Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2006. / Includes bibliographical references (leaves 26-27). Also available in electronic version.

Techn. University, Diss., 1999--Dresden.

Our lab has identified the bZIP transcription factor CCAAT/Enhancer Binding Protein beta (C/EBPβ) as a negative regulator of myogenic differentiation. C/EBPβ is highly expressed in satellite cells and is downregulated during myogenic differentiation, a step that is critical for terminal differentiation, as ectopic C/EBPβ expression blocks this process. Telomerase has been identified as a C/EBPβ target gene in liver and other systems, and has been implicated in the regulation of muscle regenerative responses in models of Duchenne Muscular Dystrophy. Given that C/EBPβ is overexpressed in models of muscle wasting, and high levels of telomerase inhibit differentiation, I hypothesized that C/EBPβ inhibits myogenic differentiation through upregulation of TERT (telomerase reverse transcriptase) expression. I demonstrate that overexpression of C/EBPβ in myoblasts increases mTERT expression under both growth and differentiation conditions. Conversely, loss of C/EBPβ expression in myoblasts using shRNA technology or after isolation of primary myoblasts from conditional knockout mice, results in a downregulation of TERT expression and activity. When TERT was pharmacologically inhibited or knocked down using a shRNA, there was a significant improvement in differentiation and fusion in C2C12 myoblasts overexpressing C/EBPβ as evidenced by an increase in the number of MHC+ fibers and expression of muscle-specific differentiation genes. Interestingly, I found that C/EBPβ and TERT expression were increased in both embryonic and alveolar models of rhabdomyosarcoma. In response to this, a knockdown of C/EBPβ in rhabdomyosarcoma cells decreased TERT expression and activity, and enhanced differentiation but not fusion in a model of embryonic rhabdomyosarcoma. These findings illustrate the novel regulation of TERT in skeletal muscle by C/EBPβ, and reveal C/EBPβ as an attractive therapeutic target for the treatment of muscle diseases such as rhabdomyosarcoma.

Note:

A Differentiation Factor (DF) was purified from rat lung conditioned medium by a four-steps procedure. The DF has a molecular weight of 27000, and an isoelectric point of 4.70. Although DF is stable up to 60°C, it is sensitive to digestion by trypsin, chymotrypsin and subtilisin. DF forms granulocyte colonies in soft agar. Studies using anti-NRK CSF antibody demonstrated that DF is distinct from GM-CSF.

No description available.

published_or_final_version / abstract / Anatomy / Master / Master of Philosophy

One of the most important research problems in tourism today, and one still to be thoroughly investigated, is the understanding of tourist decision-making processes and the way they are reflected in tourist spatial behaviour. Until very recently, the study of tourist decision-making and that of tourist flows went on independently of one another. Thus, geographers were detecting and describing tourist flows while psychologists and marketing analysts were trying to understand the destination-choice process. The current study merges these two aspects and addresses the following questions: A. What are the most important and frequently assessed destination attributes anticipated and desired by tourists? B. Is destination-choice behaviour (when based on different desired destination attributes) class-differentiated? C. Are spatial patterns of tourist flows also classdifferentiated? D. If class differentiation does exist, is there a causal connection between the manner of destination choice and tourists' consequent spatial behaviour? This study rests on two general assumptions. The first is that the process of selecting from among alternative tourist destinations is a direct outcome of the individual's evaluation of the aggregate value of utilities inherent in destination attributes. The second claims that the general tourist spatial pattern is a product of subpatterns created by different groups of tourists. The derived operational hypotheses suggest that both destination-choice and tourists' spatial behaviour are class-differentiated. Initially, the study involved the detection of the 25 most frequently assessed destination attributes. These were then introduced into a questionnaire examining the destination-choice and spatial behaviour of the North-Vest London Jewish community. Analysis of the data collected using Della Pave's 'Value Stretch' concept shows that destination-choice processes among Barnet's Jewish tourists are significantly class-differentiated. Significantly different tourist behaviour patterns were also found among them. The concept of 'Value Stretch' also revealed the possible causes of different tourist spatial behaviour emerging in the wake of class-differentiated destination-choice patterns.

No description available.