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Full-Text Articles in Biomedical Engineering and Bioengineering
Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka
Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka
Legacy Theses & Dissertations (2009 - 2024)
Ricin is a highly lethal protein toxin derived from the seeds of the castor plant, Ricinus communis. It is a Type II ribosome inactivating protein (RIP), meaning it is a heterodimer with one subunit, ricin toxin B (RTB), that mediates cell surface attachment and intracellular trafficking and a second subunit, ricin toxin A (RTA), that irreversibly shuts down protein synthesis in the cytosol. During trafficking, RTA and RTB necessarily separate in the endoplasmic reticulum, wherein RTA unfolds and translocates into the cytosol where it refolds into an enzymatically active conformation. RTA is remarkably fast acting and efficient, with few molecules …
Optical Metabolic Imaging As A Predictor Of Patient Tumor Response To Therapy And Apoptosis, Andrew Larey
Optical Metabolic Imaging As A Predictor Of Patient Tumor Response To Therapy And Apoptosis, Andrew Larey
Biomedical Engineering Undergraduate Honors Theses
Despite a plethora of medical advancements, malignant tumors remain difficult to treat due to complex cancer biology and interpatient heterogeneity. Phenotypically similar tumors may respond differently to a given treatment. In clinical oncology, it is paramount to quantify tumor response to therapy for predicting treatment outcome, monitoring tumor changes, identifying effective therapies, and avoiding unnecessary cost and toxicity to the patient. Current standards of monitoring tumor response to therapy include CT, MRI, PET, and histopathology; these methods either take a merely anatomical approach or are invasive and time consuming, necessitating a functional biomarker approach. MPM represents a metabolic-level method of …
Transport Pathway Across Hcaecs Uncer Convective Condtitions And The Role Of Apoptosis In Ldl Transport Through Hcaecs, Janpen Phupeerasupong
Transport Pathway Across Hcaecs Uncer Convective Condtitions And The Role Of Apoptosis In Ldl Transport Through Hcaecs, Janpen Phupeerasupong
Dissertations and Theses
No abstract provided.
Voltage Effects On Cells Cultured On Metallic Biomedical Implants, Seyed Morteza Haerihosseini
Voltage Effects On Cells Cultured On Metallic Biomedical Implants, Seyed Morteza Haerihosseini
Biomedical and Chemical Engineering - Dissertations
Electrochemical voltage shifts in metallic biomedical implants occur in-vivo due to a number of processes including mechanically assisted corrosion. Surface potential of biomedical implants and excursions from resting open circuit potential (OCP), which is the voltage they attain while in contact with an electrolyte, can significantly change the interfacial properties of the metallic surfaces and alter the behavior of the surrounding cells, compromising the biocompatibility of metallic implants. Voltages can also be controlled to modulate cell function and fate. To date, the details of the physico-chemical phenomena and the role of different biomaterial parameters involved in the interaction between cells …
Manipulating Cellular Growth Responses To Patterning, Apoptotic, And Environmental Cues, James N. Mcnamara
Manipulating Cellular Growth Responses To Patterning, Apoptotic, And Environmental Cues, James N. Mcnamara
Doctoral Dissertations
In this work, various methods of controlling cell growth are examined. Cell-cell interaction, apoptotic cues, three dimensional scaffolds, and non-adherent environments are evaluated for their ability to affect the differentiation, morphology, and growth rate of different cell types. Previous work has shown that cell growth and cell morphology can be influenced by patterns of polymers coated on surfaces in two dimensions, designated here as the x and y dimensions of a standard Cartesian coordinate system. Tissue engineering and regenerative medicine studies have shown limited success in modifying growth in the third, z dimension. This work considers not only the x, …
Charaterization Of Chlorpyrifos Toxicity On The Pancreatic Beta Cell Line Rinm5f, Zhongyu Yan
Charaterization Of Chlorpyrifos Toxicity On The Pancreatic Beta Cell Line Rinm5f, Zhongyu Yan
Browse all Theses and Dissertations
Chlorpyrifos (CPF) is a well-known organophosphate (OP) insecticide that inhibits acetylcholinesterase (AChE). Organophosphates have been shown to induce hyperglycemia in both humans and animals that cannot be explained by AChE inhibition alone. Pancreatic β-cells are responsible for secreting insulin and playing a fundamental role in glucose homeostasis. The aim of this research was to investigate CPF toxicity on the insulin secreting β-cell line RINm5f (RIN). In the first part of this dissertation, we determined that cytotoxic concentrations of CPF between 50 µM and 200 µM induced a dose-dependent increase in RIN cell apoptotic and necrotic death (p<0.05). Lower doses, i.e., 5-25 µM did not induce apoptosis or necrosis. In further mechanistic studies, inhibitors of c-Jun N-terminal kinase (JNK) and P38 pathways, i.e., SP600125 and SB202190, successfully attenuated CPF-induced apoptosis (p<0.05), suggesting cell death is mediated by JNK and/or p38. In addition, N-Acetyl-L-cysteine (NAC), an antioxidant, inhibited apoptosis suggesting that oxidative stress is also involved in RIN cell death. In the second part of this dissertation, low dose CPF's effects on insulin synthesis and secretion was studied. Our results showed that RIN cells treated with CPF for 4 hr exhibited a dose-dependent decrease in insulin secretion in response to stimulation by 50 mM potassium (p<0.05). Insulin secretion stimulated by 25 mM glucose also showed significant decreases upon incubation with various doses of CPF (p<0.05). Insulin synthesis involves proteolytic cleavage of proinsulin at two specific sites. The enzymes responsible for promoting proinsulin cleavage, i.e, prohormone convertase (PC) 1/3 and 2 (PC2), contain a serine hydrolase catalytic triad, His-Asp-Ser, similar to AChE. CPF modification of PC enzymes similar to AChE, could potentially interrupt the conversion of proinsulin to insulin and disrupt insulin secretion. PC2 enzyme activity was significantly inhibited by CPF at concentrations as low as 10 µM (p<0.01). RIN cells, for the first time, were found to secrete proinsulin was through a constitutive instead of a regulated pathway. In summary, our results show that CPF not only exerts a direct cytotoxic effect at concentrations above 50 µM, but also significantly impairs insulin secretion at lower doses. Low dose CPF could potentially affect endocrine function in vivo by inhibiting the proinsulin processing enzyme PC2.
A Computational Model Of Apoptotic Osteocyte Correlation To Cortical Bone Remodeling Parameters, Michael Stephen Alexander
A Computational Model Of Apoptotic Osteocyte Correlation To Cortical Bone Remodeling Parameters, Michael Stephen Alexander
Master's Theses
The onset of osteoporosis caused by aging, disease states, and post-menopausal conditions significantly impacts patient quality of life, required healthcare funding, personal autonomy losses from increased fracture risk and the subsequent corrective surgery. Research has indicated that osteocyte apoptosis may be a key parameter in bone remodeling, raising the possibility of remodeling rate modulation for the mitigation of bone mass resorption. By developing therapies that target osteocyte apoptosis, it may be possible to prevent undesired bone remodeling activity while maintaining a healthy balance between damage formation in the form of microcracks induced by the strain environment and the removal of …
Ion Transport Mechanisms During Hyposmotic Regulatory And Isosmotic Apoptotic Volume Decreases In A Human Lens Epithelial Cells Line, Ameet Ajit Chimote
Ion Transport Mechanisms During Hyposmotic Regulatory And Isosmotic Apoptotic Volume Decreases In A Human Lens Epithelial Cells Line, Ameet Ajit Chimote
Browse all Theses and Dissertations
Living cells maintain constant volume in response to physiological stresses by altering trans-membrane ion, solute and water flow. In the present study, early and late membrane transport changes in human lens epithelial (HLE-B3) cells under hyposmotic and apoptotic stress were compared. Cell potassium (Ki), rubidium (Rbi)-uptake and water content were measured by atomic absorption spectrophotometry and gravimetry, respectively. Intracellular chloride concentration [Cl]i was determined with the fluorescence dye N- (ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE), during regulatory volume decrease (RVD) after hyposmotic stress and apoptotic volume decrease (AVD) induced by staurosporine (STP), a protein-kinase inhibitor. Cell water increased in hyposmotic balanced salt solution …
Hmg-Coa Reductase Inhibitors Act Synergistically With Ucn-01 Through Ras Inhibition, Payal Khanna
Hmg-Coa Reductase Inhibitors Act Synergistically With Ucn-01 Through Ras Inhibition, Payal Khanna
Theses and Dissertations
The primary objective of this study is to elucidate the mechanism by which the reagent UCN-01 induces apoptosis when administered to leukemia cells along with HmG-CoA reductase inhibitors, mainly the statins. In this study, we demonstrated that exposure of leukemia cell lines to lovastatin (20 uM, 18 hours) and UCN-01 (100 nM, 18 hours) resulted in mitochondria dysfunction, procaspase 3 and 9 cleavage, and PAW degradation along with marked cytochrome C release and apoptosis. Although similar molecular mechanisms have not yet been confirmed in other cancers, our hypothesis holds that enhanced apoptotic effects of UCN-01 are due in part to …