Integration of miRNA and mRNA expression with DNA copy number of Ewing sarcoma cell lines

Ewing sarcoma is an aggressive and poorly differentiated malignancy of bone and soft tissue. It primarily affects children, adolescents, and young adults, with a slight male predominance. It is characterized by a translocation between chromosomes 11 and 22 resulting in the EWSR1-FLI1fusion transcription factor. The aim of this study is to identify putative Ewing sarcoma target genes through an integrative analysis of three microarray data sets. Array comparative genomic hybridization is used to measure changes in DNA copy number, and analyzed to detect common chromosomal aberrations. mRNA and miRNA microarrays are used to measure expression of protein-coding and miRNA genes, and these results integrated with the copy number data. Chromosomal aberrations typically contain also bystanders in addition to the driving tumor suppressor and oncogenes, and integration with expression helps to identify the true targets. Correlation between expression of miRNAs and their predicted target mRNAs is also evaluated to assess the results of post-transcriptional miRNA regulation on mRNA levels. The highest frequencies of copy number gains were identified in chromosome 8, 1q, and X. Losses were most frequent in 9p21.3, which also showed an enrichment of copy number breakpoints relative to the rest of the genome. Copy number losses in 9p21.3 were found have a statistically significant effect on the expression of MTAP, but not on CDKN2A, which is a known tumor-suppressor in the same locus. MTAP was also down-regulated in the Ewing sarcoma cell lines compared to mesenchymal stem cells. Genes exhibiting elevated expression in association with copy number gains and up-regulation compared to the reference samples included DCAF7, ENO2, MTCP1, andSTK40. Differentially expressed miRNAs were detected by comparing Ewing sarcoma cell lines against mesenchymal stem cells. 21 up-regulated and 32 down-regulated miRNAs were identified, includingmiR-145, which has been previously linked to Ewing sarcoma. The EWSR1-FLI1 fusion gene represses miR-145, which in turn targets FLI1 forming a mutually repressive feedback loop. In addition higher expression linked to copy number gains and compared to mesenchymal stem cells, STK40 was also found to be a target of four different miRNAs that were all down-regulated in Ewing sarcoma cell lines compared to the reference samples. SLCO5A1 was identified as the only up-regulated gene within a frequently gained region in chromosome 8. This region was gained in over 90 % of the cell lines, and also with a higher frequency than the neighboring regions. In addition, SLCO5A1 was found to be a target of three miRNAs that were down-regulated compared to the mesenchymal stem cells.

Diakoniatyön paikka ihmisten arjessa

This study examines the diaconia work of the Finnish Evangelical Lutheran Church from the standpoint of clients. The role of diaconia work has grown since the early 1990s recession, and since it established itself as one of the actors along with other social organizations. Previous studies have described the changing role of diaconal work, especially from the standpoint of diaconia workers and co-operators. This research goes back to examine, beyond the activities of the diaconia work of everyday practices, its relations of ruling which are determining practices. The theoretical and methodological framework rises from the thinking of Dorothy E. Smith, the creator of institutional ethnography. Its origins are in feminism, Marxism, phenomenology, etnomethodology, and symbolic interactionism. However, it does not represent any school. Unlike the objectivity-based traditional sociology, institutional ethnography has its starting point in everyday life, and people s subjective experience of it. Everyday life is just a starting point, and is used to examine everyday life s experiences of hidden relations of ruling, linking people and organizations. The level of generalization is just on the relations of ruling. The research task is to examine those meanings of diaconia work which are embedded in its clients experiences. The research task is investigated with two questions: how diaconia work among its clients takes shape and what kinds of relations of ruling exist in diaconia work. The meanings of diaconia work come through an examination of the relations of ruling, which create new forms of diaconal work compared with previous studies. For the study, two kinds of data were collected: a questionnaire and ethnographic fieldwork. The first data set was collected from diaconal workers using the questionnaire. It gives background information of the diaconia work process from the standpoint of the clients. In the ethnographic study there were two phases. The first ethnographic material was collected from one local parish by observing, interviewing clients and diaconal workers and gathering documents. The number of observations was 36 customer appointments, and 29 interviews. The second ethnographic material was included as a part of the analysis, in which ruling relations in people s experiences were collected from the transcribed data. Close reading and narrative analysis are used as analysing methods. The analysis has three phases. First, the experiences are identified with close reading; the following step is to select some of the institutional processes that are shaping those experiences and are relevant for the research. At the third stage, those processes are investigated in order to describe analytically how they determine people s experience. The analysis produces another narrative about diaconia work, which provides tools for examining the diaconal work from a new perspective. Through the analysis it is possible to see diaconia as an exchange ratio, in which the exchange takes place between a client and a diaconia worker, but also more broadly with other actors, such as social workers, shop clerks, or with other parishioners. The exchange ratio is examined from the perspective of power which is embedded in the client s experiences. The analysis reveals that the most important relations of ruling are humiliation and randomness in the exchange ratio of diaconia work; valuating spirituality above the bodily being; and replacing official social work. The results give a map about the relations of ruling of diaconia work which gives tools to look at diaconia work s meanings to the clients. The hidden element of humiliation in the exchange ratio breaks the current picture of diaconia work. The ethos of the holistic encounters and empathic practices are shown to be of another kind when spirituality is preferred to the bodily being. Nevertheless, diaconia appears to be a place for a respectful encounter, especially in situations where the public sector s actors are retreating on liability or clients are in a life crisis. The collapse of the welfare state structures imposes on diaconia work tasks that have not previously belonged to it. At the local level, clients receive partners from diaconia workers in order to advocate them in the welfare system. Actions to influence the wider societal structures are not reached because of lacking resources. An awareness of the oppressive practices of diaconia work and their critical reviewing are the keys to the development of diaconia work, since there are such practices even in holistic and respectful diaconia work. While the research raises new information for the development of diaconia work, it also opens up new aspects for developing other kinds of social work by emphasizing the importance of taking people s experiences seriously. Keywords: diaconia work, institutional ethnography, Dorothy E. Smith, experience, customer, relations of ruling.

Functional outcome and health-related quality of life after traumatic brain injury in the framework of the International Classification of Functioning, Disability and Health (ICF)

Traumatic brain injury (TBI) affects people of all ages and is a cause of long-term disability. In recent years, the epidemiological patterns of TBI have been changing. TBI is a heterogeneous disorder with different forms of presentation and highly individual outcome regarding functioning and health-related quality of life (HRQoL). The meaning of disability differs from person to person based on the individual s personality, value system, past experience, and the purpose he or she sees in life. Understanding of all these viewpoints is needed in comprehensive rehabilitation. This study examines the epidemiology of TBI in Finland as well as functioning and HRQoL after TBI, and compares the subjective and objective assessments of outcome. The frame of reference is the International Classification of Functioning, Disability and Health (ICF). The subjects of Study I represent the population of Finnish TBI patients who experienced their first TBI between 1991 and 2005. The 55 Finnish subjects of Studies II and IV participated in the first wave of the international Quality of life after brain injury (QOLIBRI) validation study. The 795 subjects from six language areas of Study III formed the second wave of the QOLIBRI validation study. The average annual incidence of Finnish hospitalised TBI patients during the years 1991-2005 was 101:100 000 in patients who had TBI as the primary diagnosis and did not have a previous TBI in their medical history. Males (59.2%) were at considerably higher risk of getting a TBI than females. The most common external cause of the injury was falls in all age groups. The number of TBI patients ≥ 70 years of age increased by 59.4% while the number of inhabitants older than 70 years increased by 30.3% in the population of Finland during the same time period. The functioning of a sample of 55 persons with TBI was assessed by extracting information from the patients medical documents using the ICF checklist. The most common problems were found in the ICF components of Body Functions (b) and Activities and Participation (d). HRQoL was assessed with the QOLIBRI which showed the highest level of satisfaction on the Emotions, Physical Problems and Daily Life and Autonomy scales. The highest scores were obtained by the youngest participants and participants living independently without the help of other people, and by people who were working. The relationship between the functional outcome and HRQoL was not straightforward. The procedure of linking the QOLIBRI and the GOSE to the ICF showed that these two outcome measures cover the relevant domains of TBI patients functioning. The QOLIBRI provides the patients subjective view, while the GOSE summarises the objective elements of functioning. Our study indicates that there are certain domains of functioning that are not traditionally sufficiently documented but are important for the HRQoL of persons with TBI. This was the finding especially in the domains of interpersonal relationships, social and leisure activities, self, and the environment. Rehabilitation aims to optimize functioning and to minimize the experience of disability among people with health conditions, and it needs to be based on a comprehensive understanding of human functioning. As an integrative model, the ICF may serve as a frame of reference in achieving such an understanding.