Biochemistry Commons^™

Validity Of Plasma Collection Cards For Ferritin Assessment—A Proof-Of-Concept Study, Karsten Koehler, Eileen Marks-Nelson, Camila Pereira Braga, Safiya E. Beckford, Jiri Adamec

Department of Biochemistry: Faculty Publications

Objectives: Iron depletion is common around the world and among certain risk groups in developed countries. The overall purpose was to test the suitability of a novel plasma collection card for minimally invasive iron status assessment.

Methods: Twenty participants (10 f/10 m) participated in this cross-sectional study. Ferritin and hemoglobin were measured from blood collected from a forearm vein, serving as reference method. Blood was also collected from the fingertip using the NoviplexTM Plasma Prep Card as well as capillary collection tubes.

Results: There was substantial concordance between ferritin measured from samples collected via NoviplexTM and venous ferritin (concordance correlation …

การแบ่งกลุ่มย่อยตามลักษณะทางคลินิกรูปแบบใหม่โดยอาศัยปัญญาประดิษฐ์ ร่วมกับการวิเคราะห์โอมิกส์แบบบูรณาการหลายระดับ เพื่อระบุกลุ่มตัวแทนสารบ่งชี้ทางชีวภาพสำหรับภาวะออทิซึมสเปกตรัม, กัลยภัสสร์ หัสเสม

Chulalongkorn University Theses and Dissertations (Chula ETD)

โรคออทิซึมสเปกตรัมเป็นความผิดปกติเกี่ยวกับพัฒนาการในช่วงเริ่มแรกของระบบประสาทและสมองซึ่งมีอาการทางคลินิกที่หลากหลายมาก ปัจจุบันยังไม่มีสารบ่งชี้เพื่อช่วยในการวินิจฉัยและแบ่งผู้ป่วยเป็นกลุ่มย่อย แต่การวินิจฉัยที่รวดเร็วเป็นสิ่งสำคัญที่จะช่วยให้ผู้ป่วยออทิซึมสเปกตรัมสามารถได้รับการเรียนรู้และพัฒนาพฤติกรรมที่จำเป็นในการดำรงชีวิตได้ การวินิจฉัยโรคออทิซึมสเปกตรัมตามมาตรฐานสากลใช้แบบสอบถามที่มีความซับซ้อนและใช้เวลามาก ซึ่งในปัจจุบันมีการนำเอาเทคโนโลยีปัญญาประดิษฐ์มาประยุกต์ใช้ในการวิเคราะห์ข้อมูลขนาดใหญ่ที่มีความซับซ้อน อย่างไรก็ตามการนำเอาปัญญาประดิษฐ์มาใช้วิเคราะห์อาการทางคลินิกของผู้ป่วยออทิซึมสเปกตรัมยังไม่แพร่หลายนัก ในการศึกษานี้ผู้วิจัยต้องการนำเอาปัญญาประดิษฐ์มาใช้แบ่งผู้ป่วยออทิซึมสเปกตรัมจำนวน 85 ราย ออกเป็นกลุ่มย่อยตามอาการทางคลินิกจากข้อมูลแบบทดสอบในการวินิจฉัยผู้ป่วยออทิซึมสเปกตรัม ADI-R จำนวน 123 ข้อ จากนั้นได้ทำการสร้างโมเดลในการจัดกลุ่มและเปรียบเทียบประสิทธิภาพรวมถึงจำนวนข้อคำถามที่ใช้ในแต่ละโมเดล นอกจากนี้ผู้วิจัยได้ศึกษาหาสารบ่งชี้ทางชีวภาพที่เป็นตัวแทนของโรคออทิซึมสเปกตรัมกลุ่มย่อยจากลักษณะอาการทางคลินิกโดยอาศัยการบูรณาการโอมิกส์หลายระดับ จึงได้ดำเนินการวิเคราะห์รูปแบบทรานสคริปโตม และวิเคราะห์รูปแบบโปรตีโอมของผู้ป่วยออทิซึมสเปกตรัมโดยใช้เซลล์เพาะเลี้ยงชนิดลิมโฟบลาสต์เป็นต้นแบบ โดยใช้เทคนิคการแยกโปรตีนด้วยกระแสไฟฟ้า 2 มิติ (2D-GE) จากนั้นจะทำการระบุโปรตีนด้วยเทคนิค LC-MS/MS เพื่อหาโปรตีนที่ถูกรบกวนการทำงานอย่างมีนัยสำคัญ และบูรณาการข้อมูลเพื่อศึกษาความสอดคล้องและสัมพันธ์กันระหว่างการแสดงออกของโปรตีนและยีน และทำการยืนยันระดับการแสดงออกที่ผิดปกติไปของยีนด้วยเทคนิค Real-time qPCR และโปรตีนด้วยเทคนิค Western blot ในการศึกษาครั้งนี้จากผลการวิเคราะห์ข้อมูลลักษณะอาการทางคลินิกของผู้ป่วยออทิซึมสเปกตรัมจากแบบทดสอบ ADI-R 123 ข้อ พบว่าวิธี K-means clustering ที่แบ่งผู้ป่วยออกเป็น 4 กลุ่มย่อยนั้นให้ประสิทธิภาพในการแบ่งดีที่สุด และเมื่อทำการสร้างโมเดลในการจัดกลุ่มผู้ป่วยตามผลการแบ่งกลุ่มดังกล่าว พบว่าอัลกอริทึม Random forest ที่มีจำนวนต้นไม้ 10 ต้น โดยกระบวนการคัดเลือกข้อมูลแบบ Forward selection ให้ผลการทำนายถูกต้องมากที่สุด (100%) โดยใช้ข้อคำถาม ADI-R เพียง 5 ข้อ ในการแบ่งผู้ป่วยออกเป็นกลุ่มย่อย และจากการวิเคราะห์รูปแบบโปรตีโอมจากเซลล์เพาะเลี้ยงชนิดลิมโฟบลาสต์ของผู้ป่วยออทิซึมสเปกตรัมและออทิซึมสเปกตรัมกลุ่มย่อยด้วยเทคนิค 2D-GE ผู้วิจัยได้ทำการคัดเลือกจุดโปรตีนที่มีการแสดงออกผิดปกติอย่างมีนัยสำคัญและมีค่าสัดส่วนความเข้มแตกต่างกันอย่างน้อยสองเท่ามา 19 จุด เพื่อทำการระบุชนิดของโปรตีนด้วยเทคนิค LC-MS/MS โดยพบว่าจากโปรตีนทั้งหมด HNRNPA2B1 มีระดับการแสดงออกเพิ่มขึ้นในผู้ป่วยออทิซึมสเปกตรัมกลุ่มย่อยที่ไม่มีความผิดปกติด้านภาษารุนแรง โดยที่โปรตีน HNRNPA2B1 MDH2 DLD และ MSN มีระดับการแสดงออกลดลงในผู้ป่วยออทิซึมสเปกตรัมกลุ่มย่อยที่มีความผิดปกติด้านภาษารุนแรง ดังนั้นจากการศึกษาวิจัยในครั้งนี้ได้แสดงให้เห็นว่าการใช้เทคโนโลยีปัญญาประดิษฐ์ในการแบ่งผู้ป่วยออทิซึมสเปกตรัมออกเป็นกลุ่มย่อยตามลักษณะอาการทางคลินิกนั้น สามารถลดความหลากหลายตามลักษณะอาการที่แสดงออกของโรคออทิซึมสเปกตรัมในการวิเคราะห์รูปแบบทรานสคริปโตมและโปรตีโอม รวมถึงการค้นหาโปรตีนที่จำเพาะต่อผู้ป่วยออทิซึมสเปกตรัมกลุ่มย่อย ได้อย่างมีประสิทธิภาพมากขึ้น ซึ่งโปรตีนเหล่านี้อาจใช้เป็นโปรตีนบ่งชี้ในการศึกษาเชิงลึกในประชากรผู้ป่วย เพื่อพัฒนาเป็นสารบ่งชีทางชีวภาพ (Biomarker) หรือศึกษากลไกพยาธิสภาพในระดับชีวโมเลกุลของโรคออทิซึมสเปกตรัมได้ต่อไปในอนาคต

Effect Of Mptp On Α-Synuclein Spreading, Accumulation And Toxicity In Mice With Intrastriatal Innoculation Of Human Α-Synuclein Preformed Fibril, Madiha Mohieldin Merghani

Theses

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder, characterized by abnormal accumulation of interneuronal inclusions of α-synuclein (α-syn) known as Lewy bodies (LBs) and Lewy neurites (LNs), and significant loss of dopamine neurons in the substantia nigra pars compacta (SNc) region of the brain. Recent evidence suggests that intrastriatal inoculation of α-syn Preformed Fibril (PFF) into mice induces PD-like LBs and LNs pathology formed by aggregated α-syn in anatomically interconnected brain regions which needs several months of incubation to develop the pathology. In the present study, we have evaluated the effect of different doses of 1-methyl, 4-phenyl, …

Characterization Of The Influences Of Human Cytomegalovirus Glycoprotein O (Go) Expression On Gh/Gl Complexes Assembly And Its Polymorphisms On Cell-Free And Cell-To-Cell Spread, And Antibody Neutralization., Le Z. Day

Graduate Student Theses, Dissertations, & Professional Papers

Human cytomegalovirus (HCMV) is widely spread throughout the world and immunocompromised individuals can suffer severe diseases from HCMV infection. Once the infection is established, HCMV can spread through the body and infect many major somatic cell types. The glycoproteins H and L (gH/gL) on HCMV envelope can be bound by either gO or the UL128-131 proteins to form complexes gH/gL/gO and gH/gL/UL128-131 that are critical for viral entry and spread, and these two complexes are important targets of neutralizing antibodies. Strains of HCMV vary considerably in the levels of gH/gL/gO and gH/gL/UL128-131. gO is one of the most diverse loci …

Sestrin2 Phosphorylation By Ulk1 Induces Autophagic Degradation Of Mitochondria Damaged By Copper-Induced Oxidative Stress, Heejeong Kim, Byeong Tak Jeon, Isaac M. Kim, Sydney Townsend, Carolyn M. Lorch, Martonio Viana, Jacob F. Myers, Caroline J. Trupp, Zachary T. Whipps, Mondira Kundu, Soonkyu Chung, Xinghui Sun, Oleh Khalimonchuk, Jaekwon Lee, Seung-Hyun Ro

Department of Biochemistry: Faculty Publications

Selective autolysosomal degradation of damaged mitochondria, also called mitophagy, is an indispensable process for maintaining integrity and homeostasis of mitochondria. One well-established mechanism mediating selective removal of mitochondria under relatively mild mitochondria-depolarizing stress is PINK1-Parkin-mediated or ubiquitin-dependent mitophagy. However, additional mechanisms such as LC3-mediated or ubiquitin-independent mitophagy induction by heavy environmental stress exist and remain poorly understood. The present study unravels a novel role of stress-inducible protein Sestrin2 in degradation of mitochondria damaged by transition metal stress. By utilizing proteomic methods and studies in cell culture and rodent models, we identify autophagy kinase ULK1-mediated phosphorylation sites of Sestrin2 and demonstrate …

Insights From The Inclusive Environments And Metrics In Biology Education And Research Network: Our Experience Organizing Inclusive Biology Education Research Events, Rebecca A. Campbell-Montalvo, Natalia Caporale, Gary S. Mcdowell, Candice Idlebird, Katie M. Wiens, Kimberly M. Jackson, Jana D. Marcette, Michael E. Moore

Department of Biochemistry: Faculty Publications

In contrast to efforts focusing on improving inclusion in STEM classrooms from kindergarten through un-dergraduate (K–16), efforts to improve inclusion in scientific meetings and conferences, important hubs of STEM culture, are more recent. Markers of inclusion that are sometimes overlooked at these events can include the composition of panels, how workshops are run, the affordability of conferences, and various other mechanisms that maintain pre-existing hierarchies and norms that limit the participation of early-career researchers and individuals of minoritized cultural, linguistic, and economic backgrounds. The Inclusive Environments and Metrics in Biology Education and Research (iEMBER) network coordinates efforts of researchers from …

Identifying Metabolites As Markers Of Fatigue In Athletes, Christopher D. George

Honors Theses

Fatigue in athletes caused by inadequate rest and other stressors can be severely detrimental to their health, and yet there is no reliable way to measure and track fatigue. Many classical measures of fatigue like body mass and resting heart rate are not reliable ways to track the physical fatigue of an athlete because they can change with many factors. In addition, it is not known how academic stress on top of physical stress affects fatigue. Metabolomics is a relatively new area of study and tracking metabolites offers the possibility to produce biomarkers to assess fatigue. This study collected saliva …

Mass Spectrometry Based Lipidomic Investigation Of Staphylococcus Aureus Lipid Metabolism And Characterization Of Lipase A, Naren Gajenthra Kumar

Theses and Dissertations

Staphylococcus aureus produces an arsenal of virulence factors and is adept at colonizing multiple hosts by employing specific processes to persist at different sites of infection. Infections caused by this pathogen range from self-limiting infections of the skin like folliculitis to life threatening and chronic conditions like infective endocarditis, non-healing diabetic foot ulcers and atopic dermatitis. As the field continues to expand its understanding of the mechanisms by which this pathogen rapidly develops resistance to new antibiotics, the underlying mechanisms that facilitates niche adaptation and host colonization among healthy individuals remain elusive.

Bacterial and host lipid metabolism presents and area …

Characterization Of The Dyrk1a Protein-Protein Interaction Network, Varsha Ananthapadmanabhan

Theses and Dissertations

Human Dual specificity tyrosine (Y)-Regulated Kinase 1A (DYRK1A) is a protein kinase encoded by a dosage-dependent gene. An extra copy of DYRK1A contributes to Down syndrome (DS) pathogenesis while loss of one allele causes severe mental retardation and autism. DYRK1A is involved in phosphorylation of several proteins that regulate cell cycle control and tumor suppression. However, the function and regulation of this kinase is not well understood and current knowledge does not fully explain dosage-dependent function of this important kinase. Our previous proteomic studies identified several novel DYRK1A interacting proteins including RNF169, FAM117B, TROAP, LZTS1, LZTS2 and DCAF7. In this …

Anti-Tumor Functions Of Sphingosine Kinase 1 And Sphingosine Kinase 2 In Breast Cancer Development, Melissa A. Maczis

Theses and Dissertations

Bioactive sphingolipid metabolite sphingosine-1‐phosphate (S1P) circulating levels have been implicated in breast cancer (BC) progression. BCs usually respond to 17β-Estradiol (E2) through canonical receptor ERα66 for genomic effects, however, E2 also triggers rapid, non-genomic responses. E2 has been shown to activate sphingosine kinase 1 (SphK1), increasing S1P for S1P receptors signaling important for BC. The E2 receptor activating SphK1 has not been identified. We demonstrate triple negative BC cells, expressing only novel ERα splice variant ERα36, E2-induced SphK1 activation for S1P secretion. Tamoxifen, first-line BC endocrine therapy, an ERα66 antagonist but ERα36 agonist, activates SphK1 and increases S1P secretion in …

Solid Phase Extraction And High-Precision Mass Spectrometry Analysis Methods For Crassostrea Virginica Metabolome, Alyssa Darling

Theses and Dissertations

Metabolomics is the rapidly-growing field which focuses on the endpoints of biological processes, and has the capability to provide a snapshot of an organisms’ interaction with their environment on a molecular scale. The objective of the experiment herein was to develop a standard metabolic extraction technique coupled with ultrahigh-precision analytical tools to build a global metabolic pathway of the keystone species Crassostrea virginica. To achieve this, C. virginica whole-body samples were extracted using acetonitrile and methanol, then split into a dehydrated group and a diluted group. Following reversed-phase solid phase extraction (RP-SPE) of both groups, metabolites were identified using …

Dietary Fish Oil Supplement Induces Age-Specific Contractile And Proteomic Responses In Muscles Of Male Rats, David W. Russ, Kalina Dimova, Emily Morris, Marguerite Pacheco, Sean M. Garvey, Stylianos P. Scordilis

Biological Sciences: Faculty Publications

Background: Dietary fish oil (DFO) has been identified as a micronutrient supplement with the potential to improve musculoskeletal health in old age. Few data are available for effects of DFO on muscle contractility, despite the significant negative impact of muscle weakness on age-related health outcomes. Accordingly, the effects of a DFO intervention on the contractile function and proteomic profile of adult and aged in an animal model of aging were investigated.

Methods: This preliminary study evaluated 14 adult (8 months) and 12 aged (22 months) male, Sprague-Dawley rats consuming a DFO-supplemented diet or a control diet for 8 weeks (7 …

Analysis Of Coevolving Residues Of Xcdxcdx-Phd, A Distinct Type Of Phd-Finger, Shraddha Basu

Electronic Theses and Dissertations

Plant homeodomain (PHD), a Zinc-finger scaffold, is a conserved protein module in eukaryotes that typically recognizes unstructured histone tails, and thus, PHDs play a crucial role in chromatin signaling. The sequences of Zinc-fingers, in general, diversify during the course of evolution often giving rise to subtypes (e.g., RBR-RING (Dove 2017) or zf-CxxC subtypes (Long 2013) who typically contain specific sequence signatures. We recently discovered that PHD fingers also contain a distinct subtype, namely the xCDxCDx-PHD. xCDxCDx-PHD has a distinct composition of specific amino acids that coevolved (coevolving residues) in the course of evolution, and xCDxCDx-PHD also shows a unique mechanism …

Scavenger Hunt: The Search For Sulfur Mustard-Neutralizing Compound In 2-Chloroethyl Ethyl Sulfide (Cees) Treated Human Keratinocyte (Hacat) Epithelial Cells, Tanner Diemer

Electronic Theses and Dissertations

Sulfur mustard is a highly toxic and dangerous vesicant that has been utilized as a chemical warfare agent (CWA) since World War I. Despite its extensive history, an effective antidote to sulfur mustard exposure still does not exist. With detectable levels of unreacted sulfur mustard lasting days after initial contact, a window of opportunity exists to administer a “scavenger” to affected individual immediately and in the days following exposure in hopes of reducing harm by neutralizing unreacted sulfur mustard. For this strategy to be effectively implemented, it is essential to identify a candidate compound with excellent affinity towards sulfur mustard …

The Characterization And Reactivity Of Tris(4-Methylpyrazolyl)Methane And Its Tungsten And Molybdenum Metal Complexes, Julia M. Pomeroy

Undergraduate Honors Thesis Collection

The scorpionate ligand tris(pyrazolyl)borate (Tp) has contributed to the understanding of coordination and organometallic chemistry and has proven to be useful in the synthesis of metalloprotein models. Studies focusing on the similar ligand, tris(pyrazolyl)methane (Tpm), have recently been made possible with improved synthetic techniques. Characterization of the Tpm ligand and its metal derivatives, [TpmW(CO)3L]+ and [TpmMo(CO)3L]+, unveiled unexpected activity in the 1H NMR chemical shift of the methane hydrogen after the coordination of a seventh ligand. The more electronegative the seventh ligand was, the more downfield the chemical shift appeared. Various analogs of Tpm have since been synthesized that substitute …

“C1orf150”: A Novel Regulator Of Jak2 Kinase, And Candidate Tumor Suppressor In Human Blood Cell Progenitors, Tyler M. Wade

Honors Theses and Capstones

Erythropoietin (EPO) is an essential growth factor for red blood cell (RBC) production. In response to anemia, hypoxia-sensing cells in the kidney express and release EPO. EPO then acts in bone marrow to drive RBC formation from erythroid progenitors. Upon binding to its cell surface receptor, EPO triggers a JAK2 kinase signaling cascade for progenitor cell growth. Our lab has discovered a novel regulator of JAK2, “C1ORF150” (“150”). “150” is conserved in H sapiens and primates and is a new orthologue of the B-cell receptor adaptor protein and tumor marker, HGAL. Using a shRNA knockdown approach, I investigated the actions …

Understanding The Rage Signaling Pathway And Its Contribution To Diabetic Complications, Leon Vegas Ho

Legacy Theses & Dissertations (2009 - 2024)

The binding of advanced glycation end products (AGEs) to the receptor for advanced glycation end products (RAGE) is an important feature of the RAGE signaling pathway that plays a role in the pathogenesis of diabetes. Under high glucose concentration, RAGE expression increases immensely from the formation of a Schiff base by glucose bounded to lysine. This triggers an inflammatory and immune response and upregulates the expression of RAGE and causes an accumulation of AGEs in the body. As a result, this leads to the development of diabetes and other complications such as, atherosclerosis, nephrothapy, and retinopathy. To remedy AGE accumulation, …

Novel Substrate-Free Cholinesterase Based Sensing Of Organophosphorus Compounds, Hailey J. Marini

Legacy Theses & Dissertations (2009 - 2024)

The increasing concerns of chemical weapons used by terrorists is growing, creating a need for infield detection methods that can rapidly detect these compounds that are a major health concern for civilians and military personnel. Displacement is a novel concept for the detection of cholinesterase inhibitors, including organophosphorus compounds, that could replace the classical instrumentation methods currently being used for diagnostics.

Targeting The Rage Signaling Pathway To Ameliorate The Complications Of Diabetes, Stephen James Dansereau

Legacy Theses & Dissertations (2009 - 2024)

Diabetes is a global health epidemic that can be devastating to those afflicted,

Biochemical And Chemical Methods Of Key Derivation For Cryptographic Ciphers, Leif K. Mcgoldrick

Legacy Theses & Dissertations (2009 - 2024)

Cryptography is a vital component of digital communication and digital data in general. The use of cryptography is necessary to support the veracity of data and to protect it from outside parties with malicious intent. Cryptography focuses on two main facets that are vital for this goal: data encryption and user authentication. Encryption protects the data by transforming it into an encrypted text that would not allow someone access without having or breaking the encryption method that was used to make it. User authentication is a multiple part process that allows for one to be able to identify oneself to …

Development Of Small Molecule Antibiotics Against A Conserved Rna Gene Regulatory Element In Gram-Positive Bacteria, Ville Yrjö Petteri Väre

Legacy Theses & Dissertations (2009 - 2024)

Bacterial infections and the rise of antibiotic resistance, especially multidrug resistant strains, have generated a clear need for discovery of novel therapeutics. Most antibiotics in use today are derivatives of previous antibiotics to which resistance mechanisms already exist, and traditionally they have a single target: either a protein or rRNA. Gram-positive bacteria regulate the expression of several essential genes or operons using a mechanism called the T-box. The T-box is a structurally conserved riboswitch-like gene regulator in the 5’-untranslated region (UTR) of numerous essential genes of Gram-positive bacteria. T-boxes are stabilized by cognate, unacylated tRNA ligands, allowing the formation of …

Development Of Dual Functional Dna/Rna Nanostructures For Drug Delivery, Vibhav Amit Valsangkar

Legacy Theses & Dissertations (2009 - 2024)

In addition to the traditional biochemical functions, DNA and RNA have been increasingly studied as building blocks for the formation of various 2D and 3D nanostructures. DNA has emerged as a versatile building block for programmable self-assembly. DNA-based nanostructures have been widely applied in biosensing, bioimaging, drug delivery, molecular computation and macromolecular scaffolding. A variety of strategies have been developed to functionalize these nanostructures. The major advantage is that DNA is a very stable molecule and its base-pairing properties can be easily utilized to control and program the formation of desired nanostructures. In addition, some of these DNA/RNA nanostructures have …

Role Of Microrna-483 In Pancreatic Β-Cells, Jackson Waugh

Dissertations, Master's Theses and Master's Reports

Insulin is an essential hormone produced by β-cells in the pancreas. The release of insulin is tightly regulated in healthy people in order to control blood sugar level in our body. However, people with Type 2 Diabetes have insufficient insulin secretion from pancreatic β-cells, leaving to high blood sugar (hyperglycemia) and β-cell failure. microRNAs (miRNAs or miR) are newly discovered small regulatory molecules and have emerged as important regulator of cell growth, differentiation, and organ function. Altered miRNA function has been implicated in the pathogenesis of a variety of human disease, including diabetes. In this report, we focus on dissecting …

Life In A Rural Emergency Department: Patients Speak To Underlying, Fundamental Disparities In Physician And Resource Allocation, Jessica Gustad

Honors Projects

In the Journal of Health Services Research and Policy, access to health care was defined as, “The availability of an adequate supply of health care services and the individual’s opportunity to obtain health care when it is wanted or needed” (MacKinney, 2014). Current trends in rural emergency departments are trying to communicate a critical message about the fundamental problems with the distribution of health care services in America today and the inability to properly meet the definition above. In rural communities, patient complaints and behaviors demonstrate the pressing concerns of inadequate access to primary care, limited specialty care, insufficient mental …

A Review Of Small Molecule Inhibitors And Functional Probes Of Human Cathepsin L, Dibyendu Dana, Sanjai Kumar

Publications and Research

Human cathepsin L belongs to the cathepsin family of proteolytic enzymes with primarily an endopeptidase activity. Although its primary functions were originally thought to be only of a housekeeping enzyme that degraded intracellular and endocytosed proteins in lysosome, numerous recent studies suggest that it plays many critical and specific roles in diverse cellular settings. Not surprisingly, the dysregulated function of cathepsin L has manifested itself in several human diseases, making it an attractive target for drug development. Unfortunately, several redundant and isoform-specific functions have recently emerged, adding complexities to the drug discovery process. To address this, a series of chemical …

Structural Dynamics Of Inosine Triphosphate Pyrophosphatase (Itpa) Protein And Two Clinically Relevant Mutants: Molecular Dynamics Simulations, Yao Houndonougbo, Bethany Pugh, Kandise Vanwormer, Caitlin April, Nicholas Burgis

Chemistry and Biochemistry Faculty Publications

The inosine triphosphate pyrophosphatase (ITPA) protein is responsible for removing noncanonical purine nucleoside triphosphates from intracellular nucleotide pools. Absence of ITPA results in genomic instability and increased levels of inosine in DNA and RNA. The proline to threonine substitution at position 32 (P32T) affects roughly 15% of the global population and can modulate treatment outcomes for cancer, lupus, and hepatitis C patients. The substitution of arginine with cysteine at position 178 (R178C) is extremely uncommon and has only been reported in a small cohort of early infantile encephalopathy patients suggesting that a functional ITPA protein is required for life in …

Optimization Of Dapoxyl Aptamer For Label-Free Bioanalysis, Jack E. Mordeson, Ryan P. Connelly, Pedro F. Madalozzo, Yulia Gerasimova

Digital Repository: Showcase of Undergraduate Research Excellence

No abstract provided.

Fluvial Sediment Organic Matter Degradation Identified With Elemental And Isotopic Fate During Laboratory Incubation, Brenden Riddle

Theses and Dissertations--Civil Engineering

Fluvial sediment is well recognized as a critical factor in both carbon and nutrient budgets within stream systems. However, we find very few studies of reactivity and isotope enrichment for stream water from agricultural and urban streams and the class of substrate known as fluvial sediment organic matter. This study investigated the hypothesis that fluvial sediment is subject to degradation even though many previous studies have considered this class of substrate generally inert. Therefore we qualify that elemental and isotopic signatures of fluvial sediment organic matter should be considered potentially non-conservative when used in tracer studies. Methods applied to this …

Physicochemical Characterization, Structural Determination, And Molecular Dynamic Modeling Of Proso Millet Proteins For Enhanced Food Functionality, Felix Akharume

Theses and Dissertations--Biosystems and Agricultural Engineering

More than one-third of Americans today incorporate plant-based protein into their diet and about 40% believed that plant-based protein is healthier than animal protein, especially Millennials. The increasing global demand for plant-based proteins driven by the high cost of animal proteins, consumers’ desire for lean protein, vegetarianism, and the need for more sustainable green protein products have necessitated research into alternate emerging and underutilized sources of protein to complement or supplement the major plant protein in the market- soy, pea, and gluten. Therefore, this dissertation is focused on the valorization of the proteins in proso millet. Specifically, this work focused …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).