Mild dyserythropoiesis and beta-like globin gene expression imbalance due to the loss of histone chaperone ASF1B

The expression of the human β-like globin genes follows a well-orchestrated developmental pattern, undergoing two essential switches, the first one during the first weeks of gestation (ε to γ), and the second one during the perinatal period (γ to β). The γ- to β-globin gene switching mechanism includes suppression of fetal (γ-globin, HbF) and activation of adult (β-globin, HbA) globin gene transcription. In hereditary persistence of fetal hemoglobin (HPFH), the γ-globin suppression mechanism is impaired leaving these individuals with unusual elevated levels of fetal hemoglobin (HbF) in adulthood. Recently, the transcription factors KLF1 and BCL11A have been established as master regulators of the γ- to β-globin switch. Previously, a genomic variant in the KLF1 gene, identified by linkage analysis performed on twenty-seven members of a Maltese family, was found to be associated with HPFH. However, variation in the levels of HbF among family members, and those from other reported families carrying genetic variants in KLF1, suggests additional contributors to globin switching. ASF1B was downregulated in the family members with HPFH. Here, we investigate the role of ASF1B in γ- to β-globin switching and erythropoiesis in vivo. Mouse-human interspecies ASF1B protein identity is 91.6%. By means of knockdown functional assays in human primary erythroid cultures and analysis of the erythroid lineage in Asf1b knockout mice, we provide evidence that ASF1B is a novel contributor to steady-state erythroid differentiation, and while its loss affects the balance of globin expression, it has no major role in hemoglobin switching

Speaking up when feeling job insecure: The moderating role of punishment and reward sensitivity

Purpose - The purpose of this paper is to investigate the extent to which felt job insecurity facilitates or hinders employees from raising voice (i.e. speaking up to their authority). The authors introduce punishment and reward sensitivity, two constructs of reinforcement sensitivity theory, as dispositional factors that might lead employees to appraise felt job insecurity as a hindrance vs challenge stressor. The authors propose employees high on punishment sensitivity to feel more constrained in raising voice because felt job insecurity to them is akin to a threat. Employees high on reward sensitivity should see felt job insecurity as a challenge, making it more likely that they will speak up. Design/methodology/approach - Hypotheses were tested using moderated structural equation modeling analysis. The sample consisted of 232 employees confronted with organizational change. Findings - The results are in line with the view of felt job insecurity as a hindrance stressor. Felt job insecurity negatively affected voice among both high and low punishment-sensitive individuals. Similarly, felt job insecurity was negatively related to voice in both low and high reward-sensitive individuals, although in the latter group the relationship was less pronounced. Originality/value - The literatures on felt job insecurity and voice have developed parallel to one another, without much cross-dialogue. Furthermore, the few existing studies that did relate felt job insecurity to employee voice have yielded conflicting results. The present study offers a theoretical account of the existing ambiguities in the literature, and generates new insights into why some employees more than others react to felt job insecurity by self-censoring their ideas and opinions

Social capital, team efficacy and team potency: The mediating role of team learning behaviors

Purpose – drawing on social capital theory and self-identification theory, this study aims to examine the associations of two indicators of social capital, personal networks and deep-level similarity, with team capability measures of team efficacy and team potency. The central focus of the study is to be the hypothesized mediating role of team learning behaviors.design/methodology/approach – hypotheses were tested using questionnaire data obtained from 221 teachers working in 33 teams and data were analyzed using multilevel analyses.findings – consistent with the hypotheses, the results supported the contention that team learning behaviors mediate the relationship between different types of social capital and team efficacy and team potency. Specifically, it was found that, in highly (deep-level) similar teams, the level of team learning behaviors is higher than in diverse teams, and this is hardly dependent on the extent of social capital based on personal networks. For diverse teams (i.e. Teams scoring low on deep-level similarity) more social capital based on personal networks translates into more team learning behaviors. Finally, it was found that team learning behaviors mediate the influence of social capital on team efficacy and team potency.research limitations/implications – the paper's findings suggest that it is important for managers not to focus exclusively on surface level characteristics but instead to attempt to facilitate the development of deep-level similarity. Organizations can also encourage group social capital by allowing teams to develop a shared history, rather than change membership frequently, and by increasing contact among team members.originality/value – the paper examined exchange and identification processes that are important in generating resources to increase the development of team learning behaviors, thereby emphasizing the role of the interpersonal context for understanding how interaction processes between team members shape team learning behaviors and subsequently lead to more team efficacy and team potency

Social capital, team efficacy and team potency: The mediating role of team learning behaviors

Purpose – drawing on social capital theory and self-identification theory, this study aims to examine the associations of two indicators of social capital, personal networks and deep-level similarity, with team capability measures of team efficacy and team potency. The central focus of the study is to be the hypothesized mediating role of team learning behaviors.design/methodology/approach – hypotheses were tested using questionnaire data obtained from 221 teachers working in 33 teams and data were analyzed using multilevel analyses.findings – consistent with the hypotheses, the results supported the contention that team learning behaviors mediate the relationship between different types of social capital and team efficacy and team potency. Specifically, it was found that, in highly (deep-level) similar teams, the level of team learning behaviors is higher than in diverse teams, and this is hardly dependent on the extent of social capital based on personal networks. For diverse teams (i.e. Teams scoring low on deep-level similarity) more social capital based on personal networks translates into more team learning behaviors. Finally, it was found that team learning behaviors mediate the influence of social capital on team efficacy and team potency.research limitations/implications – the paper's findings suggest that it is important for managers not to focus exclusively on surface level characteristics but instead to attempt to facilitate the development of deep-level similarity. Organizations can also encourage group social capital by allowing teams to develop a shared history, rather than change membership frequently, and by increasing contact among team members.originality/value – the paper examined exchange and identification processes that are important in generating resources to increase the development of team learning behaviors, thereby emphasizing the role of the interpersonal context for understanding how interaction processes between team members shape team learning behaviors and subsequently lead to more team efficacy and team potency

The route to employability: Examining resources and the mediating role of motivation

Purpose - Drawing from the job characteristics model and the job demands-resources model, this study aims to examine the associations of resources (i.e. feedback, autonomy, and variety) with intrinsic and extrinsic motivation, and employability. Design/methodology/approach - Hypotheses were tested using structural equation modeling on data from 611 employees of a Dutch municipality. Findings - Consistent with the hypotheses, the authors' results indicated that resources are related to both intrinsic and extrinsic motivation and that the association between resources and employability was mediated by extrinsic motivation but not by intrinsic motivation. Research limitations/implications - The authors use a one-dimensional measure of perceived employability and do not make a distinction between internal and external employability and other dimensions of employability. The authors feel that distinguishing between internal employability and external employability will contribute to understanding if internal and external opportunities relate differently to perceptions of employability with the same organization and with a different organization. Originality/value - Job resources are important for improvement of both intrinsic and extrinsic motivation, but the route from job resources to employability is via extrinsic job opportunities and not via intrinsic job opportunities. That is, the perception of performance outcome goals by employees is important for the association between job resources and employability. The paper shows that, without denying the value of intrinsic motivation, it is important for management to emphasize the instrumental value of resources embedded in the job itself that have implications for employability and career advancement

Prognostic value of HIV-1 Gag-specific CD4(+) T-cell responses for progression to AIDS analyzed in a prospective cohort study

The causal relationship between HIV-specific CD4+ T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4+ T cells were analyzed in long-term asymptomatic individuals (LTA; n = 6) and progressors to AIDS (n = 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4+ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gag-specific CD4+ T cells producing IL-2 or IFNgamma were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2+, IFNgamma+, or IL-2+IFNgamma+ CD4+ T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4+ T-cell responses, rather than HIV-specific CD4+ T-cell responses controlling HIV plasma viral loa