Using the Repertory Grid Technique to Examine Trainee Clinical Psychologists' Construal of Their Personal and Professional Development.

The repertory grid technique was used to explore how 26 third-year trainee clinical psychologists construed their personal and professional selves over the course of training and into the future. Each trainee completed a demographic questionnaire and a repertory grid with 10 elements: four 'personal self' elements, four 'professional self' elements and two 'qualified clinical psychologist' elements. They then rated the 10 elements on 10 bipolar constructs of their choosing. Trainees' personal and professional selves were construed to be similar to each other. Trainees had low self-esteem and reported currently feeling anxious, stressed, unsettled and lacking an appropriate work-life balance. These difficulties were attributed to the demands of training and were expected to resolve once training was completed with future selves being construed as similar to ideal selves. Suggestions for future research with improved methodology are made, and the implications of the findings for trainees, training providers and employers of newly qualified clinical psychologists are given. The overall implication being that stress in training is normative and the profession has a duty to normalize this and ensure that self-care and personal development are recognized as core competencies of the clinical psychologist for the benefit of its members and their clients. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Clinical psychology trainees experience training as demanding and stressful, which negatively impacts on their personal and professional self-image and self-esteem. However, they are optimistic that they will become more like their ideal self in the future. Stress in clinical training (and beyond) is normative, and thus, personal development and self-care should be recognized as clinical psychologist's core competencies.

Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism.

Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and limbs, the pattern of cellular differentiation is controlled by both the amount and the time of SHH exposure. How these two parameters are interpreted at a cellular level has been unclear. Here we provide evidence that changing the concentration or duration of SHH has an equivalent effect on intracellular signalling. Chick neural cells convert different concentrations of SHH into time-limited periods of signal transduction, such that signal duration is proportional to SHH concentration. This depends on the gradual desensitization of cells to ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1 (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient sensing. Together, the data reveal a novel strategy for morphogen interpretation, in which the temporal adaptation of cells to a morphogen integrates the concentration and duration of a signal to control differential gene expression.

The relationship between metacognitive beliefs, auditory hallucinations, and hallucination-related distress in clinical and non-clinical voice-hearers.

OBJECTIVES: To test the hypothesis that metacognitive beliefs are implicated in the development of distress associated with auditory verbal hallucinations (AVHs) rather than in their aetiology. DESIGN: A cross sectional questionnaire design was used. METHODS: Three groups of participants were recruited (n= 20 in each group); clinical voice-hearers diagnosed with psychiatric disorders; non-clinical voice-hearers with no psychiatric history; and non-clinical participants with no history of voices or psychiatric disorder. All participants were screened for psychiatric symptomatology and completed a self-report measure of their metacognitive beliefs (MCQ-30). In addition, the two groups of voice-hearers were interviewed about dimensions of their voices (i.e., content, frequency, distress, and disruption). RESULTS: The clinical group scored significantly higher than the two non-clinical groups on two subscales of the MCQ-30 (negative beliefs about worry concerning controllability and danger and negative beliefs about thoughts concerning need for control). There were no significant differences between the two non-clinical groups on MCQ-30 scores. Regression analyses revealed that the negative beliefs about need for control subscale of the MCQ-30 was the only significant predictor of voice-related distress, although this effect was no longer significant after controlling for the effect of group. CONCLUSIONS: These results are consistent with previous findings suggesting that metacognitive beliefs are not directly implicated in the aetiology of AVHs, but may be associated with psychological distress. Further research is however needed to determine whether metacognitive style may directly impact upon voice-related distress.

OK432-activated human dendritic cells kill tumor cells via CD40/CD40 ligand interactions.

In vivo, dendritic cells (DC) are programmed to orchestrate innate and adaptive immunity in response to pathogen-derived "danger" signals. Under particular circumstances, DC can also be directly cytotoxic against tumor cells, potentially allowing them to release tumor associated Ags from dying cells and then prime antitumor immunity against them. In this study, we describe the innate characteristics of DC (OK-DC) generated in vitro after exposure of immature human myeloid-derived DC to OK432, a penicillin-inactivated and lyophilized preparation of Streptococcus pyrogenes. OK-DC produced proinflammatory cytokines, stimulated autologous T cell proliferation and IFN-gamma secretion, expressed CCR7, and migrated in response to MIP-3beta. Moreover, OK-DC displayed strong, specific cytotoxicity toward tumor cell targets. This cytotoxicity was associated with novel, OK432-induced up-regulation of CD40L on the cell surface of OK-DC, and was absolutely dependent on expression of CD40 on the tumor targets. These data demonstrate that maturation of human DC with OK432, an adjuvant suitable for clinical use, induces direct tumor cell killing by DC, and describes a novel CD40/CD40L-mediated mechanism for specific DC antitumor cytotoxicity.

Biological activities encoded by the murine mesenchymal stem cell transcriptome provide a basis for their developmental potential and broad therapeutic efficacy.

We used serial analysis of gene expression to catalog the transcriptome of murine mesenchymal stem cells (MSCs) enriched from bone marrow by immunodepletion. Interrogation of this database, results of which are delineated in the appended databases, revealed that immunodepleted murine MSCs (IDmMSCs) highly express transcripts encoding connective tissue proteins and factors modulating T-cell proliferation, inflammation, and bone turnover. Categorizing the transcriptome based on gene ontologies revealed the cells also expressed mRNAs encoding proteins that regulate mesoderm development or that are characteristic of determined mesenchymal cell lineages, thereby reflecting both their stem cell nature and differentiation potential. Additionally, IDmMSCs also expressed transcripts encoding proteins regulating angiogenesis, cell motility and communication, hematopoiesis, immunity and defense as well as neural activities. Immunostaining and fluorescence-activated cell sorting analysis revealed that expression of various regulatory proteins was restricted to distinct subpopulations of IDmMSCs. Moreover, in some cases, these proteins were absent or expressed at reduced levels in other murine MSC preparations or cell lines. Lastly, by comparing their transcriptome to that of 17 other murine cell types, we also identified 43 IDmMSC-specific transcripts, the nature of which reflects their varied functions in bone and marrow. Collectively, these results demonstrate that IDmMSC express a diverse repertoire of regulatory proteins, which likely accounts for their demonstrated efficacy in treating a wide variety of diseases. The restricted expression pattern of these proteins within populations suggests that the cellular composition of marrow stroma and its associated functions are more complex than previously envisioned.

Murine mesenchymal and embryonic stem cells express a similar Hox gene profile.

Using degenerate oligonucleotide primers targeting the homeobox domain, we amplified by PCR and sequenced 723 clones from five murine cell populations and lines derived from embryonic mesoderm and adult bone marrow. Transcripts from all four vertebrate Hox clusters were expressed by the different populations. Hierarchical clustering of the data revealed that mesenchymal stem cells (MSCs) and the embryonic stem (ES) cell line D3 shared a similar Hox expression profile. These populations exclusively expressed Hoxb2, Hoxb5, Hoxb7, and Hoxc4, transcripts regulating self-renewal and differentiation of other stem cells. Additionally, Hoxa7 transcript quantified by real-time PCR strongly correlated (r2=0.89) with the number of Hoxa7 clones identified by sequencing, validating that data from the PCR screen reflects differences in Hox mRNA abundance between populations. This is the first study to catalogue Hox transcripts in murine MSCs and by comparative analyses identify specific Hox genes that may contribute to their stem cell character.

Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection.

Mesenchymal stem cells (MSCs) are typically enriched from bone marrow via isolation of the plastic adherent, fibroblastoid cell fraction. However, plastic adherent cultures elaborated from murine bone marrow are an admixture of fibroblastoid and hematopoietic cell types. Here we report a reliable method based on immunodepletion to fractionate fibroblastoid cells from hematopoietic cells within plastic adherent murine marrow cultures. The immunodepleted cells expressed the antigens Sca-1, CD29, CD44, CD81, CD106, and the stem cell marker nucleostemin (NST) but not CD11b, CD31, CD34, CD45, CD48, CD90, CD117, CD135, or the transcription factor Oct-4. They were also capable of differentiating into adipocytes, chondrocytes, and osteoblasts in vitro as well as osteoblasts/osteocytes in vivo. Therefore, immunodepletion yields a cell population devoid of hematopoietic and endothelial cells that is phenotypically and functionally equivalent to MSCs. The immunodepleted cells exhibited a population doubling time of approximately 5-7 days in culture. Poor growth was due to the dramatic down regulation of many genes involved in cell proliferation and cell cycle progression as a result of immunodepletion. Exposure of immunodepleted cells to fibroblast growth factor 2 (FGF2) but not insulin-like growth factor (IGF), murine stem cell factor, or leukemia inhibitory factor (LIF) significantly increased their growth rate. Moreover, 82% of the transcripts down regulated by immunodepletion remain unaltered in the presence of FGF2. Exposure to the later also reversibly inhibited the ability of the immunodepleted cells to differentiate into adipocytes, chondrocytes, and osteoblasts in vitro. Therefore, FGF2 appears to function as a mitogen and self-maintenance factor for murine MSCs enriched from bone marrow by negative selection.