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Ubiquitin-Proteasome System Modulates Platelet Function, Nilaksh Gupta
Ubiquitin-Proteasome System Modulates Platelet Function, Nilaksh Gupta
ETD Archive
Atherothrombotic diseases are responsible for more than 25 of all deaths worldwide. Anti-platelet drugs are the mainstay treatment because of the direct involvement of platelets in the initiation and propagation of thrombosis. However, the currently available anti-platelet drugs, such as antagonists of platelet receptors or of effector systems participating in platelet activation, have their own limitations. A new mode of affecting platelet reactivity may prove to offer unique advantages in a host of clinical settings. Proteasome inhibitors are in clinical use to treat hematologic cancers, but also reduce thrombosis. Whether the proteasome participates in platelet activation or function is opaque …
Role Of Mtorc1 And Autophagy In The Regulation Of Chemoresistance In Leukemic B-Cells, Arishya Sharma
Role Of Mtorc1 And Autophagy In The Regulation Of Chemoresistance In Leukemic B-Cells, Arishya Sharma
ETD Archive
Deregulated mTORC1 contributes to tumorigenesis and chemoresistance. However, mTORC1-specific inhibitors (rapalogs) show modest efficacy in the clinic, as they unleash the feedback inhibition on upstream, prosurvival pathways. An alternative approach is to target downstream functions of mTORC1. We investigated acquired resistance to fludarabine (Flu), a purine analog, active agent for chronic lymphocytic leukemia (CLL). Elevated phospho-p70S6k (T389), an mTORC1 activation marker, predicted Flu resistance in a panel of B-cell tumor lines, and primary CLL cells. However, the rapalogs induced moderate cell death in Flu-resistant (FluR) and primary CLL cells. Activation of oncogenic pathways, including mTORC1, induces profound metabolic reprogramming to …
Combinatorial Activation Of Stat3 By Egf And Thrombin In Endothelial Cells, Matthew S. Waitkus
Combinatorial Activation Of Stat3 By Egf And Thrombin In Endothelial Cells, Matthew S. Waitkus
ETD Archive
Endothelial cells line the luminal surface of blood vessels and form a regulatory interface between the bloodstream and underlying tissues. The endothelium responds to diverse, and potentially conflicting, environmental signals to regulate vessel growth, leukocyte adhesion, thrombogenicity, and vascular tone. Signaling pathways may interact, or "crosstalk," in combinatorial signaling environments to enable cells to process disparate extracellular information at downstream signaling nodes and formulate appropriate biological responses based on combinations of extracellular stimuli. We have reported that simultaneous stimulation of endothelial cells with EGF and thrombin synergistically induces expression of immediate early genes (IEGs) associated with growth and angiogenesis. We …
Activated Neutrophils Mediate Kim-1 Shedding And Renal Remodelling, Shreyas Lingadahalli
Activated Neutrophils Mediate Kim-1 Shedding And Renal Remodelling, Shreyas Lingadahalli
ETD Archive
Kidney performs a complex task of concentrating the urine, retention of salts and protein and excretion of metabolic toxins and by the virtue of its function, is always under the chemical stress and subject to constant tissue damage. Post injury, nephrons have the ability to regain their function by remodeling including, clearing of apoptotic and necrotic debris. Kidney Injury Molecule-1(KIM-1/TIM-1/HAVCR-1) is a phosphatidylserine receptor that recognizes the apoptotic bodies and directs them to the lysosomal degradation. KIM-1 a type I transmembrane glycoprotein, although not constitutively expressed, is expressed in injured epithelial cells. It is known that the extracellular domain is …
Regulation Of Monocyte Nadph Oxidase;Role Of Pattern Recognition Receptors, Deena H. Elsori
Regulation Of Monocyte Nadph Oxidase;Role Of Pattern Recognition Receptors, Deena H. Elsori
ETD Archive
No abstract provided.