Two Sides of the Same Coin : Unravelling the role of transcription factors and miRNAs in activated monocytes, macrophages and microglia

This thesis focusses on understanding the role of three transcriptions factors, namely ATF3, EGR3 and PU.1, and also microRNA-146a, involved in the activation of monocytes, macrophages and microglia in pathological conditions, which are thought to be driven – at least in part – by special inflammatory reactions. The diseases in question are severe psychiatric diseases, such as bipolar disorder, major depression, schizophrenia and postpartum psychosis and X-linked juvenile retinoschisis. In the introduction the immune cells, the diseases and the transcription factors + pathways will be introduced subsequently

Körper im Kulturkonflikt: Zur Vermittlung und Aushandlung von Normen und Werten in Schwimmkursen für Frauen mit Migrationshintergrund

Ausgehend vom Körper als Vermittler zwischen Subjekt und Gesellschaft wird die Frage beantwortet, wie Migrantinnen auf diskursiv erzeugte Normen und Werte der schweizerischen Mehrheitsgesellschaft im Kontext von Schwimmkursen als Integrationsmaßnahme reagieren. Die Feldaufenthalte und Interviews erlauben eine Analyse dominanter Macht- und subversiver Selbstermächtigungsprozesse innerhalb eines körperzentrierten, religiös-kulturell pluralisierten und ethnisch differenzierten Feldes. Hierbei werden Divergenzen in der verkörperten und objektiven Sozialstruktur sichtbar, was sich beispielsweise in den kontrovers geführten Debatten zur Wahl der Badekleidung und Badnutzung verdeutlicht. Bei den Aushandlungen um die Durchsetzung von Deutungs- sowie Ordnungsmustern lassen sich Prozesse der kulturellen Anpassung, Anknüpfung und des Neuentwurfs beobachten.This article offers an analysis of the ways in which women migrating to Switzerland react towards discursively constructed norms and values of the swiss majority when it comes to the field of swimming courses offered as modes of integration. In this article, observational research used in combination with interviews offers a possibility to analyse dominant power structures and subversive empowerment processes within a body-centred, pluralised and ethnically differentiated religious and cultural domain. Current findings, such as the controversial debates about the choice of the swimsuit and the use of the indoor swimming pool, indicate an embodied and objective social structure that seems to be diverging. The associated negotiations about the implementation of patterns of interpretation and classification show a dynamic process of cultural and religious assimilation, attachment and criticism

Type 2 diabetes monocyte microrna and mrna expression

There is increasing evidence that inflammatory macrophages in adipose tissue are involved in insulin resistance of type 2 diabetes (T2D). Due to a relative paucity of data on circulating monocytes in T2D, it is unclear whether the inflammatory changes of adipose tissue macrophages are reflected in these easily accessible cells. Objective To study the expression pattern of microRNAs and mRNAs related to inflammation in T2D monocytes. Design A microRNA finding study on monocytes of T2D patients and controls using array profiling was followed by a quantitative Real Time PCR (qPCR) study on monocytes of an Ecuadorian validation cohort testing the top over/under-expressed microRNAs. In addition, monocytes of the validation cohort were tested for 24 inflammation-related mRNAs and 2 microRNAs previously found deregulated in (auto)-inflammatory monocytes. Results In the finding study, 142 significantly differentially expressed microRNAs were identified, 15 having the strongest power to discriminate T2D patients from controls (sensitivity 66%, specificity 90%). However, differences in expression of these microRNAs between patients and controls were small. On the basis of >1.4 or <0.6-fold change expression 5 microRNAs were selected for further validation. One microRNA (miR-34c-5p) was validated as significantly over-expressed in T2D monocytes. In addition, we found over expression of 3 mRNAs (CD9, DHRS3 and PTPN7) in the validation cohort. These mRNAs are important for cell morphology, adhesion, shape change, and cell differentiation. Classical inflammatory genes (e.g. TNFAIP3) were only over-expressed in monocytes of patients with normal serum lipids. Remarkably, in dyslipidemia, there was a reduction in the expression of inflammatory genes (e.g. ATF3, DUSP2 and PTGS2). Conclusions The expression profile of microRNAs/mRNAs in monocytes of T2D patients indicates an altered adhesion, differentiation, and shape change potential. Monocyte inflammatory activation was only found in patients with normal serum lipids. Abnormal lipid values coincided with a reduced monocyte inflammatory state. Copyright

Study on inflammation-related genes and microRNAs, with special emphasis on the vascular repair factor HGF and miR-574-3p, in monocytes and serum of patients with T2D

Background: Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular repair (raised HGF) in the serum of Ecuadorian patients with type 2 diabetes (T2

CRX controls retinal expression of the X-linked juvenile retinoschisis (RS1) gene

X-linked juvenile retinoschisis is a heritable condition of the retina in males caused by mutations in the RS1 gene. Still, the cellular function and retina-specific expression of RS1 are poorly understood. To address the latter issue, we characterized the minimal promoter driving expression of RS1 in the retina. Binding site prediction, site-directed mutagenesis, and reporter assays suggest an essential role of two nearby cone-rod homeobox (CRX)-responsive elements (CRE) in the proximal −177/+32 RS1 promoter. Chromatin immunoprecipitation associates the RS1 promoter in vivo with CRX, the coactivators CBP, P300, GCN5 and acetylated histone H3. Transgenic Xenopus laevis expressing a green fluorescent protein (GFP) reporter under the control of RS1 promoter sequences show that the −177/+32 fragment drives GFP expression in photoreceptors and bipolar cells. Mutating either of the two conserved CRX binding sites results in strongly decreased RS1 expression. Despite the presence of sequence motifs in the promoter, NRL and NR2E3 appear not to be essential for RS1 expression. Together, our in vitro and in vivo results indicate that two CRE sites in the minimal RS1 promoter region control retinal RS1 expression and establish CRX as a key factor driving this expression

SOFRIMENTO E ADOECIMENTO NO TRABALHO DE AGENTES COMUNITÁRIOS DE SAÚDE: UM ESTUDO EM ESTRATÉGIAS DE SAÚDE DA FAMÍLIA

RESUMO: O objetivo do estudo foi investigar dimensões do contexto do trabalho de agentes comunitários de saúde (ACS) e a relação com possíveis repercussões na saúde desse trabalhador. Estudo quantitativo com 150 ACS de Estratégias de Saúde da Família (ESF) de 12 municípios da 13ª Coordenadoria Regional de Saúde/ RS. Foram utilizados como instrumentos de coleta de dados um questionário sociodemográfico e o Inventário de Trabalho e Riscos de Adoecimento (ITRA). A análise foi realizada por meio da obtenção do escore fatorial, com o cálculo da média dos itens nas quatro escalas do ITRA, considerando o ponto médio e o desvio-padrão. Os fatores do contexto de trabalho e o custo humano no trabalho foram avaliados como moderados, críticos. Quanto a situações de prazer no trabalho, verificou-se avaliação mais positiva no fator liberdade de expressão e moderada, crítica para o fator realização profissional. Os fatores esgotamento profissional e falta de reconhecimento, referentes ao sofrimento laboral, receberam avaliação mais moderada, crítica. Os danos físicos ocupacionais foram avaliados como moderados, críticos e os danos sociais e psicológicos mostraram-se mais positivos, suportáveis. O reconhecimento da realidade de trabalho dos ACS pode contribuir para transformar essa situação, revelando fragilidades, ao retirá-las da invisibilidade

High-throughput genomic technology in research and clinical management of breast cancer. Molecular signatures of progression from benign epithelium to metastatic breast cancer

It is generally accepted that early detection of breast cancer has great impact on patient survival, emphasizing the importance of early diagnosis. In a widely recognized model of breast cancer development, tumor cells progress through chronological and well defined stages. However, the molecular basis of disease progression in breast cancer remains poorly understood. High-throughput molecular profiling techniques are excellent tools for the study of complex molecular alterations. By accurately mapping changes in the genome and subsequent biological/molecular pathways, the chances of finding potential novel treatment targets as well as intervention strategies are enhanced, and ultimately lives can be saved. This review provides a brief summary of recent progress in identifying molecular markers for invasiveness in early breast lesions

Epigenetic Changes of CXCR4 and Its Ligand CXCL12 as Prognostic Factors for Sporadic Breast Cancer

Chemokines and their receptors are involved in the development and cancer progression. The chemokine CXCL12 interacts with its receptor, CXCR4, to promote cellular adhesion, survival, proliferation and migration. The CXCR4 gene is upregulated in several types of cancers, including skin, lung, pancreas, brain and breast tumors. In pancreatic cancer and melanoma, CXCR4 expression is regulated by DNA methylation within its promoter region. In this study we examined the role of cytosine methylation in the regulation of CXCR4 expression in breast cancer cell lines and also correlated the methylation pattern with the clinicopathological aspects of sixty-nine primary breast tumors from a cohort of Brazilian women. RT-PCR showed that the PMC-42, MCF7 and MDA-MB-436 breast tumor cell lines expressed high levels of CXCR4. Conversely, the MDA-MB-435 cell line only expressed CXCR4 after treatment with 5-Aza-CdR, which suggests that CXCR4 expression is regulated by DNA methylation. To confirm this hypothesis, a 184 bp fragment of the CXCR4 gene promoter region was cloned after sodium bisulfite DNA treatment. Sequencing data showed that cell lines that expressed CXCR4 had only 15% of methylated CpG dinucleotides, while the cell line that not have CXCR4 expression, had a high density of methylation (91%). Loss of DNA methylation in the CXCR4 promoter was detected in 67% of the breast cancer analyzed. The absence of CXCR4 methylation was associated with the tumor stage, size, histological grade, lymph node status, ESR1 methylation and CXCL12 methylation, metastasis and patient death. Kaplan-Meier curves demonstrated that patients with an unmethylated CXCR4 promoter had a poorer overall survival and disease-free survival. Furthermore, patients with both CXCL12 methylation and unmethylated CXCR4 had a shorter overall survival and disease-free survival. These findings suggest that the DNA methylation status of both CXCR4 and CXCL12 genes could be used as a biomarker for prognosis in breast cancer

Integration gedruckter Elektronik in Kunststoffe durch Folienhinterspritzen

Ausgehend von der Anwendung von Folienhinterspritzprozessen für dekorative Zwecke wurde deren Nutzung für die Integration elektronischer Strukturen in Kunststoffbauteile untersucht. Die Herstellung der elektronischen Bauelemente erfolgte mittels verschiedener Druckverfahren mit elektrisch leitfähigen und dielektrischen Materialien auf Polycarbonatfolien. Im Fokus standen zum einen kapazitiv auslesbare Speicherstrukturen und zum anderen Elektrolumineszenzleuchten. Nach dem Druck wurden die bedruckten Folien z. T. verformt und hinterspritzt. In der Arbeit wird auf die Auswirkungen der Verform- und Hinterspritzprozesse eingegangen. Schwerpunktmäßig wird die elektronische bzw. optische Funktionalität der Bauelemente, die Beeinflussung durch Klimaveränderungen und die Haftfestigkeit der Folien betrachtet. Im Ergebnis konnten erstmals die Realisierbarkeit hinterspritzter elektronischer Bauelemente nachgewiesen sowie verschiedene Einflussfaktoren auf deren Funktionalität identifiziert werden.Based on the application of film insert molding for graphic purposes, the utilization of this process for the integration of electronic devices into plastic components was examined. The manufacturing of the electronic devices was realized by applying electrical conductive and dielectric inks on polycarbonate foil by various printing processes. Capacitive data storage patterns and electroluminescent lamps are the main applications. The production sequence included the printing process, forming of the foil where required and back injection molding. The impact of forming and film insert molding was investigated. The electronic and/or optical functionality of the devices, the influence of ambient conditions like temperature or humidity and the adhesion strength of the foils were in the focus of the evaluation. As a result, the feasibility of film insert molded electronic devices could be verified and various impact factors could be identified for the first time