Biochemistry, Biophysics, and Structural Biology Commons^™

Detecting Linc Complex Mps3 And Nuclear Pore Complex Ndj1 Protein Interactions On Yeast Nuclear Membrane S Through Fluorescence Microscopy, Dean Boecher, Rebecca Adams

Science University Research Symposium (SURS)

Though cancer cells have been shown to have abnormal nuclear morphologies and responses to mechanical forces, the mechanisms of how mechanical stress is translated into cellular action and structural reorganization within the nuclear envelope are largely unexplored. The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex is a transmembrane protein complex that connects the actin cytoskeleton to the lamin nucleoskeleton, enabling mechanical forces to be translated between the cytoplasm and the nucleus. In cells exposed to physical stress, nuclear pore complexes (NPCs) –which control the exchange of biochemical signals and macromolecules in and out of the nucleus through mRNA export –have …

Analyzing Mex67 Interaction With The Ssa4 Transcript For Selective Export, Gretchen E. Stalnaker, Rebecca Adams

Science University Research Symposium (SURS)

In eukaryotic cells, such as the budding yeast Saccharomyces cerevisiae, mRNA export is the essential process in which mature mRNA is transported from its site of production, the nucleus, through the nuclear pore complex (NPC) to the cytoplasm, where it can then be translated into protein. This is accomplished when a transcript interacts with the mRNA export protein Mex67, which shuttles the message across the NPC. When the cell is under conditions of stress, such as heat shock, most mRNA export is prohibited, allowing for selective gene expression that prioritizes cell recovery. Specifically, SSA4, which encodes a protein that …

Testing Ssa4:Ade3 Reporters For Mcs Screening, Karah Edmonds, Rebecca Adams

Science University Research Symposium (SURS)

In eukaryotic cells, after transcription, mRNA is escorted from the nucleus to the cytoplasm to be translated. This process, called mRNA export, is essential for gene expression. However, when the cell exists in stressful conditions, mRNA export becomes regulated, and only select transcripts, including the stress-responsive SSA4 mRNA, can be exported. This project aims to uncover the mechanism of selective SSA4 mRNA export by generating a reporter that enables phenotypically visible expression under stressful conditions. Specifically, the ADE3 ORF was placed under the regulatory sequence of SSA4, which was anticipated to induce a red color for colonies only following stress. …

Identification Of Rickettsia Prowazekii Methionine Aminopeptidase Inhibitors And Development Of Thermal Shift Assays For Burkholderia Pseudomallei Ispf And Sars-Cov-2 3cl Protease, Ishpriya Sharma

Graduate Research Theses & Dissertations

There is a crucial need for new antibacterial agents to combat the increase in antibiotic resistance. Methionine aminopeptidase (MetAp) is an enzyme that removes the amino-terminal methionine residue from newly synthesized proteins, an important step in the maturation of proteins. As such, MetAp is a target for the development of antibacterial and anticancer agents. One such bacterial target is Rickettsia prowazekii (Rp), the causative agent of epidemic typhus. To discover new inhibitors of RpMetAp1, the MMV Malaria Box, which is a collection of 400 compounds with drug-like and probe-like compounds, was screened using a high throughput fluorescence-based RpMetAp1 enzyme inhibition …

Rnai-Mediated Gene Silencing In The Exotic Redbay Ambrosia Beetle, Xyleborus Glabratus, And Insect-Fungal Interactions Within The Laurel Wilt Complex, Morgan Christine Knutsen

Theses and Dissertations--Entomology

Laurel wilt disease (LWD) is a lethal vascular disease impacting lauraceous hosts caused by Harringtonia lauricola, the fungal symbiont of the redbay ambrosia beetle (Xyleborus glabratus Eichoff) (RAB) (Coleoptera: Curculionidae). LWD has caused tree mortality throughout the southeastern United States and is continuing to spread into new regions. Current management methods have not been successful in preventing spread, warranting investigation into innovative techniques including RNA interference (RNAi).

Elongation factor-1 alpha (ef1a) and actin (act) were established as stably expressed reference genes after exposing beetles to different photoperiod, temperature, and dsRNA exposure. After RAB oral …

Regulation Of Erk3 By Kras Signalling And Its Role In The Growth Of Lung Adenocarcinoma (Luad) Cells, Shreya Akunapuram

Browse all Theses and Dissertations

Extracellular signal related kinase 3 (ERK3) is one of the atypical mitogen activated protein kinases (MAPK). It is expressed ubiquitously and plays a role in a variety of cellular processes, including cell growth and differentiation. ERK3’s role in promoting migration and invasion in various cancers has been well established. ERK3 is upregulated in non-small cell lung cancers (NSCLCs) and has been shown to promote NSCLC tumor growth and progression. However, the regulation of ERK3 in lung cancers remains largely unclear. A recent study indicates that ERK3 phosphorylation at S189, an indicator of ERK3 activity, is upregulated by KRAS in NSCLCs. …

The Role Of Myocardin In The Progression Of Non-Small Cell Lung Cancer, Soromidayo Akinsiku

Biotechnology Theses

Lung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the …

การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีวิตามินดีและความเสี่ยงต่อภาวะออทิซึมสเปกตรัมในประชากรไทย, ชาญณรงค์ แซ่ฉั่ว

Chulalongkorn University Theses and Dissertations (Chula ETD)

กลุ่มอาการออทิซึมสเปกตรัม (Autism spectrum disorder; ASD) เป็นปัญหาสุขภาพระดับโลกที่สำคัญ โดยพบว่ามีความชุกของโรคที่เพิ่มสูงขึ้น อย่างไรก็ตามสาเหตุและกลไกในการเกิดภาวะออทิซึมสเปกตรัมยังไม่ทราบแน่ชัดอาจเกี่ยวข้องกับปัจจัยด้านพันธุกรรมและสิ่งแวดล้อม โดยปัจจุบันมีรายงานถึงบทบาทของวิตามินกับภาวะออทิซึมสเปกตรัม วัตถุประสงค์ของการศึกษานี้คือศึกษาการเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีนในวิถีเมทาบอลิกของวิตามินดีและความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและระดับความรุนแรงของโรคในเด็กไทย การศึกษานี้มีจำนวนอาสาสมัคร 276 ราย โดยเป็นกลุ่มเด็กที่มีภาวะออทิซึมสเปกตรัม 169 ราย และกลุ่มควบคุมเป็นเด็กที่ไม่มีโรคทางระบบประสาท 107 ราย ซึ่งได้ทำการตรวจวิเคราะห์ภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, GC และ VDR โดยเทคนิค TaqMan-based real-time Polymerase Chain Reaction (PCR) และตรวจวิเคราะห์ระดับวิตามินดีในกระแสเลือดโดยใช้เทคนิค Chemiluminescence Immunoassay (CLIA) โดยเด็กที่พบภาวะออทิซึมสเปกตรัมจะได้รับการตรวจระดับความรุนแรงของภาวะออทิซึมสเปกตรัมด้วย Childhood Autism Rating Scale, 2nd Edition (CARS2) โดยผลที่ได้จากการศึกษาพบว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน CYP2R1, CYP27B1, VDR และ GC (rs4588) ไม่มีความสัมพันธ์กับการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัม อย่างไรก็ตามการศึกษาชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงที่เพิ่มขึ้นต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมด้วย โดยเฉพาะอย่างยิ่งบุคคลที่มีการขาดระดับวิตามินดีร่วมด้วย นอกจากนี้ผลศึกษาพบว่าไอโซฟอร์มของ GC1s และ GC1s-GC1s ฟีโนไทป์มีความสัมพันธ์อย่างมีนัยสำคัญกับความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมตลอดจนความรุนแรงของอาการออทิซึมสเปกตรัม โดยสรุปการศึกษาวิจัยในครั้งนี้ชี้ให้เห็นว่า การเกิดภาวะพหุสัณฐานทางพันธุกรรมของยีน GC (rs7041 (A>C)) และไอโซฟอร์ม GC1s อาจเป็นตัวบ่งชี้ทางพันธุกรรมที่สามารถช่วยในการประเมินความเสี่ยงต่อการเกิดภาวะออทิซึมสเปกตรัมและความรุนแรงของอาการออทิซึมสเปกตรัมในเด็กไทยได้ในอนาคต อย่างไรก็ตามการศึกษาในอนาคตควรศึกษาในกลุ่มประชากรที่ใหญ่ขึ้นเพื่อยืนยันผลการศึกษาวิจัยครั้งนี้

Development And Biological Evaluation Of Selective Small-Molecule Inhibitors Of The Human Cytochrome P450 1b1, Austin Hachey

Theses and Dissertations--Chemistry

The human cytochrome P450 1B1 (CYP1B1) is an emerging target for small- molecule therapeutics. Several solid tumors overexpress CYP1B1 to the degree that it has been referred to as a universal tumor antigen. Conversely, its expression is low in healthy tissues. CYP1B1 may drive tumorigenesis through promoting the formation of reactive toxins from environmental pollutants or from endogenous hormone substrates. Additionally, the expression of CYP1B1 in tumors is associated with resistance to several common chemotherapies and with poor prognoses in cancer patients. However, inhibiting CYP1B1 with small molecules has been demonstrated in cellular and murine model systems to reverse this …

Characterization Of Parp1-Dependent Poly-Adp-Ribosylation Of Sprtn, Quincee Simonson

Electronic Theses and Dissertations

DNA-protein crosslinks (DPCs) are a type of DNA lesion that form when proteins become covalently linked to DNA. It is estimated that replicating cells experience approximately 6,000 DPCs per day per genome during exponential growth (Ruggiano & Ramadan, 2021). If left unrepaired, DPCs can be lethal to cells. For this reason, cells have evolved multiple pathways to repair or bypass DPCs to survive. One such pathway involves SPRTN, a nuclear metalloprotease that plays a key role in the repair of DPCs through direct proteolysis (Lopez-Mosqueda et al., 2016; Vaz et al., 2016). Once SPRTN degrades the bulky protein component of …

Modulatory Effects Of Deacetylated Sialic Acids (A Sugar Residue) In Nk-Mediated Cytotoxicity And Targeted Therapy By Receptor Tyrosine Kinase Inhibitors, Mathias Tawiah Anim

Electronic Theses and Dissertations

The complex nature of the biology of cancer is still an unraveling science, yielding several biomarkers that have served as molecular targets for detection and treatment of the disease. How sugars, glycans, play a role has remained relatively uninvestigated. Sialic acid (Sia), a sugar residue on the surface of cells, has been identified as a hallmark of cancer and its progression. Sialic acid can be highly functionalized, but we became interested in acetylated Sias. This functional group is modulated by Sialate O- acetylesterase (encoded by the gene SIAE) and Sialate O-acetyltransferase (encoded by CASD1), enzymes that play a crucial role …

Plant Cell Wall Composition And In Vitro Fermentation Characteristics Of Cool-Season Forage Grasses From Two Growing Seasons In Central Kentucky, Sophia Danielle Newhuis

Theses and Dissertations--Animal and Food Sciences

Grass cell walls are rich in cellulose, hemicellulosic arabinoxylan (AX) polysaccharides, and lignin. AX structural differences such as degree and pattern of branching and the ester-linked phenolic acid content could affect plants’ digestibility when used as forage for livestock. However, there is little information about how these structural elements change over the growing season in the vegetative tissue of cool-season perennial grasses. Enhanced information about the cell wall composition and carbohydrate structure of forage material will provide a foundation for expanding our knowledge of how forage cell wall carbohydrate structures are utilized by ruminants. The objectives of this study were …

Isotopic Evidence For Sources Of Dissolved Carbon And The Role Of Organic Matter Respiration In The Fraser River Basin, Canada, Britta M. Voss, Timothy I. Eglinton, Bernhard Peucker-Ehrenbrink, Valier Galy, Susan Q. Lang, Cameron Mcintyre, Robert G.M. Spencer, Ekaterina Bulygina, Zhaohui Aleck Wang, Katherine A. Guay

OES Faculty Publications

Sources of dissolved and particulate carbon to the Fraser River system vary significantly in space and time. Tributaries in the northern interior of the basin consistently deliver higher concentrations of dissolved organic carbon (DOC) to the main stem than other tributaries. Based on samples collected near the Fraser River mouth throughout 2013, the radiocarbon age of DOC exported from the Fraser River does not change significantly across seasons despite a spike in DOC concentration during the freshet, suggesting modulation of heterogeneous upstream chemical and isotopic signals during transit through the river basin. Dissolved inorganic carbon (DIC) concentrations are highest in …

Presumptive Hepatogenous Photosensitization In Beef Cattle Winter Grazing A Cover Crop Containing Brassica Spp. Turnips, Matthew M. Hille, Scott A. Fritz, Breanna C. Brown

School of Veterinary and Biomedical Sciences: Faculty Publications

Over a period of ~2 wk, 5 adult beef cows developed severe necrotizing skin lesions on the face and neck shortly after being moved to a field with a cover crop of Brassica spp. turnips. We describe here the clinical signs, hematology, and serum chemistry results, as well as gross and histopathologic findings, from this outbreak. We made a presumptive diagnosis of Brassica-associated liver disease (BALD) based on the similarities in the history and diagnostic findings observed with previously reported cases of BALD from elsewhere in the world. BALD has not been reported previously in cattle in North America, …

Investigation Into The Potential For Acquired Cross Tolerances Of Amphetamines, Benjamin Weldon

CMC Senior Theses

In the United States, the treatment of ADHD through use of psychostimulants in adolescents is a growing reality that many people know today and many more will know in the coming years. Although the effectiveness of psychostimulants is a known asset, the benefits of these medications may not be a permanent solution, suggesting not only the presence of a tolerance build up, but as many stimulants are prescribed in a joint effort to combat ADHD, a possible cross tolerance between two prescribed medications. There are minimal studies published that have addressed the topic of cross stimulation tolerance buildup between prescription …

Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey

CMC Senior Theses

Trans-arterial radioembolization (TARE) is a protracted modality of radiation therapy where radionuclides labeled with Yttrium-90 (⁹⁰Y) are inserted inside a patient's hepatic artery to treat hepatocellular carcinoma (HCC). While TARE has been shown to be a clinically effective and safe treatment, there is little understanding of the radiobiological relationship between absorbed dose and tissue response, and thus there is no dosimetric standard for treatment planning. The Biologically Effective Dose (BED) formalism, derived from the Linear-Quadratic model of radiobiology, is used to weigh the absorbed dose by the time pattern of delivery. BED is a virtual dose that can …

Arginine-178 Is An Essential Residue For Itpa Function, Nicholas E. Burgis, Caitlin April, Kandise Vanwormer

Chemistry and Biochemistry Faculty Publications

The inosine triphosphate pyrophosphatase (ITPA) enzyme plays a critical cellular role by removing noncanonical nucleoside triphosphates from nucleotide pools. One of the first pathological ITPA mutants identified is R178C (rs746930990), which causes a fatal infantile encephalopathy, termed developmental and epileptic encephalopathy 35 (DEE 35). The accumulation of noncanonical nucleotides such as inosine triphosphate (ITP), is suspected to affect RNA and/or interfere with normal nucleotide function, leading to development of DEE 35. Molecular dynamics simulations have shown that the very rare R178C mutation does not significantly perturb the overall structure of the protein, but results in a high level of structural …

Engineering And Characterizing Proteins: A Dual Study On Canine P53 Protein And Cyan Thermal Protein, Dhruv B. Sitapara

Graduate Theses/Dissertations

This research aims to explore protein development and characterization, focusing on a dual study of canine p53 protein and cyan thermal protein. For the canine p53 protein, the goal is to comprehend its structure to better understand a key component of canine cancers. This multi-step process involved expressing the canine p53 DNA-binding domain in E. coli and purifying it through affinity and ion-exchange chromatography. The purified protein was studied to test the binding of canine p53 protein to human DNA sequences using Surface Plasmon Resonance (SPR) experiments and an Electrophoretic Mobility Shift Assay (EMSA), visualized with a SYBR-safe stain. The …

Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski

Graduate Theses/Dissertations

DNA damage, such as single base lesions and mismatches, is highly prevalent within cells. If these DNA damage events are not repaired, they could lead to mutations and thus disease and cancer. Intricate repair mechanisms are in place to fix these damage events, one such being Base Excision Repair (BER) and associated enzyme: Thymine DNA Glycosylase (TDG). The first step of this repair process, recognition of the lesion by TDG, is not well understood. The following thesis presents results to better understand the fundamental biophysical question of how a DNA lesion within a mismatch context is recognized in a million …

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …

Tagging Atg5 With An Epitope Tag To Measure The Amount Of Atg12-5 Conjugation In Atg10 Mutants, Sophie Campbell

Senior Honors Theses and Projects

Autophagy is a necessary recycling process that occurs in cells, but the functions of the proteins that carry this out are not completely understood. The protein ATG10 has a distinct role in forming autophagosomes, large double membrane vesicles necessary for this process. ATG10 forms a covalent bond between the proteins ATG12 and ATG5 but its final effect on autophagosome formation is still unclear. We are using DNA manipulation techniques to add a myc epitope tag to yeast ATG5 which will allow us to measure the effect of atg10 mutants on ATG12-5 conjugation via Western Blot. These results will help us …

Functional Residues Of Cjpata, Robert Lamont

Theses and Dissertations (Comprehensive)

Antibiotic resistance in pathogenic bacteria continues to challenge clinicians and threaten the lives of infected individuals. For this reason, new classes of antibiotics or new targets for antibiotic therapy are needed to circumvent this global health crisis. In Gram-negative bacteria, the enzymes peptidoglycan O-acetyltransferase A and B (PatA and PatB), are responsible for adding acetyl groups to the C-6 hydroxyl group of N-acetyl muramic acid (MurNAc) in peptidoglycan (PG). These acetyl groups are responsible for inhibiting the activity of lysozyme from host organisms that hydrolyze the β1-4 glycosidic linkage between MurNAc and N-acetylglucosamine (GlcNAc). The acetyl groups …

Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia

Theses and Dissertations (Comprehensive)

Fluorine is the most electronegative chemical element and can drastically change molecular properties, such as drug pharmacokinetics and agrochemical half-life. Although a great deal of progress is occurring in synthetic methods to access various organofluorines, these methods struggle with harsh conditions and limited substrate scope. Biocatalytic approaches offer the potential to access organofluorines that are difficult or impossible with the current methodology. Phosphoenolpyruvate (PEP) is a central metabolite and biosynthetic precursor for diverse molecules. Phosphoenol pyruvate mutase (Ppm) catalyses the interconversion of Phosphonopyruvate (PnPy) to Phosphoenolpyruvate (PEP). This research successfully expressed and …

The Effect Of Alkalinity On Lampricide Effectiveness And Gill Physiology In Invasive Sea Lamprey (Petromyzon Marinus), Alexandre J. Walsh

Theses and Dissertations (Comprehensive)

The pesticides, 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide are used to control populations of invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes of North America. Added to streams infested with larval sea lamprey, the effectiveness of these pesticides, commonly called lampricides, are strongly influenced by water pH, with greater toxicity for both TFM and niclosamide in lower pH than higher pH water. However, the TFM and niclosamide sensitivity of sea lamprey are also greater in poorly buffered, low alkalinity water than in high alkalinity water but it is unclear why. One goal of my thesis was to propose …

Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz, Brian Lowrance

Theses and Dissertations (Comprehensive)

Bacteria inhabit many of the harshest environments on Earth; persisting and thriving in conditions thought to be unsuitable for life. One common strategy to withstand these environments is the formation of a biofilm. Biofilm composition varies greatly, depending on the underlying community that produces it. Cellulose, a polymer consistently prevalent in biofilms, has been identified as a virulence factor in many pathogens and is suspected to be involved in pathogenesis by Clostridioides difficile. C. difficile is the #1 cause of hospital acquired diarrhea, which can range from mild to life-threatening infections. Biofilm formation is hypothesized to be involved in …

Apobec3 Regulation By Thyroid Hormone, Michelle Santiago

All Graduate Theses, Dissertations, and Other Capstone Projects

Thyroid hormone (TH) is crucial for many biological processes, including the development of the auditory system. Appropriate thyroid hormone signaling is important for the development of the cochlea, leading to the successful onset of hearing. More specifically, TH influences the timing of remodeling of the greater epithelial ridge (GER), a transient cochlear structure that secretes proteins that contribute to the formation of the tectorial membrane. Developmental hypothyroidism results in delayed GER regression, whereas excess TH results in premature remodeling. Both conditions result in deafness. However, it is unknown how TH mediates GER remodeling. Expression profiling identified APOBEC3 (A3) as a …

Cisplatin - Loaded Calcium Citrate Nanoparticlesfor Inhibition Of Lung Cancer Cell Growthand Quantum Mechanical Study Of Cisplatin And Citrate, Lipika Oopkaew

Chulalongkorn University Theses and Dissertations (Chula ETD)

The International Organization for Research on Cancer (International Agency for Research on Cancer (IARC) issued a statement saying lung cancer is a cancer with high incidence rates of new cases and deaths. Although there are current therapeutic approaches such as surgery, radiation therapy, and chemotherapy. However, these treatments exhibit ineffectiveness; the main limitation is severe side effects to normal cells or non-target organs. To address this challenge, the development of targeted therapy by nanoparticle-based drug delivery system is applied to increase drug stability and control the specificity to cancer cells with target-specific proteins that play an important role in intracellular …

C-Glycopyranosyl Aldehydes: Emerging Chiral Synthons In Organic Synthesis, Sandeep Kumar, Vinod Khatri, Priyanka Mangla, Rajni Johar Chhatwal, Virinder S. Parmar, Ashok K. Prasad

Publications and Research

Herein, we have summarized the vast array of synthetic processes that have been developed for the synthesis of C-glycopyranosyl aldehydes and diverse C-glycoconjugates derived from them by covering the literature reported from 1979 to 2023. Notwithstanding its challenging chemistry, C-glycosides are considered stable pharmacophores and are used as important bioactive molecules. The discussed synthetic methodologies to access C-glycopyranosyl aldehydes take advantage of seven key intermediates, viz. allene, thiazole, dithiane, cyanide, alkene, and nitromethane. Furthermore, the integration of complex C-glycoconjugates derived from varied C-glycopyranosyl aldehydes involves nucleophilic addition/substitution, reduction, condensation, oxidation, cyclo condensation, coupling, and …

Characterizing The Dynamic Localization Of Cmi In Early Drosophila Development, Asra Habibullah

Master's Theses

The COMPASS-like family of lysine methyltransferases, MLR/MLX complexes, are epigenetic regulators that are essential for normal development through the methylation of the fourth lysine residue on histone 3 (H3K4), a universal epigenetic mark associated with active transcription. This family of complexes is highly conserved from yeast to mammals and the genes encoding the human MLR complexes have been associated with various developmental diseases and cancers (Dingwall and Fagan, 2019). In D. melanogaster, the enzymatic methyltransferase core of this complex is composed of two proteins: Cara Mitad (Cmi, also known as Lpt) and Trithorax-related (Trr). Although these proteins have been shown …

Dynamic Control Of The Cardiac Calcium Pump, Sean Robert Cleary

Dissertations

The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ into the endoplasmic reticulum of cells to establish a reservoir for Ca2+ signaling. In the heart, the activity of this transporter is tightly controlled via direct interactions with two competing regulatory micropeptides: phospholamban (PLB) and dwarf open reading frame (DWORF). PLB inhibits SERCA, while DWORF activates SERCA. These competing interactions determine cardiac performance by modulating the Ca2+ signals that drive the contraction/relaxation cycle. Previous studies indicated these SERCA-micropeptide interactions are Ca2+-sensitive; SERCA binds PLB more avidly at low cytoplasmic [Ca2+] but binds DWORF better when [Ca2+] is high. Here, FRET-microscopy demonstrated that this …