Dispositional and performance-specific music performance anxiety in young amateur musicians

IntroductionResearch on Music Performance Anxiety (MPA) among amateur musicians is of great interest due to inconsistent results in literature. In addition, amateur music represents an important part of musical culture in Germany. Accordingly, the performance experiences of young wind players represent a relevant issue for research and musical practice.MethodsIn the present study, 67 young amateur musicians of a brass choir were examined. Using two different questionnaires, both the dispositional MPA (K-MPAI) and the performance-specific MPA during a joint concert (Performance-specific Questionnaire for Musicians, PQM) were assessed. The PQM measures the symptoms of MPA, functional coping with MPA and self-efficacy before, during and after a specific performance. The PQM was completed by the musicians via an app directly after the concert.ResultsResults showed that about 90% of the young amateur musicians had a low dispositional MPA, but about 10% showed high values. For the concrete performance, however, musicians with high dispositional MPA also experienced a very moderate to low MPA in the concert. On average, the musicians were quite nervous before the performance. After the performance, they showed low levels of MPA. Three types of MPA found in previous studies could be confirmed among the amateur musicians, with three quarters being assigned to the positive type, showing low levels of symptoms associated with consistently high levels of self-efficacy and positive functional coping.DiscussionThe results provide a differentiated picture of different expressions of MPA in young amateur musicians. They also raise further questions about the correlation between dispositional and performance-specific assessment of MPA in musicians in general

Völkisch und sozial? : Neonazistische Agitation gegen die neue EU-Freizügigkeit für Arbeitnehmerinnen

Wnt/β-catenin signalling pathway is crucial for the formation of many tissues and organs during development. In recent years, this pathway has also been found to regulate the biology of stem cells in the intestine and probably in other organs in adult life. Abnormal activation of Wnt/β-catenin signalling, which controls the expression of a high number of genes, is critical for the initiation and progression of most colorectal cancers. In line with this, the gene expression signature induced by activation of the Wnt/β-catenin pathway defines the intestinal stem cells present at the bottom of the crypts and also colon cancer stem cells. This supports the importance of inhibitors of the Wnt/β-catenin pathway as potential agents in colorectal cancer therapy. However, the complexity, wide activity in the organism modulating the biology of several cell types, and characteristics of this pathway have delayed the identification of suitable targets and so, the development of such inhibitors that are only now reaching the clinic.Peer reviewe

hSrb7, an essential human Mediator component, acts as a coactivator for the thyroid hormone receptor

Nuclear hormone receptors interact with the basal-transcriptional complex and/or coactivators to regulate transcriptional activation. These activator-target interactions recruit the transcriptional machinery to the promoter and may also stimulate transcriptional events subsequent to the binding of the machinery to the promoter or enhancer element. We describe a novel functional interaction of the nuclear thyroid receptor (TR), with a human Mediator component (hSrb7), and a human TFIIH component (hMo15). In mammalian two-hybrid experiments as well as in GST-pull down assays, hSrb7 interacts with TR but not with other nuclear receptors such as the retinoic acid receptor (RAR) or the vitamin D receptor (VDR). Whereas hMo15 also interacts with VDR and RAR in mammalian two-hybrid assays, no association of hSrb7 with VDR or RAR is found. Accordingly, cotransfection of TR and hSrb7 increases thyroid hormone (T3)-dependent transcription in an AF-2-dependent manner, while hSrb7 causes no stimulation of vitamin D- or retinoic acid-mediated transactivation. These results reveal a novel co-activator role for hSrb7 and hMo15 on TR transcriptional responses, and demonstrate that different receptors can selectively target different co-activators or general transcription factors to stimulate transcription.This work has been supported by the grant BMC2001-2275 from the Dirección General de Enseñanza Superior e Investigación of the Ministerio de Ciencia y Tecnologı́a of Spain. Dr. J. Nevado is a recipient of a Research Contract from ISCIII (FIS 99/3077)

Alien/CSN2 gene expression is regulated by thyroid hormone in rat brain

Alien has been described as a corepressor for the thyroid hormone receptor (TR). Corepressors are coregulators that mediate gene silencing of DNA-bound transcriptional repressors. We describe here that Alien gene expression in vivo is regulated by thyroid hormone both in the rat brain and in cultured cells. In situ hybridization revealed that Alien is widely expressed in the mouse embryo and also throughout the rat brain. Hypothyroid animals exhibit lower expression of both Alien mRNAs and protein levels as compared with normal animals. Accordingly, we show that Alien gene is inducible after thyroid hormone treatment both in vivo and in cell culture. In cultured cells, the hormonal induction is mediated by either TRα or TRβ, while cells lacking detectable amounts of functional TR lack hormonal induction of Alien. We have detected two Alien-specific mRNAs by Northern experiments and two Alien-specific proteins in vivo and in cell lines by Western analysis, one of the two forms representing the CSN2 subunit of the COP9 signalosome. Interestingly, both Alien mRNAs and both detected proteins are regulated by thyroid hormone in vivo and in cell lines. Furthermore, we provide evidence for the existence of at least two Alien genes in rodents. Taken together, we conclude that Alien gene expression is under control of TR and thyroid hormone. This suggests a negative feedback mechanism between TR and its own corepressor. Thus, the reduction of corepressor levels may represent a control mechanism of TR-mediated gene silencing. © 2003 Elsevier Science (USA). All rights reserved.This work was supported by grants from the Deutscher Akademischer Austauschdienst (to A.B. and S.P.T.), the “Programa de Acciones Especiales y Acciones de Política Científica” (APC1999-0172) of the Ministerio de Educación y Cultura of Spain (to S.P.T.), the Grant SAF2001-2291 from the Ministerio de Ciencia y Tecnologia to A.M., and the SFB 397 from the Deutsche Forschungsgemeinschaft (to A.B.).Peer Reviewe

Dissecting tumor anatomy: Intratumoral cell heterogeneity defines response to target-directed therapies

Resumen del trabajo presentado al XXXIV Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Barcelona del 5 al 8 de septiembre de 2011.-- et al.Accumulated evidences indicate that most solid tumors are not homogeneous but built of cancer cell populations with divers biological properties. They follow a hierarchical organization in which self-renewing cancer stem cells (CSC) are in the apex of a differentiation process within the cancerous tissue. CSC can also compose the small reservoir of drug-resistant cells responsible for tumor relapse or can give rise to metastasis. Our laboratory is exploring such heterogeneity and describing novel populations of cancer cells within colon carcinomas responsible for drugresistance, relapse or metastasis, all clinical determinants of patients' survival. Blocking signaling pathways that drive CSC distinctive properties is a new strategy being recently explored in clinical oncology by the use of novel targetdirected drugs. Wnt/β-catenin and PI3K/AKT are two of these pathways playing a central role in CSC homeostasis. We have described the function of their corresponding effectors - β-catenin and FOXO3a - cooperating in colon cancer. Their activation promotes cell scatteringand metastasis regulating a set of common target genes. Unexpectedly, the anti-tumoral AKT inhibitor API-2 promotes nuclear FOXO3a accumulation and metastasis from cells with high nuclear β-catenin. β-catenin confers resistance to FOXO3a-induced apoptosis promoted by PI3K and AKT inhibitors in patient-derived cells enriched in CSC, that is reverted by Wnt/β-catenin inhibitor XAV-939. Our findings could have a serious impact on therapy since we demonstrate that nuclear β-catenin heterogeneity compromises the response of different cancer cell populations to anti-tumoral drugs currently in clinical trials and directed against PI3K/AKT oncogenic signal.Peer Reviewe

Activation of the human immunodeficiency virus type I long terminal repeat by 1α,25-dihyfroxyvitamin D3

The genetic predisposition of the host and the virus is the most important determinant for prediction of the course of human immunodeficiency virus type I (HIV-1) viral infection and acquired immune deficiency syndrome (AIDS) progression. Transcription from the HIV-1 long terminal repeat (LTR) is a crucial step for viral replication. Here, we describe a stimulatory role of the vitamin D receptor (VDR) on HIV-1 LTR transactivation. Transient transfections reveal that VDR activates the LTR in HeLa, U937, and Cos-1 cells in a ligand-dependent manner. 1α,25-Dihydroxyvitamin D3 (vitD3) promotes activation of a minimal LTR construct (from nucleotides -35 to +89), lacking a previously described hormone response element that binds several nuclear receptors. NF-κB (nuclear factor-kappa B) and Sp1-binding sites, which are responsible for most basal LTR activity in HeLa cells, are also dispensable for vitD3-dependent HIV-1 transcription. Although the tat response element element is not required for VDR-mediated HIV-1 gene expression, the viral protein Tat acts in a synergistic manner with the receptor to stimulate LTR activity. Furthermore, our data also show cooperation of the receptor with various cellular coactivators for HIV-1 transactivation by vitD3. Paradoxically, mutations in the VDR ligand-dependent transcriptional activation function-2 that abrogate vitD3-dependent stimulation through classical vitamin D response elements, do not reduce vitD3-mediated LTR transactivation. Furthermore, point mutations in the DNA-binding domain that abolish receptor binding to consensus DNA sequences do not affect ligand-dependent HIV-1 stimulation. These results show that VDR activates the HIV-1 LTR through different mechanisms, including non-classical nuclear receptor transcriptional actions that may ensure viral transcription under different physiological scenario. © 2007 Society for Endocrinology.This work has been supported by the Grant BFU2004 03465. J N is a recipient of a Research contract from ISCIII (FIS 99/3077), and A I C was supported by a postdoctoral fellowship of the Ernst Schering Research Foundation. Finally, the authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work

Alien/CSN2 gene expression is regulated by thyroid hormone in rat brain

AbstractAlien has been described as a corepressor for the thyroid hormone receptor (TR). Corepressors are coregulators that mediate gene silencing of DNA-bound transcriptional repressors. We describe here that Alien gene expression in vivo is regulated by thyroid hormone both in the rat brain and in cultured cells. In situ hybridization revealed that Alien is widely expressed in the mouse embryo and also throughout the rat brain. Hypothyroid animals exhibit lower expression of both Alien mRNAs and protein levels as compared with normal animals. Accordingly, we show that Alien gene is inducible after thyroid hormone treatment both in vivo and in cell culture. In cultured cells, the hormonal induction is mediated by either TRα or TRβ, while cells lacking detectable amounts of functional TR lack hormonal induction of Alien. We have detected two Alien-specific mRNAs by Northern experiments and two Alien-specific proteins in vivo and in cell lines by Western analysis, one of the two forms representing the CSN2 subunit of the COP9 signalosome. Interestingly, both Alien mRNAs and both detected proteins are regulated by thyroid hormone in vivo and in cell lines. Furthermore, we provide evidence for the existence of at least two Alien genes in rodents. Taken together, we conclude that Alien gene expression is under control of TR and thyroid hormone. This suggests a negative feedback mechanism between TR and its own corepressor. Thus, the reduction of corepressor levels may represent a control mechanism of TR-mediated gene silencing

The thyroid hormone receptors as tumor suppressors

In addition to the well-known role of the thyroid hormone receptors (TRs) in growth, development and metabolism, there is increasing evidence that they have profound effects on cell proliferation and malignant transformation. TRs repress transcriptional induction of cyclin D1 by the ras oncogene and block transformation and tumor formation by Ras-transformed fibroblasts in nude mice. Mutant receptors that do not bind coactivators are able to display these actions, whereas receptors defective in corepressors binding are unable to antagonize the responses to the ras oncogene. Furthermore, expression of TRΒ 1 in hepatocarcinoma and breast cancer cells abolishes anchorage-independent growth and migration, blocks responses to growth factors and represses expression of prometastatic genes, reducing tumor growth and strongly inhibiting invasiveness, extravasation and metastasis formation in euthyroid mice. By contrast, when cells are inoculated into hypothyroid host, tumor growth is retarded, but tumors are more invasive and metastatic growth is enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs, showing that changes secondary to hypothy-roidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. Finally, increased malignancy of skin tumors is found in mice lacking TRs, further demonstrating the role of these receptors as inhibitors of tumor progression and suggesting that they represent a potential therapeutic target in cancer.Research in this laboratory has been supported by grant BFU2007- 62402 from the Ministerio de Ciencia e Innovación, grant RD06/ 0020/0036 from the Fondo de Investigaciones Sanitarias and from the European Project CRESCENDO (grant FP6-018652). The authors have no conflict of interest to declar