HOXD8 exerts a tumor-suppressing role in colorectal cancer as an apoptotic inducer

Homeobox (HOX) genes are conserved transcription factors which determine the anterior-posterior body axis patterning. HOXD8 is a member of HOX genes deregulated in several tumors such as lung carcinoma, neuroblastoma, glioma and colorectal cancer (CRC) in a context-dependent manner. In CRC, HOXD8 is downregulated in cancer tissues and metastatic foci as compared to normal tissues. Whether HOXD8 acts as a tumor suppressor of malignant progression and metastasis is still unclear. Also, the underlying mechanism of its function including the downstream targets is totally unknown. Here, we clarified the lower expression of HOXD8 in clinical colorectal cancer vs. normal colon tissues. Also, we showed that stable expression of HOXD8 in colorectal cancer cells significantly reduced the cell proliferation, anchorage-independent growth and invasion. Further, using The Cancer Genome Atlas (TCGA), we identified the genes associated with HOXD8 in order to demonstrate its function as a suppressor or a promoter of colorectal carcinoma. Among inversely related genes, apoptotic inhibitors like STK38 kinase and MYC were shown to be negatively associated with HOXD8. We demonstrated the ability of HOXD8 to upregulate executioner caspases 6 & 7 and cleaved PARP, thus inducing the apoptotic events in colorectal cancer cells

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本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものである京都大学0048新制・課程博士博士(工学)甲第8524号工博第1978号新制||工||1186(附属図書館)UT51-2000-J33京都大学大学院工学研究科分子工学専攻(主査)教授 川﨑 昌博, 教授 横尾 俊信, 教授 中辻 博学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDFA

Changing roles and competencies of academics

This article presents the findings of a small study in a single school of a post-1992 university. The study considered the roles of the online academic and ascertained perceived competencies in these roles. The findings suggest gender differences in perceptions of the importance of online roles and gaps between roles and perceived competencies in these roles, suggesting some academics feel ill-equipped to meet online demands. The study indicates that appropriate learning and development programmes underpinned by relevant competency development are required. Notwithstanding, when asked to identify differences in roles and competencies in online and traditional environments, respondents indicated that their roles were similar in both environments. This suggested that a new ‘generic’ framework for academic roles and competencies was needed. The study then moved to develop a generic role model for use in all learning and teaching environments

Examining agreement between clinicians when assessing sick children.

BACKGROUND: Case management guidelines use a limited set of clinical features to guide assessment and treatment for common childhood diseases in poor countries. Using video records of clinical signs we assessed agreement among experts and assessed whether Kenyan health workers could identify signs defined by expert consensus. METHODOLOGY: 104 videos representing 11 clinical sign categories were presented to experts using a web questionnaire. Proportionate agreement and agreement beyond chance were calculated using kappa and the AC1 statistic. 31 videos were selected and presented to local health workers, 20 for which experts had demonstrated clear agreement and 11 for which experts could not demonstrate agreement. PRINCIPAL FINDINGS: Experts reached very high level of chance adjusted agreement for some videos while for a few videos no agreement beyond chance was found. Where experts agreed Kenyan hospital staff of all cadres recognised signs with high mean sensitivity and specificity (sensitivity: 0.897-0.975, specificity: 0.813-0.894); years of experience, gender and hospital had no influence on mean sensitivity or specificity. Local health workers did not agree on videos where experts had low or no agreement. Results of different agreement statistics for multiple observers, the AC1 and Fleiss' kappa, differ across the range of proportionate agreement. CONCLUSION: Videos provide a useful means to test agreement amongst geographically diverse groups of health workers. Kenyan health workers are in agreement with experts where clinical signs are clear-cut supporting the potential value of assessment and management guidelines. However, clinical signs are not always clear-cut. Video recordings offer one means to help standardise interpretation of clinical signs

Religion beyond equality

Cécile Laborde proposes a liberal egalitarian view for a liberal state to adopt in its fair treatment of religious citizens. She suggests a method where state neutrality is applied restrictively and religion is “disaggregated” across standard liberal rights. Without recourse to a legal-political category religion, she responds to the problem of religious accommodation by using main elements of a particular liberal right(s) to account for the dimension of religion that an issue of justice makes salient. In reply to the problem of state neutrality, she proposes that a liberal state can be non-neutral in its treatment of religious claims as long as religion is not a marker for social division, does not impose its comprehensive ethics, and provides publicly accessible reasons. I argue that adopting Laborde’s approach has conceptual and pragmatic advantages as a political strategy (modus vivendi) in resolving justice claims. However, its content-neutral and procedural framework partially meets the requirements of justice of religious citizens because of its egalitarian motivation. In adopting a minimal political conception of religion defined by elements of other liberal rights, the liberal state employs a narrow understanding of religion as a “collection” of beliefs and practices. This can result in religious citizens exercising partial or even distorted expressions of their religious identities. I suggest a conceptual refinement in Laborde’s theory if it aims at attracting endorsement from religious citizens as a reasonable conception of justice. I will survey some alternative frameworks and ideas (e.g. Raz value-based approach, Riordan’s capacity for truth argument) and build on their strengths. I propose vocation as a useful concept for a liberal state to employ in appropriately understanding and assessing religious commitment. My modest proposal presents a liberal understanding of religion-state relationship other than those framed in the themes of neutrality, toleration, exclusion, or limitation of practices