ABSTRACT
White adipose tissue (WAT) is a critical organ in both health and disease. However, physiologically faithful tissue culture models of primary human WAT remain limited, at best. In this study we describe a novel WAT culture system in which primary human WAT is sandwiched between tissue-engineered sheets of adipose-derived stromal cells. This construct, called "sandwiched white adipose tissue" (SWAT), can be defined as a microphysiological system (MPS) since it is a tissue-engineered, multicellular, three-dimensional organ construct produced using human cells. We validated SWAT against the National Institutes of Health MPS standards and found that SWAT is viable in culture for 8 weeks, retains physiologic responses to exogenous signaling, secretes adipokines, and engrafts into animal models. These attributes position SWAT as a powerful tool for the study of WAT physiology, pathophysiology, personalized medicine, and pharmaceutical development.
Subject(s)
Adipocytes/cytology , Adipose Tissue, White/cytology , Stromal Cells/cytology , Tissue Culture Techniques/methods , Tissue Engineering/methods , Adipocytes/metabolism , Adipokines/metabolism , Adipose Tissue, White/metabolism , Adipose Tissue, White/transplantation , Adult , Animals , Cell Differentiation , Female , Gene Expression Profiling , Humans , Lipolysis , Male , Mice , Middle Aged , Stromal Cells/metabolismABSTRACT
The epidermal growth factor receptor family member HER4 undergoes proteolytic processing at the cell surface to release the HER4 intracellular domain (4ICD) nuclear protein. Interestingly, 4ICD directly interacts with STAT5 and functions as an obligate STAT5 nuclear chaperone. Once in the nucleus 4ICD binds with STAT5 at STAT5 target genes, dramatically potentiating STAT5 transcriptional activation. These observations raise the possibility that 4ICD directly coactivates STAT5 gene expression. Using both yeast and mammalian transactivation reporter assays, we performed truncations of 4ICD fused to a GAL4 DNA binding domain and identified two independent 4ICD transactivation domains located between residues 1022 and 1090 (TAD1) and 1192 and 1225 (TAD2). The ability of the 4ICD DNA binding domain fusions to transactivate reporter gene expression required deletion of the intrinsic tyrosine kinase domain. In addition, we identified the 4ICD carboxyl terminal TVV residues, a PDZ domain binding motif (PDZ-DBM), as a potent transcriptional repressor. The transactivation activity of the HER4 carboxyl terminal domain lacking the tyrosine kinase (CTD) was significantly lower than similar EGFR or HER2 CTD. However, deletion of the HER4 CTD PDZ-DBM enhanced HER4 CTD transactivation to levels equivalent to the EGFR and HER2 CTDs. To determine if 4ICD TAD1 and TAD2 have a physiologically relevant role in STAT5 transactivation, we coexpressed 4ICD or 4ICD lacking TAD2 or both TAD1 and TAD2 with STAT5 in a luciferase reporter assay. Our results demonstrate that each 4ICD TAD contributes additively to STAT5A transactivation and the ability of STAT5A to transactivate the ß-casein promoter requires the 4ICD TADs. Taken together, published data and our current results demonstrate that both 4ICD nuclear chaperone and intrinsic coactivation activities are essential for STAT5 regulated gene expression.
Subject(s)
Receptor, ErbB-4/metabolism , STAT5 Transcription Factor/metabolism , Transcriptional Activation , Tumor Suppressor Proteins/metabolism , Binding Sites , HEK293 Cells , Humans , MCF-7 Cells , Protein Binding , Receptor, ErbB-4/chemistry , Receptor, ErbB-4/genetics , STAT5 Transcription Factor/chemistry , Tumor Suppressor Proteins/chemistryABSTRACT
PURPOSE: The purpose of the present study was to estimate the prevalence of probable mental health problems in an epidemiologic study of Vietnamese adolescents. A secondary aim was to examine the correlates of probable mental health caseness. METHODS: Interviewers visited 1,914 households that were randomly selected to participate in a multi-agency study of mental health in select provinces of Vietnam. Semi-structured interviews assessed adolescent mental health problems using the Strengths and Difficulties Questionnaire (SDQ) parent informant version, and additionally the interviewers collected information on demographic variables (age, gender, ethnic group, religious affiliation, social capital). The final sample included data on 1,368 adolescents (aged 11-18 years). RESULTS: The average score on the total problem composite of the SDQ scale was 6.66 (SD=4.89), and 9.1% of the sample was considered a case (n=124). Bivariate analyses were conducted to determine which demographic variables were related to the SDQ case/non-case score. All variables except gender were significant in bivariate analyses, and therefore were entered into a logistic regression. Results indicated that age, religion, and wealth remained significant predictors of probable caseness. CONCLUSIONS: Overall, prevalence estimates of mental health problems generated by the SDQ were consistent with those reported in the US and other Western and non-Western samples. Results of the current study suggest some concordance of risk and protective factors between Western and Vietnamese youth (i.e., age and SES).
Subject(s)
Mental Disorders/epidemiology , Parents/psychology , Adolescent , Age Distribution , Asian People/statistics & numerical data , Child , Female , Health Surveys/statistics & numerical data , Humans , Male , Mental Disorders/ethnology , Minority Groups/statistics & numerical data , Prevalence , Probability , Socioeconomic Factors , Surveys and Questionnaires , Vietnam/epidemiology , Vietnam/ethnologyABSTRACT
This study investigates the relationship between battered women's causal attributions for the violence they experience and their subsequent coping efforts. Causal attributions related to partner blame, excusing the violence, and the combination of partner blame and excusing the violence were regressed on six categories of coping strategies: placating, resistance, formal help source, informal help source, safety planning, and legal strategies. Of the 793 women approached outside of a battered women's shelter and the district court, 406 women completed the baseline measure. It was found that women who hold their partners accountable for abuse are more likely than women who excuse the violence to utilize more overall coping strategies. Also, women who blame their partners for the abuse utilize both more active and more public coping efforts. After accounting for the effects of ethnicity, violence severity, and excusing the violence, the percentage of blame attributions endorsed predicted informal (R( 2) = .077, p = .001) and safety planning (R(2) = .054, p = .014) strategies. After controlling for ethnicity, violence severity, and blaming, the percentage of excuse attributions predicted placating (R(2) = .103, p = .016) strategies.
Subject(s)
Battered Women/statistics & numerical data , Internal-External Control , Spouse Abuse/statistics & numerical data , Women's Health , Adaptation, Psychological , Adult , Battered Women/psychology , Female , Humans , Interpersonal Relations , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Patient Education as Topic/methods , Spouse Abuse/psychology , United States , Young AdultABSTRACT
Contenido del documento: Que es supervision?- por Alice T. Meyer. Planeamiento de asignaciones para la unidad de enfermeria, por Patricia A. Deiman. Evaluacion de personal, por Alicia T. Meyer y Comunicaciones en el Departamento de Enfermeria por Ernestina Nazario
Subject(s)
Nursing, Supervisory , Nursing Services , Education, Nursing , Nursing Evaluation Research , Nursing StaffABSTRACT
Contenido del documento: Programa de educacion en servicio/Desarrollo de liderazgo, por Patricia A. Deiman. Los principios del aprendizaje/Programas de educacion continuada por Alicia Meyer. Organizacion y desarrollo de un programa de adiestramiento en servicio para ayudantes de enfermeria por Nelly Garzon A
