Wu, Huang-Pin; Chu, Chien-Ming; Kao, Kuo-Chin; Huang, Shu-Huan; Chuang, Duen-Yau


    Interleukin (IL)-10 response is associated with mortality in patients with sepsis. IL-10 is primarily produced by monocytes and type 2 T helper (Th2) cells. The aim of this study was to investigate differences in IL-10 production between monocytes and Th2 cells in patients with sepsis. Forty patients with sepsis and 35 healthy controls were enrolled. Cytokine expressions in peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. The IL-10 expression in the Th2 cells of the septic patients was higher than in the healthy controls, but the expression of IL-10 in the monocytes of the septic patients was lower than in the healthy controls. After regression analysis, IL-10 expression in Th2 cells was positively associated with sepsis, but IL-10 expression in monocytes was not associated with sepsis or shock. In conclusion, the production of IL-10 in Th2 cells was higher in the patients with sepsis.

  1. Being Both Helpers and Victims: Health Professionals' Experiences of Working During a Natural Disaster. (United States)

    Hugelius, Karin; Adolfsson, Annsofie; Örtenwall, Per; Gifford, Mervyn


    In November 2013, the Haiyan typhoon hit parts of the Philippines. The typhoon caused severe damage to the medical facilities and many injuries and deaths. Health professionals have a crucial role in the immediate disaster response system, but knowledge of their experiences of working during and in the immediate aftermath of a natural disaster is limited. Aim The aim of this study was to explore health professionals' experiences of working during and in the immediate aftermath of a natural disaster. Eight health professionals were interviewed five months after the disaster. The interviews were analyzed using phenomenological hermeneutic methods. The main theme, being professional and survivor, described both positive and negative emotions and experiences from being both a helper, as part of the responding organization, and a victim, as part of the surviving but severely affected community. Sub-themes described feelings of strength and confidence, feelings of adjustment and acceptance, feelings of satisfaction, feelings of powerless and fear, feelings of guilt and shame, and feelings of loneliness. Being a health professional during a natural disaster was a multi-faceted, powerful, and ambiguous experience of being part of the response system at the same time as being a survivor of the disaster. Personal values and altruistic motives as well as social aspects and stress-coping strategies to reach a balance between acceptance and control were important elements of the experience. Based on these findings, implications for disaster training and response strategies are suggested. Hugelius K , Adolfsson A , Örtenwall P , Gifford M . Being both helpers and victims: health professionals' experiences of working during a natural disaster. Prehosp Disaster Med. 2017;32(2):117-123.

  2. Impact of adenovirus life cycle progression on the generation of canine helper-dependent vectors. (United States)

    Fernandes, P; Simão, D; Guerreiro, M R; Kremer, E J; Coroadinha, A S; Alves, P M


    Helper-dependent adenovirus vectors (HDVs) are safe and efficient tools for gene transfer with high cloning capacity. However, the multiple amplification steps needed to produce HDVs hamper a robust production process and in turn the availability of high-quality vectors. To understand the factors behind the low productivity, we analyzed the progression of HDV life cycle. Canine adenovirus (Ad) type 2 vectors, holding attractive features to overcome immunogenic concerns and treat neurobiological disorders, were the focus of this work. When compared with E1-deleted (ΔE1) vectors, we found a faster helper genome replication during HDV production. This was consistent with an upregulation of the Ad polymerase and pre-terminal protein and led to higher and earlier expression of structural proteins. Although genome packaging occurred similarly to ΔE1 vectors, more immature capsids were obtained during HDV production, which led to a ~4-fold increase in physical-to-infectious particles ratio. The higher viral protein content in HDV-producing cells was also consistent with an increased activation of autophagy and cell death, in which earlier cell death compromised volumetric productivity. The increased empty capsids and earlier cell death found in HDV production may partially contribute to the lower vector infectivity. However, an HDV-specific factor responsible for a defective maturation process should be also involved to fully explain the low infectious titers. This study showed how a deregulated Ad cycle progression affected cell line homeostasis and HDV propagation, highlighting the impact of vector genome design on virus-cell interaction.

  3. STAT6 regulates natural helper cell proliferation during lung inflammation initiated by Alternaria (United States)

    Khorram, Naseem; Chang, Jinny E.; Kim, Hee-Kyoo; Rosenthal, Peter; Croft, Michael; Broide, David H.


    Asthma exacerbations can be caused by a number of factors, including the fungal allergen Alternaria, which is specifically associated with severe and near-fatal attacks. The mechanisms that trigger lung responses are unclear and might vary between allergens. A comparison between Alternaria, Aspergillus, Candida, and house dust mite, all allergens in humans, showed that only Alternaria promoted immediate innate airway eosinophilia within 12 h of inhalation in nonsensitized mice. Alternaria, but not the other allergens, induced a rapid increase in airway levels of IL-33, accompanied by IL-33 receptor (IL-33R)-positive natural helper cell (NHC) production of IL-5 and IL-13. NHCs in the lung and bone marrow constitutively expressed transcription factors [GATA-3 and E26 transformation-specific sequence-1 (ETS-1)] that could allow for rapid induction of T helper type 2 (Th2) cytokines. Lung NHC numbers and proliferation (%Ki-67), but not IL-5 or GATA-3 expression, were significantly reduced in STAT6-deficient mice 3 days after one challenge with Alternaria. Alternaria induced NHC expression of the EGF receptor ligand amphiregulin (partially dependent on STAT6), as well as EGF receptor signaling in the airway epithelium. Finally, human peripheral blood NHCs (CRTH2+CD127+ lineage-negative lymphocytes) from allergic individuals highly expressed GATA-3 and ETS-1, similar to lung NHCs in mice. In summary, Alternaria-induced lung NHC proliferation and expression of amphiregulin are regulated by STAT6. In addition, NHCs in mouse and humans are primed to express Th2 cytokines through constitutive expression of GATA-3 and ETS-1. Thus several transcription factor pathways (STAT6, GATA-3, and ETS-1) may contribute to NHC proliferation and Th2-type responses in Alternaria-induced asthma. PMID:22865552

  4. Defining MHC class II T helper epitopes for WT1 tumor antigen. (United States)

    Kobayashi, Hiroya; Nagato, Toshihiro; Aoki, Naoko; Sato, Keisuke; Kimura, Shoji; Tateno, Masatoshi; Celis, Esteban


    The product of Wilms' tumor gene 1 (WT1) is overexpressed in diverse human tumors, including leukemia, lung and breast cancer, and is often recognized by antibodies in the sera of patients with leukemia. Since WT1 encodes MHC class I-restricted peptides recognized by cytotoxic T lymphocytes (CTL), WT1 has been considered as a promising tumor-associated antigen (TAA) for developing anticancer immunotherapy. In order to carry out an effective peptide-based cancer immunotherapy, MHC class II-restricted epitope peptides that elicit anti-tumor CD4(+) helper T lymphocytes (HTL) will be needed. In this study, we analyzed HTL responses against WT1 antigen using HTL lines elicited by in vitro immunization of human lymphocytes with synthetic peptides predicted to serve as HTL epitopes derived from the sequence of WT1. Two peptides, WT1(124-138) and WT1(247-261), were shown to induce peptide-specific HTL, which were restricted by frequently expressed HLA class II alleles. Here, we also demonstrate that both peptides-reactive HTL lines were capable of recognizing naturally processed antigens presented by dendritic cells pulsed with tumor lysates or directly by WT1+ tumor cells that express MHC class II molecules. Interestingly, the two WT1 HTL epitopes described here are closely situated to known MHC class I-restricted CTL epitopes, raising the possibility of stimulating CTL and HTL responses using a relatively small synthetic peptide vaccine. Because HTL responses to TAA are known to be important for promoting long-lasting anti-tumor CTL responses, the newly described WT1 T-helper epitopes could provide a useful tool for designing powerful vaccines against WT1-expressing tumors.

  5. Blood flow and echotextural differences between the future dominant and subordinate follicles before the beginning of diameter deviation in heifers. (United States)

    Ginther, O J; Domingues, R R; Siddiqui, M A R; Dangudubiyyam, S V


    Diameter deviation is the beginning of a decrease in growth rate of the largest subordinate follicle (SF) and a continuing growth rate of the dominant follicle (DF). In wave 1 in cattle, deviation begins 2 or 3 days after ovulation when the future DF is about 8.5 mm. Gray scale and power-flow Doppler ultrasound examinations were done in experiment 1 (daily examinations, n = 13) and experiment 2 (examinations every 8 h, n = 15). Blood flow and an anechoic layer in the follicle wall were normalized to the beginning of diameter deviation (day 0 or hour 0). Only waves with conventional diameter deviation (68% of waves) were used as identified by: (1) future SF greater than 7.0 mm when DF was 8.5 mm and (2) future DF and SF did not switch in diameter rank. In experiment 1, deviations in the extent of blood-flow signals and in the extent of anechoic layer began on the same day as deviation in diameter. In experiment 2, deviations in diameter, surface area (πd2), and anechoic layer began in synchrony, and deviation in blood-flow signals began 16 h earlier. Blood-flow deviation before diameter deviation was shown by (1) a first difference (P anechoic layer was not supported; diameter and anechoic layer deviated in synchrony. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Nurses and subordination: a historical study of mental nurses’ perceptions on administering aversion therapy for ‘sexual deviations’ (United States)

    Dickinson, Tommy; Cook, Matt; Playle, John; Hallett, Christine


    Nurses and subordination: a historical study of mental nurses’ perceptions on administering aversion therapy for ‘sexual deviations’ This study aimed to examine the meanings that nurses attached to the ‘treatments’ administered to cure ‘sexual deviation’ (SD) in the UK, 1935–1974. In the UK, homosexuality was considered a classifiable mental illness that could be ‘cured’ until 1992. Nurses were involved in administering painful and distressing treatments. The study is based on oral history interviews with fifteen nurses who had administered treatments to cure individuals of their SD. The interviews were transcribed for historical interpretation. Some nurses believed that their role was to passively follow any orders they had been given. Other nurses limited their culpability concerning administering these treatments by adopting dehumanising and objectifying language and by focussing on administrative tasks, rather than the human beings in need of their care. Meanwhile, some nurses genuinely believed that they were acting beneficently by administering these distinctly unpleasant treatments. It is envisaged that this study might act to reiterate the need for nurses to ensure their interventions have a sound evidence base and that they constantly reflect on the moral and value base of their practice and the influence that science and societal norms can have on changing views of what is considered ‘acceptable practice’. PMID:23876127

  7. Lexical and syntactic features of the male and female students argumentative essays

    Directory of Open Access Journals (Sweden)

    Maico Demi Banate Aperocho


    Full Text Available This study seeks to identify the lexical and syntactic features of the male and female freshman college students using textual analysis method. The argumentative essays written by the 50 purposively selected students were used as subjects for analysis. Students were asked to argue about the statement, “Boys are smarter than girls.” Findings show that the males’ argumentative essays are more complex than those of the girls because males used more words, morphemes, coordinators, and subordinators in their text which, consequently, increased the number of T-units. Also, the study shows that females use lesser words to explain their ideas about the topic.

  8. Above- and below-ground vertebrate herbivory may each favour a different subordinate species in an aquatic plant community. (United States)

    Hidding, Bert; Nolet, Bart A; de Boer, Thijs; de Vries, Peter P; Klaassen, Marcel


    At least two distinct trade-offs are thought to facilitate higher diversity in productive plant communities under herbivory. Higher investment in defence and enhanced colonization potential may both correlate with decreased competitive ability in plants. Herbivory may thus promote coexistence of plant species exhibiting divergent life history strategies. How different seasonally tied herbivore assemblages simultaneously affect plant community composition and diversity is, however, largely unknown. Two contrasting types of herbivory can be distinguished in the aquatic vegetation of the shallow lake Lauwersmeer. In summer, predominantly above-ground tissues are eaten, whereas in winter, waterfowl forage on below-ground plant propagules. In a 4-year exclosure study we experimentally separated above-ground herbivory by waterfowl and large fish in summer from below-ground herbivory by Bewick's swans in winter. We measured the individual and combined effects of both herbivory periods on the composition of the three-species aquatic plant community. Herbivory effect sizes varied considerably from year to year. In 2 years herbivore exclusion in summer reinforced dominance of Potamogeton pectinatus with a concomitant decrease in Potamogeton pusillus, whereas no strong, unequivocal effect was observed in the other 2 years. Winter exclusion, on the other hand, had a negative effect on Zannichellia palustris, but the effect size differed considerably between years. We suggest that the colonization ability of Z. palustris may have enabled this species to be more abundant after reduction of P. pectinatus tuber densities by swans. Evenness decreased due to herbivore exclusion in summer. We conclude that seasonally tied above- and below-ground herbivory may each stimulate different components of a macrophyte community as they each favoured a different subordinate plant species.

  9. How germinal centers evolve broadly neutralizing antibodies: the breadth of the follicular helper T cell response. (United States)

    De Boer, Rob J; Perelson, Alan S


    Many HIV-1 infected patients evolve broadly neutralizing antibodies (bnAbs). This evolutionary process typically takes several years, and is poorly understood as selection taking place in germinal centers occurs on the basis of antibody affinity. B cells with the highest affinity receptors tend to acquire the most antigen from the FDC network, and present the highest density of cognate peptides to follicular helper T cells (Tfh), which provide survival signals to the B cell. BnAbs are therefore only expected to evolve when the B cell lineage evolving breadth is consistently capturing and presenting more peptides to Tfh cells than other lineages of more specific B cells. Here we develop mathematical models of Tfh in germinal centers to explicitly define the mechanisms of selection in this complex evolutionary process.Our results suggest that broadly reactive B cells presenting a high density of pMHC are readily outcompeted by B cells responding to lineages of HIV-1 that transiently dominate the within host viral population. Conversely, if broadly reactive B cells acquire a large variety of several HIV-1 proteins from the FDC network and present a high diversity of several pMHC, they be rescued by a large fraction of the Tfh repertoire in the germinal center. Under such circumstances the evolution of bnAbs is much more consistent. Increasing the magnitude of the Tfh response, or the breadth of the Tfh repertoire, both markedly facilitate the evolution of bnAbs. Because both can be increased by vaccination with several HIV-1 proteins, this calls for experiments testing.Importance Many HIV-infected patients slowly evolve antibodies that can neutralize a large variety of viruses. Such "broadly neutralizing antibodies" (bnAbs) could in the future become therapeutic agents. BnAbs appear very late and patients are typically not protected by them. At the moment we fail to understand why this takes so long, and how the immune system selects for broadly neutralizing capacity

  10. Male Reproductive System (United States)

    ... Kidney Transplant Vision Facts and Myths Male Reproductive System KidsHealth > For Parents > Male Reproductive System Print A ... son's reproductive health. continue About the Male Reproductive System Most species have two sexes: male and female. ...

  11. Agonistic behavior enhances adult neurogenesis in male Acheta domesticus crickets. (United States)

    Ghosal, Kaushik; Gupta, Mohit; Killian, Kathleen A


    We examined the effect of agonistic behavior on cell proliferation and neurogenesis in the central nervous system (CNS) of adult male Acheta domesticus crickets. We combined 5-bromo,2'deoxyuridine (BrdU)-labeling of dividing cells with immunocytochemical detection of the neuronal marker horseradish peroxidase to examine the proliferation of progenitor cells and the survival of newborn neurons. In crickets, the mushroom bodies of the brain contain clusters of proliferative cells that divide and generate new neurons in adulthood. Pairs of male crickets were allowed to fight and establish social rank and were then injected with BrdU. Proliferation of mushroom body neurogenic cluster cells was unaffected by agonistic interactions; 24 h after a fight, the number of BrdU positive cells in fought and un-fought males did not significantly differ. However, agonistic interactions did influence cell survival. Two weeks after an agonistic interaction, fought males had more newborn neurons than males that did not fight. There was also a rank-specific effect because dominant males had significantly more new neurons than subordinates. We also report for the first time that neurogenesis in adult crickets can occur in other regions of the brain and in other CNS ganglia, including the terminal abdominal ganglion (TAG). Agonistic interactions enhanced the proliferation of these distributed precursor cells but did not increase the survival of the newborn neurons generated by these cells.

  12. Effects of sleep loss on the rest-activity circadian rhythm of helpers participating in continuous dogsled races. (United States)

    Calogiuri, Giovanna; Weydahl, Andi


    The Finnmarksløpet dogsled race lasts up to 7 days. Helpers, who keep time, coach, and transport equipment, have to be alert though they have little and fragmented sleep. This study investigated disruptions of the rest-activity rhythm among helpers. 10 helpers were monitored by actigraph a week before, during, and after the race. Sleep logs, sleepiness rate, and self-reported quality of sleep were collected. Nonparametric circadian rhythm analysis showed significant differences between the pre- and postrace interdaily stability and amplitude of rhythm. Compared to prerace, sleepiness at bedtime was increased and number of nocturnal awakenings was reduced postrace, although the actigraphic outputs showed no improvement in sleep quality. Helpers who were engaged in the race for a longer span (5-6 days) had more difficulty recovering from the sleep loss accumulated during the race than those engaged for a shorter time (2-3 days). Poor sleep combined with prolonged and demanding mental focus for 2 days or more has a negative influence upon the rest-activity cycle, though complete restoration of the cycle occurs over 1 week or more. Being in such a condition for ≥ 5 days leads to disruptions of the circadian component of the sleep-wake cycle that hampers the sleep recovery process. Disrupted sleep and demanding mental requirements are common in long-distance sporting events as well as among shift workers. Follow-up intervention should be made in such cases to ensure the return of a healthy rest-activity rhythm and sleep quality.

  13. Effects of the 20-Kilodalton Helper Protein on Cry1Ac Production and Spore Formation in Bacillus thuringiensis


    Shao, Zongze; Liu, Ziduo; Yu, Ziniu


    Bacillus thuringiensis produces large amounts of various pesticidal proteins during the stationary phase. In order to achieve a high yield and form crystals, some pesticidal proteins require the presence of other proteins. Helper protein P20 is required for efficient production of both the Cyt1A and Cry11A crystal proteins in B. thuringiensis subsp. israelensis. Although full-length Cry1 protoxins are usually independent in terms of expression and crystallization in B. thuringiensis, in this ...

  14. Effect of vitamin D on T-helper type 9 polarized human memory cells in chronic persistent asthma. (United States)

    Keating, Patricia; Munim, Amjad; Hartmann, James X


    Vitamin D suppresses inflammation and vitamin D deficiency is linked to the severity of asthma symptoms. T-helper type 9 (TH9) cells are important in the pathogenesis, yet the effects of vitamin D on this subset of inflammatory T-helper cells from patients with chronic asthma is unknown. To determine the effects of vitamin D and dexamethasone on TH9 memory cells from adults with chronic persistent asthma and on a recall response to dust mite allergen. T-helper memory cells were cultured with cytokines that drive TH9 polarization with vitamin D and/or dexamethasone. Peripheral blood mononuclear cells (PBMCs) from patients with radioallergosorbent test results for house dust mite were stimulated with allergen in the presence or absence of vitamin D. Intracellular cytokines, transcription factors, and identification of cell surface phenotypic markers were determined by flow cytometry. Vitamin D decreased interleukin (IL)-9, IL-5, and IL-8 but increased IL-13(+) cells in TH9 cultures. Transcription factors PU.1 and interferon regulatory factor 4 were downregulated by vitamin D but not GATA3 and c-MAF. When PBMCs from patients with positive radioallergosorbent test results were stimulated with dust mite allergen, vitamin D decreased IL-9, IL-5, and IL-13 in T-helper cells (CD4(+)). TH9 cells present in a recall response were classically TH2 (CD294(+)), and polarization by transforming growth factor-β and IL-4 altered that phenotype. Vitamin D decreased inflammatory cytokine profiles in TH9 memory cells and CD4(+) cells stimulated with dust mite allergen. Vitamin D is additive with dexamethasone in decreasing inflammatory cytokine production from T-cell subsets implicated in asthma. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Gene Therapy of T Helper Cells in HIV Infection. Mathematical Model of the Criteria for Clinical Effect

    DEFF Research Database (Denmark)

    Lund, Ole; Lund, Ole søgaard; Gram, Gregers


    The paper presents a mathematical model of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. Our main results are that the therapy should be designed to give the transduced cells a significant but not necessarily total protection against HIV-induced cell...... deaths, and to avoid the production of viral mutants that are insensitive to gene therapy. The transduced cells will not survive if the gene therapy only blocks the spread of virus....

  16. Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes

    Directory of Open Access Journals (Sweden)

    Merry ZC Ruan


    Full Text Available Osteoarthritis (OA is a joint disease characterized by degeneration of the articular cartilage, subchondral bone remodeling, and secondary inflammation. It is among the top three causes of chronic disability, and currently there are no treatment options to prevent disease progression. The localized nature of OA makes it an ideal candidate for gene and cell therapy. However, gene and cell therapy of OA is impeded by inefficient gene transduction of chondrocytes. In this study, we developed a broadly applicable system that retargets cell surface receptors by conjugating antibodies to the capsid of helper-dependent adenoviral vectors (HDVs. Specifically, we applied this system to retarget chondrocytes by conjugating an HDV to an α-10 integrin monoclonal antibody (a10mab. We show that a10mab-conjugated HDV (a10mabHDV-infected chondrocytes efficiently in vitro and in vivo while detargeting other cell types. The therapeutic index of an intra-articular injection of 10mabHDV-expressing proteoglycan 4 (PRG4 into a murine model of post-traumatic OA was 10-fold higher than with standard HDV. Moreover, we show that PRG4 overexpression from articular, superficial zone chondrocytes is effective for chondroprotection in postinjury OA and that α-10 integrin is an effective protein for chondrocyte targeting.

  17. AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment. (United States)

    Lindmark, Evelina; Chen, Yunying; Georgoudaki, Anna-Maria; Dudziak, Diana; Lindh, Emma; Adams, William C; Loré, Karin; Winqvist, Ola; Chambers, Benedict J; Karlsson, Mikael C I


    Autoimmune polyendocrine syndrome Type I (APS I) results in multiple endocrine organ destruction and is caused by mutations in the Autoimmune regulator gene (AIRE). In the thymic stroma, cells expressing the AIRE gene dictate T cell education and central tolerance. Although this function is the most studied, AIRE is also expressed in the periphery in DCs and stromal cells. Still, how AIRE regulated transcription modifies cell behaviour in the periphery is largely unknown. Here we show that AIRE is specifically expressed by 33D1(+) DCs and dictates the fate of antibody secreting cell movement within the spleen. We also found that AIRE expressing 33D1(+) DCs expresses self-antigens as exemplified by the hallmark gene insulin. Also, as evidence for a regulatory function, absence of Aire in 33D1(+) DCs led to reduced levels of the chemokine CXCL12 and increased co-stimulatory properties. This resulted in altered activation and recruitment of T-follicular helper cells and germinal centre B cells. The altered balance leads to a change of the early response to a T cell-dependent antigen in Aire(-/-) mice. These findings add to the understanding of how specific DC subtypes regulate the early responses during T cell-dependent antibody responses within the spleen and further define the role of AIRE in the periphery as regulator of self-antigen expression and lymphocyte migration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Combinatorial treatment with oncolytic adenovirus and helper-dependent adenovirus augments adenoviral cancer gene therapy. (United States)

    Farzad, Lisa; Cerullo, Vincenzo; Yagyu, Shigeki; Bertin, Terry; Hemminki, Akseli; Rooney, Cliona; Lee, Brendan; Suzuki, Masataka


    Oncolytic adenoviruses (Onc.Ads) produce significant antitumor effects but as single agents they rarely eliminate tumors. Investigators have therefore incorporated sequences into these vectors that encode immunomodulatory molecules to enhance antitumor immunity. Successful implementation of this strategy requires multiple tumor immune inhibitory mechanisms to be overcome, and insertion of the corresponding multiple functional genes reduces the titer and replication of Onc.Ads, compromising their direct ant-tumor effects. By contrast, helper-dependent (HD) Ads are devoid of viral coding sequences, allowing inclusion of multiple transgenes. HDAds, however, lack replicative capacity. Since HDAds encode the adenoviral packaging signal, we hypothesized that the coadministration of Onc.Ad with HDAd would allow to be amplified and packaged during replication of Onc.Ad in transduced cancer cells. This combination could provide immunostimulation without losing oncolytic activity. We now show that coinfection of Onc.Ad with HDAd subsequently replicates HDAd vector DNA in trans in human cancer cell lines in vitro and in vivo, amplifying the transgenes the HDAd encode. This combinatorial treatment significantly suppresses the tumor growth compared to treatment with a single agent in an immunocompetent mouse model. Hence, combinatorial treatment of Onc.Ad with HDAd should overcome the inherent limitations of each agent and provide a highly immunogenic oncolytic therapy.

  19. Feasibility of Applying Helper-Dependent Adenoviral Vectors for Cancer Immunotherapy. (United States)

    Farzad, Lisa M; Suzuki, Masataka


    Adenoviruses (Ads) infect a broad range of tissue types, and derived vectors have been extensively used for gene therapy. Helper-dependent Ad vectors (HDAds), devoid of viral coding sequences, allow for insertion of large or multiple transgenes in a single vector and have been preclinically used for the study of genetic disorders. However, the clinical application of Ad vectors including HDAds for genetic disorders has been hampered by an acute toxic response. This characteristic, while disadvantageous for gene replacement therapy, could be strategically advantageous for the activation of an immune response if HDAds were used as an adjunct treatment in cancer. Cancer treatments including immunotherapy are frequently limited by the inhibitory environment produced by both tumors and their stroma, each of which express numerous inhibitory molecules. Hence, multiple inhibitory mechanisms must be overcome for development of anti-tumor immunity. The large coding capacity of HDAds can accommodate multiple immune modulating transgenes that could produce a combined effect to overcome tumor-derived inhibition and ensure intratumoral effector T-cell proliferation and function. In this review, we discuss the potential advantages of HDAds to cancer immunotherapy based on potent host immune responses to Ads.

  20. Role of interleukin (IL)-17 and T-helper (Th)17 cells in cancer. (United States)

    Song, Yang; Yang, Jian Ming


    Interleukin-17 (IL-17), a pleiotropic proinflammatory cytokine, is reported to be significantly generated by a distinct subset of CD4 + T-cells, upgrading cancer-elicited inflammation and preventing cancer cells from immune surveillance. T-helper (Th)17 cells produced from naive CD4 + T cells have recently been renowned and generally accepted, gaining eminence in cancer studies and playing the effective role in context of cancer. Th17 cells are the main source of IL-17-secreting cells, It was found that other cell types produced this cytokine as well, including Group 3 innate lymphoid cells (ILC3), δγT cells, invariant natural killer T (iNKT) cells, lymphoid-tissue inducer (LTi)-like cells and Natural killer (NK) cells. Th17-associated cytokines give impetus to tumor progression, or inducing angiogenesis and metastasis. This review demonstrates an understanding on how the pro- or antitumor function of Th17 cells and IL-17 may change cancer progression, leading to the appearance of complex and pivotal biologic activities in tumor. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

    Directory of Open Access Journals (Sweden)

    Georgios Liappas


    Full Text Available Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD.

  2. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage (United States)

    Liappas, Georgios; Gónzalez-Mateo, Guadalupe Tirma; Majano, Pedro; Sánchez- Tomero, José Antonio; Ruiz-Ortega, Marta; Martín, Pilar; Sanchez-Díaz, Raquel; Selgas, Rafael; López-Cabrera, Manuel; Aguilera Peralta, Abelardo


    Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD. PMID:26064907

  3. A Location Prediction-Based Helper Selection Scheme for Suspicious Eavesdroppers

    Directory of Open Access Journals (Sweden)

    Yan Huo


    Full Text Available This paper aims to improve security performance of data transmission with a mobile eavesdropper in a wireless network. The instantaneous channel state information (CSI of the mobile eavesdropper is unknown to legitimate users during the communication process. Different from existing work, we intend to reduce power consumption of friendly jamming signals. Motivated by the goal, this work presents a location-based prediction scheme to predict where the eavesdropper will be later and to decide whether a friendly jamming measure should be selected against the eavesdropper. The legitimate users only take the measure when the prediction result shows that there will be a risk during data transmission. According to the proposed method, system power can be saved to a large degree. Particularly, we first derive the expression of the secrecy outage probability and set a secrecy performance target. After providing a Markov mobile model of an eavesdropper, we design a prediction scheme to predict its location, so as to decide whether to employ cooperative jamming or not, and then design a power allocation scheme and a fast suboptimal helper selection method to achieve targeted and efficient cooperative jamming. Finally, numerical simulation results demonstrate the effectiveness of the proposed schemes.

  4. Immune response to helper dependent adenoviral mediated liver gene therapy: challenges and prospects. (United States)

    Seiler, Michael P; Cerullo, Vincenzo; Lee, Brendan


    Adenovirus-mediated gene therapy holds significant potential especially for applications requiring high levels of target tissue transduction. While significant advances in clinical adenoviral gene therapy applications have been made in cancer, the clinical translation of adenoviral gene replacement therapy for genetic disease has lagged. Encouragingly, advances in vector production have led to the development of Helper-Dependent ("gutted" or "high capacity") adenoviral vectors (HDV) deleted of all viral coding genes. HDV significantly reduces the chronic toxicity associated with early generation adenoviral vectors that has been most significant after systemic administration in both small and large animal models. However, the field remains confounded by innate immune responses inherent to adenovirus, and more generally, to the adaptive immune response to transgene. Together they decrease the effective therapeutic index for any particular treatment. This review summarizes the current advances toward understanding the decisive cell and molecular mechanisms underlying the acute toxicity to systemic HDV administration. We focus on the complex immune response and consequences of systemic vector delivery in the context of liver-directed monogenic disease therapy. Future development of interventions to avoid the innate immune response, including vector and pharmacologic manipulations, should further contribute to minimizing vector toxicity while maximizing the efficacy of systemic HDV gene transfer.

  5. Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal Models

    Directory of Open Access Journals (Sweden)

    Xueli Fan


    Full Text Available Follicular helper CD4+ T (TFH cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS, neuromyelitis optica (NMO/neuromyelitis optica spectrum disorders (NMOSD, and myasthenia gravis (MG. This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

  6. Follicular helper T cells promote liver pathology in mice during Schistosoma japonicum infection.

    Directory of Open Access Journals (Sweden)

    Xiaojun Chen


    Full Text Available Following Schistosoma japonicum (S. japonicum infection, granulomatous responses are induced by parasite eggs trapped in host organs, particular in the liver, during the acute stage of disease. While excessive liver granulomatous responses can lead to more severe fibrosis and circulatory impairment in chronically infected host. However, the exact mechanism of hepatic granuloma formation has remained obscure. In this study, we for the first time showed that follicular helper T (Tfh cells are recruited to the liver to upregulate hepatic granuloma formation and liver injury in S. japonicum-infected mice, and identified a novel function of macrophages in Tfh cell induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of inducible costimulator ligand (ICOSL on macrophages which is regulated by CD40-CD40L signaling. Our findings uncovered a previously unappreciated role for Tfh cells in liver pathology caused by S. japonicum infection in mice.

  7. Sustained phenotypic correction in a mouse model of hypoalphalipoproteinemia with a helper-dependent adenovirus vector. (United States)

    Oka, K; Belalcazar, L M; Dieker, C; Nour, E A; Nuno-Gonzalez, P; Paul, A; Cormier, S; Shin, J-K; Finegold, M; Chan, L


    We examined the efficacy and host response to the adenovirus (Ad)-mediated delivery of human apolipoprotein A-I (APOA1) gene to the liver of APOA1(-/-) mice. Administration of a first-generation vector (FGAd-AI) resulted in a transient appearance of APOA1 in plasma and induced an anti-APOA1 antibody titer, whereas treatment with a helper-dependent vector (HDAd-AI) resulted in sustained APOA1 expression without inducing an antibody titer. With these results, we studied the effects of FGAd vectors on APOAI expression by HDAd-AI vector. Co-treatment with an FGAd vector inhibited HDAd-AI- mediated APOA1 expression independent of transgene cassettes, but only FGAd-AI induced a humoral response. Furthermore, APOA1 mRNA levels in mice co-treated with FGAd vectors were much lower than those expected from the vector copy number, suggesting that DNA of FGAd vectors interferes with the HDAd-AI vector's APOA1 promoter. A single treatment with an HDAd-AI vector produced a supraphysiological plasma APOA1 level that gradually declined to about half the normal human level over the course of 2 years, associated with a plasma cholesterol level that is persistently higher than that in controls. This investigation provides the proof of principle that liver-directed HDAd gene delivery is effective for the long-term phenotypic correction of monogenic hypoalphalipoproteinemia.

  8. Two-photon microscopy for imaging germinal centers and T follicular helper cells. (United States)

    Clatworthy, Menna R


    One of the principle features of immune cells is their dynamic nature. Lymphocytes circulate in the blood between secondary lymphoid organs and tissues in an effort to maximize the likelihood of a rapid and appropriate immune response to invading pathogens and tissue damage. Conventional experimental techniques such as histology and flow cytometry have greatly increased our understanding of immune cells, but in the last decade, two-photon microscopy has revolutionized our ability to interrogate the dynamic behavior of immune cells, a facet so critical to their function. Two-photon microscopy relies on the excitation of fluorophores by simultaneous application of two photons of longer wavelength light. This allows a greater depth of imaging with minimal photodamage. Thus, living tissues can be imaged, including immune cells in lymph nodes. This technique has been used to interrogate the events occurring in a germinal center response and the interactions between cells in the germinal center, including T follicular helper cells (Tfh), germinal center B cells, and follicular dendritic cells (FDC). Herein, a method is described by which the interactions between Tfh and B cells within a germinal center in a popliteal lymph node can be imaged in a live mouse.

  9. How T follicular helper cells and the germinal centre response change with age. (United States)

    Linterman, Michelle A


    Normal ageing is accompanied by a decline in the function of the immune system that causes an increased susceptibility to infections and an impaired response to vaccination in older individuals. This results in an increased disease burden in the aged population, even with good immunisation programmes in place. The decreased response to vaccination is partly due to the diminution of the germinal centre response with age, caused by impaired T-cell help to B cells. Within the germinal centre, T-cell help is provided by a specialised subset of CD4(+) T cells; T follicular helper (Tfh) cells. Tfh cells provide survival and selection signals to germinal centre B cells, allowing them to egress from the germinal centre and become long-live plasma cells or memory B cells, and provide life-long protection against subsequent infection. This review will discuss the cellular and molecular changes in both Tfh cells and germinal centre B cells that occur with advancing age, which result in a smaller germinal centre response and a less effective response to immunisation.

  10. Foxp3+ follicular regulatory T cells control T follicular helper cells and the germinal center response (United States)

    Linterman, Michelle A.; Pierson, Wim; Lee, Sau K.; Kallies, Axel; Kawamoto, Shimpei; Rayner, Tim F.; Srivastava, Monika; Divekar, Devina P.; Beaton, Laura; Hogan, Jennifer J.; Fagarasan, Sidonia; Liston, Adrian; Smith, Kenneth G. C.; Vinuesa, Carola G.


    Follicular helper (TFH) cells provide crucial signals to germinal center B cells undergoing somatic hypermutation and selection that results in affinity maturation. Tight control of TFH numbers maintains self-tolerance. We describe a population of Foxp3+Blimp-1+CD4+ T cells constituting 10-25% of the CXCR5highPD-1highCD4+ T cells found in germinal center after immunization. These follicular regulatory T cells (TFR) share phenotypic characteristics with TFH and conventional Foxp3+ regulatory T cells (Treg) yet are distinct from either. Similar to TFH cells, TFR development depends on Bcl-6, SAP, CD28 and B cells; however TFR originate from thymic-derived Foxp3+ precursors, not naïve or TFH cells. TFR are suppressive in vitro and limit TFH and germinal center B cell numbers in vivo. In the absence of TFR, an outgrowth of non-antigen-specific B cells in germinal centers leads to fewer antigen-specific cells. Thus, Treg cells use the TFH differentiation pathway to produce specialized suppressor cells that control the germinal center response. PMID:21785433

  11. PPARγ negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation. (United States)

    Park, Hong-Jai; Kim, Do-Hyun; Choi, Jin-Young; Kim, Won-Ju; Kim, Ji Yun; Senejani, Alireza G; Hwang, Soo Seok; Kim, Lark Kyun; Tobiasova, Zuzana; Lee, Gap Ryol; Craft, Joseph; Bothwell, Alfred L M; Choi, Je-Min


    Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates lipid and glucose metabolism. Although studies of PPARγ ligands have demonstrated its regulatory functions in inflammation and adaptive immunity, its intrinsic role in T cells and autoimmunity has yet to be fully elucidated. Here we used CD4-PPARγKO mice to investigate PPARγ-deficient T cells, which were hyper-reactive to produce higher levels of cytokines and exhibited greater proliferation than wild type T cells with increased ERK and AKT phosphorylation. Diminished expression of IκBα, Sirt1, and Foxo1, which are inhibitors of NF-κB, was observed in PPARγ-deficient T cells that were prone to produce all the signature cytokines under Th1, Th2, Th17, and Th9 skewing condition. Interestingly, 1-year-old CD4-PPARγKO mice spontaneously developed moderate autoimmune phenotype by increased activated T cells, follicular helper T cells (TFH cells) and germinal center B cells with glomerular inflammation and enhanced autoantibody production. Sheep red blood cell immunization more induced TFH cells and germinal centers in CD4-PPARγKO mice and the T cells showed increased of Bcl-6 and IL-21 expression suggesting its regulatory role in germinal center reaction. Collectively, these results suggest that PPARγ has a regulatory role for TFH cells and germinal center reaction to prevent autoimmunity.

  12. Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus. (United States)

    Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming


    Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Pathogenic T helper type 17 cells contribute to type 1 diabetes independently of interleukin-22. (United States)

    Bellemore, S M; Nikoopour, E; Krougly, O; Lee-Chan, E; Fouser, L A; Singh, B


    We have shown that pathogenic T helper type 17 (Th17) cells differentiated from naive CD4(+) T cells of BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice by interleukin (IL)-23 plus IL-6 produce IL-17, IL-22 and induce type 1 diabetes (T1D). Neutralizing interferon (IFN)-γ during the polarization process leads to a significant increase in IL-22 production by these Th17 cells. We also isolated IL-22-producing Th17 cells from the pancreas of wild-type diabetic NOD mice. IL-27 also blocked IL-22 production from diabetogenic Th17 cells. To determine the functional role of IL-22 produced by pathogenic Th17 cells in T1D we neutralized IL-22 in vivo by using anti-IL-22 monoclonal antibody. We found that blocking IL-22 did not alter significantly adoptive transfer of disease by pathogenic Th17 cells. Therefore, IL-22 is not required for T1D pathogenesis. The IL-22Rα receptor for IL-22 however, increased in the pancreas of NOD mice during disease progression and based upon our and other studies we suggest that IL-22 may have a regenerative and protective role in the pancreatic islets. © 2015 British Society for Immunology.

  14. T Follicular Helper Cells and B Cell Dysfunction in Aging and HIV-1 Infection

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    Suresh Pallikkuth


    Full Text Available T follicular helper (Tfh cells are a subset of CD4 T cells that provide critical signals to antigen-primed B cells in germinal centers to undergo proliferation, isotype switching, and somatic hypermutation to generate long-lived plasma cells and memory B cells during an immune response. The quantity and quality of Tfh cells therefore must be tightly controlled to prevent immune dysfunction in the form of autoimmunity and, on the other hand, immune deficiency. Both Tfh and B cell perturbations appear during HIV infection resulting in impaired antibody responses to vaccines such as seasonal trivalent influenza vaccine, also seen in biologic aging. Although many of the HIV-associated defects improve with antiretroviral therapy (ART, excess immune activation and antigen-specific B and T cell responses including Tfh function are still impaired in virologically controlled HIV-infected persons on ART. Interestingly, HIV infected individuals experience increased risk of age-associated pathologies. This review will discuss Tfh and B cell dysfunction in HIV infection and highlight the impact of chronic HIV infection and aging on Tfh–B cell interactions.

  15. A mycorrhiza helper bacterium enhances ectomycorrhizal and endomycorrhizal symbiosis of Australian Acacia species. (United States)

    Duponnois, R; Plenchette, C


    The aims of this study were to test the effects of a mycorrhiza helper bacterium (MHB), Pseudomonas monteilii strain HR13 on the mycorrhization of (1) an Australian Acacia, A. holosericea, by several ectomycorrhizal fungi or one endomycorrhizal fungus Glomus intraradices, and (2) several Australian Acacia species by Pisolithus alba strain IR100 under glasshouse conditions. Bacterial inoculant HR13 significantly promoted ectomycorrhizal colonization for all the Acacia species, from 45.8% ( A. mangium) to 70.3% ( A. auriculiformis). A stimulating effect of HR13 on the ectomycorrhizal establishment was recorded with all the fungal isolates (strains of Pisolithus and Scleroderma). The same effect of bacteria on the frequency of endomycorrhizal colonization of A. holosericea seedlings by G. intraradices with vesicles and hyphae frequencies was recorded. The stimulation of saprophytic fungal growth by MHB is usually the main mechanism that could explain this bacterial effect on mycorrhizal establishment. MHB could stimulate the production of phenolic compounds such as hypaphorine and increase the aggressiveness of the fungal symbiont. However, no significant effect of MHB on fungal growth was recorded with Scleroderma isolates under axenic conditions but positive bacterial effects were observed with Pisolithus strains. From a practical viewpoint, it appears that MHB could stimulate the mycorrhizal colonization of Australian Acacia species with ectomycorrhizal or endomycorrhizal fungi, and could also facilitate controlled mycorrhization in nursery practices where Acacia species are grown for forestation purposes.

  16. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. (United States)

    Yang, Xuexian O; Pappu, Bhanu P; Nurieva, Roza; Akimzhanov, Askar; Kang, Hong Soon; Chung, Yeonseok; Ma, Li; Shah, Bhavin; Panopoulos, Athanasia D; Schluns, Kimberly S; Watowich, Stephanie S; Tian, Qiang; Jetten, Anton M; Dong, Chen


    T cell functional differentiation is mediated by lineage-specific transcription factors. T helper 17 (Th17) has been recently identified as a distinct Th lineage mediating tissue inflammation. Retinoic acid receptor-related orphan receptor gamma (ROR gamma) was shown to regulate Th17 differentiation; ROR gamma deficiency, however, did not completely abolish Th17 cytokine expression. Here, we report Th17 cells highly expressed another related nuclear receptor, ROR alpha, induced by transforming growth factor-beta and interleukin-6 (IL-6), which is dependent on signal transducer and activator of transcription 3. Overexpression of ROR alpha promoted Th17 differentiation, possibly through the conserved noncoding sequence 2 in Il17-Il17f locus. ROR alpha deficiency resulted in reduced IL-17 expression in vitro and in vivo. Furthermore, ROR alpha and ROR gamma coexpression synergistically led to greater Th17 differentiation. Double deficiencies in ROR alpha and ROR gamma globally impaired Th17 generation and completely protected mice against experimental autoimmune encephalomyelitis. Therefore, Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma.

  17. Helminth Protein Vaccine Induced Follicular T Helper Cell for Enhancement of Humoral Immunity against Schistosoma japonicum

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    Jingyao Zhang


    Full Text Available Protein vaccines combined with adjuvants have been widely used to induce immune responses, especially the humoral immune response, against molecular targets including parasites. Follicular T helper (Tfh cells are the specialized providers of B-cell help, however, the induction of Tfh cells in protein vaccination has been rarely studied. Here, we report that the Schistosoma japonicum recombinant protein (SjGST-32 combined with tacrolimus (FK506 augmented the induction of Tfh cells, which expressed the canonical markers CXCR5, BCL6, and IL-21, and enhanced the humoral immune responses in BALB/c mice. Furthermore, the expression of IL-21R on germinal center (GC B cells and memory B cells increased in immunized mice, which indicated that IL-21 from the induced Tfh cells interacted with IL-21R for activation of B cells and maintenance of long-lived humoral immunity. Our results suggest that helminth protein vaccine combined with FK506 induces Tfh cell for stimulating humoral immune responses and inducing long-lived humoral immunity.

  18. Mycorrhization helper bacteria: a case of specificity for altering ectomycorrhiza architecture but not ectomycorrhiza formation. (United States)

    Aspray, Thomas J; Frey-Klett, Pascale; Jones, Julie E; Whipps, John M; Garbaye, Jean; Bending, Gary D


    Mycorrhization helper bacteria (MHB), isolated from phylogenetically distinct ectomycorrhizal symbioses involving Lactarius rufus, Laccaria bicolor or Suillus luteus, were tested for fungus specificity to enhance L. rufus-Pinus sylvestris or L. bicolor-P. sylvestris mycorrhiza formation. As MHB isolated from the L. rufus and S. luteus mycorrhiza were originally characterised using a microcosm system, we assessed their ability to enhance mycorrhiza formation in a glasshouse system in order to determine the extent to which MHB are system-specific. Paenibacillus sp. EJP73, an MHB for L. rufus in the microcosm, significantly enhanced L. bicolor mycorrhiza formation in the glasshouse, demonstrating that the MHB effect of this bacterium is neither fungus-specific nor limited to the original experimental system. Although the five MHB strains studied were unable to significantly enhance L. rufus mycorrhiza formation, two of them did have a significant effect on dichotomous short root branching by L. rufus. The effect was specific to Paenibacillus sp. EJP73 and Burkholderia sp. EJP67, the two strains isolated from L. rufus mycorrhiza, and was not associated with auxin production. Altered mycorrhiza architecture rather than absolute number of mycorrhizal roots may be an important previously overlooked parameter for defining MHB effects.

  19. TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand. (United States)

    Pattarini, Lucia; Trichot, Coline; Bogiatzi, Sofia; Grandclaudon, Maximilien; Meller, Stephan; Keuylian, Zela; Durand, Melanie; Volpe, Elisabetta; Madonna, Stefania; Cavani, Andrea; Chiricozzi, Andrea; Romanelli, Marco; Hori, Toshiyuki; Hovnanian, Alain; Homey, Bernhard; Soumelis, Vassili


    T follicular helper cells (Tfh) are important regulators of humoral responses. Human Tfh polarization pathways have been thus far associated with Th1 and Th17 polarization pathways. How human Tfh cells differentiate in Th2-skewed environments is unknown. We show that thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs) promote human Tfh differentiation from naive CD4 T cells. We identified a novel population, distinct from Th2 cells, expressing IL-21 and TNF, suggestive of inflammatory cells. TSLP-induced T cells expressed CXCR5, CXCL13, ICOS, PD1, BCL6, BTLA, and SAP, among other Tfh markers. Functionally, TSLP-DC-polarized T cells induced IgE secretion by memory B cells, and this depended on IL-4Rα. TSLP-activated DCs stimulated circulating memory Tfh cells to produce IL-21 and CXCL13. Mechanistically, TSLP-induced Tfh differentiation depended on OX40-ligand, but not on ICOS-ligand. Our results delineate a pathway of human Tfh differentiation in Th2 environments. © 2017 Pattarini et al.

  20. Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity

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    Natarajan Bhaskaran


    Full Text Available While T helper (Th cells play a crucial role in host defense, an imbalance in Th effector subsets due to dysregulation in their differentiation and expansion contribute to inflammatory disorders. Here, we show that Casz1, whose function is previously unknown in CD4+ T cells, coordinates Th differentiation in vitro and in vivo. Casz1 deficiency in CD4+ T cells lowers susceptibility to experimental autoimmune encephalomyelitis, consistent with the reduced frequency of Th17 cells, despite an increase in Th1 cells in mice. Loss of Casz1 in the context of mucosal Candida infection severely impairs Th17 and Treg responses, and lowers the ability of the mice to clear the secondary infection. Importantly, in both the models, absence of Casz1 causes a significant diminution in IFN-γ+IL-17A+ double-positive inflammatory Th17 cells (Th1* cells in tissues in vivo. Transcriptome analyses of CD4+ T cells lacking Casz1 show a signature consistent with defective Th17 differentiation. With regards to Th17 differentiation, Casz1 limits repressive histone marks and enables acquisition of permissive histone marks at Rorc, Il17a, Ahr, and Runx1 loci. Taken together, these data identify Casz1 as a new Th plasticity regulator having important clinical implications for autoimmune inflammation and mucosal immunity.

  1. Differential gene expression by integrin β7+ and β7- memory T helper cells

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    Yang Yee


    Full Text Available Abstract Background The cell adhesion molecule integrin α4β7 helps direct the migration of blood lymphocytes to the intestine and associated lymphoid tissues. We hypothesized that β7+ and β7- blood memory T helper cells differ in their expression of genes that play a role in the adhesion or migration of T cells. Results RNA was prepared from β7+ and β7- CD4+ CD45RA- blood T cells from nine normal human subjects and analyzed using oligonucleotide microarrays. Of 21357 genes represented on the arrays, 16 were more highly expressed in β7+ cells and 18 were more highly expressed in β7- cells (≥1.5 fold difference and adjusted P + memory/effector T cells than on β7- cells. Conclusions Memory/effector T cells that express integrin β7 have a distinct pattern of expression of a set of gene transcripts. Several of these molecules can affect cell adhesion or chemotaxis and are therefore likely to modulate the complex multistep process that regulates trafficking of CD4+ memory T cell subsets with different homing behaviors.

  2. Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation

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    Victoria Ryg-Cornejo


    Full Text Available Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-γ or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.

  3. Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection. (United States)

    Kopf, M; Coyle, A J; Schmitz, N; Barner, M; Oxenius, A; Gallimore, A; Gutierrez-Ramos, J C; Bachmann, M F


    It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further reduced Th1/Th2 polarization. Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS. Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4(+) subset (Th1 and Th2) responses but not CTL responses in vivo.

  4. Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis. (United States)

    Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj; Wynn, Thomas A; Madala, Satish K


    IL-4 and IL-13 are major T-helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared with wild-type mice treated with bleomycin. Furthermore, our results demonstrated that IL-13 and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased phospho-focal adhesion kinase signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments matrix metalloproteinase (MMP)-2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.

  5. The transcription factor KLF2 restrains CD4⁺ T follicular helper cell differentiation. (United States)

    Lee, June-Yong; Skon, Cara N; Lee, You Jeong; Oh, Soohwan; Taylor, Justin J; Malhotra, Deepali; Jenkins, Marc K; Rosenfeld, M Geoffrey; Hogquist, Kristin A; Jameson, Stephen C


    T follicular helper (Tfh) cells are essential for efficient B cell responses, yet the factors that regulate differentiation of this CD4(+) T cell subset are incompletely understood. Here we found that the KLF2 transcription factor serves to restrain Tfh cell generation. Induced KLF2 deficiency in activated CD4(+) T cells led to increased Tfh cell generation and B cell priming, whereas KLF2 overexpression prevented Tfh cell production. KLF2 promotes expression of the trafficking receptor S1PR1, and S1PR1 downregulation is essential for efficient Tfh cell production. However, KLF2 also induced expression of the transcription factor Blimp-1, which repressed transcription factor Bcl-6 and thereby impaired Tfh cell differentiation. Furthermore, KLF2 induced expression of the transcription factors T-bet and GATA3 and enhanced Th1 differentiation. Hence, our data indicate KLF2 is pivotal for coordinating CD4(+) T cell differentiation through two distinct and complementary mechanisms: via control of T cell localization and by regulation of lineage-defining transcription factors. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Assessment of T helper 17-associated cytokines in third trimester of pregnancy. (United States)

    Poordast, Tahereh; Najib, Fateme Sadat; Baharlou, Rasoul; Bijani, Atena; Alamdarloo, Shaghayegh Moradi; Poordast, Alieh


    Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology of preeclampsia. To determine the serum levels of IL-17, IL-21, IL-23 and TGF-β in patients with preeclampsia. Blood samples were collected from 30 preeclampsia patients, 30 normotensive pregnant women and 30 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-23 and TGF-β were measured by the enzyme linked immunosorbent assay (ELISA). The serum levels of IL-17 and TGF-β were significantly higher in preeclampsia patients compared to normal pregnant group and healthy individuals (p>0.0001) but interestingly, the opposite was the case for IL-23 (p=0.005). However, there were no significant differences in IL-21 between preeclampsia and normal pregnant group. Our results conclude that contrary to IL-21, serum levels of IL-17 and TGF-β significantly increased in preeclampsia compared to normal pregnant women, supporting an imbalance of cytokine profile in preeclamtic patients.

  7. The role of mycorrhization helper bacteria in the establishment and action of ectomycorrhizae associations

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    Tatiana Alves Rigamonte


    Full Text Available More than 95 % short roots of most terrestrial plants are colonized by mycorrhizal fungi as soon as they emerge in the upper soil profiles. The establishment of mycorrhizal association involves profound morphological and physiological changes in root and fungus. It is affected by other rhizospheric microorganisms, specifically by the bacteria. Bacteria may have developed mechanisms of selective interaction with surrounding microorganisms, with neutral or positive effects on mycorrhizal associations, but negative effect on root pathogens in general. Because of the beneficial effect of bacteria on mycorrhizae, the concept of Mycorrhization Helper Bacteria (MHB was created. Five main actions of MHB on mycorrhizae were proposed: in the receptivity of root to the mycobiont, in root-fungus recognition, in fungal growth, in the modification of rhizospheric soil and in the germination of fungal propagules. MHB appear to develop a gradation of specificity for the mycobiont, but little or no specificity for the host plant in symbiosis. One of the main groups of MHB is the fluorescent Pseudomonas, well represented in diversity and cell density studies of mycorrhizal associations. This review covers the activity of MHB in the establishment of ectomycorrhizae, taking as model the effects of Pseudomonas sp. described in scientific literature.

  8. Mycorrhization between Cistus ladanifer L. and Boletus edulis Bull is enhanced by the mycorrhiza helper bacteria Pseudomonas fluorescens Migula. (United States)

    Mediavilla, Olaya; Olaizola, Jaime; Santos-del-Blanco, Luis; Oria-de-Rueda, Juan Andrés; Martín-Pinto, Pablo


    Boletus edulis Bull. is one of the most economically and gastronomically valuable fungi worldwide. Sporocarp production normally occurs when symbiotically associated with a number of tree species in stands over 40 years old, but it has also been reported in 3-year-old Cistus ladanifer L. shrubs. Efforts toward the domestication of B. edulis have thus focused on successfully generating C. ladanifer seedlings associated with B. edulis under controlled conditions. Microorganisms have an important role mediating mycorrhizal symbiosis, such as some bacteria species which enhance mycorrhiza formation (mycorrhiza helper bacteria). Thus, in this study, we explored the effect that mycorrhiza helper bacteria have on the efficiency and intensity of the ectomycorrhizal symbiosis between C. ladanifer and B. edulis. The aim of this work was to optimize an in vitro protocol for the mycorrhizal synthesis of B. edulis with C. ladanifer by testing the effects of fungal culture time and coinoculation with the helper bacteria Pseudomonas fluorescens Migula. The results confirmed successful mycorrhizal synthesis between C. ladanifer and B. edulis. Coinoculation of B. edulis with P. fluorescens doubled within-plant mycorrhization levels although it did not result in an increased number of seedlings colonized with B. edulis mycorrhizae. B. edulis mycelium culture time also increased mycorrhization levels but not the presence of mycorrhizae. These findings bring us closer to controlled B. edulis sporocarp production in plantations.

  9. Male ruff colour as a rank signal in a monomorphic-horned mammal: behavioural correlates (United States)

    Lovari, S.; Fattorini, N.; Boesi, R.; Bocci, A.


    Coexistence of individuals within a social group is possible through the establishment of a hierarchy. Social dominance is achieved through aggressive interactions, and, in wild sheep and goats, it is related mainly to age, body size and weapon size as rank signals. Adult male Himalayan tahr are much larger than females and subadult males. They have a prominent neck ruff, ranging in colour from yellow (5.5-9.5 years old, i.e. young adults, golden males) to brown (7.5-14.5 years old, i.e. older individuals, pale and dark brown males), with golden males being the most dominant. We investigated the social behaviour of male tahr and analysed the relationships between ruff colour, courtship and agonistic behaviour patterns during the rut. Colour classes varied in their use of several behaviour patterns (male dominance: approach, stare, horning vegetation; courtship: low stretch, naso- genital contact, rush). Golden-ruffed males used more threats than darker ones. Pale brown and dark brown males addressed threats significantly more often to males of lower or their own colour classes, respectively, whereas golden ones addressed threats to all colour classes, including their own. The courtship of dominant males was characterised by the assertive rush, whereas that of subordinates did not. Ruff colour of male Himalayan tahr may have evolved as a rank signal, homologous to horn size in wild sheep and goats.

  10. Social rank and response to the "male effect" in the Australian Cashmere goat. (United States)

    Alvarez, L; Zarco, L; Galindo, F; Blache, D; Martin, G B


    The present study was conducted to determine if the social status of Australian Cashmere goats affects their response to the male effect in terms of LH secretion, ovulation and expression of estrus. Australian Cashmere goats were kept isolated from the males during 5 months. The index of success (SI) of each goat was calculated to establish their social rank. In the first experiment, the ten most dominant and the 10 most subordinate goats were separated from the original herd and housed in two pens (5 dominant and 5 subordinate animals in each pen). An androgenized wether was then introduced into each pen. Luteinizing hormone (LH) was measured every 20 min from 2h before to 4h after introduction of the male in the goats of first pen and from 4 to 8h after male introduction in the second pen. In the second experiment, the remaining 50 goats were exposed in their original pen to two androgenized wethers. Their association index with the males (AI) was calculated for each of these 50 goats, and the intervals from exposure to the males to the onset of estrus and to ovulation were determined. During the first 4h after male introduction, the dominant goats had more LH pulses (0.65+/-0.06 compared with 0.3+/-0.09; P0.05). Although the number of goats ovulating in response to male exposure was similar between dominance groups (high: 100%, medium: 94% and low ranking: 92%), the high and medium dominance goats showed a greater incidence of expression of estrus than low-dominance goats (94.4%, 89.5% and 53.8%, respectively, P<0.05). It is concluded that the social rank of the Australian Cashmere goat influences their response to the male effect in terms of early LH secretion and expression of estrus.

  11. [Effects of helper protein P20 from Bacillus thuringiensis on Vip3A expression]. (United States)

    Shi, Yong-xia; Yuan, Mei-jin; Chen, Jian-wu; Sun, Fan; Pang, Yi


    Insecticidal crystal proteins (ICPs) produced in Bacillus thuringiensis accumulate as crystalline inclusions that represent up to 30% of total dry weight the cell produces. The mechanisms of in vivo crystallization of these insecticidal proteins remain interests, yet unclear. A 20-kDa protein (P20), the product of the third open reading frame of cry11A operon in B. thuringiensis subsp. israelensis has been defined to be an important molecular chaperone (helper protein) for forming Cyt1A crystal and enhancing Cry11A expression. The novel vegetative insecticidal proteins (VIPs) are secreted outside the cell of B. thuringiensis during mid-logarithmic growth. VIP3A shows activity against many lepidopteran insect larvae in a different mechanism from that of ICPs. To investigate the influence of helper protein P20 on Vip3A production and its insecticidal activity, P20 was coexpressed with Vip3A protein in B. thuringiensis and the yields and insecticidal toxicity of Vip3A were also analyzed. The recombinant plasmid pHVP20 was constructed by inserting a 5.4kb foreign fragment containing both vip3A gene and p20 gene into the shuttle vector pHT3101. The plasmid pHPT3 only containing vip3A gene was used as control. pHVP20 and pHPT3 were transformed into the B. thuringiensis acrystalliferous strain CryB not containing vip3A gene by electroporation. The obtained B. thuringiensis transformants were CryB(pHVP20) and CryB(pHPT3) respectively. Western blot showed that Vip3A protein reached its maximum yield after 48h of CryB (pHVP20) growth and remained high expression level during the sporulation. The maximum yield of Vip3A protein in CryB (pHVP20) was about 1.5 fold as compared with that in CryB(pHPT3) by the mean of ImageMaster VDS software. It is considered that P20 might combine with the native Vip3A protein during the sporulation, stabilize Vip3A and protect Vip3A from unspecific full proteolysis. Bioassay showed that the cell pellets of CryB (pHVP20) and CryB(pHPT3

  12. T Helper Cells in the Immunopathogenesis of Systemic Sclerosis – Current Trends

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    Krasimirova E.


    Full Text Available Systemic sclerosis (SSc is a chronic progressive autoimmune disease characterized by skin and multiorgan involvement with alterations in both the innate and adaptive immunities. The hallmark of the disease is widespread fibrosis engaging the skin and multiple internal organs, as well as the musculoskeletal system. There is mounting evidence that T cells are key players in the pathogenesis of scleroderma. The current review discusses the role of the different T helper (Th lymphocyte subsets in the processes of inflammation and fibrosis, characteristics for the pathogenesis of the disease. Cytokines produced by Th cell populations have a major effect on endothelial cells and fibroblasts in the context of favoring/inhibiting the vasculopathy and the fibrosis spread. The Th2 pro-fibrotic cytokines IL-4 and IL-13 have been shown to induce collagen synthesis by fibroblasts, whereas IFN-γ demonstrates an inhibitory effect. Increased Th17 cells are present in the scleroderma skin infiltrates. The combination of IL-17, IFN-γ and TGF-β levels in CD45RO and CD45RA cells from patients with SSc is useful to distinguish between the limited and the diffuse phenotype of the disease. There are accumulating data for functional and numerical alterations in the Tregs in SSc. High levels of TNF-α which might reduce the suppressive ability of Tregs have been described. According to some studies, the number of Tregs in scleroderma skin biopsies has been decreased against the normal absolute number of Tregs in peripheral blood of the same patients, which suggests suppressed immunomodulatory response. Other studies reported increased frequency of Tregs in peripheral blood of patients with systemic sclerosis and established a correlation with disease activity. The main immunological challenge remains the identification of the trigger of the autoimmune response in SSc, the causes for preferential Th2-type cell responses and the immunological differences between the

  13. Germinal center B cell depletion diminishes CD4+ follicular T helper cells in autoimmune mice.

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    Isharat Yusuf

    Full Text Available BACKGROUND: Continuous support from follicular CD4(+ T helper (Tfh cells drives germinal center (GC responses, which last for several weeks to produce high affinity memory B cells and plasma cells. In autoimmune Sle1 and NZB/W F1 mice, elevated numbers of Tfh cells persist, promoting the expansion of self-reactive B cells. Expansion of circulating Tfh like cells have also been described in several autoimmune diseases. Although, the signals required for Tfh differentiation have now been well described, the mechanisms that sustain the maintenance of fully differentiated Tfh are less understood. Recent data demonstrate a role for GC B cells for Tfh maintenance after protein immunization. METHODS AND FINDING: Given the pathogenic role Tfh play in autoimmune disease, we explored whether B cells are required for maintenance of autoreactive Tfh. Our data suggest that the number of mature autoreactive Tfh cells is controlled by GC B cells. Depletion of B cells in Sle1 autoimmune mice leads to a dramatic reduction in Tfh cells. In NZB/W F1 autoimmune mice, similar to the SRBC immunization model, GC B cells support the maintenance of mature Tfh, which is dependent mainly on ICOS. The CD28-associated pathway is dispensable for Tfh maintenance in SRBC immunized mice, but is required in the spontaneous NZB/W F1 model. CONCLUSION: These data suggest that mature Tfh cells require signals from GC B cells to sustain their optimal numbers and function in both autoimmune and immunization models. Thus, immunotherapies targeting B cells in autoimmune disease may affect pathogenic Tfh cells.

  14. Elevated Urinary T Helper 1 Chemokine Levels in Newly Diagnosed Hypertensive Obese Children (United States)

    Övünç Hacıhamdioğlu, Duygu; Zeybek, Cengiz; Gök, Faysal; Pekel, Aysel; Muşabak, Uğur


    Objective: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines. Methods: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post-treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG). In the hypertensive obese group, urine microalbumin: creatinine ratio was examined before and after treatment. We recommended lifestyle changes to all patients. Captopril was started in those who could not be controlled with lifestyle changes and those who had stage 2 hypertension. Results: Twenty-four hypertensive obese (mean age 13.1), 27 healthy (mean age 11.2) and 22 non-hypertensive obese (mean age 11.5) children were investigated. The pre-treatment urine albumin: creatinine ratio was positively correlated with pre-treatment MIG levels (r=0.41, phypertensive and non-hypertensive obese group than in the controls. The urinary IP10 and MIG levels were higher in the pre-treatment hypertensive obese group than in the non-hypertensive obese. Comparison of the pre- and post-treatment values indicated significant decreases in RANTES, IP10, and MIG levels in the hypertensive obese group (phypertensive children before the onset of clinical indicators of target organ damage. Urinary RANTES seemed to be affected by both hypertension and obesity, and urinary IP10 and MIG seemed to be affected predominantly by hypertension. PMID:26831550

  15. Flexible Programs of Chemokine Receptor Expression on Human Polarized T Helper 1 and 2 Lymphocytes (United States)

    Sallusto, Federica; Lenig, Danielle; Mackay, Charles R.; Lanzavecchia, Antonio


    Chemokines and their receptors are important elements for the selective attraction of various subsets of leukocytes. To better understand the selective migration of functional subsets of T cells, chemokine receptor expression was analyzed using monoclonal antibodies, RNase protection assays, and the response to distinct chemokines. Naive T cells expressed only CXC chemokine receptor (CXCR)4, whereas the majority of memory/activated T cells expressed CXCR3, and a small proportion expressed CC chemokine receptor (CCR)3 and CCR5. When polarized T cell lines were analyzed, CXCR3 was found to be expressed at high levels on T helper cell (Th)0s and Th1s and at low levels on Th2s. In contrast, CCR3 and CCR4 were found on Th2s. This was confirmed by functional responses: only Th2s responded with an increase in [Ca2+]i to the CCR3 and CCR4 agonists eotaxin and thymus and activation regulated chemokine (TARC), whereas only Th0s and Th1s responded to low concentrations of the CXCR3 agonists IFN-γ–inducible protein 10 (IP-10) and monokine induced by IFN-γ (Mig). Although CCR5 was expressed on both Th1 and Th2 lines, it was absent in several Th2 clones and its expression was markedly influenced by interleukin 2. Chemokine receptor expression and association with Th1 and Th2 phenotypes was affected by other cytokines present during polarization. Transforming growth factor β inhibited CCR3, but enhanced CCR4 and CCR7 expression, whereas interferon α inhibited CCR3 but upregulated CXCR3 and CCR1. These results demonstrate that chemokine receptors are markers of naive and polarized T cell subsets and suggest that flexible programs of chemokine receptor gene expression may control tissue-specific migration of effector T cells. PMID:9500790

  16. CD4 T Follicular Helper and Regulatory Cell Dynamics and Function in HIV Infection. (United States)

    Miles, Brodie; Miller, Shannon M; Connick, Elizabeth


    T follicular helper cells (TFH) are a specialized subset of CD4 T cells that reside in B cell follicles and promote B cell maturation into plasma cells and long-lived memory B cells. During chronic infection prior to the development of AIDS, HIV-1 (HIV) replication is largely concentrated in TFH. Paradoxically, TFH numbers are increased in early and midstages of disease, thereby promoting HIV replication and disease progression. Despite increased TFH numbers, numerous defects in humoral immunity are detected in HIV-infected individuals, including dysregulation of B cell maturation, impaired somatic hypermutation, and low quality of antibody production despite hypergammaglobulinemia. Clinically, these defects are manifested by increased vulnerability to bacterial infections and impaired vaccine responses, neither of which is fully reversed by antiretroviral therapy (ART). Deficits in TFH function, including reduced HIV-specific IL-21 production and low levels of co-stimulatory receptor expression, have been linked to these immune impairments. Impairments in TFH likely contribute as well to the ability of HIV to persist and evade humoral immunity, particularly the inability to develop broadly neutralizing antibodies. In addition to direct infection of TFH, other mechanisms that have been linked to TFH deficits in HIV infection include upregulation of PD-L1 on germinal center B cells and augmented follicular regulatory T cell responses. Challenges to development of strategies to enhance TFH function in HIV infection include lack of an established phenotype for memory TFH as well as limited understanding of the relationship between peripheral TFH and lymphoid tissue TFH. Interventions to augment TFH function in HIV-infected individuals could enhance immune reconstitution during ART and potentially augment cure strategies.

  17. Role played by T-helper 2 in resetting the cytokine balance in allergic patients

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    Mohamed Y Attia


    Full Text Available Background Bronchial asthma is an allergic disorder characterized by excessive hyperactive nature of the airways, which depends on many cytokines such as interleukin-4 (IL-4 and IL-5 that are responsible for the allergic inflammatory response. One of the strategies in the management of bronchial asthma is the induction of synthesis of IL-10; it has an inhibitory effect on the synthesis of the T-helper-2 (Th2 cytokines. Th2 cells play a triggering role in the activation/recruitment of immunoglobulin E antibody-producing B cells, mast cells, and eosinophil cells. To assess regulatory changes in the immune system, in patients with allergy and asthma, we studied the cytokine profile in serum in comparison with normal healthy controls. The study was carried out in Allergy and Immunology Unit, Ain Shams University Hospitals. A total of 170 patients with various allergies and asthmatic conditions were studied, for cytokines in the serum by enzyme-linked immunosorbent assay using kits from Immune Technology, and analyzed to identify the triggering factors or main contributors toward allergy and asthma. Our study showed increase in the levels of IL-4, IL-5, and IL-6 in all groups, which was nonsignificant. However, the levels of IL-10, IL-13, and tumor necrosis factor-α were highly significantly increased. Besides, we found correlation of granulocyte macrophage colony-stimulating factor with IL-10. Significant positive correlation with different cytokines was observed. Most of these patients showed increase in immunoglobulin E levels. This study gives a better understanding of how cytokines are the mediators of balance of Th1 and Th2 immune responses and how immunoglobulin E synthesis is controlled by cytokines. Further studies will eventually lead to improved treatment strategies in the clinical management of immunoglobulin E-mediated allergy.

  18. Increased hyphal branching and growth of ectomycorrhizal fungus Lactarius rufus by the helper bacterium Paenibacillus sp. (United States)

    Aspray, T J; Jones, E E; Davies, M W; Shipman, M; Bending, G D


    Paenibacillus sp. EJP73 has been previously demonstrated as a mycorrhization helper bacterium (MHB) for the Lactarius rufus-Pinus sylvestris symbiosis in both laboratory and glasshouse experiments. In the present study, the effect of Paenibacillus sp. EJP73 metabolites on L. rufus EO3 pre-symbiotic growth was tested in two agar plate-based systems. Specifically, volatile metabolites were investigated using a dual plate system, in which the presence of strain EJP73 resulted in a significant negative effect on L. rufus EO3 hyphal radial growth but enhanced hyphal branching and reduced internode distance. Soluble metabolites produced by strain EJP73 were tested on L. rufus EO3 growth in single-agar plate assays by incorporating bacterial cell-free whole or molecular weight fraction spent broth into the agar. Whole spent broth had a negative effect on hyphal growth, whereas a low molecular weight fraction (100-1,000) promoted colony radial growth. Headspace and spent broth analysis of strain EJP73 cultures revealed 2,5-diisopropylpyrazine to be the most significant component. Synthesised 2,5-diisopropylpyrazine and elevated CO2 (2,000 ppm) were tested as specific volatile metabolites in the dual plate system, but neither produced the response shown when strain EJP73 was present. Increased pre-symbiotic hyphal branching leading to increased likelihood of plant infection may be an important MHB mechanism for strain EJP73. Although the precise signal molecules could not be identified, the work suggests a number of metabolites may work synergistically to increase L. rufus root colonisation.

  19. Alternative male mating behaviors dependent on relative body size in captive oval squid Sepioteuthis lessoniana (Cephalopoda, Loliginidae). (United States)

    Wada, Toshifumi; Takegaki, Takeshi; Mori, Tohru; Natsukari, Yutaka


    We observed the reproductive behavior of the oval squid Sepioteuthis lessoniana in captivity. The male used three different mating behaviors: male-parallel (MP), male-upturned (MU) and sneaking. Male competition over females frequently occurred before and during the female egg-laying period, and the outcome of most fights depended on male body size. Larger males guarded their partners from other males and performed MP mating during the egg-laying period of the paired females. In contrast, there was no pairing and mate guarding in MU mating and sneaking, which were adopted by smaller subordinate males as alternative tactics outside female egg-laying period and during the period, respectively. MP matings were 95% successful, but more than half of MU matings were unsuccessful. Higher mating success in MP mating was achieved through pairing, whereas males in MU mating were less successful because mating attempts without pair formation were often foiled by escape of the female. Sneaking was successful in all cases but occurred less frequently. Spermatophores were attached at the opening of the oviduct in MP mating, whereas they were attached around the female buccal membrane in MU mating and sneaking. Considering the route of egg transportation, higher fertilization success can be expected in MP mating because of the advantageous location of the attached spermatophores. Our results suggest that MP mating is used by larger, paired males during the female egg-laying period, and that MU mating and sneaking are alternative tactics adopted by smaller, subordinate males. These alternative mating behaviors would be conditional strategy dependent on relative body size, because some individual males displayed both MP and MU mating behaviors.

  20. Effect of N-methyl-D-aspartate receptor antagonist on T helper cell differentiation induced by phorbol-myristate-acetate and ionomycin. (United States)

    Gao, Mei; Jin, Wenjie; Qian, Yanning; Ji, Lulu; Feng, Genbao; Sun, Jie


    To investigate the effect of N-methyl-D-aspartate (NMDA) receptor antagonist on T helper (TH) cell differentiation and intracellular transcriptional factors in vitro. Ten male healthy volunteers (aged 20-45 y, BMI 18-25) were enrolled in this study. Twenty milliliters peripheral blood was collected in the morning from fasted volunteers and peripheral blood mononuclear cells (PBMC) were isolated. PBMC were incubated with phorbol-myristate-acetate (25 ng/ml) (PMA) plus ionomycin (1 μg/ml) in the presence of ketamine or MK-801 at 37 °C. TH subsets, supernatant interferon γ (IFN-γ), interleukin 4 (IL-4), and intracellular transcriptional factors T-bet and GATA3 were analyzed 4 h later. The number of TH0 cells was kept constant and at baseline before PMA and ionomycin stimulation in each group. TH1 cells, TH2 cells, IFN-γ and IL-4 levels were significantly increased after PMA and ionomycin stimulation. Ketamine and MK-801 decreased TH1 cells, TH2 cells, IFN-γ and IL-4 levels but increased the ratio of TH1/TH2 and IFN-γ/IL-4 in the presence of PMA and ionomycin. Ketamine or MK-801 alone had no effect on either of them. T-bet and GATA3 activities in PBMC were significantly increased after PMA and ionomycin stimulation. Ketamine and MK-801 decreased T-bet and GATA3 activities but increased the ratio of T-bet/GATA3 following PMA and ionomycin stimulation. Ketamine or MK-801 alone had no effect on the activity of T-bet, GATA3 or T-bet/GATA3. NMDA antagonist can suppress TH cell differentiation and subsequent cytokines production but increase TH1/TH2 ratio following PMA and ionomycin stimulation, it may be related to its regulation on T-bet and GATA3 activities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Induction of interleukin-10 in the T helper type 17 effector population by the G protein coupled estrogen receptor (GPER) agonist G-1 (United States)

    Brunsing, Ryan L; Prossnitz, Eric R


    Interleukin-10 (IL-10) is a potent suppressor of the immune system, commonly produced by CD4+ T cells to limit ongoing inflammatory responses minimizing host damage. Many autoimmune diseases are marked by large populations of activated CD4+ T cells within the setting of chronic inflammation; therefore, drugs capable of inducing IL-10 production in CD4+ T cells would be of great therapeutic value. Previous reports have shown that the small molecule G-1, an agonist of the membrane-bound G-protein-coupled estrogen receptor GPER, attenuates disease in an animal model of autoimmune encephalomyelitis. However, the direct effects of G-1 on CD4+ T-cell populations remain unknown. Using ex vivo cultures of purified CD4+ T cells, we show that G-1 elicits IL-10 expression in T helper type 17 (Th17) -polarized cells, increasing the number of IL-10+ and IL-10+ IL-17A+ cells via de novo induction of IL-10. T-cell cultures differentiated in the presence of G-1 secreted threefold more IL-10, with no change in IL-17A, tumour necrosis factor-α, or interferon-γ. Moreover, inhibition of extracellular signal-regulated kinase (but not p38 or Jun N-terminal kinase) signalling blocked the response, while analysis of Foxp3 and RORγt expression demonstrated increased numbers of IL-10+ cells in both the Th17 (RORγt+) and Foxp3+ RORγt+ hybrid T-cell compartments. Our findings translated in vivo as systemic treatment of male mice with G-1 led to increased IL-10 secretion from splenocytes following T-cell receptor cross-linking. These results demonstrate that G-1 acts directly on CD4+ T cells, and to our knowledge provide the first example of a synthetic small molecule capable of eliciting IL-10 expression in Th17 or hybrid T-cell populations. PMID:21722102

  2. Generation of Helper Plasmids Encoding Mutant Adeno-associated Virus Type 2 Capsid Proteins with Increased Resistance against Proteasomal Degradation

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    Naghmeh Ahmadiankia


    Full Text Available   Objective(s: Adeno-associated virus type 2 (AAV2 vectors are widely used for both experimental and clinical gene therapy. A recent research has shown that the performance of these vectors can be greatly improved by substitution of specific surface-exposed tyrosine residues with phenylalanines. In this study, a fast and simple method is presented to generate AAV2 vector helper plasmids encoding capsid proteins with single, double or triple Y→F mutations.   Materials and Methods: A one-step, high-fidelity polymerase chain reaction (PCR cloning procedure involving the use of two partially overlapping primers to amplify a circular DNA template was applied to produce AAV2 cap genes encoding VP1 mutants with Y→F substitutions in residues 444, 500 or 730. The resulting constructs were used to make the different double and triple mutant by another round of PCR (Y444500F mutant, subcloning (Y444730F and Y500730F mutants or a combination of both techniques (Y444500730F mutant. Results: Nucleotide sequence analysis revealed successful introduction of the desired mutations in the AAV2 cap gene and showed the absence of any unintended mutations in the DNA fragments used to assemble the final set of AAV2 vector helper plasmids. The correctness of these plasmids was further confirmed by restriction mapping. Conclusion: PCR-based, single-step site-directed mutagenesis of circular DNA templates is a highly efficient and cost-effective method to generate AAV2 vector helper plasmids encoding mutant Cap proteins for the production of vector particles with increased gene transfer efficiency.

  3. Helper-independent piggyBac plasmids for gene delivery approaches: Strategies for avoiding potential genotoxic effects (United States)

    Urschitz, Johann; Kawasumi, Miyuri; Owens, Jesse; Morozumi, Kazuto; Yamashiro, Hideaki; Stoytchev, Ilko; Marh, Joel; Dee, James A.; Kawamoto, Kris; Coates, Craig J.; Kaminski, Joseph M.; Pelczar, Pawel; Yanagimachi, Ryuzo; Moisyadi, Stefan


    Efficient integration of functional genes is an essential prerequisite for successful gene delivery such as cell transfection, animal transgenesis, and gene therapy. Gene delivery strategies based on viral vectors are currently the most efficient. However, limited cargo capacity, host immune response, and the risk of insertional mutagenesis are limiting factors and of concern. Recently, several groups have used transposon-based approaches to deliver genes to a variety of cells. The piggyBac (pB) transposase in particular has been shown to be well suited for cell transfection and gene therapy approaches because of its flexibility for molecular modification, large cargo capacity, and high transposition activity. However, safety considerations regarding transposase gene insertions into host genomes have rarely been addressed. Here we report our results on engineering helper-independent pB plasmids. The single-plasmid gene delivery system carries both the piggyBac transposase (pBt) expression cassette as well as the transposon cargo flanked by terminal repeat element sequences. Improvements to the helper-independent structure were achieved by developing new plasmids in which the pBt gene is rendered inactive after excision of the transposon from the plasmid. As a consequence, potentially negative effects that may develop by the persistence of an active pBt gene posttransposition are eliminated. The results presented herein demonstrate that our helper-independent plasmids represent an important step in the development of safe and efficient gene delivery methods that should prove valuable in gene therapy and transgenic approaches. PMID:20404201

  4. Circulating CXCR5+CD4+ T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines


    Ken Matsui; Adelsberger, Joseph W.; Kemp, Troy J; Michael W Baseler; Julie E Ledgerwood; Pinto, Ligia A


    Through the interaction of T follicular helper (Tfh) cells and B cells, efficacious vaccines can generate high-affinity, pathogen-neutralizing antibodies, and memory B cells. Using CXCR5, CXCR3, CCR6, CCR7, PD1, and ICOS as markers, Tfh-like cells can be identified in the circulation and be classified into three functionally distinct subsets that are PD1+ICOS+, PD1+ ICOS-, or PD1-ICOS-. We used these markers to identify different subsets of CXCR5+CD4+ Tfh-like cells in response to highly immu...

  5. An investigation of the relationship between recurrent spontaneous abortion and memory T follicular helper cells. (United States)

    Luan, Xiaorui; Kang, Xiaomin; Li, Weiping; Dong, Qian


    Immune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells' function comes from immune-related diseases. However, the true physiological characteristics of memory Tfh cells and their mode of action in pregnancy remain unclear. Deciduas and blood were obtained from 25 recurrent spontaneous abortion (RSA) patients undergoing surgical abortion and 19 normal women in early pregnancy undergoing elective termination. RSA patients were grouped into antibody-positive patients and antibody-negative patients, respectively. The memory Tfh cells with the CD4+ CXCR5+ PD1+ CCR7- and CD4+ CXCR5+ PD-1+ ICOS+ phenotypes were assessed by flow cytometry. The B cells were evaluated by flow cytometry. A correlation analysis of the subsets of memory Tfh cells and B cells in antibody-positive RSA patients was made by the Pearson test. Memory Tfh cells with the CD4+ CXCR5+ PD1+ CCR7- and CD4+ CXCR5+ PD-1+ ICOS+ phenotypes showed a significant increase in RSA patients compared to women with a normal pregnancy who had chosen termination. When RSA patients were grouped according positive or negative antibodies, it was surprising to find that decidual CD4+ CXCR5+ PD-1+ ICOS+ memory Tfh cells significantly increased in RSA patients with positive antibody compared to RSA patients with negative antibody. However, the percentages of CD4+ CXCR5+ PD1+ CCR7- memory Tfh cells did not change in the deciduas of the two groups. Circulating and decidual B cells significantly increased in antibody-positive RSA patients compared with antibody-negative RSA patients. Correlation analysis indicated a strong association between the decidual CD4+ CXCR5+ PD-1+ ICOS+ memory Tfh cells and B cells in antibody-positive RSA patients. These new findings provide unique insights into memory Tfh cells in mediating feto

  6. Follicular helper T cells in peripheral blood of patients with rheumatoid arthritis. (United States)

    Costantino, Alicia Beatriz; Acosta, Cristina Del Valle; Onetti, Laura; Mussano, Eduardo; Cadile, Ignacio Isaac; Ferrero, Paola Virginia

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by the presence of different autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies. CD4T cells expressing CXCR5, referred as follicular helper T cells (Tfh), collaborate with B cells to produce antibodies. Differential expression of CXCR3 and CCR6 within CD4+CXCR5+ T cells defines three mayor subsets: CXCR3+CCR6- (Tfh1), CXCR3-CCR6- (Tfh2) and CXCR3-CCR6+ (Tfh17). The aim of the study was to assess whether there is an association between the percentage of these cells and RA and whether there is a correlation with disease activity. Twenty-four RA patients, 22 healthy controls (HC) and 16 undifferentiated arthritis (UA) patients were included. Percentage of CD4+CXCR5+ T cells and their subsets were analyzed by flow cytometry. No differences were found in the percentages of CD4+CXCR5+ T cells in the comparison of RA vs HC or RA vs UA patients. Tfh1, Tfh2 and Tfh17 subsets showed no differences either. There was no correlation between CD4+CXCR5+T cells, Tfh1, Tfh2 and Tfh17, and Disease Activity Score in twenty-eight joints (DAS28) or erythrocyte sedimentation rate. Surprisingly, there was a positive correlation between Tfh17 cells and C-reactive protein. Finally, there was no correlation between CD4+CXCR5+ T cells, or their subsets, and anti-mutated citrullinated vimentin, or between the cells and RF. There were no differences between the percentages of CD4+CXCR5+ T cells and their subsets in peripheral blood of RA patients and the percentages of cells in the control groups. This finding does not rule out a pathogenic role of these cells in the development and activity of RA. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. Attenuation of antigen-specific T helper 1 immunity by Neolitsea hiiranensis and its derived terpenoids

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    Yin-Hua Cheng


    -dependent manner. N. hiiranensis-derived β-caryophyllene oxide inhibited several aspects of adaptive immune responses, including T-cell differentiation, IFN-γ production, and Th1-assocaited genes. Conclusion As IFN-γ is the key cytokine secreted by T helper-1 cells and plays a pivotal role in Th1 immune responses, our results suggested that the N. hiiranensis and its terpenoids may possess potential therapeutic effects on Th1-mediated immune disorders.

  8. Male professional footballers' experiences of mental health difficulties and help-seeking. (United States)

    Wood, Susan; Harrison, Lesley K; Kucharska, Jo


    Male professional footballers (soccer) represent an at-risk population of developing mental health difficulties and not accessing professional support. One in four current footballers report mental health difficulties. Higher prevalence is reported after retirement. This qualitative study aimed to provide in-depth insight into male professional footballers' lived experiences of mental health difficulties and help-seeking. Seven participants were interviewed. Data were analysed using interpretative phenomenological analysis. One superordinate theme emerged; 'Survival'. This related to survival in the professional football world, of mental health difficulties and after transition into the 'real world'. Six subordinate themes are explored alongside literature pertaining to male mental health, identity, injury, transition, and emotional development. Shame, stigma, fear and level of mental health literacy (knowledge of mental health and support) were barriers to help-seeking. Support for professional footballers' mental wellbeing requires improvement. Recommendations are made for future research, mental health education and support.

  9. IFN-γ production by memory helper T cells is required for CD40-independent alloantibody responses. (United States)

    Gorbacheva, Victoria; Fan, Ran; Wang, Xi; Baldwin, William M; Fairchild, Robert L; Valujskikh, Anna


    Cognate T-B cell interactions and CD40-CD154 costimulation are essential for productive humoral immunity against T-dependent Ags. We reported that memory CD4 T cells can deliver help to B cells and induce pathogenic IgG alloantibodies in the absence of CD40-CD154 interactions. To determine cytokine requirements for CD40-independent help, we used CD40(-/-) mice containing differentiated subsets of donor-reactive memory Th cells as heart allograft recipients. Th1 and Th17, but not Th2, memory CD4 T cells elicited high titers of anti-donor Ab. Abs induced by Th17 memory CD4 T cells had decreased reactivity against donor MHC class I molecules and inferior ability to cause complement deposition in heart allografts compared with Abs induced by Th1 cells, suggesting a requirement for IFN-γ during CD40-independent help. IFN-γ neutralization inhibited helper functions of memory CD4 T cells in both CD40(-/-) recipients and wild type recipients treated with anti-CD154 mAb. Our results suggest that IFN-γ secreted by pre-existing memory helper cells determines both isotype and specificity of donor-reactive alloantibodies and can thus affect allograft pathology. This information may be valuable for identifying transplant patients at risk for de novo development of pathogenic alloantibodies and for preventing alloantibody production in T cell-sensitized recipients. Copyright © 2015 by The American Association of Immunologists, Inc.

  10. Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV. (United States)

    Weaver, Eric A; Nehete, Pramod N; Nehete, Bharti P; Yang, Guojun; Buchl, Stephanie J; Hanley, Patrick W; Palmer, Donna; Montefiori, David C; Ferrari, Guido; Ng, Philip; Sastry, K Jagannadha; Barry, Michael A


    Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m.) or intravaginal (ivag.) routes with helper-dependent adenoviral (HD-Ad) vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5) prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm) responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination.

  11. Construction of adeno-associated virus packaging plasmids and cells that directly select for AAV helper functions. (United States)

    Whiteway, Alistair; Deru, Wale; Prentice, H Grant; Anderson, Robert


    Recombinant adeno-associated virus type 2 (rAAV) has promise for use as a gene therapy vector. Potential problems in the production of rAAV stocks are both the limited amount of recombinant virus that is produced by traditional methods and the possibility of wild-type replication competent adeno-associated virus (wtAAV) contamination. The presence of these contaminants is largely dependent upon the helper plasmid used. Whilst wtAAV is not a pathogen, the presence of these contaminants is undesirable as they may affect experiments concerning the biology of rAAV. Additionally as protocols using rAAV with altered tropism are becoming more prevalent, it is important that no recombination be permitted that may cause the creation of a replication competent AAV with modified (targeting) capsids. Many experimental protocols require the generation of large amounts of high titre rAAV stocks. We describe the production of several AAV helper plasmids and cell lines designed to achieve this goal. These plasmids possess split AAV rep and cap genes to eliminate the production of wtAAV and they possess a selection mechanism which is operatively linked to expression from the AAV cap gene. This allows positive selection of those cells expressing the highest level of the structural capsid proteins and therefore those cells which yield the highest amount of rAAV.

  12. Biophysical characterization data of the artificial protein Octarellin V.1 and binding test with its X-ray helpers

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    Maximiliano Figueroa


    Full Text Available The artificial protein Octarellin V.1 ( [1] was obtained through a direct evolution process over the de novo designed Octarellin V ( [2]. The protein has been characterized by circular dichroism and fluorescence techniques, in order to obtain data related to its thermo and chemical stability. Moreover, the data for the secondary structure content studied by circular dichroism and infra red techniques is reported for the Octarellin V and V.1. Two crystallization helpers, nanobodies ( [3] and αRep ( [4], have been used to create stable complexes. Here we present the data obtained of the binding characterization of the Octarellin V.1 with the crystallization helpers by isothermal titration calorimetry.

  13. Comparison of Systemic and Mucosal Immunization with Helper-Dependent Adenoviruses for Vaccination against Mucosal Challenge with SHIV (United States)

    Nehete, Bharti P.; Yang, Guojun; Buchl, Stephanie J.; Hanley, Patrick W.; Palmer, Donna; Montefiori, David C.; Ferrari, Guido; Ng, Philip; Sastry, K. Jagannadha; Barry, Michael A.


    Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m.) or intravaginal (ivag.) routes with helper-dependent adenoviral (HD-Ad) vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5) prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm) responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination. PMID:23844034

  14. Intrinsic features of the CD8α(-) dendritic cell subset in inducing functional T follicular helper cells. (United States)

    Shin, Changsik; Han, Jae-A; Choi, Bongseo; Cho, Yoon-Kyoung; Do, Yoonkyung; Ryu, Seongho


    T follicular helper (Tfh) cells, a true B cell helper, have a critical role in enhancing humoral immune responses. However, the initial differentiation of Tfh cells by dendritic cells (DCs), the most potent antigen presenting cells, has not been clearly understood, particularly in the knowledge of the two major conventional dendritic cell subsets, CD8α(+) DCs or CD8α(-) DCs. Here we demonstrated that the localization of CD8α(-) DCs in the marginal zone (MZ) bridging channels is closely associated with the induction of CXCR5(+)CCR7(low) Tfh cells. We also showed that the major source of IL-6 for inducing Tfh cells is provided from the activated CD4(+) T cells induced by CD8α(-) DCs, and IL-6 directly secreted from the DC subsets seems minor. CD8α(-) DCs were superior in inducing functional Tfh cells over other antigen presenting cells including B cells. We here observed the unknown intrinsic features of the DC subsets, suggesting the potential of utilizing the CD8α(-) DC subset as therapeutic vaccine for the regulation of humoral immune responses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. A rapid Q-PCR titration protocol for adenovirus and helper-dependent adenovirus vectors that produces biologically relevant results (United States)

    Gallaher, Sean D.; Berk, Arnold J.


    Adenoviruses are employed in the study of cellular processes and as expression vectors used in gene therapy. The success and reproducibility of these studies is dependent in part on having accurate and meaningful titers of replication competent and helper-dependent adenovirus stocks, which is problematic due to the use of varied and divergent titration protocols. Physical titration methods, which quantify the total number of viral particles, are used by many, but are poor at estimating activity. Biological titration methods, such as plaque assays, are more biologically relevant, but are time consuming and not applicable to helper-dependent gene therapy vectors. To address this, a protocol was developed called “infectious genome titration” in which viral DNA is isolated from the nuclei of cells ~3 h post-infection, and then quantified by Q-PCR. This approach ensures that only biologically active virions are counted as part of the titer determination. This approach is rapid, robust, sensitive, reproducible, and applicable to all forms of adenovirus. Unlike other Q-PCR-based methods, titers determined by this protocol are well correlated with biological activity. PMID:23624118


    Directory of Open Access Journals (Sweden)

    Yu. I. Rovda


    Full Text Available Thymectomy is a stage of surgery when treating some congenital heart defects. Thymus gland is the central organ of immune system. This organ is the primary site of T-cell lymphopoiesis and central tolerance to autoantigens during fetal and early postnatal life. If performed neonatally or in infancy, the thymectomy may cause restriction of these immune functions. Suppression of T-cell lymphopoiesis in children with thymectomy can be estimated as a subpopulation of thymic naive T helper cells (CD3+CD4+CD45RA+CD31+. To perform this task, we evaluated subpopulations of thymic naive T helper lymphocytes with CD3+CD4+CD45RA+CD31+ phenotype in the children (n = 40 who underwent thymectomy during surgical treatment of congenital heart diseases in neonates, or in early postnatal life. Their data were compared with children who underwent surgical treatment of congenital heart disease without thymectomy at the same age periods (n = 12, and healthy children (n = 23. We have revealed that thymectomy in frames of surgery of congenital heart disease leads to reduced thymic naive T helper lymphocytes with CD3+CD4+CD45RA+CD31+ phenotype in peripheral blood. Early execution of thymectomy is associated with deficiency of the thymic naive T helper lymphocytes in the peripheral blood, as well as a decrease in T helper cells (CD3+CD4+. The number thymic naive T helper lymphocytes in peripheral blood negatively corrrelated with terms elapsed after the surgery of congenital heart defects in children.

  17. Feasibility of Audio-Computer-Assisted Self-Interviewing With Color-Coding and Helper Assistance (ACASI-H) for Hmong Older Adults. (United States)

    Lor, Maichou; Bowers, Barbara J


    Many older adult immigrants in the US, including Hmong older adults, have limited English proficiency (LEP), and cannot read or have difficulty reading even in their first language (non-literate [NL]). Little has been done to identify feasible data collection approaches to enable inclusion of LEP or NL populations in research, limiting knowledge about their health. This study's purpose was to test the feasibility of culturally and linguistically adapted audio computer-assisted self-interviewing (ACASI) with color-labeled response categories and helper assistance (ACASI-H) for collection of health data with Hmong older adults. Thirty dyads (older adult and a helper) completed an ACASI-H survey with 13 health questions and a face-to-face debriefing interview. ACASI-H survey completion was video-recorded and reviewed with participants. Video review and debriefing interviews were audio-recorded and transcribed. Directed and conventional content analyses were used to analyze the interviews. All respondents reported that ACASI-H survey questions were consistent with their health experience. They lacked computer experience and found ACASI-H's interface user-friendly. All used the pre-recorded Hmong oral translation except for one, whose helper provided translation. Some Hmong older adults struggled with the color labeling at first, but helpers guided them to use the colors correctly. All dyads liked the color-labeled response categories and confirmed that a helper was necessary during the survey process. Findings support use of oral survey question administration with a technologically competent helper and color-labeled response categories when engaging LEP older adults in health-related data collection. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Male pattern baldness (image) (United States)

    Male pattern baldness is a sex-linked characteristic that is passed from mother to child. A man can more accurately predict his chances of developing male pattern baldness by observing his mother's father than by looking ...

  19. [Male urinary incontinence

    NARCIS (Netherlands)

    Boer, TA de; Heesakkers, J.P.F.A.


    *Urinary incontinence in males is gaining increasingly more attention. *Male urinary incontinence can be classified as storage incontinence due to overactive bladder syndrome or stress incontinence due to urethral sphincter dysfunction. *Most patients benefit from the currently available treatment

  20. El subjuntivo introducido por verbos y el problema de las “oraciones sustantivas” / Subjunctive introduced by verbs and the problem of “subordinating clauses”

    Directory of Open Access Journals (Sweden)

    David Pérez Rodríguez


    Full Text Available Attempting to explain when a subjunctive should be used in subordinating noun clauses is always a problem in an SSL class since they do not behave in the same way as other subordinate clauses which, in spite of having a great variety of uses, are very well defined thanks in part to the fact that their classification is based on their syntactic function and not on a classification of verbs based on semantics. For this reason, in this article we will attempt to provide a new perspective to the study of these clauses, paying attention to their function and behavior, and not to the meaning of the verb that introduces them, all in search of a workable systematization for students and teachers of Spanish.RESUMEN: Intentar explicar cuándo debe aparecer un subjuntivo en las oraciones subordinadas sustantivas en la clase de E/Le siempre es un problema, puesto que no se comportan de igual forma que el resto de subordinadas en las que a pesar de haber una amplia variedad de usos, están bien definidas gracias en parte a que su clasificación se debe a su función sintáctica y no a una clasificación de verbos basada en la semántica. Por este motivo, a lo largo de estas líneas vamos a intentar aportar una nueva perspectiva al estudio de estas oraciones sustantivas atendiendo a sus funciones y comportamientos, y no al significado del verbo que las introducen, en busca de una sistematización práctica para los estudiantes y docentes de español.

  1. Varicocele and male infertility

    DEFF Research Database (Denmark)

    Fuglesang Jensen, Christian S.; Østergren, Peter; Dupree, James M


    The link between varicoceles and male infertility has been a matter of debate for more than half a century. Varicocele is considered the most common correctable cause of male infertility, but some men with varicoceles are able to father children, even without intervention. In addition, improvements...... if the male partner has a clinically palpable varicocele and affected semen parameters....

  2. Opposing Development of Cytotoxic and Follicular Helper CD4 T Cells Controlled by the TCF-1-Bcl6 Nexus

    Directory of Open Access Journals (Sweden)

    Tiziano Donnarumma


    Full Text Available CD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB+ CD4+ CTLs, which distinguishes them from other CD4+ T helper (Th cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh cell signature. The balance between CD4+ CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors Bcl6 and Tcf7 (encoding TCF-1 and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4+ CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4+ T cells with either helper or killer functions.

  3. Antigen-specific helper activity in serum of mice primed with sheep red cells I. Definition of the test system and comparison with other systems

    NARCIS (Netherlands)

    Dijk, H. van; Rademaker, P.M.; Slotboom, A.; Willers, J.M.

    An adoptive transfer system is described to measure serum helper activity in the primary antibody response to sheep red blood cells (SRBC). Mice injected with a high dose of cyclophosphamide and reconstituted with rabbit anti-thymocyte serum-treated spleen cells were used as recipients. Serum

  4. CCR3, CCR5, CCR8 and CXCR3 expression in memory T helper cells from allergic rhinitis patients, asymptomatically sensitized and healthy individuals

    DEFF Research Database (Denmark)

    Holse, Mille; Assing, Kristian; Poulsen, Lars K.


    Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial....

  5. Soil-Transmitted Helminth Infections Are Associated With an Increase in Human Papillomavirus Prevalence and a T-Helper Type 2 Cytokine Signature in Cervical Fluids


    Gravitt, Patti E.; Marks, Morgan; Kosek, Margaret; Huang, Christine; Cabrera, Lilia; Olortegui, Maribel Paredes; Medrano, Alberto Mejia; Trigoso, Dixner R.; Qureshi, Sarah; Bardales, Gustavo S.; Manrique-Hinojosa, Javier; Cardenas, Albert Z.; Larraondo, Manuel A.; Cok, Jaime; Qeadan, Fares


    Background.?An ecological correlation between invasive cervical cancer incidence and burden of soil-transmitted helminths (STH) is hypothesized to explain the excess in detectable human papillomavirus (HPV) infection in Latin America, via a global T-helper type 2 (Th2)?biased mucosal immune response secondary to STH infection.

  6. Helpers at the Nest Improve Late-Life Offspring Performance : Evidence from a Long-Term Study and a Cross-Foster Experiment

    NARCIS (Netherlands)

    Brouwer, Lyanne; Richardson, David S.; Komdeur, Jan; Waterman, Jane M.


    Background: Conditions during an individual's rearing period can have far reaching consequences for its survival and reproduction later in life. Conditions typically vary due to variation in parental quality and/or the environment, but in cooperative breeders the presence of helpers adds an

  7. Male urine signals social rank in the Mozambique tilapia (Oreochromis mossambicus

    Directory of Open Access Journals (Sweden)

    Miranda António


    Full Text Available Abstract Background The urine of freshwater fish species investigated so far acts as a vehicle for reproductive pheromones affecting the behaviour and physiology of the opposite sex. However, the role of urinary pheromones in intra-sexual competition has received less attention. This is particularly relevant in lek-breeding species, such as the Mozambique tilapia (Oreochromis mossambicus, where males establish dominance hierarchies and there is the possibility for chemical communication in the modulation of aggression among males. To investigate whether males use urine during aggressive interactions, we measured urination frequency of dye-injected males during paired interactions between size-matched males. Furthermore, we assessed urinary volume stored in the bladder of males in a stable social hierarchy and the olfactory potency of their urine by recording of the electro-olfactogram. Results Males released urine in pulses of short duration (about one second and markedly increased urination frequency during aggressive behaviour, but did not release urine whilst submissive. In the stable hierarchy, subordinate males stored less urine than males of higher social rank; the olfactory potency of the urine was positively correlated with the rank of the male donor. Conclusion Dominant males store urine and use it as a vehicle for odorants actively released during aggressive disputes. The olfactory potency of the urine is positively correlated with the social status of the male. We suggest that males actively advertise their dominant status through urinary odorants which may act as a 'dominance' pheromone to modulate aggression in rivals, thereby contributing to social stability within the lek.

  8. Immune polarization by hookworms: taking cues from T helper type 2, type 2 innate lymphoid cells and alternatively activated macrophages. (United States)

    Nair, Meera G; Herbert, De'Broski R


    Cellular and molecular investigation of parasitic helminth infections has greatly accelerated the understanding of type 2 immune responses. However, there remains considerable debate regarding the specific leucocytes that kill parasites and whether these mechanisms are distinct from those responsible for tissue repair. Herein, we chronicle discoveries over the past decade highlighting current paradigms in type 2 immunity with a particular emphasis upon how CD4(+) T helper type 2 cells, type 2 innate lymphoid cells and alternatively activated macrophages coordinately control helminth-induced parasitism. Primarily, this review will draw from studies of the murine nematode parasite Nippostrongylus brasiliensis, which bears important similarities to the human hookworms Ancylostoma duodenale and Necator americanus. Given that one or more hookworm species currently infect millions of individuals across the globe, we propose that vaccine and/or pharmaceutical-based cure strategies targeting these affected human populations should incorporate the conceptual advances outlined herein. © 2016 John Wiley & Sons Ltd.

  9. Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses. (United States)

    Yang, Jialong; Lin, Xingguang; Pan, Yun; Wang, Jinli; Chen, Pengcheng; Huang, Hongxiang; Xue, Hai-Hui; Gao, Jimin; Zhong, Xiao-Ping


    T follicular helper (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In Mtor(f/f)-Cd4Cre mice, both constitutive and inducible Tfh differentiation is severely impaired, leading to defective germinal center B cell formation and antibody production. Moreover, both mTORC1 and mTORC2 contribute to Tfh and GC B cell development but may do so via distinct mechanisms. mTORC1 mainly promotes CD4 T cell proliferation to reach the cell divisions necessary for Tfh differentiation, while Rictor/mTORC2 regulates Tfh differentiation by promoting Akt activation and TCF1 expression without grossly influencing T cell proliferation. Together, our results reveal crucial but distinct roles for mTORC1 and mTORC2 in CD4 T cells during Tfh differentiation and germinal center responses.

  10. A novel helper phage for HaloTag-mediated co-display of enzyme and substrate on phage. (United States)

    Delespaul, Wouter; Peeters, Yves; Herdewijn, Piet; Robben, Johan


    Phage display is an established technique for the molecular evolution of peptides and proteins. For the selection of enzymes based on catalytic activity however, simultaneous coupling of an enzyme and its substrate to the phage surface is required. To facilitate this process of co-display, we developed a new helper phage displaying HaloTag, a modified haloalkane dehalogenase that binds specifically and covalently to functionalized haloalkane ligands. The display of functional HaloTag was demonstrated by capture on streptavidin-coated magnetic beads, after coupling a biotinylated haloalkane ligand, or after on-phage extension of a DNA oligonucleotide primer with a biotinylated nucleotide by phi29 DNA polymerase. We also achieved co-display of HaloTag and phi29 DNA polymerase, thereby opening perspectives for the molecular evolution of this enzyme (and others) towards new substrate specificities. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. The transcription factor Runx3 guards cytotoxic CD8+effector T cells against deviation towards follicular helper T cell lineage. (United States)

    Shan, Qiang; Zeng, Zhouhao; Xing, Shaojun; Li, Fengyin; Hartwig, Stacey M; Gullicksrud, Jodi A; Kurup, Samarchith P; Van Braeckel-Budimir, Natalija; Su, Yao; Martin, Matthew D; Varga, Steven M; Taniuchi, Ichiro; Harty, John T; Peng, Weiqun; Badovinac, Vladimir P; Xue, Hai-Hui


    Activated CD8 + T cells differentiate into cytotoxic effector (T EFF ) cells that eliminate target cells. How T EFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in T EFF cells. Runx3-deficient CD8 + T EFF cells aberrantly upregulated genes characteristic of follicular helper T (T FH ) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the T FH program. Ablating Tcf7 in Runx3-deficient CD8 + T EFF cells prevented the upregulation of T FH genes and ameliorated their defective induction of cytotoxic genes. As such, Runx3-mediated Tcf7 repression coordinately enforced acquisition of cytotoxic functions and protected the cytotoxic lineage integrity by preventing T FH -lineage deviation.

  12. T-helper 17-related cytokines and IgE antibodies during hepatitis A virus infection in children

    Directory of Open Access Journals (Sweden)

    Jorge L Trujillo-Ochoa


    Full Text Available We determined the serum IgE levels and T-helper (Th17-related cytokines during distinct hepatitis A virus (HAV-induced clinical courses in children. A significantly higher concentration of macrophage inflammatory protein 3α, interleukin (IL-17E and IL-17F in HAV-infected children with intermediate liver injury compared with those with minor liver damage was found. A reduction in the IgE levels in those patients who showed the highest levels of IL-17F in the group of intermediate liver injury was found. The data suggested that the Th17-related profile is associated with the severity of HAV infection and might play a role on the modulation achieved by HAV during allergies.

  13. Interaction in vivo between hapten-specific suppressor T cells and an in vitro cultured helper T cell line

    DEFF Research Database (Denmark)

    Owens, T; Miller, J F


    (ABA). Transfer of splenic T cells from these mice by i.v. injection suppressed the induction in syngeneic assay hosts of ABA-reactive helper and cytotoxic T cell (Tc) responses. Although the Th responses and their suppression were ABA specific, in that they were not induced or activated...... on the provision of exogenous Th by reducing the antigen dose. This stratagem allowed the assay in vivo of a long-term cultured ABA-specific Th cell line (E9). Injection of 10(5) E9 cells/mouse (with antigen, in the rear footpad) helped the induction of both Tc and Th in response to a reduced dose of antigen...

  14. Mechanisms of Low Dose Radiation-induced T helper Cell Function

    Energy Technology Data Exchange (ETDEWEB)

    Gridley, Daila S.


    Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of “dirty bombs” by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset of lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to

  15. Antipredator Vocalization Usage in the Male Ring-Tailed Lemur (Lemur catta). (United States)

    Bolt, Laura M; Sauther, Michelle L; Cuozzo, Frank P; Youssouf Jacky, Ibrahim Antho


    The ring-tailed lemur (Lemur catta) is a group-living strepsirrhine primate endemic to Madagascar that faces considerable predation pressure from aerial and terrestrial predators. This species engages in mobbing and vigilance behavior in response to predators, and has referential alarm vocalizations. Because L. catta is female dominant, less is known about the alarm calls of males. We tested 3 hypotheses for male antipredator vocalization behavior on L. catta at the Bezà Mahafaly Special Reserve in Madagascar: the predator confusion, group maintenance, and predation risk allocation hypotheses. We found support for 2 hypotheses. When a male L. catta made an antipredator call, other group members vocalized in response. Dominant males did not make alarm calls at higher rates than subordinate males. Predators were more abundant on the western side of Parcel 1, but an even greater number of antipredator vocalizations occurred in this area than predator abundance warranted. We show that male L. catta consistently participated in group-level antipredator vocalization usage in high-risk locations. Although female L. catta are known to hold the primary role in group defense, male L. catta are also key participants in group-wide behaviors that may confuse or drive away predators. © 2015 S. Karger AG, Basel.

  16. Chemical diplomacy in male tilapia: urinary signal increases sex hormone and decreases aggression. (United States)

    Saraiva, João L; Keller-Costa, Tina; Hubbard, Peter C; Rato, Ana; Canário, Adelino V M


    Androgens, namely 11-ketotestosterone (11KT), have a central role in male fish reproductive physiology and are thought to be involved in both aggression and social signalling. Aggressive encounters occur frequently in social species, and fights may cause energy depletion, injury and loss of social status. Signalling for social dominance and fighting ability in an agonistic context can minimize these costs. Here, we test the hypothesis of a 'chemical diplomacy' mechanism through urinary signals that avoids aggression and evokes an androgen response in receiver males of Mozambique tilapia (Oreochromis mossambicus). We show a decoupling between aggression and the androgen response; males fighting their mirror image experience an unresolved interaction and a severe drop in urinary 11KT. However, if concurrently exposed to dominant male urine, aggression drops but urinary 11KT levels remain high. Furthermore, 11KT increases in males exposed to dominant male urine in the absence of a visual stimulus. The use of a urinary signal to lower aggression may be an adaptive mechanism to resolve disputes and avoid the costs of fighting. As dominance is linked to nest building and mating with females, the 11KT response of subordinate males suggests chemical eavesdropping, possibly in preparation for parasitic fertilizations.

  17. Reversed sex change by widowed males in polygynous and protogynous fishes: female removal experiments in the field (United States)

    Kuwamura, Tetsuo; Suzuki, Shohei; Kadota, Tatsuru


    Sex change, either protogyny (female to male) or protandry (male to female), is well known among fishes, but evidence of bidirectional sex change or reversed sex change in natural populations is still very limited. This is the first report on female removal experiments for polygnous and protogynous fish species to induce reversed sex change in the widowed males in the field. We removed all of the females and juveniles from the territories of dominant males in the cleaner wrasse Labroides dimidiatus (Labridae) and the rusty angelfish Centropyge ferrugata (Pomacanthidae) on the coral reefs of Okinawa. In both species, if new females or juveniles did not immigrate into the territories of the widowed males, some of them emigrated to form male-male pairs. When a male-male pair formed, the smaller, subordinate partner began to perform female sexual behaviours ( n = 4 in L. dimidiatus; n = 2 in C. ferrugata) and, finally, released eggs ( n = 1, respectively). Thus, the reversed sex change occurred in the widowed males according to the change of their social status. These results suggest that such female removal experiments will contribute to the discovery of reversed sex change in the field also in other polygnous and protogynous species.

  18. Drosophila Male Meiosis. (United States)

    Bonaccorsi, Silvia; Gatti, Maurizio


    In Drosophila males, there is no synaptonemal complex and recombination does not occur. Thus, Drosophila male meiosis is a good model system for the analysis of achiasmate chromosome segregation. In addition, due to their large size, the meiotic spindles of Drosophila males are an excellent system for mutational dissection of the mechanisms of spindle assembly. Here, we describe the main techniques for visualization of live Drosophila testes and for preparation of fixed meiotic chromosomes and spindles.

  19. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, S., E-mail: [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom); Steel, J.; Porter, G. [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom)


    Male breast cancer is rare, with some pathological and radiological differences from female breast cancer. There is less familiarity with the imaging appearances of male breast cancer, due to its rarity and the more variable use of preoperative imaging. This review will illustrate the commonest imaging appearances of male breast cancer, with emphasis on differences from female breast cancer and potential pitfalls in diagnosis, based on a 10 year experience in our institution.

  20. De la recherche salariée en France : lien de subordination et liberté de la recherche

    Directory of Open Access Journals (Sweden)

    Constance Perrin-Joly


    Full Text Available Au travers de l’expérience d’une thèse de sociologie menée en entreprise (sous convention industrielle de formation par la recherche, nous chercherons en quoi le lien de subordination attaché au salariat et la dépendance économique associée nuisent à la liberté de la recherche, le sociologue ne pouvant s’appuyer sur les ressources d’une profession constituée ou s’intégrer dans une organisation logocratique. Le chercheur, pris entre des injonctions dissonantes risque de favoriser son intérêt personnel à court terme de salarié, parfois au détriment de celui attaché à sa position de sociologue, pour rendre la situation tenable. Les liens qui se créent avec la mise en place de relations de travail approfondies et du fait de l’intégration dans des logiques de pouvoir internes gênent également la distance affective nécessaire à la co-construction des résultats.About salary research in France: subordination link and freedom researchBased on a PhD done within a company (with special French contract named CIFRE, this article deals with how subordination link in salary and economic dependency harm research’s freedom. In fact, sociologist can neither draw on a system of profession resources, nor be integrated into a “logocratic firm”. The researcher which undergoes paradoxical injunctions risks promoting his own short-term salary interest to the detriment of scientific interest, in order to make the situation bearable. Furthermore, the affective distance necessary to achieve results - with people concerned by the request (“co-construction”, is affected by close working relationships and socially-influenced relationships.De la investigación asalariada en Francia: vínculo de subordinación entre libertad e investigaciónMediante  la experiencia de una tesis sociológica llevada a cabo en una empresa (bajo convención industrial de formación por investigación, buscaremos la forma en la que el vínculo de

  1. Personality predicts social dominance in male domestic fowl.

    Directory of Open Access Journals (Sweden)

    Anna Favati

    Full Text Available Individuals in social species commonly form dominance relationships, where dominant individuals enjoy greater access to resources compared to subordinates. A range of factors such as sex, age, body size and prior experiences has to varying degrees been observed to affect the social status an individual obtains. Recent work on animal personality (i.e. consistent variation in behavioural responses of individuals demonstrates that personality can co-vary with social status, suggesting that also behavioural variation can play an important role in establishment of status. We investigated whether personality could predict the outcome of duels between pairs of morphologically matched male domestic fowl (Gallus gallus domesticus, a species where individuals readily form social hierarchies. We found that males that more quickly explored a novel arena, or remained vigilant for a longer period following the playback of a warning call were more likely to obtain a dominant position. These traits were uncorrelated to each other and were also uncorrelated to aggression during the initial part of the dominance-determining duel. Our results indicate that several behavioural traits independently play a role in the establishment of social status, which in turn can have implications for the reproductive success of different personality types.

  2. Male Adolescent Contraceptive Utilization. (United States)

    Finkel, Madelon Lubin; Finkel, David J.


    The contraceptive utilization of a sample of sexually active, urban, high school males (Black, Hispanic, and White) was examined by anonymous questionnaire. Contraceptive use was haphazard, but White males tended to be more effective contraceptors than the other two groups. Reasons for nonuse were also studied. (Author/SJL)

  3. Male breast cancer

    DEFF Research Database (Denmark)

    Lautrup, Marianne D; Thorup, Signe S; Jensen, Vibeke


    Objective: Describe prognostic parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980–2009. Determine all-cause mortality compared to the general male population and analyze survival/mortality compared with Danish female breast cancer patients (FBCP) in the same period...

  4. Patterns of male dispersal in Verreaux's sifaka (Propithecus verreauxi) at Kirindy Mitea National Park. (United States)

    Leimberger, Kara G; Lewis, Rebecca J


    Males of many group-living mammals emigrate from their social groups to improve mating opportunities. To help mitigate the social and locational costs of dispersal and to increase reproductive benefits, they may immigrate seasonally, immigrate alongside a partner, and/or replace the alpha male (versus entering a group as a subordinate). Verreaux's sifaka (Propithecus verreauxi) are highly seasonally breeding primates characterized by male-biased dispersal. We hypothesized that (i) males time immigrations to pursue immediate mating opportunities, (ii) entrances with partners more often result in alpha male replacement, and (iii) male competitive ability affects immigration strategy and alpha male tenure length. To assess these proximate aspects of male dispersal, we examined 7 years of demographic, morphological, and behavioral data for five social groups of Verreaux's sifaka in the Kirindy Mitea National Park in western Madagascar. Contrary to expectations and studies of sifaka dispersal in other populations, we detected no strong seasonal pattern in immigrations. Immigrations occurred individually and with partners, and a trend existed for partners to increase the likelihood of replacing an alpha male. Pronounced activity of the sternal scent gland (a proxy for testosterone and prior dominance status), but not body mass, canine size, or potential correlates of leaping ability, significantly influenced immigration strategy. The absence of a seasonal immigration pattern suggests that fluid group boundaries may allow mating success without establishment in a social group before the mating season. Our results also suggest that male immigration strategies are affected by age, prior dominance status, and testosterone levels but not morphological indicators of individual competitive ability. Coalitions may be used to improve competitive ability. Finally, differences in seasonal immigration patterns and length of alpha male vacancies observed at Kirindy Mitea may be due

  5. Reward Behavior by Male and Female Leaders: A Causal Inference Analysis. (United States)

    Szilagyi, Andrew D.


    Investigated causal inferences between leader reward behavior and subordinate goal attainment, absenteeism, and work satisfaction. Results revealed that no significant differences were attributed to sex and that the leader reward behavior and subordinate attitudes and behavior were independent of the effects of sex of supervisor or subordinate.…

  6. Demand for male contraception. (United States)

    Dorman, Emily; Bishai, David


    The biological basis for male contraception was established decades ago, but despite promising breakthroughs and the financial burden men increasingly bear due to better enforcement of child support policies, no viable alternative to the condom has been brought to market. Men who wish to control their fertility must rely on female compliance with contraceptives, barrier methods, vasectomy or abstinence. Over the last 10 years, the pharmaceutical industry has abandoned most of its investment in the field, leaving only nonprofit organisations and public entities pursuing male contraception. Leading explanations are uncertain forecasts of market demand pitted against the need for critical investments to demonstrate the safety of existing candidate products. This paper explores the developments and challenges in male contraception research. We produce preliminary estimates of potential market size for a safe and effective male contraceptive based on available data to estimate the potential market for a novel male method.

  7. Male Reproductive System (For Teens) (United States)

    ... Why Exercise Is Wise Are Detox Diets Safe? Male Reproductive System KidsHealth > For Teens > Male Reproductive System ... and female reproductive systems. continue What Is the Male Reproductive System? Most species have two sexes: male ...

  8. Love is blind: indiscriminate female mating responses to male courtship pheromones in newts (Salamandridae.

    Directory of Open Access Journals (Sweden)

    Dag Treer

    Full Text Available Internal fertilization without copulation or prolonged physical contact is a rare reproductive mode among vertebrates. In many newts (Salamandridae, the male deposits a spermatophore on the substrate in the water, which the female subsequently takes up with her cloaca. Because such an insemination requires intense coordination of both sexes, male newts have evolved a courtship display, essentially consisting of sending pheromones under water by tail-fanning towards their potential partner. Behavioral experiments until now mostly focused on an attractant function, i.e. showing that olfactory cues are able to bring both sexes together. However, since males start their display only after an initial contact phase, courtship pheromones are expected to have an alternative function. Here we developed a series of intraspecific and interspecific two-female experiments with alpine newt (Ichthyosaura alpestris and palmate newt (Lissotriton helveticus females, comparing behavior in male courtship water and control water. We show that male olfactory cues emitted during tail-fanning are pheromones that can induce all typical features of natural female mating behavior. Interestingly, females exposed to male pheromones of their own species show indiscriminate mating responses to conspecific and heterospecific females, indicating that visual cues are subordinate to olfactory cues during courtship.

  9. Do Low-quality Leader-Member Relationships Matter for Subordinates? Evidence from Three Samples on the Validity of the Norwegian LMX Scale

    Directory of Open Access Journals (Sweden)

    Trude Furunes


    Full Text Available Theories on the relations between leaders and subordinates have been of interest to researchers for decades; however, these theories have received less attention in the Nordic countries. The aim of this study is twofold: to investigate the validity of the Leader-Member-Exchange Scale, LMX-7, in three Norwegian samples, and to explore potentially negative relationships between leader–member relationships and work-environment quality indicators. Data were collected from teachers (n = 409, industrial workers (n = 406, and bus drivers (n = 1024. All hypotheses were supported. Results supported use of the measure LMX-7 as indicated by factor structure, high construct validity, sufficient criterion-related validity, discriminant validity, and internal reliability as measured by Cronbach’s alpha above 0.90. Poor quality relationships were associated with higher levels of role conflict, stress, bullying, turnover intentions, age discrimination, and negative affectivity, and lower levels of job satisfaction, commitment, skills utilization, autonomy, participation, perceived fairness, and social support. Potential consequences of low-quality relations and implications of findings are discussed.

  10. Ernst Rüdin's Unpublished 1922-1925 Study "Inheritance of Manic-Depressive Insanity": Genetic Research Findings Subordinated to Eugenic Ideology.

    Directory of Open Access Journals (Sweden)

    Gundula Kösters


    Full Text Available In the early 20th century, there were few therapeutic options for mental illness and asylum numbers were rising. This pessimistic outlook favoured the rise of the eugenics movement. Heredity was assumed to be the principal cause of mental illness. Politicians, scientists and clinicians in North America and Europe called for compulsory sterilisation of the mentally ill. Psychiatric genetic research aimed to prove a Mendelian mode of inheritance as a scientific justification for these measures. Ernst Rüdin's seminal 1916 epidemiological study on inheritance of dementia praecox featured large, systematically ascertained samples and statistical analyses. Rüdin's 1922-1925 study on the inheritance of "manic-depressive insanity" was completed in manuscript form, but never published. It failed to prove a pattern of Mendelian inheritance, counter to the tenets of eugenics of which Rüdin was a prominent proponent. It appears he withheld the study from publication, unable to reconcile this contradiction, thus subordinating his carefully derived scientific findings to his ideological preoccupations. Instead, Rüdin continued to promote prevention of assumed hereditary mental illnesses by prohibition of marriage or sterilisation and was influential in the introduction by the National Socialist regime of the 1933 "Law for the Prevention of Hereditarily Diseased Offspring" (Gesetz zur Verhütung erbkranken Nachwuchses.

  11. Immunologic Overlap of Helper T-Cell Subtypes 17 and 22 in Erythrodermic Psoriasis and Atopic Dermatitis. (United States)

    Moy, Andrea Primiani; Murali, Mandakolathur; Kroshinsky, Daniela; Duncan, Lyn M; Nazarian, Rosalynn M


    Psoriasis and atopic dermatitis (AD) are inflammatory diseases thought to be mediated by helper T-cell subtypes 1 and 2 (TH1 and TH2), respectively. Although psoriasis and AD show histopathologic differences during chronic disease, they are difficult to distinguish histologically during erythrodermic exacerbations. To determine whether the immune phenotype of helper T cells can differentiate erythrodermic psoriasis and erythrodermic AD by studying skin biopsy specimens of patients with psoriasis and AD during erythrodermic and chronic disease phases. We conducted a retrospective study using biopsy samples of psoriasis, AD, and erythroderma belonging to the surgical pathology files of the James Homer Wright Pathology Laboratories, Massachusetts General Hospital, and collected from January 1, 2004, through December 31, 2011. Samples were obtained from patients with chronic psoriasis (n = 20), chronic AD (n = 20), erythroderma subsequently diagnosed as psoriasis (n = 7), and erythroderma subsequently diagnosed as AD (n = 5). We evaluated immunohistochemical stains for CD3 and dual stains for CD4 and T-bet, GATA binding protein 3 (GATA3), signal transducer and activator of transcription 3 (STAT3), or basonuclin 2 (BNC2), which are transcription factors reported to be specific and mutually exclusive for TH1, TH2, TH17, and TH22 cells, respectively. Two investigators independently counted CD3+ cells and dual-labeled CD4+/T-bet+, CD4+/GATA3+, CD4+/STAT3+, and CD4+/BNC2+ cells in 5 consecutive high-power fields. We evaluated the percentage of TH1, TH2, TH17, and TH22 cells in CD3+ T cells and the TH1:TH2 ratio in chronic psoriasis, chronic AD, erythrodermic psoriasis, and erythrodermic AD. We found a significant difference in the TH1:TH2 ratio between chronic psoriasis and chronic AD (0.26 and 0.09, respectively; P = .005). However, we detected no significant difference in the percentage of TH1 (6.5% and 4.8%), TH2 (55.2% and 64.6%), TH17 (14.7% and 30

  12. Male depression in females? (United States)

    Möller-Leimkühler, Anne Maria; Yücel, Mete


    Scientific evidence for a male-typed depression ("male depression") is still limited, but mainly supports this concept with respect to single externalizing symptoms or symptom clusters. In particular, studies on non-clinical populations including males and females are lacking. The present study aims at assessing general well-being, the risk and the symptoms of male depression dependent on biological sex and gender-role orientation on instrumental (masculine) and expressive (feminine) personality traits in an unselected community sample of males and females. Students (518 males, 500 females) of the Ludwig-Maximilians-University of Munich, Germany, were asked to participate in a "stress study" and complete the following self-report questionnaires: the WHO-5 Well-being Index [Bech, P., 1998. Quality of Life in the Psychiatric Patient. Mosby-Wolfe, London], the Gotland Scale for Male Depression [Walinder, J., Rutz, W., 2001. Male depression and suicide. International Clinical Psychopharmacology 16 (suppl 2), 21-24] and the German Extended Personal Attribute Questionnaire [Runge, T.E., Frey, D., Gollwitzer, P.M., et al., 1981. Masculine (instrumental) and feminine (expressive) traits. A comparison between students in the United States and West Germany. Journal of Cross-Cultural Psychology 12, 142-162]. General well-being of the students was significantly lower compared to population norms. Contrary to expectations, female students had a greater risk of male depression than male students (28.9% vs. 22.4%; pmasculinity/instrumentality significantly predicted higher risk of male depression, independent of biological sex. The study sample is not representative to the general population. Self-reports of the participants were not validated by a clinical evaluation. The results suggest that male depression might also be highly prevalent in females, at least in university students. This can be explained by a growing social acceptance of aggression in women, by a greater

  13. Pseudocyesis in the male. (United States)

    Evans, D L; Seely, T J


    This report describes a case of pseudocyesis in a male patient and reviews the literature in pseudocyesis in the male and female. Pseudocyesis is a rare psychiatric syndrome with only about 100 cases reported in females and three in males in the past 45 years. The authors suggest that somatic factors may play a role in the genesis of some cases of pseudocyesis by stimulating pregnancy wishes and interacting with these wishes to set up a psychophysiological interaction leading to the clinical syndrome of pseudocyesis.

  14. Predictors of male microchimerism

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Mortensen, Laust Hvas; Andersen, Anne-Marie Nybo


    confounding and reverse causation. To address the issue of confounding, we conducted an analysis of predictors of male microchimerism in 272 female participants of the Danish Diet, Cancer and Health cohort. Buffy coat DNA was tested for Y chromosome presence as a marker of male microchimerism. First, we used...... logistic regression and thereafter random forest modeling to evaluate the ability of a range of reproductive, lifestyle, hospital or clinic visit history, and other variables to predict whether women tested positive for male microchimerism. We found some indication that current use of contraceptive pills...

  15. Effect of narrow band ultraviolet B phototherapy on T helper 17 cell specific cytokines (interleukins-17, 22 and 23) in psoriasis vulgaris. (United States)

    Bajaj, S; Gautam, R K; Khurana, A; Arora, P; Sharma, N


    Psoriasis is mediated by a T helper 17 (Th17) cell inflammatory process. This study describes the changes in serum levels of IL-17, 22 and 23 in patients of psoriasis vulgaris treated with narrow band ultraviolet B (NBUVB). The serum levels of IL-17, 22 and 23 were compared with a control group (n = 30) before and after NBUVB. In addition, post-NBUVB levels were compared with healthy controls. Psoriasis Area Severity Score (PASI) and Body Surface Area scoring were used to evaluate severity of disease. When compared with the non-psoriasis control group, IL-17, 22 and 23 were higher in psoriasis patients (p psoriasis. Post-phototherapy only the IL-17 levels decrease to that of non-psoriasis controls. Our study supports the role of T helper 17 cell specific cytokines in psoriasis and a possible mechanism of action of NBUVB via inhibition of these cytokines.

  16. Males and Eating Disorders (United States)

    ... Bar Home Current Issue Past Issues Males and Eating Disorders Past Issues / Spring 2008 Table of Contents ... this page please turn Javascript on. Photo: PhotoDisc Eating disorders primarily affect girls and women, but boys ...

  17. The tuberous male breast. (United States)

    Hamilton, S; Gault, D


    Whilst tuberous female breasts are well described, the tuberous male breast is a very unusual variant of gynaecomastia. Two cases are presented, the development of the condition is considered and the surgical management is discussed.

  18. Male hypogonadism (Part 1

    Directory of Open Access Journals (Sweden)

    Ye.V. Luchytskyy


    Full Text Available The first part of the review presents the current data on the prevalence of male hypogonadism, methods of diagnosing different forms of hypogonadism, describes the clinical manifestations of the most common forms of this disease.

  19. Cytogenetic of Male Infertility

    Directory of Open Access Journals (Sweden)

    Lutfiye Ozpak


    Full Text Available Infertility by definition, is not to get pregnant within one year of regular sexual relationship without protection, affects 15-20% of reproductive age couples. Approximately 30% of infertility cases are male originated. Male infertility is caused by endocrine-related genetic defects affecting urogenital system function. These defects adversely affect subsequent spermatogenesis, sexual function, fertility, early embryonic stage of sexual maturation. Autosomal and gonosomal, numerical and structural chromosome abnormalities and related syndromes rank at the top causes of male infertility. Similar chromosome abnormalities are detected in male infertility and as the rate of these abnormalities increase, it was found to reduce sperm count especially in azospermic and oligozoospermic men. [Archives Medical Review Journal 2011; 20(4.000: 230-245

  20. CD4+ T helper cell responses to NY-ESO-1 tumor antigen in ovarian cancer resist perversion into immunosuppressive Tregs (United States)

    Valmori, Danila; Ayyoub, Maha


    In a recent study, we have demonstrated that T helper type 1 (TH1) cells specific for the tumor antigen NY-ESO-1 are amplified at ovarian tumor sites but are not “perverted” into immunosuppressive FOXP3+ regulatory T cells (Tregs). These findings encourage the development of protocols aiming to eliminate, or inactivate, FOXP3+ Tregs and reinforce Type I anticancer immunity, to improve clinical outcomes. PMID:26587312

  1. Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke


    Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH...... a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS....

  2. Thyroid and male reproduction

    Directory of Open Access Journals (Sweden)

    Anand Kumar


    Full Text Available Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH, pituitary luteinizing hormone (LH and follicle stimulating hormone (FSH and the gonadal steroid, principally, testosterone. Thyroid hormones have been shown to exert a modulatory influence on this axis and consequently the sexual and spermatogenic function of man. This review will examine the modulatory influence of thyroid hormones on male reproduction.

  3. Thyroid and male reproduction. (United States)

    Kumar, Anand; Shekhar, Skand; Dhole, Bodhana


    Male reproduction is governed by the classical hypothalamo-hypophyseal testicular axis: Hypothalamic gonadotropin releasing hormone (GnRH), pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) and the gonadal steroid, principally, testosterone. Thyroid hormones have been shown to exert a modulatory influence on this axis and consequently the sexual and spermatogenic function of man. This review will examine the modulatory influence of thyroid hormones on male reproduction.

  4. Update on male contraception. (United States)

    Naz, Rajesh K; Rowan, Shon


    To review current options of contraception available for men and the recent developments in the field of male contraception. Current options for male contraception are the barrier methods such as condoms and the surgical methods such as vasectomy. Condoms are coital-dependent and not always reliable as they are prone to slippage and breakage. Vasectomy has the advantage of being coital-independent but is permanent. Recent surveys have shown that men want to be more involved in contraception decisions, and women trust their male partners to take an active role in this area. Nonsurgical steroidal methods comprising various derivatives of the androgens and their receptors are in various phases of clinical trials in men. The ideal male contraceptive should be coitalin-dependent, nonsurgical, reversible, effective, and should not alter androgen levels or libido. Several nonsteroidal molecules and vaccines are being investigated in animal models for male contraception. Male hormonal contraception may become a reality in the near future. Nonsteroidal methods including contraceptive vaccines targeting various molecules are an exciting proposition and are under investigation.

  5. Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys. (United States)

    Czoty, P W; Gould, R W; Gage, H D; Nader, M A


    Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy. In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration. Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [ 18 F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined. D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys. These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

  6. Infectivity, effects on helper viruses and whitefly transmission of the deltasatellites associated with sweepoviruses (genus Begomovirus, family Geminiviridae). (United States)

    Hassan, Ishtiaq; Orílio, Anelise F; Fiallo-Olivé, Elvira; Briddon, Rob W; Navas-Castillo, Jesús


    Begomoviruses (family Geminiviridae) are whitefly-transmitted viruses with single-stranded DNA genomes that are frequently associated with DNA satellites. These satellites include non-coding satellites, for which the name deltasatellites has been proposed. Although the first deltasatellite was identified in the late 1990s, little is known about the effects they have on infections of their helper begomoviruses. Recently a group of deltasatellites were identified associated with sweepoviruses, a group of phylogenetically distinct begomoviruses that infect plants of the family Convolvulaceae including sweet potato. In this work, the deltasatellites associated with sweepoviruses are shown to be transreplicated and maintained in plants by the virus with which they were identified, sweet potato leaf curl virus (SPLCV). These deltasatellites were shown generally to reduce symptom severity of the virus infection by reducing virus DNA levels. Additionally they were shown to be maintained in plants, and reduce the symptoms induced by two Old World monopartite begomoviruses, tomato yellow leaf curl virus and tomato yellow leaf curl Sardinia virus. Finally one of the satellites was shown to be transmitted plant-to-plant in the presence of SPLCV by the whitefly vector of the virus, Bemisia tabaci, being the first time a deltasatellite has been shown to be insect transmitted.

  7. From dendritic cells to B cells dysfunctions during HIV-1 infection: T follicular helper cells at the crossroads. (United States)

    Ruffin, Nicolas; Hani, Lylia; Seddiki, Nabila


    T follicular helper (Tfh) cells are essential for B-cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal centre, where they are the main source of replicative HIV-1 and represent a major reservoir. Paradoxically, Tfh cell numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV-1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure. The purpose of this review is to summarize the recent advance in our understanding of Tfh cell dynamics during HIV/SIV infection. In particular, to explore the possible causes of their expansion in lymphoid tissues by discussing the impact of HIV-1 infection on dendritic cells, to identify the molecular players rendering Tfh cells highly susceptible to HIV-1 infection, and to consider the contribution of regulatory follicular T cells in shaping Tfh cell functions. © 2017 John Wiley & Sons Ltd.

  8. Evaluation of the 113Online Suicide Prevention Crisis Chat Service: Outcomes, Helper Behaviors and Comparison to Telephone Hotlines. (United States)

    Mokkenstorm, Jan K; Eikelenboom, Merijn; Huisman, Annemiek; Wiebenga, Jasper; Gilissen, Renske; Kerkhof, Ad J F M; Smit, Johannes H


    Recognizing the importance of digital communication, major suicide prevention helplines have started offering crisis intervention by chat. To date there is little evidence supporting the effectiveness of crisis chat services. To evaluate the reach and outcomes of the 113Online volunteer-operated crisis chat service, 526 crisis chat logs were studied, replicating the use of measures that were developed to study telephone crisis calls. Reaching a relatively young population of predominantly females with severe suicidality and (mental) health problems, chat outcomes for this group were found to be comparable to those found for crisis calls to U.S. Lifeline Centers in 2003-2004, with similar but not identical associations with specific helpers' styles and attitudes. Our findings support a positive effect of the 113Online chat service, to be enhanced by practice standards addressing an apparent lack of focus on the central issue of suicidality during chats, as well as by the development of best practices specific for online crisis intervention. © 2016 The American Association of Suicidology.

  9. Recombinant rabies virus expressing IL-21 enhances immunogenicity through activation of T follicular helper cells and germinal centre B cells. (United States)

    Zhang, Yajing; Zhou, Ming; Wang, Zhao; Yang, Jie; Li, Mingming; Wang, Kunlun; Cui, Min; Chen, Huanchun; Fu, Zhen F; Zhao, Ling


    Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signalling could affect specific antibody induction after rabies vaccination. Here, to further investigate the over-expression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that in mice immunized with LBNSE-IL21, there was a substantial increase in the number of T follicular helper cells and germinal centre B cells but no enhancement of dendritic cell activation. Furthermore, significantly higher rabies virus-neutralizing antibody (VNA) titres were produced in mice immunized with LBNSE-IL21 than in mice immunized with the parent virus LBNSE in the first six weeks, resulting in higher protection. Together, these results suggest that LBNSE-IL21 can induce a rapid and robust VNA titre, and it has the potential to be developed as a promising rabies vaccine.

  10. Control of Epstein-Barr virus infection in vitro by T helper cells specific for virion glycoproteins. (United States)

    Adhikary, Dinesh; Behrends, Uta; Moosmann, Andreas; Witter, Klaus; Bornkamm, Georg W; Mautner, Josef


    Epstein-Barr virus (EBV) establishes lifelong persistent infections in humans by latently infecting B cells, with occasional cycles of reactivation, virus production, and reinfection. Protective immunity against EBV is mediated by T cells, but the role of EBV-specific T helper (Th) cells is still poorly defined. Here, we study the Th response to the EBV lytic cycle proteins BLLF1 (gp350/220), BALF4 (gp110), and BZLF1 and show that glycoprotein-specific Th cells recognize EBV-positive cells directly; surprisingly, a much higher percentage of target cells than those expressing lytic cycle proteins were recognized. Antigen is efficiently transferred to bystander B cells by receptor-mediated uptake of released virions, resulting in recognition of target cells incubated with virus entry before latency is established. Glycoprotein-specific Th cells are cytolytic and inhibit proliferation of lymphoblastoid cell lines (LCL) and the outgrowth of LCL after infection of primary B cells with EBV. These results establish a novel role for glycoprotein-specific Th cells in the control of EBV infection and identify virion proteins as important immune targets. These findings have implications for the treatment of diseases associated with EBV and potentially other coated viruses infecting MHC class II-positive cells.

  11. Single-Cell RNA Sequencing Reveals T Helper Cells Synthesizing Steroids De Novo to Contribute to Immune Homeostasis

    Directory of Open Access Journals (Sweden)

    Bidesh Mahata


    Full Text Available T helper 2 (Th2 cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines. It is likely that there are undiscovered Th2 signaling molecules. Although steroids are known to be immunoregulators, de novo steroid production from immune cells has not been previously characterized. Here, we demonstrate production of the steroid pregnenolone by Th2 cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. In support of this, we show that pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching. We also show that steroidogenic Th2 cells inhibit Th cell proliferation in a Cyp11a1 enzyme-dependent manner. We propose pregnenolone as a “lymphosteroid,” a steroid produced by lymphocytes. We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis.

  12. Regulation of Autoimmune Germinal Center Reactions in Lupus-Prone BXD2 Mice by Follicular Helper T Cells (United States)

    Kim, Young Uk; Lim, Hoyong; Jung, Ha Eun; Wetsel, Rick A.; Chung, Yeonseok


    BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis, offering a useful animal model to study autoimmune lupus. Although initial studies showed a critical contribution of IL-17 and Th17 cells in mediating autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh) cells remains incompletely understood. We found that both the frequency of Th17 cells and the levels of IL-17 in circulation in BXD2 mice were comparable to those of wild-type. By contrast, the frequency of PD-1+CXCR5+ Tfh cells was significantly increased in BXD2 mice compared with wild-type mice, while the frequency of PD-1+CXCR5+Foxp3+ follicular regulatory T (Tfr) cells was reduced in the former group. The frequency of Tfh cells rather than that of Th17 cells was positively correlated with the frequency of germinal center B cells as well as the levels of autoantibodies to dsDNA. More importantly, CXCR5+ CD4+ T cells isolated from BXD2 mice induced the production of IgG from naïve B cells in an IL-21-dependent manner, while CCR6+ CD4+ T cells failed to do so. These results together demonstrate that Tfh cells rather than Th17 cells contribute to the autoimmune germinal center reactions in BXD2 mice. PMID:25768299

  13. T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP

    Directory of Open Access Journals (Sweden)

    Lisa Perruzza


    Full Text Available The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh cell abundance in the Peyer’s patches (PPs of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help.

  14. Immunomodulation and T helper TH₁/TH₂ response polarization by CeO₂ and TiO₂ nanoparticles.

    Directory of Open Access Journals (Sweden)

    Brian C Schanen

    Full Text Available Immunomodulation by nanoparticles, especially as related to the biochemical properties of these unique materials, has scarcely been explored. In an in vitro model of human immunity, we demonstrate two catalytic nanoparticles, TiO₂ (oxidant and CeO₂ (antioxidant, have nearly opposite effects on human dendritic cells and T helper (T(H cells. For example, whereas TiO₂ nanoparticles potentiated DC maturation that led towards T(H1-biased responses, treatment with antioxidant CeO₂ nanoparticles induced APCs to secrete the anti-inflammatory cytokine, IL-10, and induce a T(H2-dominated T cell profile. In subsequent studies, we demonstrate these results are likely explained by the disparate capacities of the nanoparticles to modulate ROS, since TiO₂, but not CeO₂ NPs, induced inflammatory responses through an ROS/inflammasome/IL-1β pathway. This novel capacity of metallic NPs to regulate innate and adaptive immunity in profoundly different directions via their ability to modulate dendritic cell function has strong implications for human health since unintentional exposure to these materials is common in modern societies.

  15. A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Lianxiang Bi


    Full Text Available Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

  16. Expansion of Circulating T Follicular Helper Cells in Children with Acute Henoch-Schönlein Purpura

    Directory of Open Access Journals (Sweden)

    Jue Xie


    Full Text Available Henoch-Schönlein purpura (HSP is a common systemic small vessel vasculitis in children with disorder autoimmune responses. T follicular helper (TFH cells play crucial roles in regulating immune responses. The aim of our study was to investigate the probable role of TFH cells in the pathogenesis of children with HSP. In this study, the frequency of circulating CXCR5+CD4+TFH cells with inducible costimulator (ICOS expression in the children with acute HSP was significantly higher than that in healthy controls (HCs but not CXCR5+CD4+TFH cells with programmed death-1 (PD-1 expression. Moreover, serum levels of IL-21 and IL-6 cytokines, IgA, and C3 in HSP children were also significantly higher than those in HCs. A positive correlation was observed between the frequencies of circulating ICOS+CXCR5+CD4+TFH cells and the serum IL-21 or IgA levels of acute HSP children, respectively. Additionally, the mRNA expression levels of interleukin- (IL- 21, IL-6, and transcriptional factors (B-cell lymphoma-6, Bcl-6 were also significantly increased in peripheral blood from acute HSP children compared to HCs. Taken together, these findings suggest that TFH cells and associated molecules might play critical roles in the pathogenesis of HSP, which are possible therapeutic targets in HSP children.

  17. Mycorrhiza helper bacterium Streptomyces AcH 505 induces differential gene expression in the ectomycorrhizal fungus Amanita muscaria. (United States)

    Schrey, Silvia D; Schellhammer, Michael; Ecke, Margret; Hampp, Rüdiger; Tarkka, Mika T


    The interaction between the mycorrhiza helper bacteria Streptomyces nov. sp. 505 (AcH 505) and Streptomyces annulatus 1003 (AcH 1003) with fly agaric (Amanita muscaria) and spruce (Picea abies) was investigated. The effects of both bacteria on the mycelial growth of different ectomycorrhizal fungi, on ectomycorrhiza formation, and on fungal gene expression in dual culture with AcH 505 were determined. The fungus specificities of the streptomycetes were similar. Both bacterial species showed the strongest effect on the growth of mycelia at 9 wk of dual culture. The effect of AcH 505 on gene expression of A. muscaria was examined using the suppressive subtractive hybridization approach. The responsive fungal genes included those involved in signalling pathways, metabolism, cell structure, and the cell growth response. These results suggest that AcH 505 and AcH 1003 enhance mycorrhiza formation mainly as a result of promotion of fungal growth, leading to changes in fungal gene expression. Differential A. muscaria transcript accumulation in dual culture may result from a direct response to bacterial substances.

  18. The Role of Protein Modifications of T-Bet in Cytokine Production and Differentiation of T Helper Cells

    Directory of Open Access Journals (Sweden)

    Sera Oh


    Full Text Available T-Bet (T-box protein expressed in T cells, also called as TBX21 was originally cloned as a key transcription factor involved in the commitment of T helper (Th cells to the Th1 lineage. T-Bet directly activates IFN-γ gene transcription and enhances development of Th1 cells. T-Bet simultaneously modulates IL-2 and Th2 cytokines in an IFN-γ-independent manner, resulting in an attenuation of Th2 cell development. Numerous studies have demonstrated that T-bet plays multiple roles in many subtypes of immune cells, including B cell, dendritic cells, natural killer (NK cells, NK T cells, and innate lymphoid cells. Therefore, T-bet is crucial for the development and coordination of both innate and adaptive immune responses. To fulfill these multiple roles, T-bet undergoes several posttranslational protein modifications, such as phosphorylation at tyrosine, serine, and threonine residues, and ubiquitination at lysine residues, which affect lineage commitment during Th cell differentiation. This review presents a current overview of the progress made in understanding the roles of various types of T-bet protein modifications in the regulation of cytokine production during Th cell differentiation.

  19. Follicular Helper T Cells in Systemic Lupus Erythematosus: Why Should They Be Considered as Interesting Therapeutic Targets?

    Directory of Open Access Journals (Sweden)

    Matthieu Sawaf


    Full Text Available Systemic lupus erythematosus (SLE is a chronic autoimmune disease characterized by B cell hyperactivity leading to the production of autoantibodies, some of which having a deleterious effect. Reducing autoantibody production thus represents a way of controlling lupus pathogenesis, and a better understanding of the molecular and cellular factors involved in the differentiation of B cells into plasma cells could allow identifying new therapeutic targets. Follicular helper T cells (TFH represent a distinct subset of CD4+ T cells specialized in providing help to B cells. They are required for the formation of germinal centers and the generation of long-lived serological memory and, as such, are suspected to play a central role in SLE. Recent advances in the field of TFH biology have allowed the identification of important molecular factors involved in TFH differentiation, regulation, and function. Interestingly, some of these TFH-related molecules have been described to be dysregulated in lupus patients. In the present review, we give an overview of the aberrant expression and/or function of such key players in lupus, and we highlight their potential as therapeutic targets.

  20. Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis. (United States)

    Mahata, Bidesh; Zhang, Xiuwei; Kolodziejczyk, Aleksandra A; Proserpio, Valentina; Haim-Vilmovsky, Liora; Taylor, Angela E; Hebenstreit, Daniel; Dingler, Felix A; Moignard, Victoria; Göttgens, Berthold; Arlt, Wiebke; McKenzie, Andrew N J; Teichmann, Sarah A


    T helper 2 (Th2) cells regulate helminth infections, allergic disorders, tumor immunity, and pregnancy by secreting various cytokines. It is likely that there are undiscovered Th2 signaling molecules. Although steroids are known to be immunoregulators, de novo steroid production from immune cells has not been previously characterized. Here, we demonstrate production of the steroid pregnenolone by Th2 cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. In support of this, we show that pregnenolone inhibits Th cell proliferation and B cell immunoglobulin class switching. We also show that steroidogenic Th2 cells inhibit Th cell proliferation in a Cyp11a1 enzyme-dependent manner. We propose pregnenolone as a "lymphosteroid," a steroid produced by lymphocytes. We speculate that this de novo steroid production may be an intrinsic phenomenon of Th2-mediated immune responses to actively restore immune homeostasis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII. (United States)

    Hu, Chuhong; Cela, Racel G; Suzuki, Masataka; Lee, Brendan; Lipshutz, Gerald S


    Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential "cure." Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.

  2. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

    Directory of Open Access Journals (Sweden)

    Daniel H. Libraty


    Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

  3. Chitinases and chitinase-like proteins: potential therapeutic targets for the treatment of T-helper type 2 allergies. (United States)

    Sutherland, T E; Maizels, R M; Allen, J E


    Mammalian chitinase and chitinase-like proteins (CLPs) are a family of mediators increasingly associated with infection, T cell-mediated inflammation, wound healing, allergy and asthma. Although our current knowledge of the function of mammalian chitinases and CLPs is very limited, important information can be deduced from research carried out in lower organisms, and in different immunopathological conditions. Enzymatically active mammalian chitinase proteins may have evolved to degrade the copious amounts of chitin mammals are exposed to on a daily basis, and to form an innate barrier to chitin-containing organisms. CLPs are homologous to chitinases but lack the ability to degrade chitin. It is most striking that both chitinases and CLPs are up-regulated in T-helper type 2 (Th2)-driven conditions, and the first evidence is now emerging that these proteins may accentuate Th2 reactivity, and possibly contribute to the repair process that follows inflammation. Following studies demonstrating that chitinase inhibition leads to an attenuated allergic response, several strategies are being used to develop enzyme inhibitors for therapeutic use in human diseases. In this review, we will summarize recent insights into the effects of chitinases and CLPs in the context of Th2-dominated pathology with particular focus on allergy and asthma, discussing whether chitinase enzyme inhibitors may be of therapeutic value.

  4. ATRA alters humoral responses associated with amelioration of EAMG symptoms by balancing Tfh/Tfr helper cell profiles. (United States)

    Xie, Xiaoli; Mu, Lili; Yao, Xiuhua; Li, Na; Sun, Bo; Li, Ying; Zhan, Xiaoxia; Wang, Xinyue; Kang, Xiaoying; Wang, Jinghua; Liu, Yumei; Zhang, Yao; Wang, Guangyou; Wang, Dandan; Liu, Xijun; Kong, Qingfei; Li, Hulun


    All-trans retinoic acid (ATRA) is a vitamin A metabolite with diverse immunomodulatory actions used therapeutically in the treatment of some autoimmune diseases. However, the effects that ATRA may have on diminishing myasthenia gravis (MG) symptoms remain undefined. This study investigated the effect of ATRA on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. Data presented in this study demonstrated that intraperitoneal injection of ATRA ameliorated EAMG pathology in rats associated with reduced total anti-acetylcholine receptor (AChR) serum IgG levels. We observed that EAMG development was accompanied by an increase in follicular helper T cells (Tfh, defined as CD4(+)CXCR5(+)ICOS(high)) and a decrease of follicular regulatory T cells (Tfr, defined as CD4(+)Foxp3(+)CXCR5(+)ICOS(median)) and that the Tfh:Tfr ratio was altered following ATRA administration. In addition, ATRA treatment restored the Th1/Th2/Th17/Treg balance. In vitro, ATRA inhibited AChR-specific cell proliferation and eliciting apoptosis in these cells without affecting the cell cycle. ATRA also altered the Th distribution in animals presenting with EAMG resulting in a reduction in Th1/Th17/Tfh cells and increasing the number of Th2/Treg/Tfr cell types. These results suggested that ATRA reduced EAMG severity by regulating Th cell profiles thereby providing new insights into the development of novel MG (or related) therapies. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Splenic Marginal Zone Granulocytes Acquire an Accentuated Neutrophil B-Cell Helper Phenotype in Chronic Lymphocytic Leukemia. (United States)

    Gätjen, Marcel; Brand, Franziska; Grau, Michael; Gerlach, Kerstin; Kettritz, Ralph; Westermann, Jörg; Anagnostopoulos, Ioannis; Lenz, Peter; Lenz, Georg; Höpken, Uta E; Rehm, Armin


    Recruitment of tumor-associated macrophages and neutrophils (TAM and TAN) to solid tumors contributes to immunosuppression in the tumor microenvironment; however, their contributions to lymphoid neoplasms are less clear. In human chronic lymphocytic leukemia (CLL), tumor B cells lodge in lymph nodes where interactions with the microenvironment occur. Tumor cell homing stimulates proliferation, such that engagement of the B-cell receptor is important for malignant progression. In the Eμ-Tcl1 murine model of CLL, we identified gene expression signatures indicative of a skewed polarization in the phenotype of monocytes and neutrophils. Selective ablation of either of these cell populations in mice delayed leukemia growth. Despite tumor infiltration of these immune cells, a systemic inflammation was not detected. Notably, in progressive CLL, splenic neutrophils were observed to differentiate toward a B-cell helper phenotype, a process promoted by the induction of leukemia-associated IL10 and TGFβ. Our results suggest that targeting aberrant neutrophil differentiation and restoring myeloid cell homeostasis could limit the formation of survival niches for CLL cells. Cancer Res; 76(18); 5253-65. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. The Transcription Factor T-bet Limits Amplification of Type I IFN Transcriptome and Circuitry in T Helper 1 Cells. (United States)

    Iwata, Shigeru; Mikami, Yohei; Sun, Hong-Wei; Brooks, Stephen R; Jankovic, Dragana; Hirahara, Kiyoshi; Onodera, Atsushi; Shih, Han-Yu; Kawabe, Takeshi; Jiang, Kan; Nakayama, Toshinori; Sher, Alan; O'Shea, John J; Davis, Fred P; Kanno, Yuka


    Host defense requires the specification of CD4 + helper T (Th) cells into distinct fates, including Th1 cells that preferentially produce interferon-γ (IFN-γ). IFN-γ, a member of a large family of anti-pathogenic and anti-tumor IFNs, induces T-bet, a lineage-defining transcription factor for Th1 cells, which in turn supports IFN-γ production in a feed-forward manner. Herein, we show that a cell-intrinsic role of T-bet influences how T cells perceive their secreted product in the environment. In the absence of T-bet, IFN-γ aberrantly induced a type I IFN transcriptomic program. T-bet preferentially repressed genes and pathways ordinarily activated by type I IFNs to ensure that its transcriptional response did not evoke an aberrant amplification of type I IFN signaling circuitry, otherwise triggered by its own product. Thus, in addition to promoting Th1 effector commitment, T-bet acts as a repressor in differentiated Th1 cells to prevent abberant autocrine type I IFN and downstream signaling. Published by Elsevier Inc.

  7. T-helper Cell Type-1 Transcription Factor T-Bet Is Down-regulated in Type 1 Diabetes. (United States)

    Vaseghi, Hajar; Sanati, Mohammad Hossein; Jadali, Zohreh


    T cells have been identified as key players in the pathogenesis of type 1 diabetes. However, the exact role of T-cell subpopulations in this pathway is presently unknown. The purpose of this study was to assess the expression pattern of two lineage-specifying transcription factors GATA-3 and T-bet, which are important in T helper type 1 (Th1) and Th2 cell development, respectively. Gene expression analysis of peripheral blood mononuclear cells (PBMCs) was performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Plasma levels of IFN-γ and IL-4 were also determined by ELISA. T-bet and IFN-γ gene expression was significantly lower in patients group compared with healthy controls (p<0.05). The expression of GATA-3 was relatively similar in patients and controls; however, IL-4 mRNAs were significantly increased in the PBMCs from patients as compared with normal controls (p<0.05). In addition, a marked increase in plasma IL-4 levels were observed in patient group compared with controls (p<0.001). To the contrary, IFN-γ protein levels were decreased in patients in comparison with controls (p<0.001). These data suggest additional implications of the role of Th1/Th2 imbalance for the immunopathogenesis of type 1 diabetes.

  8. Foxo3 Transcription Factor Drives Pathogenic T Helper 1 Differentiation by Inducing the Expression of Eomes. (United States)

    Stienne, Caroline; Michieletto, Michaël F; Benamar, Mehdi; Carrié, Nadège; Bernard, Isabelle; Nguyen, Xuan-Hung; Lippi, Yannick; Duguet, Fanny; Liblau, Roland S; Hedrick, Stephen M; Saoudi, Abdelhadi; Dejean, Anne S


    The transcription factor Foxo3 plays a crucial role in myeloid cell function but its role in lymphoid cells remains poorly defined. Here, we have shown that Foxo3 expression was increased after T cell receptor engagement and played a specific role in the polarization of CD4 + T cells toward pathogenic T helper 1 (Th1) cells producing interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). Consequently, Foxo3-deficient mice exhibited reduced susceptibility to experimental autoimmune encephalomyelitis. At the molecular level, we identified Eomes as a direct target gene for Foxo3 in CD4 + T cells and we have shown that lentiviral-based overexpression of Eomes in Foxo3-deficient CD4 + T cells restored both IFN-γ and GM-CSF production. Thus, the Foxo3-Eomes pathway is central to achieve the complete specialized gene program required for pathogenic Th1 cell differentiation and development of neuroinflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. An allospecific murine T helper clone which can help both T and B cell responses in vitro and in vivo

    DEFF Research Database (Denmark)

    Crispe, I N; Gascoigne, N R; Owens, T


    Both B lymphocytes and cytotoxic T lymphocytes respond to signals from the T helper (Th) compartment, and such signals are mediated by a number of biochemically distinct factors. This raises the question whether help for B cells and T cells is a function of one or several different kinds of Th cell....... Here we describe an in vitro and in vivo study of this problem, using a Th clone, designated MTH-1. The clone carries the cell surface markers Thy-1 and L3T4a, but lacks Lyt-2. It recognizes a minor alloantigen shared by DBA/2, B10.D2 and NZB spleen cells, and such recognition is restricted by H-2Ed....... Recognition of antigen in vitro is accompanied by secretion of IL-2. In vivo, both primary and secondary CTL responses to multiple minor alloantigens are enhanced by small numbers (less than or equal to 10(4] of MTH-1 cells. Recognition of alloantigen in a T-depleted B cell population results...

  10. The minimal sequence essential for replication and movement of Cotton leaf curl Multan betasatellite DNA by a helper virus in plant cells. (United States)

    Eini, Omid; Behjatnia, S A Akbar


    Betasatellites are single-stranded circular DNAs associated with a number of monopartite begomoviruses. Betasatellites rely on the helper begomoviruses for replication and movement in plant tissues and plant-to-plant transmission by vectors. Their genomes are approximately half the size of the helper viruses and consist of three main regions including the βC1 gene, an adenine-rich (A-rich) region, and the satellite conserved region (SCR). In this study, we investigated the minimal sequences required for Cotton leaf curl Multan betasatellite (CLCuMB) replication and movement. Mutational analysis of CLCuMB DNA genome indicated that βC1 gene and A-rich region were not required for trans-replication and movement of CLCuMB in host plants by a helper virus. Deletion of βC1 gene and a fragment (135 nt in length) upstream of this gene impaired CLCuMB replication. However, CLCuMB mutant with deletion of βC1 gene and a further 163 nucleotides replicated at a lower level as compared to the wild-type betasatellite. This suggests that there are essential elements in the fragment upstream of βC1 gene, which are required for the replication of CLCuMB rather than the size limitation of CLCuMB DNA.

  11. Sensitive and selective amplification of methylated DNA sequences using helper-dependent chain reaction in combination with a methylation-dependent restriction enzymes. (United States)

    Rand, Keith N; Young, Graeme P; Ho, Thu; Molloy, Peter L


    We have developed a novel technique for specific amplification of rare methylated DNA fragments in a high background of unmethylated sequences that avoids the need of bisulphite conversion. The methylation-dependent restriction enzyme GlaI is used to selectively cut methylated DNA. Then targeted fragments are tagged using specially designed 'helper' oligonucleotides that are also used to maintain selection in subsequent amplification cycles in a process called 'helper-dependent chain reaction'. The process uses disabled primers called 'drivers' that can only prime on each cycle if the helpers recognize specific sequences within the target amplicon. In this way, selection for the sequence of interest is maintained throughout the amplification, preventing amplification of unwanted sequences. Here we show how the method can be applied to methylated Septin 9, a promising biomarker for early diagnosis of colorectal cancer. The GlaI digestion and subsequent amplification can all be done in a single tube. A detection sensitivity of 0.1% methylated DNA in a background of unmethylated DNA was achieved, which was similar to the well-established Heavy Methyl method that requires bisulphite-treated DNA.

  12. They need to be recognized as a person in everyday life: Teachers' and helpers' experiences of teacher-student relationships in upper secondary school. (United States)

    Krane, Vibeke; Karlsson, Bengt; Ness, Ottar; Binder, Per-Einar


    The aim of this study was to explore how teachers and helpers experience that teacher-student relationship (TSR) is developed and promoted in upper secondary school.We also explored their experiences of qualities of TSR with students with mental health problems or at risk of dropping out. The study used a qualitative and participative approach; key stakeholders were included as co-researchers. Focus group interviews were held with 27 teachers and helpers. A thematic analysis was conducted. The participants' descriptions of important experiential dimensions of TSR were clustered around four themes: (1) to be recognized as a person with strengths and challenges in everyday life, (2) collaborative relationships between students and teachers, (3) flexible boundaries in the relationship between teachers and students and (4) organization of classes and procedures set the stage for TSR. Collaborative, emotional and contextual qualities were found important to the development of TSR in upper secondary school. Experiences of negative qualities of TSR can contribute to push students out of school. Teachers and helpers experience that TSR may have the potential to play a role in promoting mental health in students' everyday life.

  13. Targeting the adolescent male. (United States)

    Pitt, E


    The National Urban League regards too early parenting among adolescents as an issue requiring high level, active attention from all segments of the Black community. Poverty, single parent households and adolescent pregnancies are not exclusively female problems. The role that males play has been missing from too many studies of these phenomena. In light of the fact that most sexual activity is male initiated, and most sexual behavior is male influenced, it becomes clear that there will be no resolution of the problem of teenage pregnancy without directing greater attention to the male. The issue of male responsibility is skirted too often due to parental pride on the part of mothers and fathers when their male children seek sexual relations with female partners. It is viewed as a sign that they are developing sexually within the norm. This is especially true, in many instances, in female headed households where the mother is concerned that she may not be providing her son with an adequate male role model. Sexual activity by female adolescents, however, is generally not condoned. This confusing double standard is further compounded by the disjointed fashion in which American society responds to adolescent sexuality on the whole. Although the home should be the focal point, many parents reluctantly admit an inability to communicate effectively about sex with their pre-adolescent children. Thus, the school, church, community and social agencies have all been enlisted in this task. The National Urban League's initiative in this area is expected to have significant impact on the course of adolescent sexuality and reproductive responsibility.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. The dynamics of male male competition in Cardiocondyla obscurior ants


    Cremer Sylvia; Suefuji Masaki; Schrempf Alexandra; Heinze Jürgen


    Abstract Background The outcome of male-male competition can be predicted from the relative fighting qualities of the opponents, which often depend on their age. In insects, freshly emerged and still sexually inactive males are morphologically indistinct from older, sexually active males. These young inactive males may thus be easy targets for older males if they cannot conceal themselves from their attacks. The ant Cardiocondyla obscurior is characterised by lethal fighting between wingless ...

  15. Blood T Follicular Regulatory Cells / T Follicular Helper Cells ratio Marks Ectopic Lymphoid Structure Formation and PD-1+ ICOS+ T Follicular Helper Cells Indicate Disease Activity in Primary Sjögren's Syndrome. (United States)

    Fonseca, Valter R; Romão, Vasco C; Agua-Doce, Ana; Santos, Mara; López-Presa, Dolores; Ferreira, Ana Cristina; Fonseca, João Eurico; Graca, Luis


    To investigate whether the balance of blood T follicular helper (Tfh) and Foxp3+ T follicular regulatory (Tfr) cells can inform on ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS). We prospectively recruited 56 patients with clinical suspicion of SS, 16 of which subsequently fulfilled American European Consensus Group primary SS classification criteria and were compared with 16 patients with non-Sjögren sicca syndrome. Paired blood and minor salivary gland (MSG) biopsies were analysed to study Tfh subsets and Tfr cells in both compartments. Primary SS patients had normal Tfh cell counts in peripheral blood, however, blood activated PD-1+ ICOS+  Tfh cells were strongly associated with disease activity assessed by EULAR SS Disease Activity Index (r=0.85, p=0.0008). Conversely, blood Tfr/Tfh ratio indicated ectopic lymphoid structure formation in MSG, being strongly associated with B, CD4+ T and PD-1+ ICOS+  T cell infiltration in MSG, and especially increased in patients with focal sialadenitis (FSA). Further analysis showed that blood Tfr/Tfh ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (OR=12.96, p=0.028) and FSA presence (OR=10.0, p=0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. Blood Tfr/Tfh ratio and PD-1+ ICOS+  Tfh cells constitute potential novel biomarkers for different features of primary SS. While blood Tfr/Tfh ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Male gametogenesis without centrioles. (United States)

    Riparbelli, Maria Giovanna; Callaini, Giuliano


    The orientation of the mitotic spindle plays a central role in specifying stem cell-renewal by enabling interaction of the daughter cells with external cues: the daughter cell closest to the hub region is instructed to self-renew, whereas the distal one starts to differentiate. Here, we have analyzed male gametogenesis in DSas-4 Drosophila mutants and we have reported that spindle alignment and asymmetric divisions are properly executed in male germline stem cells that lack centrioles. Spermatogonial divisions also correctly proceed in the absence of centrioles, giving rise to cysts of 16 primary spermatocytes. By contrast, abnormal meiotic spindles assemble in primary spermatocytes. These results point to different requirements for centrioles during male gametogenesis of Drosophila. Spindle formation during germ cell mitosis may be successfully supported by an acentrosomal pathway that is inadequate to warrant the proper execution of meiosis. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Managing Male Mammary Maladies. (United States)

    Fentiman, Ian S


    This review examines the symptoms, need for referral and management of the benign breast conditions which afflict males, together with the steps that are necessary to exclude or confirm male breast cancer. The most common complaint is gynaecomastia, either true or pseudo, and the majority of these cases need reassurance without over-investigation. Drugs that induce breast enlargement are described in order that, when possible, a medication switch can be made. Men receiving endocrine therapy for prostate cancer may develop painful gynaecomastia and this can be relieved with tamoxifen. All men with breast cancer need mammography as part of their work-up but this should not be used as a screening technique for symptomatic males. Because of lack of lobular development, both cysts and fibroadenomas are very rare in men; but those with nipple discharge need referral and investigation as some will have underlying malignancy.

  18. Stages of Male Breast Cancer (United States)

    ... Breast & Gynecologic Cancers Breast Cancer Screening Research Male Breast Cancer Treatment (PDQ®)–Patient Version General Information about Male Breast Cancer Go to Health Professional Version Key Points Male ...

  19. Social status-dependent nest choice of territorial males under reproductive parasitism in a Lake Tanganyika cichlid Telmatochromis vittatus. (United States)

    Ota, K; Kohda, M


    Field and laboratory studies were conducted to examine how territorial males of a Lake Tanganyika cichlid Telmatochromis vittatus balance the conflicting demands on nest choice between occupying large nests with more females and avoiding reproductive parasitism (nest piracy, which is adopted by the largest males in the population). Pirates less frequently intruded the nests farther from neighbours, perhaps due to the costs associated with travelling between nests. The field experiment showed that territorial male T. vittatus sacrificed the fitness benefits that large nests offer and instead prioritized occupying the nests farther from neighbours on which fewer pirates intruded. The field observations suggested that they adopt different strategies for nest choice according to their relative competitive ability to pirates; the large territorial males, who are size-matched to pirates and can defend their nests against them, compete for larger nests among the more-isolated nests, whereas subordinate territorial males, which are smaller than pirates and thus inferior to them, compete for the more-isolated nests among the less-isolated nests. These findings suggest that the territorial male T. vittatus chooses the more-isolated nests to avoid pirate males at the expense of occupying large nests. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

  20. Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis. (United States)

    Khare, P; Jaiswal, A K; Tripathi, C D P; Sundar, S; Dube, A


    It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-β. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL. © 2016 British Society for Immunology.

  1. The circulating T helper subsets and regulatory T cells in patients with common variable immunodeficiency with no known monogenic disease. (United States)

    Azizi, G; Mirshafiey, A; Abolhassani, H; Yazdani, R; Ansariha, F J; Shaghaghi, M; Mortazavi-Jahromi, S S; Noorbakhsh, F; Rezaei, N; Aghamohammadi, A


    Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID), characterized by heterogeneous clinical manifestations and defects in B- and T- cells. In the present study, we investigated the T helper (Th) cell subsets and regulatory T (Treg) cells, and their related cytokines and transcription factors in the CVID patients with no definite genetic diagnosis. The study population comprised 13 CVID patients and 13 healthy controls (HC). Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. Th subsets and Treg were examined by flow cytometry. The expression of determinant cytokines (IFN-γ, IL-17, IL-22, and IL-10), and cell subset specific transcription factors were evaluated before and after stimulation. The main clinical presentations of these patients were infections only and lymphoproliferations phenotypes, but no autoimmune and allergy phenotype were recorded. The frequencies of CD4+ T cells, Th17, and Treg cells were significantly reduced in CVID patients, however the subsets of Th1, Th1-like Th17 and Th22 cells were normal. After stimulation, retinoic-acid-orphan-receptor-C (RORC), and runt-related transcription factor 1 (RUNX1), IL17, and IL10 genes' expression in CVID patients were significantly lower, in comparison to the HC. Moreover, there was a lower concentration of IL-17 and IL-10 in cell culture supernatants of stimulated CD4+ T cells of CVID patients than HC. Our findings demonstrate that the imbalance of Th17 and Tregs could be an associated with infections only and lymphoproliferations phenotype in CVID patients without monogenic disorders.

  2. Nonencapsulated Trichinella pseudospiralis Infection Impairs Follicular Helper T Cell Differentiation with Subclass-Selective Decreases in Antibody Responses. (United States)

    Asano, Kazunobu; Wu, Zhiliang; Srinontong, Piyarat; Ikeda, Takahide; Nagano, Isao; Morita, Hirokuyi; Maekawa, Yoichi


    Infectious microorganisms often modify host immunity to escape from immune elimination. Trichinella is a unique nematode of the helminth family, whose members parasitize the muscle cells inside the host without robust eliminative reactions. There are several species of Trichinella; some develop in muscle cells that become encapsulated (e.g., Trichinella spiralis) and others in cells that do not encapsulate (e.g., Trichinella pseudospiralis). It has already been established that Trichinella infection affects host immune responses in several experimental immune diseases in animal models; however, most of those studies were done using T. spiralis infection. As host immune responses to T. spiralis and T. pseudospiralis infections have been reported to be different, it is necessary to clarify how T. pseudospiralis infection influences the host immune responses. In this study, we investigated the influence on host humoral immunity in T. pseudospiralis-infected mice. We demonstrated that T. pseudospiralis infection decreased antigen-specific IgG2a and IgG2b antibody (Ab) production in mice immunized with a model antigen. This selective decrease in gamma interferon (IFN-γ)-dependent Ab production was not due to a decrease in IFN-γ production, and we instead found impaired follicular helper T (Tfh) cell differentiation. The affinity maturation of antigen-specific Ab tended to be delayed but was not significant in T. pseudospiralis-infected mice. We also observed that CD11b(+) spleen cells in T. pseudospiralis-infected mice expressed CD206 and PD-L2, the phenotype of which was M2 macrophages with weak production of interleukin-6 (IL-6), possibly resulting in impaired Tfh differentiation. Taken together, our results indicate that nonencapsulated Trichinella infection induces selective dampening in humoral immunity with the suppression of Tfh differentiation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. IFN Regulatory Factor 3 Balances Th1 and T Follicular Helper Immunity during Nonlethal Blood-Stage Plasmodium Infection. (United States)

    James, Kylie R; Soon, Megan S F; Sebina, Ismail; Fernandez-Ruiz, Daniel; Davey, Gayle; Liligeto, Urijah N; Nair, Arya Sheela; Fogg, Lily G; Edwards, Chelsea L; Best, Shannon E; Lansink, Lianne I M; Schroder, Kate; Wilson, Jane A C; Austin, Rebecca; Suhrbier, Andreas; Lane, Steven W; Hill, Geoffrey R; Engwerda, Christian R; Heath, William R; Haque, Ashraful


    Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection of blood-stage Plasmodium parasites, yet their influence over Th cell immunity remains unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4+ T cells, termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL infection in mice, to examine Th cell development in vivo. We found no role for caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling protein, and only modest roles for MyD88 and TRIF-dependent signaling in controlling PbTII cell expansion. In contrast, IFN regulatory factor 3 (IRF3) was important for supporting PbTII expansion, promoting Th1 over T follicular helper (Tfh) differentiation, and controlling parasites during the first week of infection. IRF3 was not required for early priming by conventional dendritic cells, but was essential for promoting CXCL9 and MHC class II expression by inflammatory monocytes that supported PbTII responses in the spleen. Thereafter, IRF3-deficiency boosted Tfh responses, germinal center B cell and memory B cell development, parasite-specific Ab production, and resolution of infection. We also noted a B cell-intrinsic role for IRF3 in regulating humoral immune responses. Thus, we revealed roles for IRF3 in balancing Th1- and Tfh-dependent immunity during nonlethal infection with blood-stage Plasmodium parasites. Copyright © 2018 by The American Association of Immunologists, Inc.

  4. PU.1 Expression in T Follicular Helper Cells Limits CD40L-Dependent Germinal Center B Cell Development. (United States)

    Awe, Olufolakemi; Hufford, Matthew M; Wu, Hao; Pham, Duy; Chang, Hua-Chen; Jabeen, Rukhsana; Dent, Alexander L; Kaplan, Mark H


    PU.1 is an ETS family transcription factor that is important for the development of multiple hematopoietic cell lineages. Previous work demonstrated a critical role for PU.1 in promoting Th9 development and in limiting Th2 cytokine production. Whether PU.1 has functions in other Th lineages is not clear. In this study, we examined the effects of ectopic expression of PU.1 in CD4(+) T cells and observed decreased expression of genes involved with the function of T follicular helper (Tfh) cells, including Il21 and Tnfsf5 (encoding CD40L). T cells from conditional mutant mice that lack expression of PU.1 in T cells (Sfpi1(lck-/-)) demonstrated increased production of CD40L and IL-21 in vitro. Following adjuvant-dependent or adjuvant-independent immunization, we observed that Sfpi1(lck-/-) mice had increased numbers of Tfh cells, increased germinal center B cells (GCB cells), and increased Ab production in vivo. This correlated with increased expression of IL-21 and CD40L in Tfh cells from Sfpi1(lck-/-) mice compared with control mice. Finally, although blockade of IL-21 did not affect GCB cells in Sfpi1(lck-/-) mice, anti-CD40L treatment of immunized Sfpi1(lck-/-) mice decreased GCB cell numbers and Ag-specific Ig concentrations. Together, these data indicate an inhibitory role for PU.1 in the function of Tfh cells, germinal centers, and Tfh-dependent humoral immunity. Copyright © 2015 by The American Association of Immunologists, Inc.

  5. Repopulated antigen presenting cells induced an imbalanced differentiation of the helper T cells in whole body gamma irradiated mice

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    Park, Hae Ran; Jo, Sung Kee [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Paik, Sang Kee [Chungnam National University, Taejon (Korea, Republic of)


    Therapeutic irradiation of cancer patients, although it may be protected by several antioxidant agents against free radicals, often induces chronic sequelae such as inflammation (allergic inflammation). This is a limiting factor for radiotherapy. Following radiotherapy, the inflammation or injury can occur in any organ with a high radiosensitivity such as the lung, bladder, kidney, liver, stomach and intestine. The mechanism by which ionizing radiation initiates inflammation is, however, poorly understood. In recent studies, it was suggested that a factor for irradiation-induced inflammation might be the over production of IL-4 that enhances fibroblast proliferation and collagen synthesis. During the early stages after irradiation, type 2 of the helper T cells might be the major source of IL-4, and later on there seems to be an activation of the other IL-4 producing cell types, e.q. macrophages or mast cells. This is interesting because inflammation is classically seen to be dominated by Th1 cells secreting IFN-{gamma}. In the previous study, we were interested in the enhancement of the IL-4 and the IgE production during the development of immune cells after {gamma}-irradiation. We were able to deduce that IL-4 production was increased because of the shifted differentiation of the naive Th cells by the repopulated antigen presenting cells after irradiation. The aim of the present study was to precisely define whether antigen-presenting cells (APCs) of whole body irradiation-treated mice could influence the shifted differentiation of the Th cells. This view can be demonstrated by confirming that the shifted functional status of the Th cells is induced by the altered function of the repopulated macrophages after whole body irradiation (WBI)

  6. A preliminary study of new single polymorphisms in the T helper type 17 pathway for psoriasis in the Korean population. (United States)

    Kim, S Y; Hur, M S; Choi, B G; Kim, M J; Lee, Y W; Choe, Y B; Ahn, K J


    Psoriasis is a polygenic and multi-factorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin (IL)-17A, IL-17 receptor (IL-17R) and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper type 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis. In 208 patients and 266 normal controls, we analysed 31 single nucleotide polymorphisms in 12 genes (CAMP, IL17A, IL17F, IL17RA, IL22, JAK1, JAK2, JAK3, STAT3, TLR7, TLR9 and TYK2; abbreviations: CAMP, human cathelicidin antimicrobial peptide; STAT-3, signal transducer and activator of transcription 3; TLR, Toll-like receptor; TYK2, tyrosine kinase 2). Patients with psoriasis showed a strong association for IL17F rs763780 [odds ratio (OR) = 3·27, P = 0·04], which results in a histidine-to-arginine substitution, and JAK2 rs2274471 (OR = 2·66, P = 0·02). In addition, JAK2 rs7849191 showed a protective pattern, met the significance threshold (OR = 0·77, P = 0·05) and showed a tendency for an inverse association with the frequency of early-onset psoriasis under age 40 years (P = 0·07). In haplotype analysis, JAK1 rs310241A/rs2780889T showed a protective effect (OR = 0·73, P = 0·03) in psoriasis. In conclusion, we report two new psoriasis-susceptibility loci, in IL17F and JAK2, as well as a newly identified late-onset associated protective JAK2 locus and a protective JAK1 haplotype in the Korean population. © 2016 British Society for Immunology.

  7. Transfer of tolerance to collagen type V suppresses T-helper-cell-17 lymphocyte-mediated acute lung transplant rejection. (United States)

    Braun, Ruedi K; Molitor-Dart, Melanie; Wigfield, Christopher; Xiang, Zhuzai; Fain, Sean B; Jankowska-Gan, Ewa; Seroogy, Christine M; Burlingham, William J; Wilkes, David S; Brand, David D; Torrealba, Jose; Love, Robert B


    Rat lung allograft rejection is mediated by collagen type V (col(V)) specific T-helper-cell 17 (Th17) cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T cells from tolerant rats could suppress the Th17-mediated rejection in the syngeneic model of lung transplantation. Rats were subjected to syngeneic left lung transplantation, and acute rejection was induced by adoptive transfer of lymph node cells from col(V)-immunized rats. Tolerance was induced by intravenous injection of col(V), and spleen lymphocytes were used for adoptive transfer. CD4+ T cells were depleted using magnetic beads. Lung isografts were analyzed using micro-positron emission tomography imaging and histochemistry. The transvivo delayed type hypersensitivity assay was used to analyze the Th17 response. Adoptive cotransfer of col(V)-specific effector cells with cells from col(V)-tolerized rats suppressed severe vasculitis and bronchiolitis with parenchymal inflammation, and the expression of interleukin (IL)-17 transcripts in mediastinal lymph nodes induced by effector cells alone. Analysis by transvivo delayed type hypersensitivity showed that the reactivity to col(V) was dependent on the presence of tumor necrosis factor-alpha and IL-17 but not interferon-gamma. Depletion of CD4+ T cells from the suppressor cell population abrogated the col(V)-specific protection. Th17-mediated acute rejection after lung transplantation is ameliorated by CD4+ col(V)-specific regulatory T cells. The mechanism for this Th17 suppression is consistent with tolerance induction to col(V). The goal of transplantation treatment, therefore, should target Th17 development and not suppression of T-cell activation by suppressing IL-2.

  8. Effects of the 20-kilodalton helper protein on Cry1Ac production and spore formation in Bacillus thuringiensis. (United States)

    Shao, Z; Liu, Z; Yu, Z


    Bacillus thuringiensis produces large amounts of various pesticidal proteins during the stationary phase. In order to achieve a high yield and form crystals, some pesticidal proteins require the presence of other proteins. Helper protein P20 is required for efficient production of both the Cyt1A and Cry11A crystal proteins in B. thuringiensis subsp. israelensis. Although full-length Cry1 protoxins are usually independent in terms of expression and crystallization in B. thuringiensis, in this study P20 significantly enhanced production of Cry1Ac protoxin (133 kDa) in an acrystalliferous and plasmid-negative strain. In the presence of P20, the yield of Cry1Ac protoxin increased 2.5-fold, and on average the resulting crystals were 1.85 microm long and 0.85 microm wide, three times the size of the crystals formed in the control lacking P20. Correspondingly, the recombinant strain that coexpressed P20 and Cry1Ac exhibited higher toxicity against Heliothis armigera larvae than the control. Furthermore, serious degradation of Cry1Ac in vivo was observed, which has seldom been reported previously. Actually, most protein was completely degraded during synthesis, and after synthesis about one-third of the expressed protoxins were degraded further before crystallization. In this process, P20 protected only nascent Cry1Ac from degradation, indicating that it acted as a molecular chaperon. In addition, spores were smaller and rounder and had a thinner exosporium layer when they were produced in the presence of P20. In summary, Cry1Ac was severely degraded during synthesis; this degradation was effectively relieved by P20, which resulted in enhanced production. Our results indicated that P20 is an effective tool for optimizing protein production in vivo.

  9. Simian Immunodeficiency Virus Infects Follicular Helper CD4 T Cells in Lymphoid Tissues during Pathogenic Infection of Pigtail Macaques (United States)

    Xu, Yin; Weatherall, Chris; Bailey, Michelle; Alcantara, Sheilajen; De Rose, Robert; Estaquier, Jerome; Wilson, Kim; Suzuki, Kazuo; Corbeil, Jacques; Cooper, David A.; Kent, Stephen J.; Kelleher, Anthony D.


    T follicular helper (Tfh) cells are a specialized subset of memory CD4+ T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1high CD127low memory CD4+ T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4+ memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir. PMID:23325697

  10. Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer

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    Heemskerk Mirjam HM


    Full Text Available Abstract Background Infection with high risk Human Papilloma Virus (HPV is associated with cancer of the cervix, vagina, penis, vulva, anus and some cases of head and neck carcinomas. The HPV derived oncoproteins E6 and E7 are constitutively expressed in tumor cells and therefore potential targets for T cell mediated adoptive immunotherapy. Effective immunotherapy is dependent on the presence of both CD4+ and CD8+ T cells. However, low precursor frequencies of HPV16 specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer purposes. An alternative to generate HPV specific CD4+ and CD8+ T cells is TCR gene transfer. Methods HPV specific CD4+ T cells were generated using either a MHC class I or MHC class II restricted TCR (from clones A9 and 24.101 respectively directed against HPV16 antigens. Functional analysis was performed by interferon-γ secretion, proliferation and cytokine production assays. Results Introduction of HPV16 specific TCRs into blood derived CD4+ recipient T cells resulted in recognition of the relevant HPV16 epitope as determined by IFN-γ secretion. Importantly, we also show recognition of the endogenously processed and HLA-DP1 presented HPV16E6 epitope by 24.101 TCR transgenic CD4+ T cells and recognition of the HLA-A2 presented HPV16E7 epitope by A9 TCR transgenic CD4+ T cells. Conclusion Our data indicate that TCR transfer is feasible as an alternative strategy to generate human HPV16 specific CD4+ T helper cells for the treatment of patients suffering from cervical cancer and other HPV16 induced malignancies.

  11. Galactomyces fermentation filtrate prevents T helper 2-mediated reduction of filaggrin in an aryl hydrocarbon receptor-dependent manner. (United States)

    Takei, K; Mitoma, C; Hashimoto-Hachiya, A; Takahara, M; Tsuji, G; Nakahara, T; Furue, M


    The aryl hydrocarbon receptor (AhR) recognizes diverse small molecules such as dioxins, tryptophan photoproducts and phytochemicals. It also plays crucial roles in epidermal homeostasis by upregulating epidermal barrier proteins. In preliminary screening, we found that Galactomyces fermentation filtrate (GFF), a cosmetic compound, was capable of activating AhR. To examine whether GFF upregulates the expression of the filaggrin and loricrin genes, FLG and LOR, in an AhR-dependent manner. The activation (cytoplasmic to nuclear translocation) of AhR was confirmed by immunofluorescence study and by upregulation of an AhR-specific marker, cytochrome P450-1A1 (CYP1A1). Gene expression levels were compared by quantitative reverse transcription PCR with or without GFF, interleukin (IL)-4 or IL-13 in normal human keratinocytes. AhR or control knockdown was carried out by transfection with AhR or control small interfering RNA. The protein expression of FLG and LOR was examined by immunohistochemistry using a three-dimensional epidermal equivalent treated with or without GFF or T helper (Th)2 cytokines. GFF induced the nuclear translocation of AhR with significant and dose-dependent upregulation of CYP1A1, FLG and LOR gene expression. The enhancing effects of GFF were abolished in AhR-knockdown keratinocytes. Th2 cytokines decreased expression of genes for FLG and LOR, and this expression was completely restored in the presence of GFF. The downregulated expression of the FLG gene with its restoration by GFF was also evident in the epidermal equivalent. GFF also upregulated the gene expression of genes encoding occludin, claudin-1 and 4, and kallikrein 5 and 7. Use of GFF is feasible to prevent the Th2-mediated reduction of FLG in an AhR-dependent fashion. © 2015 The Authors Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists, North American Clinical Dermatologic Society and St Johns Dermatological

  12. T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination

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    Masahisa Hemmi


    Full Text Available Few current vaccines can establish antigen (Ag-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adenovirus vector (Adv has been shown to induce Ag-specific cytotoxic T lymphocytes (CTLs in both systemic and gut-mucosal compartments. We previously found that type I interferon (IFN signaling is required for induction of gut-mucosal, but not systemic, CTLs following vaccination; however, the molecular mechanism involving type I IFN signaling remains unknown. Here, we found that T helper 17 (Th17-polarizing cytokine expression was down-regulated in the inguinal lymph nodes (iLNs of Ifnar2−/− mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice. We also found that prior transfer of Th17 cells reversed the decrease in the number of Ag-specific gut-mucosal CTLs in Ifnar2−/− mice following Adv vaccination. Additionally, prior transfer of Th17 cells into wild-type mice enhanced the induction of Ag-specific CTLs in the gut mucosa, but not in systemic compartments, suggesting a gut mucosa-specific mechanism where Th17 cells regulate the magnitude of vaccine-elicited Ag-specific CTL responses. These data suggest that Th17 cells translate systemic type I IFN signaling into a gut-mucosal CTL response following vaccination, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity.

  13. Transcription Factor Ets-2 Acts as a Preinduction Repressor of Interleukin-2 (IL-2) Transcription in Naive T Helper Lymphocytes. (United States)

    Panagoulias, Ioannis; Georgakopoulos, Tassos; Aggeletopoulou, Ioanna; Agelopoulos, Marios; Thanos, Dimitris; Mouzaki, Athanasia


    IL-2 is the first cytokine produced when naive T helper (Th) cells are activated and differentiate into dividing pre-Th0 proliferating precursors. IL-2 expression is blocked in naive, but not activated or memory, Th cells by the transcription factor Ets-2 that binds to the antigen receptor response element (ARRE)-2 of the proximal IL-2 promoter. Ets-2 acts as an independent preinduction repressor in naive Th cells and does not interact physically with the transcription factor NFAT (nuclear factor of activated T-cells) that binds to the ARRE-2 in activated Th cells. In naive Th cells, Ets-2 mRNA expression, Ets-2 protein levels, and Ets-2 binding to ARRE-2 decrease upon cell activation followed by the concomitant expression of IL-2. Cyclosporine A stabilizes Ets-2 mRNA and protein when the cells are activated. Ets-2 silences directly constitutive or induced IL-2 expression through the ARRE-2. Conversely, Ets-2 silencing allows for constitutive IL-2 expression in unstimulated cells. Ets-2 binding to ARRE-2 in chromatin is stronger in naive compared with activated or memory Th cells; in the latter, Ets-2 participates in a change of the IL-2 promoter architecture, possibly to facilitate a quick response when the cells re-encounter antigen. We propose that Ets-2 expression and protein binding to the ARRE-2 of the IL-2 promoter are part of a strictly regulated process that results in a physiological transition of naive Th cells to Th0 cells upon antigenic stimulation. Malfunction of such a repression mechanism at the molecular level could lead to a disturbance of later events in Th cell plasticity, leading to autoimmune diseases or other pathological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. A new Defective Helper RNA to produce recombinant Sindbis virus that infects neurons but does not propagate

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    Justus M Kebschull


    Full Text Available Recombinant Sindbis viruses are important tools in neuroscience because they combine rapid and high transgene expression with a capacity to carry large transgenes. Currently, two packaging systems based on the DH(26S5’SIN and the DH-BB(tRNA;TE12 Defective Helper (DH RNAs are available for generating recombinant Sindbis virus that is neurotropic (able to infect neurons and potentially other cells. Both systems produce a fraction of viral particles that can propagate beyond the primary infected neuron. When injected into mouse brain, viruses produced using these DH RNAs produce transgene expression at the injection site, but also elsewhere in the brain. Such ectopic labeling caused recombinant Sindbis viruses to be classified as anterograde viruses with limited retrograde spread, and can complicate the interpretation of neuroanatomical and other experiments.Here we describe a new DH RNA, DH-BB(5’SIN;TE12ORF, that can be used to produce virus that is both neurotropic and propagation-incompetent. We show in mice that DH-BB(5’SIN;TE12ORF-packaged virus eliminates infection of cells outside the injection site. We also provide evidence that ectopically labeled cells observed in previous experiments with recombinant Sindbis virus resulted from secondary infection by propagation-competent virus, rather than from inefficient retrograde spread. Virus produced with our new packaging system retains all the advantages of previous recombinant Sindbis viruses, but minimizes the risks of confounding results with unwanted ectopic labeling. It should therefore be considered in future studies in which a neurotropic, recombinant Sindbis virus is needed.

  15. Lycopene and male infertility (United States)

    Durairajanayagam, Damayanthi; Agarwal, Ashok; Ong, Chloe; Prashast, Pallavi


    Excessive amounts of reactive oxygen species (ROS) cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility—lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4–8 mg of lycopene daily for 3–12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility. PMID:24675655

  16. Eating Disordered Adolescent Males. (United States)

    Eliot, Alexandra O.; Baker, Christina Wood


    Described a sample of eating disordered adolescent males who were seen for treatment at Boston Children's Hospital Outpatient Eating Disorders Clinic. Findings suggest the idea that clinicians, coaches, peers, and family should encourage young men to share concerns about body image and weight at an earlier, less severe juncture, with the assurance…

  17. Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice. (United States)

    Golden, S A; Aleyasin, H; Heins, R; Flanigan, M; Heshmati, M; Takahashi, A; Russo, S J; Shaham, Y


    We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 × C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 × D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  18. To Group or Not to Group? Good Practice for Housing Male Laboratory Mice

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    Sarah Kappel


    Full Text Available It is widely recommended to group-house male laboratory mice because they are ‘social animals’, but male mice do not naturally share territories and aggression can be a serious welfare problem. Even without aggression, not all animals within a group will be in a state of positive welfare. Rather, many male mice may be negatively affected by the stress of repeated social defeat and subordination, raising concerns about welfare and also research validity. However, individual housing may not be an appropriate solution, given the welfare implications associated with no social contact. An essential question is whether it is in the best welfare interests of male mice to be group- or singly housed. This review explores the likely impacts—positive and negative—of both housing conditions, presents results of a survey of current practice and awareness of mouse behavior, and includes recommendations for good practice and future research. We conclude that whether group- or single-housing is better (or less worse in any situation is highly context-dependent according to several factors including strain, age, social position, life experiences, and housing and husbandry protocols. It is important to recognise this and evaluate what is preferable from animal welfare and ethical perspectives in each case.

  19. Physiological response to etho-ecological stressors in male Alpine chamois: timescale matters! (United States)

    Corlatti, Luca; Palme, Rupert; Lovari, Sandro


    From a life history perspective, glucocorticoids secreted by the neuroendocrine system, integrating different sources of stress through an adaptive feedback mechanism, may have important consequences on individual fitness. Although stress responses have been the object of several investigations, few studies have explored the role of proximate mechanisms responsible for the potential trade-offs between physiological stress and life history traits integrating social and environmental stressors. In 2011 and 2012, we collected data on faecal cortisol metabolites (FCM) in a marked male population of Alpine chamois, within the Gran Paradiso National Park (Italy). Using a model selection approach we analysed the effect of potential etho-ecological stressors such as age, social status (territorial vs. non-territorial males), minimum temperature, snow depth and precipitation on FCM variation. To correctly interpret environmentally and socially induced stress responses, we conducted model selections over multiple temporal scales defined a priori: year, cold months, spring, warm months, mating season. Over the year, FCM levels showed a negative relationship with minimum temperature, but altogether, climatic stressors had negligible effects on glucocorticoid secretion, possibly owing to good adaptations of chamois to severe weather conditions. Age was negatively related to FCM during the rut, possibly due to greater experience of older males in agonistic contests. Social status was an important determinant of FCM excretion: while both the `stress of subordination' and the `stress of domination' hypotheses received some support in spring and during the mating season, respectively, previous data suggest that only the latter may have detrimental fitness consequences on male chamois.

  20. Male genital lichen sclerosus

    Directory of Open Access Journals (Sweden)

    Christopher Barry Bunker


    Full Text Available Male genital lichen sclerosus (MGLSc is a chronic inflammatory skin disease responsible for male sexual dyspareunia and urological morbidity. An afeared complication is squamous cell carcinoma (SCC of the penis. The precise etiopathogenesis of MGLSc remains controversial although genetic, autoimmune and infective (such as human papillomavirus (HPV hepatitis C (HCV, Epstein-Barr virus (EBV and Borrelia factors have been implicated: Consideration of all the evidence suggests that chronic exposure of susceptible epithelium to urinary occlusion by the foreskin seems the most likely pathomechanism. The mainstay of treatment is topical ultrapotent corticosteroid therapy. Surgery is indicated for cases unresponsive to topical corticosteroid therapy, phimosis, meatal stenosis, urethral stricture, carcinoma in situ (CIS and squamous cell carcinoma.