310 research outputs found
The Nation and its citizens: Tales of Bondage and Belonging
No full textThe Nation and Its Citizens: Tales of Bondage and Belonging is about nationalism as a uniquely modern political doctrine, shaped by the lived experience of citizens. Nationalism has changed in its appeal through history, as have its manifestations. Getting to know these may be part of the challenge of negotiating the ongoing turmoil, both internal and external to the nation.
In addressing these issues, this book offers several propositions on how the construct of ‘identity’ is crafted, with all its power to influence modern politics. It then explores how well India’s practice of republican democracy has lived up to the competing dynamics of identity and equality.
As India celebrates 75 years of Independence, author Sukumar Muralidharan takes the readers on a journey into how the sense of fellow-feeling and mutual dependence of the nation are consolidated, and under what circumstances these could fray. The Nation and Its Citizens offers many fresh perspectives in understanding India’s unique political trajectory
HOXA5, A CELL FATE TRANSITION REGULATOR, IMPEDES TUMOR INITIATION AND PROGRESSION IN BREAST CANCER
No full textThis thesis focuses on understanding the biological functions of HOXA5 in mammary epithelial differentiation and breast cancer progression. Members of HOX cluster have long been associated with cellular differentiation. Nonetheless, how HOX genes drive differentiation in mammalian cells is poorly understood. The expression of HOXA5 is frequently deregulated in breast cancer, while higher HOXA5 expression predicts better relapse free survival in breast cancer patients. My research has demonstrated that depleting HOXA5, a key regulator during embryogenesis, increases cell plasticity and stemness in the human breast epithelial cell line, MCF10A. Comparison of MCF10A cells and HOXA5-depleted MCF10A cells by expression array analysis revealed HOXA5’s ability to regulate several traits of epithelial lineage, including E-cadherin and CD24. Analysis of the expression array by gene set enrichment analysis (GSEA) confirmed the negative correlation between epithelial traits and the transcriptome of HOXA5-depleted MCF10A cells. Using an inducible HOXA5-knockdown system, we demonstrated how HOXA5 depletion restrained state transition from CD24-/CD44+ to CD24+/CD44+ cells upon treatment of retinal. The increase of expression of adhesions proteins was, however, impeded when HOXA5 was simultaneously repressed. Failure of state transition upon depletion of HOXA5 resulted in increased ability for mammosphere formation. Furthermore, depleting HOXA5 in MCF10A-KRAS transformed cells reduced CD24+/CD44lo population and enhanced the self-renewal capacity of MCF10A-KRAS cells in culture. In Matrigel, these cells exhibited stellate and protrusive morphology which suggested the transition of the cancer cell to a more progenitor-like state. HOXA5-depleted MCF10-KRAS cells failed to develop pseudo-luminal architecture in orthotopically engrafted xenografts. Ectopic expression of HOXA5 in SUM149, on the other hand, resulted in an increased CD24+/CD44- population and inhibition of mammosphere formation in culture and tumor initiation in vivo. Mechanistically, we showed that wild type HOXA5 induced luciferase activity regulated by the proximal promoter region of E-cadherin and CD24 in 293T cells. We further confirmed the recruitment of HOXA5 to putative consensus HOXA5 binding site, TAAT, to these promoters by ChIP analysis. Collectively, these findings support a role for HOXA5 in cell differentiation by up-regulating epithelial traits and suppressing tumor aggressiveness in breast cancer
Imaging the Vascular and Metabolic Impact of Claudin-7, a Tight Junction Protein in Transgenic Human Breast Cancer Models
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