Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons™

Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology

PDF

Biochemistry

Articles 1 - 22 of 22

Full-Text Articles in Medicine and Health Sciences

Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman Jun 2024

Computational Analysis Of O6-Methylated Guanine And Thioguanine Complexes, Kirsten Stinson, Michael Bowman

Lux et Fides: A Journal for Undergraduate Christian Scholars

DNA methylation occurring on the O6 position of guanine has been linked to the formation of cancer. DNA complexes with O6-methylated guanine have been studied experimentally, yet questions remain concerning the carcinogenic properties of O6-methylguanine. This present research explored the interaction between O6-methylguanine and its potential nucleobase pairs of cytosine and adenine in hopes of elucidating the mutagenic characteristics of O6-methylguanine. A variety of computational methods including Density Functional Theory (DFT), Symmetry Adapted Perturbation Theory (SAPT), Noncovalent Interaction (NCI) analysis, and Natural Bond Orbital (NBO) analysis were employed to comprehensively probe …

Go to article

First Course Portfolio For Bioc205: Scientific Analysis And Technical Writing, Lindsey B. Crawford Jun 2023

First Course Portfolio For Bioc205: Scientific Analysis And Technical Writing, Lindsey B. Crawford

UNL Faculty Course Portfolios

BIOC205: Scientific Analysis and Technical Writing is a core course for the Department of Biochemistry at the University of Nebraska-Lincoln. This course is geared for second year (sophomore students) with minimal prerequisites and as a foundation for future classes. Challenges include 1) teaching the needed scientific background and elements of scientific analysis and writing to a broad cohort of students with diverse backgrounds and interests, 2) building student skills towards analysis of primary peer-reviewed scientific literature, 3) developing students as writers of scientific information for different audiences. This course used Genetic Engineering as a broad topic choice to capture students …

Go to article

Development Of New Treatments For Asthma And Neuropathic Pain Based On Ɣ-Aminobutyric Acid A Receptor (Gabaar) Ligands, Nicolas Mark Zahn May 2022

Development Of New Treatments For Asthma And Neuropathic Pain Based On Ɣ-Aminobutyric Acid A Receptor (Gabaar) Ligands, Nicolas Mark Zahn

Theses and Dissertations

The γ-aminobutyric acid A receptor (GABAAR) is a ligand-gated pentameric chloride channel consisting of several identified subunits: α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3.1-2 Typical arrangement of subunits consists of two α subunits, two β subunits, and one γ subunit.3 GABAARs have two binding sites for the endogenous ligand γ-aminobutyric acid (GABA), between the α and β subunits. GABAARs also have a binding site for positive allosteric modulators, such as benzodiazepines, between the α and γ subunits.4-5 Due to their ability to treat anxiety, epilepsy, insomnia, and muscle relaxation, benzodiazepines are widely prescribed pharmaceuticals.6-7 Still, adverse effects result from …

Go to article

Targeting Platelets Using Ionic Liquid Coated Nanoparticles, Karen Mun Wong Apr 2022

Targeting Platelets Using Ionic Liquid Coated Nanoparticles, Karen Mun Wong

Honors Theses

Platelets are key players in our body’s inflammatory processes upon activation, which can create physiological problems. Researchers are actively seeking solutions by targeting platelets with therapeutics. The objective of the research in this thesis was to investigate a new and potentially less invasive drug delivery platform using nanoparticles. The topic of the project was to explore the world of ionic liquids and their abilities, when coated on nanoparticles, to bind to platelets. A library of choline carboxylic acid-based ionic liquids (ILs) was first synthesized via salt metathesis while PLGA-based nanoparticles were simultaneously being synthesized via the nanoprecipitation method. The ionic …

Go to article

Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma Aug 2021

Application Of Artificial Intelligence And Machine Learning In Chemistry, Niraj Verma

Chemistry Theses and Dissertations

In the last four years, I have been exposed to various topics in scientific research under the supervision of Dr. Kraka in the CATCO group. Numerous involved chemistry projects were undertaken to gain an understanding of the basic laws of nature involving vibrational spectroscopy, molecular acidity, and catalysts based on transition metals for halogen chemistry. The insights from computational chemistry were then applied to model and predict various complicated problems in chemistry via artificial intelligence. With the help of classical artificial intelligence, the non-covalent interactions governing the properties of proteins and water properties were analyzed. Significant improvements were made in …

Go to article

Purification And Functional Characterization Of The Iron-Responsive Transcription Factor Aft1 From C. Glabrata, Jade Ikahihifo-Bender Apr 2021

Purification And Functional Characterization Of The Iron-Responsive Transcription Factor Aft1 From C. Glabrata, Jade Ikahihifo-Bender

Senior Theses

Due to its unique ability to serve as both an electron donor and acceptor, iron is utilized as a co-factor for many biological processes, including electron transfer, oxygen binding, and vitamin synthesis. Iron is also a key factor during fungal infections as the human host and invading pathogens battle over limited iron pools. The primary iron-responsive transcription factor Aft1 in the opportunistic pathogenic yeast Candida glabrata responds to iron deficiency by activating expression of iron acquisition genes. However, the mechanisms for sensing intracellular iron levels and regulating Aft1 activity in response to iron are unknown. The C. glabrata iron regulation …

Go to article

Development Of Linked-Domain Protein Inhibitors Of The E2-Conjugating Enzyme Ube2d, Anneroos E. Nederstigt Jan 2021

Development Of Linked-Domain Protein Inhibitors Of The E2-Conjugating Enzyme Ube2d, Anneroos E. Nederstigt

University of the Pacific Theses and Dissertations

In most eukaryotic organisms, the ubiquitination pathway is one of the most important and versatile signaling systems in use. It is integral to processes such as protein degradation and homeostasis, DNA repair cell cycle regulation, signaling and regulation, epigenetics, and many more. Ubiquitin (Ub) is a short polypeptide of 8.6 kDa, 76 residues that functions as a reversible post-translation modification (PTM). It furthermore contains 7 different lysine residues (K6, K11, K27, K29, K33, K48, K63), all of which can form isopeptide linkages with one another to link individual Ub moieties to form unique polyUb chains onto substrates. The type of …

Go to article

Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu Dec 2020

Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu

Molecular and Cellular Biochemistry Faculty Publications

Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (β-catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of N-((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. KDM3A is a Jumonji (JmjC) domain-containing demethylase that is significantly upregulated in CRC. KDM3A regulates the demethylation of histone H3's lysine …

Go to article

Investigating The Interactions Between Individual Calmodulin And Hiv-1 Protein Domains, Riley K. Kendall, Jerry Larue May 2020

Investigating The Interactions Between Individual Calmodulin And Hiv-1 Protein Domains, Riley K. Kendall, Jerry Larue

Student Scholar Symposium Abstracts and Posters

The World Health Organization found that 37.9 million people were living with HIV by the end of 2018. HIV is a virus that weakens the immune system through viral replication and the destruction of CD4+ T-cells, which are white blood cells that detect infection and make antibodies. A cure for HIV has not yet been discovered. HIV-1 contains a Gag polyprotein which regulates the stages of viral replication. Previous studies suggest that the myristoyl group of a matrix protein peptide found on the Gag polyprotein, MA, forms a complex with a calcium-binding, multifunctional regulatory protein called Calmodulin (CaM). CaM …

Go to article

A Study Of The Antioxidant Versus Pro-Oxidant Nature Of The Amyloid Beta Peptide And An Analysis Of The Natural Products, Isorhamnetin And Narignenin, As Antioxidants, Kaylee Holmes Apr 2020

A Study Of The Antioxidant Versus Pro-Oxidant Nature Of The Amyloid Beta Peptide And An Analysis Of The Natural Products, Isorhamnetin And Narignenin, As Antioxidants, Kaylee Holmes

Honors Theses

Alzheimer’s disease is a neurodegenerative disorder with no cure. Due to the widespread effects of this disease, abundant research efforts have gone towards finding a cure. The amyloid beta (Ab) peptide has been shown to be a potential cause of the disease due to destructive effects on tissues that it can have both by itself and through reactive oxygen species (ROS) generation. This study was performed in order to assess the structural properties of Ab42monomers, fibrils and oligomers, to assess the antioxidant versus pro-oxidant behavior of the Ab peptide, and to assess the antioxidant nature of the natural …

Go to article

The Role Of Inositol Polyphosphate-4-Phosphatase Type Ii B (Inpp4b) In Obese Models And Endocrine Cancers, Manqi Zhang Nov 2019

The Role Of Inositol Polyphosphate-4-Phosphatase Type Ii B (Inpp4b) In Obese Models And Endocrine Cancers, Manqi Zhang

FIU Electronic Theses and Dissertations

INPP4B is a dual-specificity phosphatase and a tumor suppressor in prostate and breast cancers. Progression of the prostate and breast cancers depends on the androgen receptor (AR) or estrogen receptor alpha (ERα) signaling, respectively. In this work we demonstrated that INPP4B reprograms ERα transcriptional activity in breast cancer. INPP4B maintains expression and protein levels of progesterone receptor (PR), an ERα direct target gene required for mammary gland development. Consistently we demonstrated that Inpp4b knockout severely impairs lateral branching in the mammary gland of maturing virgin females. In advanced prostate cancer, activation and transcriptional reprogramming of AR frequently coincides with the …

Go to article

Knob-Socket Investigation Of Stability And Specificity In Alpha-Helical Secondary And Quaternary Packing Structure, Taylor Renee Rabara Jan 2019

Knob-Socket Investigation Of Stability And Specificity In Alpha-Helical Secondary And Quaternary Packing Structure, Taylor Renee Rabara

University of the Pacific Theses and Dissertations

The novel knob-socket (KS) model provides a construct to interpret and analyze the direct contributions of amino acid residues to the stability in α-helical protein structures. Based on residue preferences derived from a set of protein structures, the KS construct characterizes intra- and inter-helical packing into regular patterns of simple motifs. The KS model was used in the de novo design of an α-helical homodimer, KSα1.1. Using site-directed mutagenesis, KSα1.1 point mutants were designed to selectively increase and decrease stability by relating KS propensities with changes to α-helical structure. This study suggests that the sockets from the KS Model can …

Go to article

Identification Of Antibiotic Ge37468a From Pseudonocardia Symbionts Of Trachymyrmex Septentrionalis Ants, Krithika Rao Jan 2019

Identification Of Antibiotic Ge37468a From Pseudonocardia Symbionts Of Trachymyrmex Septentrionalis Ants, Krithika Rao

Scripps Senior Theses

In response to the growing rates of antibiotic resistance in human bacterial pathogens, this study explores the natural products involved in the defensive symbiosis between actinobacteria and fungus-growing ants to uncover new potential antibiotics. This study also seeks to understand the function of natural antibiotics in their ecological contexts, especially those involved in defensive symbioses. Defensive symbiosis can be a beneficial platform for discovering useful antibiotics, because antibiotics in these relationships must be able to selectively inhibit enemies without harming hosts, and are therefore likely more specific and less toxic. Pseudonocardia sp. associated with Trachymyrmex septentrionalis ants demonstrated antibiotic activity …

Go to article

The Beta-Catenin/Muc1.Ct Interaction In Pancreatic Cancer, Edwin Wiest May 2018

The Beta-Catenin/Muc1.Ct Interaction In Pancreatic Cancer, Edwin Wiest

Theses & Dissertations

MUC1 is overexpressed in over 90% of pancreatic cancer cases, and its interaction with beta-catenin promotes progression of the disease. Various in vitro and in vivo methods show that beta-catenin and MUC1 interact by way of the cytoplasmic tail of MUC1 (MUC1.CT). This interaction occurs in the membrane of pancreatic cancer cells but is found to a smaller extent in the nucleus as well. Biophysical methods suggest that MUC1 interacts with beta-catenin through a sequence of amino acids in the tail of MUC1 that sit very near the transmembrane domain of MUC1. In pancreatic ductal adenocarcinoma cells, it appears that …

Go to article

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo Apr 2018

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Go to article

Traf3 Negatively Regulates Platelet Activation And Thrombosis, Rui Zhang, Guoying Zhang, Binggang Xiang, Xiaofeng Chen, Lijang Tang, Shaojun Shi, Yani Liu, Xun Ai, Ping Xie, Zhenyu Li Dec 2017

Traf3 Negatively Regulates Platelet Activation And Thrombosis, Rui Zhang, Guoying Zhang, Binggang Xiang, Xiaofeng Chen, Lijang Tang, Shaojun Shi, Yani Liu, Xun Ai, Ping Xie, Zhenyu Li

Internal Medicine Faculty Publications

CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily, binds to CD40, leading to many effects depending on target cell type. Platelets express CD40L and are a major source of soluble CD40L. CD40L has been shown to potentiate platelet activation and thrombus formation, involving both CD40-dependent and -independent mechanisms. A family of proteins called TNF receptor associated factors (TRAFs) plays key roles in mediating CD40L-CD40 signaling. Platelets express several TRAFs. It has been shown that TRAF2 plays a role in CD40L-mediated platelet activation. Here we show that platelet also express TRAF3, which plays a negative role in …

Go to article

Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre Feb 2016

Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. The T4R RHO mutant dog retina shows retinal degeneration with exposures to light comparable to those used in clinical eye examinations of patients. To define the molecular mechanisms of the degeneration, AP-1 DNA-binding activity, composition, posttranslational modification of the protein complex, and modulation of ERK/MAPK signaling pathways were examined in light-exposed mutant retinas. METHODS. Dark-adapted retinas were exposed to short-duration light flashes from a retinal camera used clinically for retinal photography and were collected at different time points after exposure. Electrophoretic mobility shift assay (EMSA), supershift EMSA, Western blot analysis, and immunocytochemistry were used to examine AP-1 signaling. RESULTS. …

Go to article

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre Feb 2016

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. …

Go to article

Biochemical Effects Of Meditation: A Literature Review, William C. Daube, Charles E. Jakobsche Oct 2015

Biochemical Effects Of Meditation: A Literature Review, William C. Daube, Charles E. Jakobsche

Scholarly Undergraduate Research Journal at Clark (SURJ)

Meditation is an activity that can help reduce stress and anxiety from daily life as well as help cultivate overall feel- ings of peacefulness, relaxation, and contentment. This review describes several studies that have been used to assess how meditation can influence the body at the molecular level. The presented results focus on small-molecule metab- olites, which are broadly defined as naturally-produced molecules that weigh less than approximately 1000 Da. The results show that meditation can significantly affect hormones and neurotransmitters such as cortisol, dehydroepi- androstrone, serotonin, melatonin, and epinephrine. Some common and modern experimental techniques that are relevant to …

Go to article

Evolutionary Convergence Of The Caffeine Biosynthetic Pathway In Chocolate Followed Duplication Of A Constrained Ancestral Enzyme, Andrew J. O'Donnell Jun 2015

Evolutionary Convergence Of The Caffeine Biosynthetic Pathway In Chocolate Followed Duplication Of A Constrained Ancestral Enzyme, Andrew J. O'Donnell

Masters Theses

Caffeine biosynthesis is widely distributed in flowering plants and requires three consecutive methylation steps of xanthine alkaloids. Genes that have previously been reported to participate in the multi-step pathway in Coffea sp. (coffee) and Camellia sinensis (tea) encode members of the SABATH family of methyltransferases. Two genes highly expressed in fruits of Theobroma cacao (cacao) are orthologous to the caffeine genes in tea and appear to have diversified following gene duplication. Biochemical characterization of the enzymes (XMTs) encoded by these genes strongly suggest an unprecedented major pathway to theobromine, a precursor to caffeine. These findings imply that caffeine biosynthesis evolved …

Go to article

Novel Role Of Antioxidant-1 (Atox1) As A Copper-Dependent Transcription Factor Involved In Cell Proliferation, S. Itoh, H. W. Kim, O. Nakagawa, K. Ozumi, Susan M. Lessner, H. Aoki, K. Akram, R. D. Mckinney, M. Ushio-Fukai, T. Fukai Feb 2008

Novel Role Of Antioxidant-1 (Atox1) As A Copper-Dependent Transcription Factor Involved In Cell Proliferation, S. Itoh, H. W. Kim, O. Nakagawa, K. Ozumi, Susan M. Lessner, H. Aoki, K. Akram, R. D. Mckinney, M. Ushio-Fukai, T. Fukai

Faculty Publications

Copper plays a fundamental role in regulating cell growth. Many types of human cancer tissues have higher copper levels than normal tissues. Copper can also induce gene expression. However, transcription factors that mediate copper-induced cell proliferation have not been identified in mammals. Here we show that antioxidant-1 (Atox1), previously appreciated as a copper chaperone, represents a novel copper-dependent transcription factor that mediates copper-induced cell proliferation. Stimulation of mouse embryonic fibroblasts (MEFs) with copper markedly increased cell proliferation, cyclin D1 expression, and entry into S phase, which were completely abolished in Atox1-/- MEFs. Promoter analysis and EMSA revealed that copper …

Go to article

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng May 2006

In Vitro Expression And Purification Of Class I Mhc Molecules, Loi Cheng

Honors Scholar Theses

The major histocompatibility complex (MHC) is a gene family responsible for many critical functions of the immune system in most vertebrates. The MHC consists of three classes differentiated by their structure and function, and MHC class I encodes antigen binding proteins as well as chaperone and accessory proteins such as tapasin. The purpose of this project is to reconstitute several human MHC class I molecules in their peptide-filled and peptide-deficient forms, and to purify these proteins for biochemical study. The expressed proteins include wild type and mutant variants of the fusion protein human leukocyte antigen HLA-B*0801-fos, and human beta-2-microglobulin (β2m). …

Go to article