RESUMO
Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells, resulting in clonal selection. Although most cancer-causing mutations have been detected in the protein-coding regions of the cancer genome; driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention. Here we report a C-to-T single nucleotide transition that occurs as a somatic mutation in noncoding sequences 4 kb upstream of the transcriptional start site of the LMO1 oncogene in primary samples from patients with T-cell acute lymphoblastic leukaemia. This single nucleotide alteration conforms to an APOBEC-like cytidine deaminase mutational signature, and generates a new binding site for the MYB transcription factor, leading to the formation of an aberrant transcriptional enhancer complex that drives high levels of expression of the LMO1 oncogene. Since APOBEC-signature mutations are common in a broad spectrum of human cancers, we suggest that noncoding nucleotide transitions such as the one described here may activate potent oncogenic enhancers not only in T-lymphoid cells but in other cell lineages as well.
Assuntos
Desaminases APOBEC/metabolismo , Proteínas de Ligação a DNA/biossíntese , Elementos Facilitadores Genéticos/genética , Regulação Leucêmica da Expressão Gênica/genética , Proteínas com Domínio LIM/biossíntese , Proteínas de Neoplasias/biossíntese , Mutação Puntual , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Fatores de Transcrição/biossíntese , Transcriptoma , Regiões 5' não Traduzidas/genética , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Criança , Imunoprecipitação da Cromatina , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Genes myb , Humanos , Células Jurkat , Proteínas com Domínio LIM/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogênicas c-myb/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.
Assuntos
Neoplasias da Mama/metabolismo , Histona Desacetilase 1/metabolismo , Histona Desacetilases/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Ovarianas/metabolismo , Animais , Biomarcadores , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Descoberta de Drogas , Feminino , Técnicas de Silenciamento de Genes , Genes Letais , Xenoenxertos , Histona Desacetilase 1/genética , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Humanos , Camundongos , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Ovarianas/genética , Fenótipo , RNA Interferente Pequeno/genéticaAssuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Regulação Leucêmica da Expressão Gênica , Redes Reguladoras de Genes , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Western Blotting , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Células Jurkat , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Proteína 1 de Leucemia Linfocítica Aguda de Células TRESUMO
Engaging in visual creative expression individually and in a therapeutic setting can be a beneficial experience for cancer survivors; however, most research in this field has been conducted with older adults. The current study aimed to address this gap by utilising van Manen's hermeneutic phenomenology to answer the following question: 'What is the lived experience and meaning of visual creative expression for young adult cancer survivors?' Seven young adults, diagnosed with cancer between the ages of 18 and 35, were interviewed about creative expression experiences, which they engaged in individually and/or in a therapeutic setting. Data analysis included a thematic reflection, guided existential reflection, and a process of writing and rewriting. Two superordinate themes were identified: increased self-understanding and a healing experience. Seven subthemes were also identified and included the following: being in the flow, allowing the body to express itself, renegotiating control, changing one's environment, being seen, respect for art as a separate entity and giving back. Findings suggest that visual creative expression can be a meaningful experience for young adult cancer survivors, and that this experience espouses both similarities and differences from experiences of older adult survivors. Recommendations are made for future research, in addition to implications for practitioners.
Assuntos
Criatividade , Neoplasias/psicologia , Sobreviventes/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
We review key insights into transcriptional regulation of cell state that have emerged from the study of embryonic stem cells. These insights are described in the context of historical studies of the roles of transcription factors, signal transduction pathways, and regulators of chromatin structure. We highlight recent studies that have led to the model that mediator and cohesin physically and functionally connect the enhancers and core promoters of a key subset of active genes in cells, thus generating cell-type-specific DNA loops linked to the gene-expression program of each cell. Mutations in the genes encoding mediator and cohesin components can cause an array of human developmental syndromes and diseases, and we discuss the implications of these findings for the mechanisms involved in these diseases.
Assuntos
Cromossomos Humanos/química , Doença/genética , Regulação da Expressão Gênica , Transcrição Gênica , Células-Tronco Embrionárias/metabolismo , Humanos , Transdução de Sinais/genéticaRESUMO
The process by which a single fertilized egg develops into a human being with more than 200 cell types--each with a distinct gene expression pattern controlling its cellular state--is poorly understood. Knowledge of the transcriptional regulatory circuitry that establishes and maintains gene expression programs in mammalian cells is fundamental to understanding development and should provide the foundation for improved diagnosis and treatment of disease. Although it is not yet feasible to map the entirety of this circuitry in vertebrate cells, recent work in embryonic stem (ES) cells has demonstrated that core features of the circuitry can be discovered through studies involving selected regulators. Here, we highlight the fundamental insights that have emerged from studies that examined the role of transcription factors, chromatin regulators, signaling pathways, and noncoding RNAs in the regulatory circuitry of ES cells. Maps of regulatory circuitry and the insights that have emerged from these studies have improved our understanding of global gene expression and are facilitating efforts to reprogram cells for disease therapeutics and regenerative medicine.
Assuntos
Células-Tronco Embrionárias/fisiologia , Transcrição Gênica , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Humanos , Modelos Genéticos , Proteínas do Grupo Polycomb , RNA não Traduzido/genética , Proteínas Repressoras/genética , Proteínas Repressoras/fisiologia , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologiaRESUMO
OBJECTIVES: To determine consultants' compliance with motor traffic regulations on recall to hospital to attend emergencies, and ownership and use of green warning lights (GWLs). To determine the views of senior police officers on consultants complying with traffic regulations on emergency recall with and without GWLs. METHOD: Questionnaire survey of all consultants in obstetrics and gynaecology, paediatrics and emergency medicine in the Yorkshire Deanery, UK, and members of the Association of Chief Police Officers (ACPO). RESULTS: 220 consultant questionnaires were distributed and 166 replies were received; 21% of respondents owned a GWL. Almost 50% of consultants would consider exceeding speed limits when returning to an emergency. Between 43% and 80% consultants would cross red traffic lights; driving habits varied with usage and ownership of a GWL. 12.7% (21) of respondents had been stopped for traffic violations attending emergencies, 2.4% (4) had been prosecuted and 4.8% (8) had been involved in accidents. The ACPO advised that consultants should observe all traffic regulations at all times. CONCLUSION: Consultants recalled to their hospitals for emergencies disregard speed restrictions and traffic light signals both with and without GWLs and risk both accident and prosecution for ignoring traffic legislation. They should consider using a GWL to ease their progress through traffic when attending an emergency and observe all traffic laws.
Assuntos
Acidentes de Trânsito/prevenção & controle , Condução de Veículo/legislação & jurisprudência , Medicina de Emergência , Médicos , Segurança , Acidentes de Trânsito/estatística & dados numéricos , Humanos , Polícia , Estatísticas não Paramétricas , Inquéritos e Questionários , Reino UnidoRESUMO
In the present study we examined to what extent persons who attempt suicide describe their attempt in terms of social, joint processes. Psychotherapists interviewed 40 patients hospitalized in a general hospital for a few days after an attempted suicide. The content of the interviews was analyzed for the level of systemic processes the patients referred to (that is, action, project, and career). The most common processes to which the patients referred were relationship careers and projects and conflicts and argumentative actions. Our analysis indicates that a social process can be found at all levels of the patient's organization of the suicide attempt, within a system of goal-directed action, project, and career.
Assuntos
Objetivos , Relações Interpessoais , Motivação , Meio Social , Tentativa de Suicídio/psicologia , Teoria de Sistemas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Psicoterapia , Tentativa de Suicídio/prevenção & controle , Suíça , Gravação em VídeoRESUMO
DNA replication origins are fundamental to chromosome organization and duplication, but understanding of these elements is limited because only a small fraction of these sites have been identified in eukaryotic genomes. Origin Recognition Complex (ORC) and minichromosome maintenance (MCM) proteins form prereplicative complexes at origins of replication. Using these proteins as molecular landmarks for origins, we identified ORC- and MCM-bound sites throughout the yeast genome. Four hundred twenty-nine sites in the yeast genome were predicted to contain replication origins, and approximately 80% of the loci identified on chromosome X demonstrated origin function. A substantial fraction of the predicted origins are associated with repetitive DNA sequences, including subtelomeric elements (X and Y') and transposable element-associated sequences (long terminal repeats). These findings identify the global set of yeast replication origins and open avenues of investigation into the role(s) ORC and MCM proteins play in chromosomal architecture and dynamics.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Replicação do DNA , Proteínas de Ligação a DNA/metabolismo , Genoma Fúngico , Origem de Replicação , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Sítios de Ligação , Cromossomos Fúngicos/metabolismo , Elementos de DNA Transponíveis , DNA Fúngico/biossíntese , DNA Fúngico/genética , DNA Fúngico/metabolismo , DNA Intergênico , Componente 4 do Complexo de Manutenção de Minicromossomo , Componente 7 do Complexo de Manutenção de Minicromossomo , Proteínas Nucleares/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Complexo de Reconhecimento de Origem , RNA Fúngico/genética , RNA Fúngico/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Sequências Repetitivas de Ácido Nucleico , Saccharomyces cerevisiae/metabolismo , Telômero/metabolismo , Sequências Repetidas TerminaisRESUMO
TFIIB is an RNA polymerase II general transcription factor (GTF) that has also been implicated in the mechanism of action of certain promoter-specific activators (see, for examples, [1-11]). TFIIB enters the preinitiation complex (PIC) primarily through contact with the TATA box binding protein (TBP), an interaction mediated by three TBP residues [12-14]. To study the role of TFIIB in transcription activation in vivo, we randomly mutagenized these three residues in yeast TBP and screened for promoter-specific activation mutants. One mutant bearing a single conservative substitution, TBP-E186D, is the focus of this study. As expected, TBP-E186D binds normally to the TATA box but fails to support the entry of TFIIB into the PIC. Cells expressing TBP-E186D are viable but have a severe slow-growth phenotype. Whole-genome expression analysis indicates that transcription of 17% of yeast genes are compromised by this mutation. Chimeric promoter analysis indicates that the region of the gene that confers sensitivity to the TBP-E186D mutation is the UAS (upstream activating sequence), which contains the activator binding sites. Most interestingly, other TBP mutants that interfere with different interactions (TFIIB, TFIIA, or the TATA box) and a TFIIB mutant defective for interaction with TBP all manifest distinct and selective promoter-specific activation defects. Our results implicate the entry of TFIIB into the PIC as a critical step in the activation of certain promoters and reveal diverse mechanisms of transcription activation.
Assuntos
Citocromos c , Proteínas de Ligação a DNA/metabolismo , Regulação Fúngica da Expressão Gênica , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Ativação Transcricional , Proteínas de Transporte , Ciclinas/genética , Grupo dos Citocromos c/genética , Proteínas de Ligação a DNA/genética , Metalotioneína/genética , Mutagênese Sítio-Dirigida , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , TATA Box , Proteína de Ligação a TATA-Box , Fator de Transcrição TFIIB , Fatores de Transcrição/genéticaRESUMO
Dendritic cells are involved in the initiation of both innate and adaptive immunity. To systematically explore how dendritic cells modulate the immune system in response to different pathogens, we used oligonucleotide microarrays to measure gene expression profiles of dendritic cells in response to Escherichia coli, Candida albicans, and influenza virus as well as to their molecular components. Both a shared core response and pathogen-specific programs of gene expression were observed upon exposure to each of these pathogens. These results reveal that dendritic cells sense diverse pathogens and elicit tailored pathogen-specific immune responses.
Assuntos
Candida albicans/imunologia , Células Dendríticas/imunologia , Escherichia coli/imunologia , Regulação da Expressão Gênica , Vírus da Influenza A/imunologia , Apresentação de Antígeno/genética , Células Cultivadas , Células Dendríticas/metabolismo , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Fatores Imunológicos/genética , Inflamação/imunologia , Leucócitos/imunologia , Lipopolissacarídeos/imunologia , Mananas/imunologia , Análise de Sequência com Séries de Oligonucleotídeos , Fagocitose , RNA de Cadeia Dupla/imunologiaRESUMO
An approach is described to modify yeast artificial chromosomes (YACs) with cassettes that can be easily excised for embryonic stem (ES) cell gene targeting experiments. YAC targeting technology (YTT) uses the WIBR/MIT-820 C57BL/6-mapped YAC library derived from the C57BL/6 mouse as the starting point for Internet- or PCR-based clone isolation, although in principle any YAC system can be used. Homologous recombination is initially performed in yeast using cassettes that function in Saccharomyces cerevisiae, Escherichia coli, and ES cells, followed by cloning or conversion of the targeted locus into a plasmid. The completed targeting vector can be transfected into C57BL/6 ES cells and clones selected with G418 followed by injection into Balb/c blastocysts. YTT increases the speed of targeting vector construction and obviates the need for extensive backcrossing to the C57BL/6 background.
Assuntos
Cromossomos Artificiais de Levedura , Marcação de Genes/métodos , Camundongos Endogâmicos C57BL/genética , Animais , Escherichia coli , Deleção de Genes , Camundongos , Dados de Sequência Molecular , Saccharomyces cerevisiae/genética , Células-Tronco/fisiologia , TransfecçãoRESUMO
Genome-wide location analysis was used to determine how the yeast cell cycle gene expression program is regulated by each of the nine known cell cycle transcriptional activators. We found that cell cycle transcriptional activators that function during one stage of the cell cycle regulate transcriptional activators that function during the next stage. This serial regulation of transcriptional activators forms a connected regulatory network that is itself a cycle. Our results also reveal how the nine transcriptional regulators coordinately regulate global gene expression and diverse stage-specific functions to produce a continuous cycle of cellular events. This information forms the foundation for a complete map of the transcriptional regulatory network that controls the cell cycle.
Assuntos
Ciclo Celular/genética , Regulação Fúngica da Expressão Gênica , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Quinases Ciclina-Dependentes/genética , Ciclinas/genética , Genoma FúngicoRESUMO
The budding yeast transcriptional activator Gcn4 is rapidly degraded in an SCF(Cdc4)-dependent manner in vivo. Upon fractionation of yeast extracts to identify factors that mediate Gcn4 ubiquitination, we found that Srb10 phosphorylates Gcn4 and thereby marks it for recognition by SCF(Cdc4) ubiquitin ligase. Srb10 is a physiological regulator of Gcn4 stability because both phosphorylation and turnover of Gcn4 are diminished in srb10 mutants. Gcn4 is almost completely stabilized in srb10Delta pho85Delta cells, or upon mutation of all Srb10 phosphorylation sites within Gcn4, suggesting that the Pho85 and Srb10 cyclin-dependent kinases (CDKs) conspire to limit the accumulation of Gcn4. The multistress response transcriptional regulator Msn2 is also a substrate for Srb10 and is hyperphosphorylated in an Srb10-dependent manner upon heat-stress-induced translocation into the nucleus. Whereas Msn2 is cytoplasmic in resting wild-type cells, its nuclear exclusion is partially compromised in srb10 mutant cells. Srb10 has been shown to repress a subset of genes in vivo, and has been proposed to inhibit transcription via phosphorylation of the C-terminal domain of RNA polymerase II. We propose that Srb10 also inhibits gene expression by promoting the rapid degradation or nuclear export of specific transcription factors. Simultaneous down-regulation of both transcriptional regulatory proteins and RNA polymerase may enhance the potency and specificity of transcriptional inhibition by Srb10.
Assuntos
Quinases Ciclina-Dependentes/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Quinases/metabolismo , Proteínas de Saccharomyces cerevisiae , Fatores de Transcrição/metabolismo , Aminoácidos/metabolismo , Núcleo Celular/metabolismo , Meios de Cultura , Quinase 8 Dependente de Ciclina , Quinases Ciclina-Dependentes/genética , Mutação , Peptídeo Sintases/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Subunidades Proteicas , RNA Polimerase II/metabolismo , Proteínas Ligases SKP Culina F-Box , Transativadores/metabolismo , Ubiquitinas/metabolismo , Leveduras/genética , Leveduras/metabolismoRESUMO
NC2 (Dr1-Drap1 or Bur6-Ydr1) has been characterized in vitro as a general negative regulator of RNA polymerase II (Pol II) transcription that interacts with TATA-binding protein (TBP) and inhibits its function. Here, we show that NC2 associates with promoters in vivo in a manner that correlates with transcriptional activity and with occupancy by basal transcription factors. NC2 rapidly associates with promoters in response to transcriptional activation, and it remains associated under conditions in which transcription is blocked after assembly of the Pol II preinitiation complex. NC2 positively and negatively affects approximately 17% of Saccharomyces cerevisiae genes in a pattern that resembles the response to general environmental stress. Relative to TBP, NC2 occupancy is high at promoters where NC2 is positively required for normal levels of transcription. Thus, NC2 is associated with the Pol II preinitiation complex, and it can play a direct and positive role at certain promoters in vivo.
Assuntos
Proteínas Fúngicas/metabolismo , Fosfoproteínas/metabolismo , RNA Polimerase II/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Genes Fúngicos , Regiões Promotoras Genéticas , Proteínas Repressoras/metabolismo , Proteína de Ligação a TATA-Box , Fator de Transcrição TFIIB , Transcrição GênicaRESUMO
We propose a model-driven approach for analyzing genomic expression data that permits genetic regulatory networks to be represented in a biologically interpretable computational form. Our models permit latent variables capturing unobserved factors, describe arbitrarily complex (more than pair-wise) relationships at varying levels of refinement, and can be scored rigorously against observational data. The models that we use are based on Bayesian networks and their extensions. As a demonstration of this approach, we utilize 52 genomes worth of Affymetrix GeneChip expression data to correctly differentiate between alternative hypotheses of the galactose regulatory network in S. cerevisiae. When we extend the graph semantics to permit annotated edges, we are able to score models describing relationships at a finer degree of specification.
Assuntos
Perfilação da Expressão Gênica/estatística & dados numéricos , Modelos Genéticos , Teorema de Bayes , Galactose/metabolismo , Regulação Fúngica da Expressão Gênica , Genoma Fúngico , Modelos Estatísticos , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismoRESUMO
The effects of pinosylvin, pinosylvin monomethyl ether, pinosylvin dimethyl ether, and resveratrol on the fungal shoot blight and canker pathogen of conifers Sphaeropsis sapinea were examined in vitro. Effects of compounds, isolates, and concentrations on both conidial germination and mycelial growth were significant (values of P < 0.001), indicating inhibitory activity of these compounds.
Assuntos
Ascomicetos/efeitos dos fármacos , Estilbenos/farmacologia , Ascomicetos/crescimento & desenvolvimentoRESUMO
We used genome-wide expression analysis to explore how gene expression in Saccharomyces cerevisiae is remodeled in response to various changes in extracellular environment, including changes in temperature, oxidation, nutrients, pH, and osmolarity. The results demonstrate that more than half of the genome is involved in various responses to environmental change and identify the global set of genes induced and repressed by each condition. These data implicate a substantial number of previously uncharacterized genes in these responses and reveal a signature common to environmental responses that involves approximately 10% of yeast genes. The results of expression analysis with MSN2/MSN4 mutants support the model that the Msn2/Msn4 activators induce the common response to environmental change. These results provide a global description of the transcriptional response to environmental change and extend our understanding of the role of activators in effecting this response.
Assuntos
Adaptação Fisiológica/genética , Regulação Fúngica da Expressão Gênica , Proteínas de Saccharomyces cerevisiae , Leveduras/fisiologia , Proteínas de Ligação a DNA/genética , Enzimas/genética , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genoma Fúngico , Resposta ao Choque Térmico/genética , Peróxido de Hidrogênio/farmacologia , Concentração de Íons de Hidrogênio , Mutação , Pressão Osmótica , Sais/farmacologia , Fatores de Transcrição/genética , Leveduras/efeitos dos fármacosRESUMO
Based on an action theory approach, 32 videotaped parent-adolescent conversations about health in two Canadian ethno-cultural groups were analyzed to identify and describe the joint action of parents and adolescents in the health domain. The data include manifest behavior (the conversation), internal processes (recalled thoughts and feelings on viewing the videotape of the conversation), and social meaning. These data were analyzed using the goals, functions, and elements of the conversations. Five categories of joint actions emerged from these data: sharing and exploring information, values, and beliefs about health; negotiating and struggling about aspects of the adolescent's independence; providing and receiving guidance; adjusting to family and home issues; and fostering joint understanding by giving voice to the adolescent.
Assuntos
Comunicação , Comportamentos Relacionados com a Saúde , Relações Pais-Filho , Psicologia do Adolescente , Adolescente , Adulto , Canadá , Feminino , Humanos , Masculino , Gravação de VideoteipeRESUMO
How do we see the motion of objects as well as their shapes? The Gaussian Derivative (GD) spatial model is extended to time to help answer this question. The GD spatio-temporal model requires only two numbers to describe the complete three-dimensional space-time shapes of individual receptive fields in primate visual cortex. These two numbers are the derivative numbers along the respective spatial and temporal principal axes of a given receptive field. Nine transformation parameters allow for a standard geometric association of these intrinsic axes with the extrinsic environment. The GD spatio-temporal model describes in one framework the following properties of primate simple cell fields: motion properties, number of lobes in space-time, spatial orientation. location, and size. A discrete difference-of-offset-Gaussians (DOOG) model provides a plausible physiological mechanism to form GD-like model fields in both space and time. The GD model hypothesizes that receptive fields at the first stage of processing in the visual cortex approximate 'derivative analyzers' that estimate local spatial and temporal derivatives of the intensity profile in the visual environment. The receptive fields as modeled provide operators that can allow later stages of processing in either a biological or machine vision system to estimate the motion as well as the shapes of objects in the environment.