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Full-Text Articles in Life Sciences

Evolution And Flower Shape From The Hawaiian Lobelioids To The Campanulaceae, Jingjing Tong Jan 2021

Evolution And Flower Shape From The Hawaiian Lobelioids To The Campanulaceae, Jingjing Tong

Theses and Dissertations

Campanulaceae, with roughly 2,400 species, is divided into five subfamilies, in part, by differences in their floral orientation and symmetry, with broad transitions between radial and bilateral floral symmetry. The Hawaiian lobelioids in the Campanulaceae is the largest endemic clade of Hawaiian angiosperms, and they have long been viewed as one of the most spectacular examples of an adaptive radiation in plants. In the first part of our study, we focus on Clermontia, which is one of the largest genera of Hawaiian lobelioids, employing variable low-copy nuclear gene sequences to determine their phylogenetic relationships. We use intron regions from four …


Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen Jan 2021

Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen

Theses and Dissertations

Parkinson’s disease (PD) is the most common movement disorder and is characterized by neuronal loss and the presence of Lewy bodies in dopaminergic neurons of the substantia nigra pars compacta. PD is a chronic, progressive, and irreversible neurodegenerative disorder associated with the selective loss of dopaminergic neurons. Initially described in an Ayurvedic medical treatise and Galen’s writings, and later by James Parkinson in 1817, the most common symptoms of PD are resting tremors, abnormal posture and gait, and muscle rigidity. Approximately 1 million people are living with PD in the United States and worldwide estimates are between 7 and 10 …


Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi Jan 2021

Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi

Theses and Dissertations

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder predominately affecting the aging population. It is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) affecting over 1 million individuals in the US alone. Recent studies have tried to understand the exact nature in which healthy neurons transition to a degenerative state in PD. There are a multitude of combinatory factors that can lead to the development of PD including environmental factors, genetic factors, and aging. The majority of PD cases are sporadic in nature, however familial cases account for 5-10% of total PD cases world-wide. The hallmark …


The Ion Channel Trpm7 Regulates Zinc Depletion-Induced Mdmx Degradation, Herui Wang Jan 2021

The Ion Channel Trpm7 Regulates Zinc Depletion-Induced Mdmx Degradation, Herui Wang

Theses and Dissertations

Zinc deficiency has been linked to human diseases including cancer. p53, a zinc-containing transcription factor, is the most frequently mutated tumor suppressor protein in human cancer. MDM2 and MDMX are zinc- containing proteins and crucial negative regulators of p53, which have been found to be amplified or overexpressed in various cancers. To investigate the effects of zinc depletion on the p53 signaling pathway, we have used ion chelators TPEN and bispicen as well as zinc-deficient medium to treat cells. We report here that zinc depletion results in MDMX degradation in a ubiquitination-independent and 20S proteasome-dependent manner. Restoration of zinc recovers …


Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain Jan 2021

Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain

Theses and Dissertations

Gene expression is regulated at multiple levels, including transcription, RNA editing, pre-mRNA splicing, mRNA export, translation, and posttranslational modifications. Alternative splicing is a process by which exons can be included or excluded, giving rise to multiple mRNA isoforms from the same transcript. Alternative splicing is an important mechanism in developmental, tissue- and cell-specific control of gene expression, and it is key for expanding proteomic diversity and complexity from a limited number of genes. Moreover, more than 95% of multiexon genes undergo alternative splicing in humans, and about half of all disease-causing point mutations in humans affect pre-mRNA splicing, including neurological …


Characterizing Ferroptosis Pathways In In Vitro Motor Neuron Models, Alejandra Martinez Jan 2021

Characterizing Ferroptosis Pathways In In Vitro Motor Neuron Models, Alejandra Martinez

Theses and Dissertations

Ferroptosis is a non-apoptotic regulated form of cell death driven by the toxic accumulation of lipid peroxides and the presence of iron. The mechanism by which ferroptosis operates requires further investigation; here I will discuss the findings regarding the role of ferroptosis in different cellular models as well as the genes that may be involved with either promoting or hindering the ferroptotic pathway. NSC-34 is a hybrid cell line of neuroblastoma and primary spinal cord cells that can be differentiated into a motor neuron-like state allowing the characterization of ferroptosis in two distinct cellular conditions. Additionally, iNIL cells are a …


Boost The Dsicovery Of Mrp7/Abcc10 Substrates And Inhibitors: Establishment Of New In Vitro And In Silico Models, Jingquan Wang Jan 2021

Boost The Dsicovery Of Mrp7/Abcc10 Substrates And Inhibitors: Establishment Of New In Vitro And In Silico Models, Jingquan Wang

Theses and Dissertations

ATP-binding cassette (ABC) transporters are responsible for the efflux of structurally distinct endo- and xenobiotics energized by ATP hydrolysis. MRP7/ABCC10 belongs to the 10th member of subfamily C and responsible for mediating MDR against a series of chemotherapeutic drugs such as taxanes, epothilones, Vinca alkaloids, anthracyclines and epipodophyllotoxins. Establishment of new in silico and in vitro models for MRP7 substrates/inhibitors prediction Considering the limited knowledge of MRP7, we established a homology model based on bovine MRP1 cryo-EM models. The final model was used for protein global motion analysis and docking analysis. Before docking, potential drug binding pockets were identified and …


Anticancer Effect Of Indanone-Based Thiazolyl Hydrazone Derivative On P53 Mutant Colon Cancer Cell Lines: In Vitro And In Vivo Study, Silpa Narayanan Jan 2021

Anticancer Effect Of Indanone-Based Thiazolyl Hydrazone Derivative On P53 Mutant Colon Cancer Cell Lines: In Vitro And In Vivo Study, Silpa Narayanan

Theses and Dissertations

Colorectal cancer is the third leading cause of cancer related deaths in the United States. Currently, irinotecan, a topoisomerase I inhibitor, is an important anticancer drug approved for patients with advanced or recurrent colorectal cancer. Considering the low response rate and the events of high toxicity caused by irinotecan, we evaluated a series of thirteen thiazolyl hydrazone derivatives of 1-indanone for their potential antineoplastic activity and four compounds showed promising anticancer activity against most of the tested colon cancer cell lines with IC50 values ranging from 0.41 ± 0.19 to 6.85 ± 1.44 μM. It is noteworthy that the compound, …


Design, Synthesis And Pharmacological Evaluation Of Quinazolinamine Derivatives As Bcrp And P-Gp Inhibitors With Improved Metabolic Stability, Chao-Yun Cai Jan 2021

Design, Synthesis And Pharmacological Evaluation Of Quinazolinamine Derivatives As Bcrp And P-Gp Inhibitors With Improved Metabolic Stability, Chao-Yun Cai

Theses and Dissertations

A series of twenty-two quinazolinamine derivatives showing potent inhibitory activities on BCRP and P-gp was synthesized. The reversal study showed that when combined with the potent dual BCRP and P-gp inhibitors 7-8, 29-31, and 34, the IC50 value of mitoxantrone was decreased from 6.50 µM to the range of 0.24 - 0.35 µM for BCRP, and IC50 value of colchicine was decreased from 7.34 μM to the range of 0.12 - 0.29 µM for P-gp. Cyclopropyl quinazolinamine 29 (VKCY-1), which was a dual BCRP and P-gp inhibitor, and azide quinazolinamine 40 (VKCY-2), which was a BCRP inhibitor, were selected for …


Mechanism Of Dna Damage Checkpoint (Ddc)- Mediated Repression Of Histone Mrnas And Role Of Acetyl-Coa In Histone Transcription, Madhura Bhagwat Jan 2021

Mechanism Of Dna Damage Checkpoint (Ddc)- Mediated Repression Of Histone Mrnas And Role Of Acetyl-Coa In Histone Transcription, Madhura Bhagwat

Theses and Dissertations

My dissertation contains two projects. The first project is focused on the mechanism of DNA damage checkpoint (DDC)- mediated repression of histone mRNAs. The second project deals with the role of acetyl-CoA in histone transcription. Proliferating cells coordinate histone and DNA synthesis to maintain correct stoichiometric amounts for chromatin assembly. Histone mRNA levels must be repressed when DNA replication is inhibited to prevent toxicity and genome instability due to free non-chromatinized histone proteins. In the first project we show that, unlike in mammalian cells, DNA replication stress does not trigger decay of histone mRNAs in the yeast Saccharomyces cerevisiae. However, …


Effect Of Inhibition Of Glycogen Catabolism In Hepatocellular Carcinoma Cells, Shrikant Barot Jan 2021

Effect Of Inhibition Of Glycogen Catabolism In Hepatocellular Carcinoma Cells, Shrikant Barot

Theses and Dissertations

Metabolic reprogramming is one of the important features of cancers, and there has been growing interest in targeting metabolic proteins to treat cancer. Glycogen is a polymer of glucose and serves as its storage unit in cells. Glycogen can provide energy to cells during the situations of high energy demand. A number of tumors are known to contain high levels of glycogen than their normal tissue counterparts. The liver plays an essential role in maintaining glucose homeostasis in the body via storing it into glycogen. The significance of glycogen metabolism in patients suffering from hepatocellular carcinoma (HCC) has not been …