The Oncogenic EWS-FLI1 Protein Binds In Vivo GGAA Microsatellite Sequences with Potential Transcriptional Activation Function

The fusion between EWS and ETS family members is a key oncogenic event in Ewing tumors and important EWS-FLI1 target genes have been identified. However, until now, the search for EWS-FLI1 targets has been limited to promoter regions and no genome-wide comprehensive analysis of in vivo EWS-FLI1 binding sites has been undertaken. Using a ChIP-Seq approach to investigate EWS-FLI1-bound DNA sequences in two Ewing cell lines, we show that this chimeric transcription factor preferentially binds two types of sequences including consensus ETS motifs and microsatellite sequences. Most bound sites are found outside promoter regions. Microsatellites containing more than 9 GGAA repeats are very significantly enriched in EWS-FLI1 immunoprecipitates. Moreover, in reporter gene experiments, the transcription activation is highly dependent upon the number of repeats that are included in the construct. Importantly, in vivo EWS-FLI1-bound microsatellites are significantly associated with EWS-FLI1-driven gene activation. Put together, these results point out the likely contribution of microsatellite elements to long-distance transcription regulation and to oncogenesis

Concepções alternativas em eletroquímica e circulação da corrente elétrica

This investigation deals with students� conceptions about redox reactions that are responsible for electric current generation as well as the relations they established with electric current circulation in materials. We chose two problem-solving situations: phenomena that occur in a cell and in electrolysis, trying to focus on the microscopic aspects of charge motion. Questions about these two situations were applied to third year High School students and to third year Undergraduate University Chemistry students. Results show their difficulty for explaining electric current circulation and for relating it to chemical reactions in the considered situations. In general students show alternative conceptions that are incoherent and far from the accepted scientific explanation. These results and the questions that were elaborated for the analysis may form an alternative didacticpedagogical material for teaching electrochemistry; the questions constitute appropriate activities to evidence the conceptions of students and the results pointing to the outbreak of a discussion in the classroom.Esta pesquisa trata das concepções dos estudantes sobre as reações de óxido-redução, responsáveis pela geração de corrente elétrica, bem como as relações que eles estabelecem com a circulação de corrente elétrica nos materiais. Escolhemos duas situações problematizadoras: fenômenos que ocorrem numa pilha e numa eletrólise, procurando focalizar particularmente os aspectos microscópicos relativos à movimentação das cargas. Foram elaboradas questões sobre essas duas situações e aplicadas a alunos da 3ª série do Ensino Médio e do 3º ano do curso de Licenciatura e Bacharelado em Química. Os resultados mostram dificuldades em explicar a circulação de corrente elétrica e de relacioná-la com as reações químicas nos sistemas considerados. De modo geral, os estudantes apresentam concepções alternativas incoerentes e longe da explicação científica aceita. Esses resultados e as questões elaboradas para o diagnóstico podem se constituir em um material didático-pedagógico alternativo para o ensino de eletroquímica; as questões constituindo atividades adequadas para evidenciar as concepções dos estudantes e os resultados apontando para o foco de uma discussão em sala de aula

Concepções alternativas em eletroquímica e circulação da corrente elétrica

Esta pesquisa trata das concepções dos estudantes sobre as reações de óxido-redução, responsáveis pela geração de corrente elétrica, bem como as relações que eles estabelecem com a circulação de corrente elétrica nos materiais. Escolhemos duas situações problematizadoras: fenômenos que ocorrem numa pilha e numa eletrólise, procurando focalizar particularmente os aspectos microscópicos relativos à movimentação das cargas. Foram elaboradas questões sobre essas duas situações e aplicadas a alunos da 3ª série do Ensino Médio e do 3º ano do curso de Licenciatura e Bacharelado em Química. Os resultados mostram dificuldades em explicar a circulação de corrente elétrica e de relacioná-la com as reações químicas nos sistemas considerados. De modo geral, os estudantes apresentam concepções alternativas incoerentes e longe da explicação científica aceita. Esses resultados e as questões elaboradas para o diagnóstico podem se constituir em um material didático-pedagógico alternativo para o ensino de eletroquímica; as questões constituindo atividades adequadas para evidenciar as concepções dos estudantes e os resultados apontando para o foco de uma discussão em sala de aula

Concepções alternativas em eletroquímica e circulação da corrente elétrica

http://dx.doi.org/10.5007/2175-7941.2011v28n1p7Esta pesquisa trata das concepções dos estudantes sobre as reações de óxido-redução, responsáveis pela geração de corrente elétrica, bem como as relações que eles estabelecem com a circulação de corrente elétrica nos materiais. Escolhemos duas situações problematizadoras: fenômenos que ocorrem numa pilha e numa eletrólise, procurando focalizar particularmente os aspectos microscópicos relativos à movimentação das cargas. Foram elaboradas questões sobre essas duas situações e aplicadas a alunos da 3ª série do Ensino Médio e do 3º ano do curso de Licenciatura e Bacharelado em Química. Os resultados mostram dificuldades em explicar a circulação de corrente elétrica e de relacioná-la com as reações químicas nos sistemas considerados. De modo geral, os estudantes apresentam concepções alternativas incoerentes e longe da explicação científica aceita. Esses resultados e as questões elaboradas para o diagnóstico podem se constituir em um material didático-pedagógico alternativo para o ensino de eletroquímica; as questões constituindo atividades adequadas para evidenciar as concepções dos estudantes e os resultados apontando para o foco de uma discussão em sala de aula.

Plasticity of melanoma and EMT-TF reprogramming.

Plasticity of melanoma and EMT-TF reprogramming

The effects of individual music therapy in nursing home residents with dementia to improve general well-being:study protocol of a randomized controlled trial

BACKGROUND: Dementia is often associated with Neuropsychiatric Symptoms (NPS) such as agitation, depression, hallucinations, anxiety, that can cause distress for the resident with dementia in long-term care settings and can impose emotional burden on the environment. NPS are often treated with psychotropic drugs, which, however, frequently cause side effects. Alternatively, non-pharmacological interventions can improve well-being and maintain an optimal quality of life (QoL) of those living with dementia. Other QoL related outcomes, such as pain, discomfort and sleep disruption are relevant outcomes in music trials as well. Music therapy is a non-pharmacological intervention that can reduce NPS and improve well-being, and its associated symptoms in dementia.METHODS: The research will be conducted at eight nursing home facilities of a health care organization in the Netherlands. A sample size of 30 in each group (experimental and control group) is required, totalling 60 residents increased to 80 when considering expected drop out to follow up. The participants in the intervention group receive 30 min of individual music therapy (MT) in their own room by a music therapist twice a week for 12 weeks. The participants in the control group will receive 30 min of individual attention in their own room by a volunteer twice a week for 12 weeks. Assessments will be done at baseline, 6 weeks and 12 weeks. An independent observer, blinded for the intervention or control condition, will assess directly observed well-being (primary outcome) and pain (secondary outcome) before and after the sessions. Nurses will assess other secondary outcomes unblinded, i.e., perceived quality of life and NPS, both assessed with validated scales. The sleep duration will be indirectly assessed by a wrist device called MotionWatch. Information about psychotropic drug use will be derived from electronic medical chart review.DISCUSSION: The main purpose of this study is to assess the effects of individual music therapy on directly observed well-being controlled for individual attention in nursing home residents with dementia with NPS. The outcomes refer to both short-term and long-term effects consistent with therapeutic goals of care for a longer term. We hope to overcome limitations of previous study designs such as not blinded designs and music facilitators that were not only music therapists but also occupational therapists and nurses. This study should lead to more focused recommendations for practice and further research into non-pharmacological interventions in dementia such as music therapy.TRIAL REGISTRATION: The trial is registered at the International Clinical Trials Registry Platform (ICTRP) search portal in the Netherlands Trial Registration number NL7708, registration date 04-05-2019.</p

The hepatitis B virus X protein functionally interacts with CREB-binding protein/p300 in the regulation of CREB-mediated transcription

The hepatitis B virus infects more than 350 million people worldwide and is a leading cause of liver cancer. The virus encodes a multifunctional regulator, the hepatitis B virus X protein (HBx), that is essential for virus replication. HBx is involved in modulating signal transduction pathways and transcription mediated by various factors, notably CREB that requires the recruitment of the coactivators CREB-binding protein (CBP)/p300. Here we investigated the role of HBx and its potential interaction with CBP/p300 in regulating CREB transcriptional activity. We show that HBx and CBP/p300 synergistically enhanced CREB, activity and that CREB phosphorylation by protein kinase A was a prerequisite for the cooperative action of HBx and CBP/p300. We further show that HBx interacted directly with CBP/p300 in vitro and in vivo. Using chromatin immunoprecipitation, we provide evidence that HBx physically occupied the CREB-binding domain of CREB-responsive promoters of endogenous cellular genes such as interleukin 8 and proliferating cell nuclear antigen. Moreover expression of HBx increased the recruitment of p300 to the interleukin 8 and proliferating cell nuclear antigen promoters in cells, and this is associated with increased gene expression. As recruitment of CBP/p300 is known to represent the limiting event for activating CREB target genes, HBx may disrupt this cellular regulation, thus predisposing cells to transformation