Effective group training techniques in job-search training.

The aim was to examine the effects of group training techniques in job-search training on later reemployment and mental health. The participants were 278 unemployed workers in Finland in 71 job-search training groups. Five group-level dimensions of training were identified. The results of hierarchical linear modeling demonstrated that preparation for setbacks at the group level significantly predicted decreased psychological distress and decreased symptoms of depression at the half-year follow-up. Trainer skills at the group level significantly predicted decreased symptoms of depression and reemployment to stable jobs. Interaction analyses showed that preparation for setbacks at the group level predicted fewer symptoms of psychological distress and depression, and shared perceptions of skilled trainers at the group level predicted fewer symptoms of depression among those who had been at risk for depression.

A conserved lysine in the estrogen receptor DNA binding domain regulates ligand activation profiles at AP-1 sites, possibly by controlling interactions with a modulating repressor.

BACKGROUND: Estrogen receptors alpha and beta (ERalpha and ERbeta) differentially activate genes with AP-1 elements. ERalpha activates AP-1 targets via activation functions with estrogens (the AF-dependent pathway), whereas ERbeta, and a short version of ERalpha (ERalpha DBD-LBD) activate only with anti-estrogens (AF-independent pathway). The DNA binding domain (DBD) plays an important role in both pathways, even though neither pathway requires ERE recognition. RESULTS: Mutations of a highly conserved DBD lysine (ERalpha.K206A/G), lead to super-activation of AP-1 through activation function dependent pathways, up to 200 fold. This super-activity can be elicited either through ER AFs 1 or 2, or that of a heterologous activation function (VP16). The homologous substitution in ERbeta, K170A, or in ERalpha DBD-LBD leads to estrogen-dependent AP-1 activation and loss of the usually potent anti-estrogen effects. Each of numerous K206 substitutions in ERalpha, except K206R, eliminates anti-estrogen activation and this loss correlates perfectly with a loss of ability to titrate a repressive function from the RU486 bound progesterone receptor. CONCLUSION: We conclude that ER DBDs contain a complex regulatory function that influences ligand activation profiles at AP-1. This function, which requires the integrity of the conserved lysine, both allows for activation at AP-1 with anti-estrogens (with ERbeta and ERalpha DBD-LBD), and prevents ERalpha from becoming superactive at AP-1 with estrogens. We discuss the possibility that a repressor interaction with the DBD both mediates the AF-independent pathway and dampens the AF dependent pathway. Mutations in the conserved lysine might, by this model, disrupt the binding or function of the repressor.

Underemployment: consequences for the health and well-being of workers.

This paper addresses the question of how the adequacy of a person's employment status influences their health. We draw on and extend the Labor Utilization Framework to distinguish between different forms of underemployment (hours, income, skills, and status) and test their relative effects on a range of physical health and psychological well-being outcomes. Using data drawn from a nationally representative sample (N = 1,429) of adults of working age, we assess the concurrent effects of underemployment through a longitudinal design that controls for prior levels of health and well-being. The results indicate that underemployed workers do report lower levels of health and well-being than adequately employed workers. However, the relationship varies by both types of underemployment and indicator of health and well-being. We conclude by discussing future research to explore the relationship between underemployment and health and well-being.

ERbeta Binds N-CoR in the Presence of Estrogens via an LXXLL-like Motif in the N-CoR C-terminus.

Nuclear receptors (NRs) usually bind the corepressors N-CoR and SMRT in the absence of ligand or in the presence of antagonists. Agonist binding leads to corepressor release and recruitment of coactivators. Here, we report that estrogen receptor beta (ERbeta) binds N-CoR and SMRT in the presence of agonists, but not antagonists, in vitro and in vivo. This ligand preference differs from that of ERalpha interactions with corepressors, which are inhibited by estradiol, and resembles that of ERbeta interactions with coactivators. ERbeta /N-CoR interactions involve ERbeta AF-2, which also mediates coactivator recognition. Moreover, ERbeta recognizes a sequence (PLTIRML) in the N-CoR C-terminus that resembles coactivator LXXLL motifs. Inhibition of histone deacetylase activity specifically potentiates ERbeta LBD activity, suggesting that corepressors restrict the activity of AF-2. We conclude that the ER isoforms show completely distinct modes of interaction with a physiologically important corepressor and discuss our results in terms of ER isoform specificity in vivo.

Working Pasteur's Quadrant: harnessing science and action for community change.

Community psychology in general and the field of prevention in particular has unquestioningly accepted the assumption that the research process should proceed in a linear fashion from a search for basic knowledge to application in the community context. This ignores the compelling insight offered by Stokes (1997) that the drive for new knowledge and the pursuit of application can be combined in a single effort. If research in community psychology pursues the drive for application without an equal commitment to the development of knowledge about underlying community processes of social cooperation and change, it will become a field less capable of innovative and enduring contributions to community well-being and effectiveness Opportunities abound in community psychology for the simultaneous pursuit of new knowledge and more effective practice. We offer the example of a community leadership development program to promote collective efficacy as a case in point.

Links in the chain of adversity following job loss: how financial strain and loss of personal control lead to depression, impaired functioning, and poor health.

The authors tested hypotheses concerning risk mechanisms that follow involuntary job loss resulting in depression and the link between depression and poor health and functioning. A 2-year longitudinal study of 756 people experiencing job loss indicates that the critical mediating mechanisms in the chain of adversity from job loss to poor health and functioning are financial strain (FS) and a reduction in personal control (PC). FS mediates the relationship of job loss with depression and PC, whereas reduced PC mediates the adverse impacts of FS and depression on poor functioning and self-reports of poor health. Results suggest that loss of PC is a pathway through which economic adversity is transformed into chronic problems of poor health and impaired role and emotional functioning.

Androgen receptors in human synoviocytes and androgen regulation of interleukin 1beta (IL-1beta) induced IL-6 production: a link between hypoandrogenicity and rheumatoid arthritis?

OBJECTIVE: To investigate the hypothesis that synoviocytes possess androgen receptors (AR) that could be modulated by the non-aromatizable androgen, dihydrotestosterone (DHT), resulting in altered levels of inflammatory cytokines. METHODS: Using molecular analyses of AR in combination with the multiprobe ribonuclease protection assay and ELISA, we investigated the presence of AR and the effect of DHT on interleukin 1beta (IL-1beta) induced expression of the IL-6 superfamily of cytokines in synoviocytes. RESULTS: Our studies corroborate the presence of AR in synoviocytes. DHT exerts a suppressive effect on IL-1beta induced IL-6, macrophage-colony stimulating factor (CSF), and granulocyte-CSF production by synoviocytes. This modulatory effect is exerted at both the transcriptional and translational level; 17beta-estradiol, at high concentrations, had a stimulatory effect. CONCLUSION: The identification of functional AR in synoviocytes and the modulatory effect of DHT on the inflammatory process in the joint suggest a direct link between hypoandrogenicity and rheumatoid arthritis (RA) disease status. Understanding the complex regulation of inflammatory cytokines by hormones may contribute to the development of new therapeutic targets for clinical intervention in RA.

Androgen receptor messenger RNA and protein in adult rat sciatic nerve: implications for site of androgen action.

Gonadal androgens exert a wide variety of effects on several neuromuscular systems, including controlling the developmental fate of motoneurons and neuromuscular synapses and promoting the growth of adult dendrites and axons. Paramount in understanding the molecular mechanisms behind androgen action is determining where androgen acts; does androgen act directly or indirectly on cells to change their fate and function? One step toward answering this question has been to determine which cells express androgen receptors (ARs). Motoneurons and skeletal muscles both have ARs and are, therefore, potential sites of androgen action. Recent evidence indicates that the sciatic nerve in rats also contains AR mRNA (Magnaghi et al. [1999] Brain Res. Mol. Brain Res. 70:36-44), although which cell type expresses ARs remains unanswered. In this study, we explored the question of which cell populations in the rat sciatic nerve express ARs. Using immunocytochemistry and reverse transcriptase-PCR, we confirmed the presence of AR protein and mRNA in sciatic nerve from adult rats and found a sex difference, favoring males, in the number of cell nuclei immunopositive for AR. This difference was not due to a sex difference in the overall number of cell nuclei. We also found a difference favoring males in AR mRNA, evidence also suggesting that AR expression is higher in males than in females. Results from double-immmunolabeling experiments in sciatic nerve from adult males suggest that, within the endoneurial compartment, endoneurial fibroblasts stain prominently for AR, with some endothelial cells also AR(+). Although Schwann cells showed light AR immunostaining, this staining is apparently nonspecific. We conclude that cells within peripheral nerve have ARs and may, therefore, mediate some of the effects of androgens on neuromuscular systems.

Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression.

Induction of cyclin D1 gene transcription by estrogen receptor alpha (ERalpha) plays an important role in estrogen-mediated proliferation. There is no classical estrogen response element in the cyclin D1 promoter, and induction by ERalpha has been mapped to an alternative response element, a cyclic AMP-response element at -57, with possible participation of an activating protein-1 site at -954. The action of ERbeta at the cyclin D1 promoter is unknown, although evidence suggests that ERbeta may inhibit the proliferative action of ERalpha. We examined the response of cyclin D1 promoter constructs by luciferase assay and the response of the endogenous protein by Western blot in HeLa cells transiently expressing ERalpha, ERalphaK206A (a derivative that is superactive at alternative response elements), or ERbeta. In each case, ER activation at the cyclin D1 promoter is mediated by both the cyclic AMP-response element and the activating protein-1 site, which play partly redundant roles. The activation by ERbeta occurs only with antiestrogens. Estrogens, which activate cyclin D1 gene expression with ERalpha, inhibit expression with ERbeta. Strikingly, the presence of ERbeta completely inhibits cyclin D1 gene activation by estrogen and ERalpha or even by estrogen and the superactive ERalphaK206A. The observation of the opposing action and dominance of ERbeta over ERalpha in activation of cyclin D1 gene expression has implications for the postulated role of ERbeta as a modulator of the proliferative effects of estrogen.

The Työhön Job Search Program in Finland: benefits for the unemployed with risk of depression or discouragement.

The impact of preventive interventions for the unemployed may vary depending on the context of the labor policies and benefit systems of the country where it is implemented. The Työhön Job Search Program was based on a method developed in the United States for recently unemployed workers. This study examined outcomes of the intervention in the context of the European labor market for participants who had been unemployed for a longer period. A total of 1,261 unemployed Finnish job seekers participated in a randomized field study. At the 6-month follow-up, the program had a beneficial impact on the quality of reemployment, especially among those who had been unemployed for a moderate time period. The program also significantly decreased psychological distress.