Life Course Events and Migration in the Transition to Adulthood.

Do life course events stimulate migration during the transition to adulthood? We identify nine specific life events in the family, education, and employment domains and test whether they lead to migration in the short term, using fixed-effects models that remove the influence of all stable individual-level characteristics and controlling for age. Marital and school completion events have substantively large effects on migration compared to individual work transitions, although there are more of the latter over the young adult years. Furthermore, young adults who are white and from higher class backgrounds are more likely to migrate in response to life events, suggesting that migration may be a mechanism for the reproduction of status attainment. Overall, the results demonstrate a close relationship between life course events and migration, and suggest a potential role for migration in explaining the effect of life course events on well-being and behavior.

Relative Education and the Advantage of a College Degree.

What is the worth of a college degree when higher education expands? The relative education hypothesis posits that when college degrees are rare, individuals with more education have less competition to enter highly-skilled occupations. When college degrees are more common, there may not be enough highly-skilled jobs to go around; some college-educated workers lose out to others and are pushed into less-skilled jobs. Using new measurements of occupation-level verbal, quantitative, and analytic skills, this study tests the changing effect of education on skill utilization across 70 years of birth cohorts from 1971 to 2010, net of all other age, period, and cohort trends. Higher-education expansion erodes the value of a college degree, and college-educated workers are at greater risk for underemployment in less cognitively demanding occupations. This raises questions about the sources of rising income inequality, skill utilization across the working life course, occupational sex segregation, and how returns to education have changed across different life domains.

Who Is This "We" You Speak of? Grounding Activist Identity in Social Psychology.

What is an activist identity? Prior answers have focused almost exclusively on collective identity, without a) considering the possibility of role-based identities or b) grounding collective identities in broader social-psychological theories. The present study investigates activist identity through the lens of role-based and category-based identities, and reports two major findings. First, there is a distinct role-based activist identity, one that involves internalizing role responsibilities and the expectations of friends and family. Second, collective identity represents a relationship between a social identity and an injustice frame; it either involves incorporating an injustice frame into a pre-existing social identity, or using the injustice frame to create a new in-group. The present findings help to illuminate the processes underlying collective identity, indicate that a great deal of role-based activist identity is mistaken for collective identity, and suggest new directions for the study of micro-mobilization and organizational forms and tactics in social movements.

Discrepancies in Leader and Follower Ratings of Transformational Leadership: Relationship with Organizational Culture in Mental Health.

The role of leadership in the management and delivery of health and allied health services is often discussed but lacks empirical research. Discrepancies are often found between leaders' self-ratings and followers' ratings of the leader. To our knowledge no research has examined leader-follower discrepancies and their association with organizational culture in mental health clinics. The current study examines congruence, discrepancy, and directionality of discrepancy in relation to organizational culture in 38 mental health teams (N = 276). Supervisors and providers completed surveys including ratings of the supervisor transformational leadership and organizational culture. Polynomial regression and response surface analysis models were computed examining the associations of leadership discrepancy and defensive organizational culture and its subscales. Discrepancies between supervisor and provider reports of transformational leadership were associated with a more negative organizational culture. Culture suffered more where supervisors rated themselves more positively than providers, in contrast to supervisors rating themselves lower than the provider ratings of the supervisor. Leadership and leader discrepancy should be a consideration in improving organizational culture and for strategic initiatives such as quality of care and the implementation and sustainment of evidence-based practice.

Changes in the prevalence of mood and anxiety disorders among male and female current smokers in the United States: 1990-2001.

PURPOSE: The present study investigated whether the prevalence of mood and anxiety disorders has increased over time among current smokers and whether these trends differ by gender and in comparison with nonsmokers. METHODS: Data were drawn from the National Comorbidity Survey (1990) and the National Comorbidity Survey-Replication (2001), representative samples of the US adult population. Binomial regression analyses were used to determine differences between mood and anxiety disorders among current smokers in 1990 and 2001 and whether these differed by gender and in comparison with those who were former or never current smokers. RESULTS: Any anxiety disorder, panic attacks, panic disorder, social anxiety disorder and dysthymia were all significantly more common among current smokers in 2001 compared with 1990 and except for social anxiety disorder these increases were significantly greater than any trend found in non-smokers. Increases in panic attacks, social anxiety disorder, and dysthymia were more pronounced in female than in male smokers. Major depressive disorder and generalized anxiety disorder were not found to increase over time among smokers. CONCLUSIONS: The prevalence of several anxiety disorders and dysthymia among current smokers appears to have increased from 1990 to 2001. Future studies are needed to determine whether these trends have continued. If so, interventions aimed at moving the prevalence lower may have limited success if treatment of mental health problems such as anxiety disorders and certain mood disorders are not considered in the development and dissemination of tobacco control programs.

Neural development is dependent on the function of specificity protein 2 in cell cycle progression.

Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.

Constitutive autotaxin transcription by Nmyc-amplified and non-amplified neuroblastoma cells is regulated by a novel AP-1 and SP-mediated mechanism and abrogated by curcumin.

The motility, angiogenesis and metastasis-stimulating factor Autotaxin (Atx), over expressed by human neuroblastomas (NB), is constitutively expressed by human Nmyc-amplified SK-N-BE and non-Nmyc-amplified SH-SY5Y NB cells. Here, we characterise a novel Atx transcriptional mechanism, utilised by both cell lines, that is restricted to the first 285bp of the Atx promoter and involves AP-1 and SP transcription factors, acting through a CRE/AP-1-like element at position -142 to -149 and a GAbox at position -227 to -235 relative to the Atx translational start site. This novel transcriptional mechanism can be inhibited by internally initiated SP-3 and the natural phenol curcumin.

Overexpression of transcription factor sp2 inhibits epidermal differentiation and increases susceptibility to wound- and carcinogen-induced tumorigenesis.

Sp proteins are evolutionarily conserved transcription factors required for the expression of a wide variety of genes that are critical for development and cell cycle progression. Deregulated expression of certain Sp proteins is associated with the formation of a variety of human tumors; however, direct evidence that any given Sp protein is oncogenic has been lacking. Here, we report that Sp2 protein abundance in mice increases in concert with the progression of carcinogen-induced murine squamous cell carcinomas. Transgenic mice specifically overexpressing murine Sp2 in epidermal basal keratinocytes were highly susceptible to wound- and carcinogen-induced papillomagenesis. Transgenic animals that were homozygous rather than hemizygous for the Sp2 transgene exhibited a striking arrest in the epidermal differentiation program, perishing within 2 weeks of birth. Our results directly support the likelihood that Sp2 overexpression occurring in various human cancers has significant functional effect.

Measuring the intra-individual variability of the plasma proteome in the chicken model of spontaneous ovarian adenocarcinoma.

The domestic chicken (Gallus domesticus) has emerged as a powerful experimental model for studying the onset and progression of spontaneous epithelial ovarian cancer (EOC) with a disease prevalence that can exceed 35% between 2 and 7 years of age. An experimental strategy for biomarker discovery is reported herein that combines the chicken model of EOC, longitudinal plasma sample collection with matched tissues, advanced mass spectrometry-based proteomics, and concepts derived from the index of individuality (Harris, Clin Chem 20: 1535-1542, 1974). Blood was drawn from 148 age-matched chickens starting at 2.5 years of age every 3 months for 1 year. At the conclusion of the 1 year sample collection period, the 73 birds that remained alive were euthanized, necropsied, and tissues were collected. Pathological assessment of resected tissues from these 73 birds confirmed that five birds (6.8%) developed EOC. A proteomics workflow including in-gel digestion, nanoLC coupled to high-performance mass spectrometry, and label-free (spectral counting) quantification was used to measure the biological intra-individual variability (CV(W)) of the chicken plasma proteome. Longitudinal plasma sample sets from two birds within the 73-bird biorepository were selected for this study; one bird was considered "healthy" and the second bird developed late-stage EOC. A total of 116 proteins from un-depleted plasma were identified with 80 proteins shared among all sample sets. Analytical variability (CV(A)) of the label-free proteomics workflow was measured using a single plasma sample analyzed five times and was found to be ≥CV(W) in both birds for 16 proteins (20%) and in either bird for 25 proteins (31%). Ovomacroglobulin (ovostatin) was found to increase (p < 0.001) over a 6 month period in the late-stage EOC bird providing an initial candidate protein for further investigation.

Transcription of mouse Sp2 yields alternatively spliced and sub-genomic mRNAs in a tissue- and cell-type-specific fashion.

The Sp-family of transcription factors is comprised by nine members, Sp1-9, that share a highly conserved DNA-binding domain. Sp2 is a poorly characterized member of this transcription factor family that is widely expressed in murine and human cell lines yet exhibits little DNA-binding or trans-activation activity in these settings. As a prelude to the generation of a "knock-out" mouse strain, we isolated a mouse Sp2 cDNA and performed a detailed analysis of Sp2 transcription in embryonic and adult mouse tissues. We report that (1) the 5' untranslated region of Sp2 is subject to alternative splicing, (2) Sp2 transcription is regulated by at least two promoters that differ in their cell-type specificity, (3) one Sp2 promoter is highly active in nine mammalian cell lines and strains and is regulated by at least five discrete stimulatory and inhibitory elements, (4) a variety of sub-genomic messages are synthesized from the Sp2 locus in a tissue- and cell-type-specific fashion and these transcripts have the capacity to encode a novel partial-Sp2 protein, and (5) RNA in situ hybridization assays indicate that Sp2 is widely expressed during mouse embryogenesis, particularly in the embryonic brain, and robust Sp2 expression occurs in neurogenic regions of the post-natal and adult brain.

Sp2 is a maternally inherited transcription factor required for embryonic development.

The Sp family of transcription factors is required for the expression of cell cycle- and developmentally regulated genes, and the deregulated expression of a handful of family members is associated with human tumorigenesis. Sp2 is a relatively poorly characterized member of the Sp family that, although widely expressed, exhibits little or no DNA binding or transcriptional activity in human and mouse cell lines. To begin to address the role(s) played by Sp2 in early metazoan development we have cloned and characterized Sp2 from zebrafish (Danio rerio). We report that 1) the intron/exon organization and amino acid sequence of zebrafish Sp2 is closely conserved with its mammalian orthologues, 2) zebrafish Sp2 weakly stimulates an Sp-dependent promoter in vitro and associates with the nuclear matrix in a DNA-independent fashion, 3) zebrafish Sp2 is inherited as a maternal transcript, is transcribed in zebrafish embryos and adult tissues, and is required for completion of gastrulation, and 4) zebrafish lines carrying transgenes regulated by the Sp2 promoter recapitulate patterns of endogenous Sp2 expression.

An exploration of the relationship between mental pollution and OCD symptoms.

Rachman [(1994). Pollution of the mind. Behaviour Research and Therapy, 32, 311-314] theorized that a subtype of compulsive washing exists which has its compulsions triggered by feelings of internal dirtiness, or 'mental pollution'. Since this construct was proposed, few empirical studies have examined it in relation to obsessive-compulsive contamination fear. This study represents a validation of the Mental Pollution Questionnaire (MPQ), which was developed for the measurement of mental pollution. Psychometric data were obtained from two studies using non-clinical samples. The final version of the MPQ consisted of eight items and two subscales related to washing and ideation. Higher mental pollution scores were associated with greater obsessions, contamination, and washing symptoms. In addition, MPQ scores were positively associated with inflated responsibility beliefs and thought-action fusion. Lastly, a third study found that both MPQ subscales predicted OC symptoms after controlling for general distress, trait guilt, and disgust sensitivity. Potential uses of the MPQ as a clinical and research instrument are discussed.

Psychological approaches in the treatment of specific phobias: a meta-analysis.

Data from 33 randomized treatment studies were subjected to a meta-analysis to address questions surrounding the efficacy of psychological approaches in the treatment of specific phobia. As expected, exposure-based treatment produced large effects sizes relative to no treatment. They also outperformed placebo conditions and alternative active psychotherapeutic approaches. Treatments involving in vivo contact with the phobic target also outperformed alternative modes of exposure (e.g., imaginal exposure, virtual reality, etc.) at post-treatment but not at follow-up. Placebo treatments were significantly more effective than no treatment suggesting that specific phobia sufferers are moderately responsive to placebo interventions. Multi-session treatments marginally outperformed single-session treatments on domain-specific questionnaire measures of phobic dysfunction, and moderator analyses revealed that more sessions predicted more favorable outcomes. Contrary to expectation, effect sizes for the major comparisons of interest were not moderated by type of specific phobia. These findings provide the first quantitative summary evidence supporting the superiority of exposure-based treatments over alternative treatment approaches for those presenting with specific phobia. Recommendations for future research are also discussed.

Dissociation and pain perception: an experimental investigation.

Dissociative symptoms and abnormalities in pain perception have been associated with a range of disorders. The authors tested whether experimentally induced increases in state dissociation would cause an analgesic response. Participants (N = 120) were randomized to a dissociation induction condition via audiophotic stimulation or a credible control condition and were compared on pre- and postchanges in subjective pain and immersion time in response to a standard cold pressor test. Unexpectedly, the dissociation induction led to small, but significant increases in subjective pain and did not lead to greater immersion time. An exploratory analysis revealed that increases in absorption and derealization significantly predicted increased subjective pain and increased immersion time, respectively.

A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia.

The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention.

Early growth response gene-1 regulates hypoxia-induced expression of tissue factor in glioblastoma multiforme through hypoxia-inducible factor-1-independent mechanisms.

Hypoxia strongly up-regulates tissue factor and promotes plasma clotting by glioblastoma multiforme, but transcriptional mechanisms remain undefined. Here, we investigated the potential roles of early growth response gene-1 (Egr-1), Sp1, nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), and hypoxia-inducible factor-1 (HIF-1) in the hypoxic regulation of tissue factor by glioblastoma multiforme cells in vitro. Hypoxia (1% O2) strongly induced Egr-1 mRNA within 1 hour and led to nuclear localization of Egr-1 protein. Using luciferase reporter plasmids in glioma cells, we found that hypoxia dramatically increased luciferase activity in cells with constructs containing Egr-1-binding sites but not in cells with constructs containing AP-1- or NF-kappaB-binding sites. Electrophoretic mobility shift assays revealed hypoxia-induced Egr-1, but not Sp1, binding to oligonucleotides containing the Egr-1/Sp1 motif of tissue factor gene promoter. Using an expression vector containing the minimal tissue factor promoter (-111 to +14 bp) and small interfering RNA (siRNA) directed at Egr-1 and Sp1 mRNAs, we found that Egr-1 was required for maximal hypoxic induction of promoter activity. Forced overexpression of Egr-1 but not Sp1 by cDNA transfection caused up-regulation of tissue factor in glioma cells under normoxia (21% O2), whereas siRNA directed at Egr-1 strongly attenuated hypoxia-induced tissue factor expression. To examine the effects of HIF-1alpha on tissue factor expression, we used glioma cells stably transfected with a HIF-1alpha siRNA expression vector and found that HIF-1alpha mRNA silencing did not affect tissue factor expression under hypoxia. We conclude that hypoxic up-regulation of tissue factor in glioblastoma multiforme cells depends largely on Egr-1 and is independent of HIF-1.

Sp2 localizes to subnuclear foci associated with the nuclear matrix.

We have reported that extracts prepared from many human and mouse cell lines show little or no Sp2 DNA-binding activity and that Sp2 has little or no capacity to stimulate transcription of promoters that are activated by Sp1, Sp3, and Sp4. Using an array of chimeric Sp1/Sp2 proteins we showed further that Sp2 DNA-binding activity and trans-activation are each negatively regulated in mammalian cells. As part of an ongoing effort to study Sp2 function and regulation we characterized its subcellular localization in comparison with other Sp-family members in fixed and live cells. We report that 1) Sp2 localizes largely within subnuclear foci associated with the nuclear matrix, and 2) these foci are distinct from promyelocytic oncogenic domains and appear to be stable during an 18-h time course of observation. Deletion analyses identified a 37 amino acid sequence spanning the first zinc-"finger" that is sufficient to direct nuclear matrix association, and this region also encodes a bipartite nuclear localization sequence. A second nuclear matrix targeting sequence is encoded within the Sp2 trans-activation domain. We conclude that Sp2 preferentially associates with the nuclear matrix and speculate that this subcellular localization plays an important role in the regulation of Sp2 function.

Nkx3.1 binds and negatively regulates the transcriptional activity of Sp-family members in prostate-derived cells.

Nkx3.1 is a homeodomain-containing transcription factor that is expressed early in the development of the prostate gland and is believed to play an important role in the differentiation of prostatic epithelia. Loss of Nkx3.1 protein expression is often an early event in prostate tumorigenesis, and the abundance of Nkx3.1-negative epithelial cells increases with disease progression. In a number of systems, homeodomain proteins collaborate with zinc-finger-containing transcription factors to bind and regulate target genes. In the present paper, we report that Nkx3.1 collaborates with Sp-family members in the regulation of PSA (prostate-specific antigen) in prostate-derived cells. Nkx3.1 forms protein complexes with Sp proteins that are dependent on their respective DNA-binding domains and an N-terminal segment of Nkx3.1, and Nkx3.1 negatively regulates Sp-mediated transcription via Trichostatin A-sensitive and -insensitive mechanisms. A distal 1000 bp portion of the PSA promoter is required for transrepression by Nkx3.1, although Nkx3.1 DNA-binding activity is itself not required. We conclude that Nkx3.1 negatively regulates Sp-mediated transcription via the tethering of histone deacetylases and/or by inhibiting the association of Sp proteins with co-activators.

Sumoylation of internally initiated Sp3 isoforms regulates transcriptional repression via a Trichostatin A-insensitive mechanism.

Sp3 is a ubiquitously expressed member of the Sp family of transcription factors that encodes three proteins, Sp3, M1 and M2, with differing capacities to stimulate or repress transcription. As part of ongoing efforts to study the functions of Sp3 isoforms, we employed a yeast "two-hybrid" screen to identify Sp3-binding proteins. This screen resulted in the identification of Ubc9, a SUMO-1 conjugating enzyme, as an M2-binding protein, and consistent with these results sequence analyses identified consensus sumoylation motifs within several Sp family members. Western blots probed with anti-Sp3 detected a high molecular weight Sp3 isoform that is stabilized by a SUMO-1 hydrolase inhibitor, and this protein is also bound by anti-SUMO-1 antiserum. Transient transfection assays with epitope-tagged-SUMO-1 and GFP-SUMO-1 fusion proteins confirmed that Sp3, M1 and M2 proteins are sumoylated in vivo. Substitution of arginine for lysine at one putative site of sumoylation, lysine(551), blocked sumoylation of all Sp3 isoforms in vivo and led to a marginal increase in Sp3-mediated trans-activation in insect and mammalian cells. In contrast, introduction of this amino acid substitution within M1 converted it into a potent transcriptional trans-activator. We conclude that Sp3 isoforms are sumoylated in vivo and this post-translational modification plays an important role in the regulation of Sp3-mediated transcription.

Sp2 DNA binding activity and trans-activation are negatively regulated in mammalian cells.

Previous studies have indicated that Sp2 binds poorly to GC-rich sequences bound by Sp1 and Sp3, and further functional analyses of Sp2 have been limited. To study Sp2-mediated transcription, we employed a PCR-based protocol to determine the Sp2 consensus DNA-binding sequence (5'-GGGCGGGAC-3') and performed kinetic experiments to show that Sp2 binds this consensus sequence with high affinity (225 pm) in vitro. To determine the functional consequence of Sp2 interaction with this sequence in vivo, we transformed well characterized Sp-binding sites within the dihydrofolate reductase (DHFR) promoter to consensus Sp2-binding sites. Incorporation of Sp2-binding sites within the DHFR promoter increased Sp2-mediated trans-activation in transient co-transfection experiments but also revealed Sp2 to be a relatively weak trans-activator with little or no capacity for additive or synergistic trans-activation. Using chimeric molecules prepared with portions of Sp1 and Sp2 and the human prostate-specific antigen promoter, we show that Sp2 DNA binding activity and trans-activation are negatively regulated in mammalian cells. Taken together, our data indicate that Sp2 is functionally distinct relative to other Sp family members and suggest that Sp2 may play a unique role in cell physiology.