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Articles 1 - 8 of 8
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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 …
Acute And Chronic Rejection: Compartmentalization And Kinetics Ff Counterbalancing Signals In Cardiac Transplants, Anupurna Kaul
Acute And Chronic Rejection: Compartmentalization And Kinetics Ff Counterbalancing Signals In Cardiac Transplants, Anupurna Kaul
ETD Archive
Heart disease is the major cause of mortality in the United States and other parts of the world. Heart transplantation is the treatment of choice for patients with end stage heart failure. However, transplanted organs fail due to either acute or chronic rejection. This acute and chronic rejection impacts distinct compartments of cardiac allografts. Acute rejection is characterized by infiltration of mononuclear cells whereas chronic rejection is characterized by progressive narrowing of coronary arteries. In a minor histoincompatibility mismatch mouse model we found hearts transplanted from male to female C57BL/6 mice undergo an acute rejection with diffuse interstitial infiltrates at …
Circadian Regulation Of Mtor Signaling Via Bmal1 Dependent Mechanism, Rohini Vishal Khapre
Circadian Regulation Of Mtor Signaling Via Bmal1 Dependent Mechanism, Rohini Vishal Khapre
ETD Archive
Understanding mechanisms of aging is important for the treatment and prevention of age-associated pathologies. However, these mechanisms are not well understood. Recently we have demonstrated that the circadian clock (an internal time keeping system) regulates longevity in mammals, but the molecular mechanisms are not known. The aim of our current study is to investigate a possible interconnection between the circadian clock and mTORC1 (mammalian target of Rapamycin) signaling pathway. mTORC1 pathway is a nutrient response pathway involved in many cellular processes many recent studies indicate a role of mTORC1 pathway in aging. Here we demonstrate that circadian system regulates mTORC1 …
Trypanosoma Brucei Telomere Functions In Antigenic Variation, Unnati M. Pandya
Trypanosoma Brucei Telomere Functions In Antigenic Variation, Unnati M. Pandya
ETD Archive
Trypanosoma brucei is a protozoan parasite that causes sleeping sickness in humans and Nagana in cattle. They evade the host's immune defense by periodically switching their major surface antigen, variant surface glycoprotein (VSG), a phenomenon termed antigenic variation. Inside its mammalian host, bloodstream form (BF) T. brucei monoallelically expresses its major surface molecule VSG from the VSG Expression Sites (ESs) located at subtelomeric loci. Monoallelic VSG expression ensures effective antigenic variation and maximizes the efficiency of T. brucei pathogenesis. In the mid-gut of its insect host (tsetse), procyclic form (PF) T. brucei expresses procyclins as the major surface molecules and …
Study Of Role Of Ribosomal Protein L13a In Resolving Inflammation, Darshana Poddar
Study Of Role Of Ribosomal Protein L13a In Resolving Inflammation, Darshana Poddar
ETD Archive
Inflammation is an obligatory attempt of the host immune system to protect the body against infection. However, unregulated synthesis of pro-inflammatory products can have detrimental effects. Though mechanisms which contribute to inflammation are well appreciated, those that resolve inflammation are poorly understood. Therefore, understanding the molecular basis of such pathways will provide an entirely novel approach to treat and prevent inflammatory diseases. Transcript-selective translational control can regulate the expression of a set of inflammatory genes. We have identified one such mechanism in a novel animal model which relies on the abrogation of ribosomal protein L13a-dependent translational silencing by creating macrophage-specific …
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 …
Conformational Regulation Of Membrane Localization And Activation Of Talin, Pallavi Dwivedi
Conformational Regulation Of Membrane Localization And Activation Of Talin, Pallavi Dwivedi
ETD Archive
Talin is a cytosolic protein which is known to be one of the key players involved in integrin mediated cell adhesion dependent processes, including blood coagulation, and tissue remodeling. It connects the extracellular matrix with the actin cytoskeleton. Talin comprises of a head domain (talin-H) and a rod domain (talin-R). Talin-H is further subdivided in F0, F1, F2 and F3 domains. Talin-R contains 13 contiguous helical bundle domains (R1-R13) followed by an actin binding dimerization domain (DD). The F3 domain contains a key integrin binding site that regulates integrin activation. In our previous studies, we have shown that cytosolic talin …