Digital Commons Network^™

The Effects Of Exogenously Applied Antioxidants On Plant Growth And Resilience, Aline Rodrigues De Queiroz, Connor Hines, Jeremy Brown, Seema Sahay, Jithesh Vijayan, Julie M. Stone, Nate Bickford, Melissa Wuellner, Katarzyna Glowacka, Nicole R. Buan, Rebecca Roston

Department of Biochemistry: Faculty Publications

Plant growth and resilience require balancing an inherently oxidative metabolism with powerful antioxidant systems that help maintain homeostasis. When the environment changes, reactive oxygen species are potent indicators of that change, allowing adaptation through re-balancing metabolism and antioxidant systems. A large body of evidence supports the use of exogenously applied antioxidants to improve both plant growth and their resilience to stress. Notably, some phenotypic effects are similar upon the application of chemically diverse antioxidants, while others are distinct. In this review, we analyze research from antioxidant treatment experiments and highlight the similarities in their practical applications and their effects on …

Botanical Assessment Of Remnant Floodplain Habitats Along Plaster Creek, Kent County, Michigan: Assessing Changes Since The 1890s, Haley R. Weesies, Garrett Crow, David Warners

Faculty and Professional Research

Plaster Creek, a tributary of the Grand River, drains a 58-square mile watershed in Kent County, Michigan. Its headwaters originate in the agriculturally dominated southwestern portion of the county, and then it meanders through residential, commercial, and urban areas of Kentwood and Grand Rapids before it empties into the Grand River about one mile south of downtown Grand Rapids. Much of Plaster Creek’s original floodplain, like the rest of its watershed, has been drastically altered and degraded over time due to the development of residential neighborhoods, commercial properties, agriculture, and industrial zones. Floodplains house unique assemblages of Michigan’s native biodiversity …

Effect Of Molecular Crowders On The Activation Of Cholera Toxin By Protein Disulfide Isomerase, Niral Shah

Honors Undergraduate Theses

Cholera toxin (CT) is a classic A-B type protein toxin that has an A subunit (A1 + A2) and a pentameric B subunit. The catalytic A1 domain is linked to the A2 domain via a disulfide linkage. CTA1 must be dissociated from the rest of the toxin to cause a cytopathic effect. Protein disulfide isomerase (PDI) can reduce the CTA1/CTA2 disulfide bond, but disassembly of the reduced toxin requires the partial unfolding of PDI that occurs when it binds to CTA1. This unfolding event allows PDI to push CTA1 away from the rest of the toxin.

My research question is …

Observing Ceramide Pathway With Ferroptosis Via Mia Paca-2 Cell Treatment With Rsl3, Tazrin Rahman

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Composed of sphingosine and a fatty acid, ceramides are lipid molecules that serve as key metabolic signaling molecules of a sphingolipid pathway. While it acts as a precursor of complex sphingolipids, inducing ceramide generation can cause cell stress leading to subsequent cell death via apoptosis, necrosis, and even mitophagy. With regards to cell death specifically, a novel form of regulated cell death, ferroptosis, has recently been recognized of necrotic nature. Its unique morphological features and distinct properties have been observed over the last several decades; however, the molecular features were not identifiable as pure evidence of cell death, until recently …

Following Faculty Engaging In Collaborative Action Research To Approach Curricular Change In Undergraduate Biochemistry, Christopher Nix

Electronic Theses and Dissertations, 2020-2023

This study engaged in a curricular redesign of an undergraduate biochemistry course undertaken by a collaborative action research group. The initial portion of this study investigated student conceptual understanding of foundational concepts via a rigorously tested concept inventory. the impact of the redesign on the student foundational conceptual understanding was determined by comparison with a baseline data set. Findings suggest that students enter and exit the biochemistry course with little understanding of key foundational concepts. Examination of student performance after the incorporation of creative exercises showed a significant impact of the curricular changes on two of the concepts of interest. …

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 …

Tissue And Sex-Dependent Regulation Of Innate Immunity And Rna Editing In Mice, Kelsey R. Kendrick

Graduate Theses/Dissertations

Inflammation occurs as a result of insult or infection within the body. Individual cells respond to inflammation by upregulating genes that help mediate the immune response, such as ADAR1. ADAR1 helps regulate the immune response but also catalyzes a process called RNA editing. RNA editing alters the sequence of select mRNAs to alter the encoded proteins. The result is altered function of the encoded protein, which is often beneficial for the cell. Our goal was to determine how inflammation affects the function of ADAR1. Since we know that the effects of inflammation vary between different organs and sexes, we examined …

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 …

Molecular Investigation Of Minor Genomic Populations And Biological Exposures In Human Health, Brandon Ned Johnson

Dissertations and Theses

The study of genetics has contributed to countless discoveries related to human health and disease. However, the complexities of human biology reside not only in the genome but also in the contributions from environmental exposures, as measured via the classical twin design. To understand the influence of biological exposures, I implemented study designs to explore both the health associations and propagation of foreign genetic material. Microchimerism has been studied for association with several clinical conditions, and I further investigated if male microchimerism could elucidate the etiology of Mayer-Rokitansky-Küster-Hauser syndrome. Prevalence of male microchimerism in women with no history of pregnancy …

Dcaf14 Regulates Cdt2 To Promote Set8-Dependent Replication Fork Protection, Neysha Tirado-Class, Caitlin Hathaway, Anthony Nelligan, Huzefa Dungrawala

Molecular Biosciences Faculty Publications

DDB1- and CUL4-associated factors (DCAFs) CDT2 and DCAF14 are substrate receptors for Cullin4–RING E3 ubiquitin ligase (CRL4) complexes. CDT2 is responsible for PCNA-coupled proteolysis of substrates CDT1, p21, and SET8 during S-phase of cell cycle. DCAF14 functions at stalled replication forks to promote genome stability, but the mechanism is unknown. We find that DCAF14 mediates replication fork protection by regulating CRL4CDT2 activity. Absence of DCAF14 causes increased proteasomal degradation of CDT2 substrates. When forks are challenged with replication stress, increased CDT2 function causes stalled fork collapse and impairs fork recovery in DCAF14-deficient conditions. We further show that stalled fork protection …

Otud5 Limits Replication Fork Instability By Organizing Chromatin Remodelers, Angelo De Vivo, Hongseon Song, Yujin Lee, Neysha Tirado-Class, Anthony Sanchez, Sandy D. Westerheide, Huzefa Dungrawala, Younghoon Kee

Molecular Biosciences Faculty Publications

Proper regulation of replication fork progression is important for genomic maintenance. Subverting the transcription-induced conflicts is crucial in preserving the integrity of replication forks. Various chromatin remodelers, such as histone chaperone and histone deacetylases are known to modulate replication stress, but how these factors are organized or collaborate are not well understood. Here we found a new role of the OTUD5 deubiquitinase in limiting replication stress. We found that OTUD5 is recruited to replication forks, and its depletion causes replication fork stress. Through its C-terminal disordered tail, OTUD5 assembles a complex containing FACT, HDAC1 and HDAC2 at replication forks. A …

The Identification Of Two M20b Family Peptidases Required For Full Virulence In Staphylococcus Aureus, Nathanial James Torres, Devon Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey Neil Shaw

Molecular Biosciences Faculty Publications

We have previously demonstrated that deletion of an intracellular leucine aminopeptidase results in attenuated virulence of S. aureus. Herein we explore the role of 10 other aminopeptidases in S. aureus pathogenesis. Using a human blood survival assay we identified mutations in two enzymes from the M20B family (PepT1 and PepT2) as having markedly decreased survival compared to the parent. We further reveal that pepT1, pepT2 and pepT1/2 mutant strains are impaired in their ability to resist phagocytosis by, and engender survival within, human macrophages. Using a co-infection model of murine sepsis, we demonstrate impairment of dissemination and survival …

S-Acylation Is A Key Regulator Of Orai1/Stim1-Mediated Store-Operated Calcium Entry In T Cells, Savannah J. West Diaz

Dissertations and Theses (Open Access)

Orai1 and STIM1 proteins are the essential components of the Ca²⁺ release activated Ca²⁺ (CRAC) channel which is required for store-operated Ca²⁺ entry (SOCE) in T cells and subsequent signaling events leading to T cell activation, proliferation, and differentiation. Plasma membrane (PM)-localized Orai1 is the pore-forming subunit of the CRAC channel, and STIM1 is the Ca²⁺ sensor localized to the endoplasmic reticulum (ER) membrane in quiescent T cells. T cell receptor (TCR) stimulation leads to depletion of ER Ca²⁺ stores resulting in Ca²⁺ no longer being bound to STIM1. This activates STIM1 by triggering …

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 …

Establishing A Biochemical System For The Purification And Atpase Activity Of Gst-Dbp5, Sarah Utley, Rachel E. Rigsby Phd, Rebecca L. Adams Phd

Science University Research Symposium (SURS)

The export of mRNA out of the nucleus is a crucial step for eukaryotic gene expression. The export of mRNA transcripts is aided by Mex67, which allows export through the nuclear pore complex doorways in the nuclear envelope. Once out of the nucleus, a protein known as Dbp5, bound to ATP, Gle1, and Nup42 aids in the directionality of mRNA export by helping remove Mex67 from the mRNA strand. Following interaction with RNA, Dbp5 then hydrolyzes ATP so that it unbinds the mRNA, allowing for enzyme recycling. The goal of this study is to explore the ATPase activity of Saccharomyces …

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. …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

College of Graduate Studies: Theses & Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Structure–Activity Relationship Studies On 6-Chloro-1-Phenylbenzazepines Leads To The Identification Of A New Dopamine D1 Receptor Antagonist, Rajan Giri, Hari K. Namballa, Vishwashiv Emogaje, Wayne W. Harding

Publications and Research

The 1-phenylbenzazepine template has yielded a number of D1R-like ligands, which, though useful as pharmacological tools, have significant drawbacks in terms of selectivity versus D5R as well as pharmacokinetic behavior. A number of 1-phenylbenzazepines contain a 6-chloro functional group, but extensive SAR studies around the 6-chloro-1-phenylbenzazepine framework have not been reported in the literature. To further understand the tolerance of the 6-chloro-1-phenylbenzazepine template for various substituent groups towards affinity and selectivity at D1R, we synthesized two series of analogs with structural variations at the C-7, C-8, N-3, C-3′ and C-4′ positions. The series 2 analogs differed from …

Reactive Oxygen Species (Ros)-Responsive Size-Reducible Nanoassemblies For Deeper Atherosclerotic Plaque Penetration And Enhanced Macrophage-Targeted Drug Delivery, Jianhua He, Wenli Zhang, Xiaoju Zhou, Fengfei Xu, Jiahui Zou, Qiqi Zhang, Yi Zhao, Hongliang He, Hu Yang, Jianping Liu

Chemical and Biochemical Engineering Faculty Research & Creative Works

Nanoparticle-Based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nano assemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP3ST) and hyaluronic acid-ferrocene (HA-Fc) conjugates. the HA-Fc/NP3ST nano assemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP3ST, allowing for further plaque penetration, macrophage-targeted cholesterol efflux and …

Effects Of Depth, Distance To Shore, And Water Velocity On Organismal And Extra-Organismal Environmental Dna Concentrations In A Large River, Dylan Keel

Cal Poly Humboldt theses and projects

Environmental DNA (eDNA) is a sensitive tool for detection of aquatic species and concentrations of eDNA in water samples have been useful for estimating abundance. This study evaluated the effects of depth, distance to shore, and water velocity on the concentration of organismal and extra-organismal eDNA concentrations in the Klamath River, California (basin area ≅ 40,000 km²). At each of six river cross sections 32 water samples were collected, including surface samples and depth samples evenly distributed across the cross section, and eDNA concentrations were determined for the parasite Ceratonova shasta and Chinook salmon, Oncorhynchus tshawytscha, using …

Plastic Recognition And Electrogenic Uniport Translocation Of 1st-, 2nd-, And 3rd-Row Transition And Post-Transition Metals By Primary-Active Transmembrane P1b-2-Type Atpase Pumps, Sameera S. Abeyrathna, Nisansala S. Abeyrathna, Priyanka Basak, Gordon W. Irvine, Limei Zhang, Gabriele Meloni

Department of Biochemistry: Faculty Publications

Transmembrane P-type ATPase pumps catalyze the extrusion of transition metal ions across cellular lipid membranes to maintain essential cellular metal homeostasis and detoxify toxic metals. Zn()-pumps of the P-type subclass, in addition to Zn , select diverse metals (Pb, Cdand Hg) at their transmembrane binding site and feature promiscuous metal-dependent ATP hydrolysis in the presence of these metals. Yet, a comprehensive understanding of the transport of these metals, their relative translocation rates, and transport mechanism remain elusive. We developed a platform for the characterization of primary-active Zn()-pumps in proteoliposomes to study metal selectivity, translocation events and transport mechanism in real-time, …

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 …

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 …

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 …