Involvement of the WT1 and p16 genes in Wilms' tumour and human malignant mesothelioma

Normal cellular homeostasis is established and maintained by the positive and negative regulatory activities of many genes. When these genes are mutated to forms that can contribute to tumorigenesis, either by dominant, gain of function mutations in positive regulators or recessive, loss of function mutations in negative regulators, they are termed oncogenes or tumour suppressor genes, respectively. Identified human tumour suppressor genes, though still relatively few in number, are found to be active in many different cellular processes. I have studied two such genes, the WT1 and p16 genes, which in their wild type forms are known to contribute to development of the urogenital system and the mesothelium (WTI) and to control of the cell cycle (pi6).WT1 was identified as a gene repeatedly disrupted in Wilms' tumour, a common paediatric renal malignancy. This study is one of many which sought to confirm and understand some of the roles of WTI in both normal development and tumorigenesis. Mutation analysis of WTI in samples from patients with sporadic, bilateral and syndrome-associated Wilms' tumour has produced a pattern of results consistent with the findings of other groups. No mutations were detected in the sporadic and bilateral tumours, however exonic point mutations were detected in 7 out of 9 syndrome-associated Wilms' tumour samples that were analysed in detail. Studies examining parental WTI status, genomic imprinting and allele loss distal to the WTI locus are detailed for the syndrome-associated Wilms' tumour samples. Additionally, analysis of WTI in samples from patients with testicular tumours or malignant mesothelioma did not identify any mutations believed to be significant in tumorigenesis.The contribution, resulting effects and complementary nature of WTI and p16 mutations in Wilms' tumour and malignant mesothelioma is discussed

The University of Kitakyushu-Tacoma Community College Semester Study Abroad Program: Overview, Goals and Reflections

Although declining in recent years, the number of Japanese students studying in the United States every year is still over 20,000. According to Open Doors International, in 2009, 24,264 Japanese students spent time studying for some length of time at an American university (2009). Many of these students participated in a program of a semester of less. Recent research (Dwyer, 2004) has shown that while perhaps longterm programs (a semester or more) have a more significant impact on language growth, most students studying abroad, regardless of length, report increase in intercultural development and personal growth (quoted in Chieffo and Griffiths 2009, pp. 367-368). All study abroad programs can have an impact on a student\u27s life. In the past few years, the University of Kitakyushu (UKK) has been putting a stronger emphasis on English-language learning in an effort to produce more globallyminded citizens. One result of that emphasis has been the implementation of a regular semester-long study abroad program at Tacoma Community College (TCC) in the United States. This program, and the effect on students\u27 lives is the focus of this paper. First, a brief history of the Kitakyushu-Tacoma sister city relationship will be given, along with a description of mutual exchange programs; next, the University of Kitakyushu-Tacoma Community College study abroad program will be covered in detail. This will be followed by student comments on the good points and bad points of this program, as well as reflections on how this program changed them. Lastly, the authors will reflect on the usefulness of this program, and how it can be made better and have a more lasting language and cultural impact on UKK students\u27 lives, helping to shape them into more confident global citizens

Low Tech and High Tech: The Spectrum of Special Collections Use in a Technological Institute

The gradual expansion of the Georgia Institute of Technology ‘s Library and Special Collection has resulted in a unique and outstanding science and technological research facility. The process was expanded by a number of individuals who dedicated their professional years to improving the holdings. Unique among these treasures is the first edition of Newton’s Principia. Collecting, preserving, and utilizing the new technologies to expand access to this outstanding collection has proved challenging. The primary materials, carefully collected over the years, are being protected and made available through traditional means; while at the same time technological advances are being utilized to enhance access to the intellectual and visual content of these materials

Pole cell determination and differentiation : a molecular screen for germ cell markers in Drosophila melanogaster

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1995.Includes bibliographical references.by Anne Williamson.Ph.D

The rise of companies from emerging markets in global health governance: opportunities and challenges

The article analyses the involvement of pharmaceutical companies from emerging markets in global health governance. It finds that they play a central role as low-cost suppliers of medicines and vaccines and, increasingly, new technologies. In so doing, pharmaceutical companies from emerging markets have facilitated the implementation of a key goal of global health policy: widening access to pharmaceutical treatment and prevention. Yet, looking closer at the political economy underlying their involvement, the article exposes a tension between this policy goal and the political economy of pharmaceutical development and production. By declaring access to pharmaceuticals a goal of global health policy, governments and global health partnerships have made themselves dependent on pharmaceutical companies to supply them. Moreover, to provide pharmaceutical treatment and prevention at the global level, they depend on companies to supply medicines and vaccines at extremely low prices. Yet, the development and production of pharmaceuticals is organized around commercial incentives that are at odds with the prices required. The increasing involvement of low-cost suppliers from emerging markets mitigates this tension in the short run. In the long run, this tension endangers the sustainability of global access policies and may even undermine some of the successes already achieved

Expression of the wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet‐derived growth factor A and insulin‐like growth factor 2 expression

Mutations in the WT1 tumor suppressor gene are known to contribute to the development of Wilms' tumor (WT) and associated gonadal abnormalities. WT1 is expressed principally in the fetal kidney, developing gonads, and spleen and also in the mesothelium, which lines the coelomic cavities. These tissues develop from mesenchymal components that have subsequently become epithelialized, and it has therefore been proposed that WT1 may play a role in this transition of cell types. To test the possible involvement of this gene in malignant mesothelioma, we have first studied its expression in a panel of human normal and malignant mesothelial cell lines. WT1 mRNA expression levels varied greatly between the cell lines and no specific chromosomal aberration on 11p, which could be related to the variation in WT1 expression in these cell lines, was observed. Furthermore, no gross deletions, rearrangements, or functionally inactivating point mutations in the WT1 coding region were identified. All four WT1 splice variants were observed at similar levels in these cell lines. The WT1 gene encodes a zinc‐finger transcription factor and the four protein isoforms are each believed to act as transcriptional repressors of certain growth factor genes. Lack of WT1 expression is thus predicted to result in growth stimulation of tumor cells. Binding of one particular WT1 isoform construct to the insulin‐like growth factor 2 (IGF2) and platelet‐derived growth factor A (PDGFA) gene promoters has been demonstrated to result in repression of these genes in transient transfection studies. Analysis of IGF2 and PDGFA mRNA expression levels compared with WT1 mRNA expression levels failed to demonstrate an inverse correlation in the mesothelial cell lines, which endogenously express these genes. Finally, the putative role of WT1 in the transition of cell types was investigated. No obvious correlation between WT1 expression levels and cell morphology of the malignant mesothelial cell lines was evident from this study. Moreover, no change in WT1 expression was observed in normal mesothelial cells which were, by alteration of culture conditions, manipulated to switch from the mesenchymal to epithelial morphology.</p

Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin- like growth factor 2 expression

Mutations in the WT1 tumor suppressor gene are known to contribute to the development of Wilms' tumor (WT) and associated gonadal abnormalities. WT1 is expressed principally in the fetal kidney, developing gonads, and spleen and also in the mesothelium, which lines the coelomic cavities. These tissues develop from mesenchymal components that have subsequently become epithelialized, and it has therefore been proposed that WT1 may play a role in this transition of cell types. To test the possible involvement of this gene in malignant mesothelioma, we have first studied its expression in a panel of human normal and malignant mesothelial cell lines. WT1 mRNA expression levels varied greatly between the cell lines and no specific chromosomal aberration on 11p, which could be related to the variation in WT1 expression in these cell lines, was observed. Furthermore, no gross deletions, rearrangements, or functionally inactivating point mutations in the WT1 coding region were identified. All four WT1 splice variants were observed at similar levels in these cell lines. The WT1 gene encodes a zinc-finger transcription factor and the four protein isoforms are each believed to act as transcriptional repressors of certain growth factor genes. Lack of WT1 expression is thus predicted to result in growth stimulation of tumor cells. Binding of one particular WT1 isoform construct to the insulin-like growth factor 2 (IGF2) and platelet-derived growth factor A (PDGFA) gene promoters has been demonstrated to result in repression of these genes in transient transfection studies. Analysis of IGF2 and PDGFA mRNA expression levels compared with WT1 mRNA expression levels failed to demonstrate an inverse correlation in the mesothelial cell lines, which endogenously express these genes. Finally, the putative role of WT1 in the transition of cell types was investigated. No obvious correlation between WT1 expression levels and cell morphology of the malignant mesothelial cell lines was evident from this study. Moreover, no change in WT1 expression was observed in normal mesothelial cells which were, by alteration of culture conditions, manipulated to switch from the mesenchymal to epithelial morphology

Case studies of training advantage for remote Aboriginal and Torres Strait Island learners

[Extract] The case studies that follow are a compilation of learnings derived from the research project, Enhancing training advantage for remote Aboriginal and Torres Strait Islander learners. The project, funded by the National Centre for Vocational Education Research (NCVER), was conducted by a consortium of researchers from five institutions: TAFE SA, Batchelor Institute of Indigenous Tertiary Education, University of New England, James Cook University and the University of Notre Dame Australia. The research was conducted during 2016 with participants from five locations: the Anangu Pitjantjatjara Yankunytjatjara Lands of South Australia, the Northern Territory, western New South Wales, the Kimberley region of Western Australia, and the Cape York and Torres Strait Island regions of Queensland. Based on training programs considered to be successful, the project was designed in order to gain an understanding of the dynamics of retention and completion towards employability. Nationally, for very remote Aboriginal and Torres Strait Islander trainees, completion rates for VET courses are on average 16.6%, with an even lower figure for certificate I courses. Full details about the project and its cross-cutting findings, with a literature review and additional statistical information, are contained in the report, available from the NCVER Portalat . The case studies presented here mostly present qualitative findings

Enhancing training advantage for remote Aboriginal and Torres Strait Islander learners

[Extract] Aboriginal and Torres Strait Islanders in very remote parts of Australia are increasingly participating in vocational education and training (VET); however, completion rates remain low and employment outcomes are not improving. This project identifies how retention and completion can be improved and what other indicators of success are important outcomes of training in remote communities. Using a case study approach to investigate five unique training programs in remote areas of Australia, the report finds a that range of factors contribute to retention, including: - trainer qualities and characteristics of delivery - family, personal, community and cultural factors - training coordination and support - supportive relationships with other students - local community ownership of training - training that is connected to culture and local knowledge