Biochemistry, Biophysics, and Structural Biology Commons^™

Developmental And Molecular Changes Underlying The Vernalization-Induced Transition To Flowering In Aquilegia Coerulea (James), Bharti Sharma, Timothy A. Batz, Rakesh Kaundal, Elena M. Kramer, Uriah R. Sanders, Valerie J. Mellano, Naveen Duhan, Rousselene B. Larson

Center for Integrated Biosystems Publications

Reproductive success in plants is dependent on many factors but the precise timing of flowering is certainly among the most crucial. Perennial plants often have a vernalization or over-wintering requirement in order to successfully flower in the spring. The shoot apical meristem undergoes drastic developmental and molecular changes as it transitions into inflorescence meristem (IM) identity, which then gives rise to floral meristems (FMs). In this study, we have examined the developmental and gene expression changes underlying the transition from the vegetative to reproductive phases in the basal eudicot Aquilegia coerulea, which has evolved a vernalization response independently relative …

Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall

Forum Lectures

The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance, …

The Alfalfa Insecticide Management (Aim) Toolkit: Linking Insecticide Fate Modelling With Alfalfa Pest And Beneficial Insect Toxicity Endpoints, Kimberly J. Hageman

Funded Research Records

No abstract provided.

Endoglin Protein Interactome Profiling Identifies Trim21 And Galectin-3 As New Binding Partners, Eunate Gallardo-Vara, Lidia Ruiz-Llorente, Juan Casado-Vela, María J. Ruiz-Rodríguez, Natalia López-Andrés, Asit K. Pattnaik, Miguel Quintanilla

School of Veterinary and Biomedical Sciences: Faculty Publications

Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause herediatry hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectase, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions and appears to contribute to endothelial dysfunction and cancer development through unknown mechanisms. Membrane-bound endoglin is an auxiliary component of the TGF-B receptor complex and …

Theoretical Studies Of Ir And Nmr Spectral Changes Induced By Sigma-Hole Hydrogen, Halogen, Chalcogen, Pnicogen, And Tetrel Bonds In A Model Protein Environment, Mariusz Michalczyk, Wiktor Zierkiewicz, Rafał Wysokiński, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Various types of σ-hole bond complexes were formed with FX, HFY, H₂FZ, and H₃FT (X = Cl, Br, I; Y = S, Se, Te; Z = P, As, Sb; T = Si, Ge, Sn) as Lewis acid. In order to examine their interactions with a protein, N-methylacetamide (NMA), a model of the peptide linkage was used as the base. These noncovalent bonds were compared by computational means with H-bonds formed by NMA with XH molecules (X = F, Cl, Br, I). In all cases, the A–F bond, which lies opposite the base and is responsible for …

9th Annual Postdoctoral Science Symposium, University Of Texas Md Anderson Cancer Center Postdoctoral Association

Annual Postdoctoral Science Symposium Abstracts

The mission of the Annual Postdoctoral Science Symposium (APSS) is to provide a platform for talented postdoctoral fellows throughout the Texas Medical Center to present their work to a wider audience. The MD Anderson Postdoctoral Association convened its inaugural Annual Postdoctoral Science Symposium (APSS) on August 4, 2011.

The APSS provides a professional venue for postdoctoral scientists to develop, clarify, and refine their research as a result of formal reviews and critiques of faculty and other postdoctoral scientists. Additionally, attendees discuss current research on a broad range of subjects while promoting academic interactions and enrichment and developing new collaborations.

Environmental Cost Vs. Health Benefit Of Radioisotope Usage In Medicine, Nicholas Whiting

Open Educational Resources

This module is developed for implementation in a class that discusses the use of radioisotopes in a biomedical setting. The inspiration is a class I teach (Advanced Biomedical Instrumentation), which covers the use of radioisotopes as tracers in biomedical imaging (scintigraphy, SPECT, PET, etc.). The goal of the module is to go further in depth regarding the environmental impact of the use of radioisotopes (from their generation to their disposal—keeping track of any radioactive byproducts), and compare that to the potential for benefits in the quality and/or quantity of a patient’s life (does using the radioisotopes allow patients to live …

Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick J. Cullen, James Curtin

Articles

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma …

Evaluation Of Epas1 Variants For Association With Bovine Congestive Heart Failure [Version 1; Peer Review: 2 Approved], Michael P. Heaton, Adam S. Bassett, Katherine J. Whitman, Greta M. Krafsur, Sang M. Lee, Jaden M. Carlson, Halden J. Clark, Helen R. Smith, Madeline C. Pelster, Veronica Basnayake, Dale M. Grotelueschen, B. Vander Ley

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).

Methods: Paired samples of clinical cases and unaffected controls …

Rompi-Cdsa: Ring-Opening Metathesis Polymerization-Induced Crystallization-Driven Self-Assembly Of Metallo-Block Copolymers, Ye Sha, Md Anisur Rahman, Tianyu Zhu, Yujin Cha, C Wayne Mcalister, Chuanbing Tang

Faculty Publications

Polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are among the most prevailing methods for block copolymer self-assembly. Taking the merits of scalability of PISA and dimension control of CDSA, we report one-pot synchronous PISA and CDSA ring-opening metathesis polymerization (ROMP) to prepare nano-objects based on a crystalline poly(ruthenocene) motif. We denote this self-assembly methodology as ROMPI-CDSA to enable a simple, yet robust approach for the preparation of functional nanomaterials.

Nitric Oxide Is Involved In Heavy Ion-Induced Non-Targeted Effects In Human Fibroblasts, Megumi Hada, Premkumar B. Saganti, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the …

Chemical Epitope Targeting: Review Of A Novel Screening Technology, Qurrat Ul-Ain, Rene Kandler, Dylan Gillespie, Arundhati Nag

Scholarly Undergraduate Research Journal at Clark (SURJ)

Chemical Epitope Targeting is a novel technology developed for designing peptide ligands with high affinity and specificity against specific regions of a protein that may be inaccessible to small molecules or antibodies. In this review, we summarize the key steps and significant applications of this technology. Operating on the same principles as antibody-antigen interactions, this technique involves chemically synthesizing the region of interest on the protein, called the epitope, as a polypeptide with a biotin detection tag and a strategically placed alkyne or azide presenting amino acid. The constructed epitope is screened against a comprehensive linear or cyclic One Bead …

Odx: A Fitness Tracker-Based Device For Continuous Bacterial Growth Monitoring, Venkata V.B. Yallapragada, Uday Gowda, David Wong, Liam O'Faolain, Mark Tangney, Ganga C.R. Devarapu

Cappa Publications

Continuous monitoring of bacterial growth in aqueous media is a crucial process in academic research as well as in the biotechnology industry. Bacterial growth is usually monitored by measuring the optical density of bacteria in liquid media, using benchtop spectrophotometers. Due to the large form factor of the existing spectrophotometers, they cannot be used for live monitoring of the bacteria inside bacterial incubation chambers. Additionally, the use of benchtop spectrometers for continuous monitoring requires multiple samplings and is labour intensive. To overcome these challenges, we have developed an optical density measuring device (ODX) by modifying a generic fitness tracker. The …

Multigene Signatures Of Responses To Chemotherapy Derived By Biochemically-Inspired Machine Learning., Peter K. Rogan

Biochemistry Publications

Pharmacogenomic responses to chemotherapy drugs can be modeled by supervised machine learning of expression and copy number of relevant gene combinations. Such biochemical evidence can form the basis of derived gene signatures using cell line data, which can subsequently be examined in patients that have been treated with the same drugs. These gene signatures typically contain elements of multiple biochemical pathways which together comprise multiple origins of drug resistance or sensitivity. The signatures can capture variation in these responses to the same drug among different patients.

Minimalistic Peptide-Based Supramolecular Systems Relevant To The Chemical Origin Of Life, Daniela Kroiss

Dissertations, Theses, and Capstone Projects

All forms of life are based on biopolymers, which are made up of a selection of simple building blocks, such as amino acids, nucleotides, fatty acids and sugars. Their individual properties govern their interactions, giving rise to complex supramolecular structures with highly specialized functionality, including ligand recognition, catalysis and compartmentalization. In this thesis, we aim to answer the question whether short peptides could have acted as precursors of modern proteins during prebiotic evolution. Using a combination of experimental and computational techniques, we screened a large molecular search space for peptide sequences that are capable of forming supramolecular complexes with adenosine …

Molecular Dynamics Simulations Of Supramolecular Assemblies In Biology And Bionanotechnology, Anjela Manandhar

Dissertations, Theses, and Capstone Projects

Molecular self-assembly is an energy driven process where randomly organized building blocks interact noncovalently to form highly organized supramolecular nanostructures. In biology, the cytoskeleton is a classic example of a dynamic self-assembly, forming long filamentous structures from monomeric protein subunits. Similarly, the self-assembly process is widely exploited in nanotechnology to build bio-functional nanostructures. In this work, we studied biological (microtubule) and synthetic (peptide drug amphiphile nanotube) self-assembled systems. We utilized long time-scale molecular dynamics simulation to investigate the structural and dynamical properties of these systems.

At the molecular level, the dynamic instability (random growth and shrinkage) of the microtubule (MT) …

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of the …

Exploration Of The Inhibitory Properties Of The Nucleoside Antibiotic Salicyl-Ams And Analogues Targeting Siderophore Biosynthesis In Mycobacterium Tuberculosis, Glennon Bythrow

Dissertations, Theses, and Capstone Projects

Mycobacterium tuberculosis (Mtb) is a resilient, obligate bacterial pathogen responsible for pulmonary tuberculosis disease (TB), that has upheld a significant impact on global public health throughout history. The World Health Organization (WHO) approximates nearly 10 million new TB cases arose in 2017 alone, accounting for 1.6 million deaths. There has been a notable rise in TB cases produced by multidrug‑resistant (MDR) and extensively drug-resistant (XDR) strains of Mtb. This, along with the intrinsic resistance of Mtb to many standard drugs and poor patient compliance, is deeply impacting global control of TB. Among the several strategies currently in …

Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago

Dissertations, Theses, and Capstone Projects

A variety of biological functions depend on actin organization. The organization of actin is tightly regulated by a plethora of extracellular and intracellular signaling, scaffolding, and actin-binding proteins. Dysfunctions in this regulation lead to immune diseases, increased susceptibility to pathogens, neurodegenerative diseases, developmental disorders, and cancer metastasis. A variety of actin-dependent processes, including cell motility, are regulated by several proteins of interest: Paxillin, a scaffolding protein; WASP, an actin nucleating protein; SCAR/WAVE, another WASP family actin nucleating protein; Talin, a cortex-to-membrane binding protein; Myosin II, an F-actin contracting motor protein; and Protein Kinase C, a protein kinase. D. discoideum cells …

Characterization Of Early Biofilm Formation And Physiology In Neisseria Gonorrhoeae, Kelly Eckenrode

Dissertations, Theses, and Capstone Projects

Many bacteria rely on the dynamics of their extracellular appendages to perform important tasks, like motility and biofilm formation. Interestingly, these dynamics have been linked to physiological responses in some pathogenic bacteria; therefore, it is important to understand more about the role of physical forces in bacteria. I used the causative agent of the human disease gonorrhea, Neisseria gonorrhoeae, as a model system to study the role of physical force on early biofilm formation. The advantage of this system is that cell-cell interactions are controlled by extracellular filaments called type IV pili (tfp). Tfp is composed of monomers that give …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

Renal Specific Rnai Delivery By Fibrillar Nanoparticle Excipients, Sam Wong

Dissertations, Theses, and Capstone Projects

RNA interference (RNAi) is a powerful tool to manipulate the phenotype of an organism by silencing the expression of specific genes and is viewed as a highly promising platform for treating undruggable targets and disorders where small molecule drugs and antibodies would fail. However, development of RNAi based therapies has faced major barriers including cellular and tissue-specific uptake of the Small Interfering RNA (siRNA). Utilizing different nanoparticles as RNAi excipients, cellular uptake and gene silencing potency can be greatly improved. The research in Dr. McDevitt groups has fibrillar carbon nanotubes (CNT) as carriers for siRNA for gene silencing in vitro …

Systematics Of Carex Section Laxiflorae (Cyperaceae), Jenna Dorey

Dissertations, Theses, and Capstone Projects

Carex, with more than 2100 species, is the most species-rich genus of flowering plants in temperate regions of the world. Members of the family Cyperaceae are colloquially known as sedges, and members of the genus Carex are called “true sedges.” Carex occur on every continent except for Antarctica, they thrive in a panoply of habitats, and are ecologically important as a forage source for wildlife, carbon sequestration, prevention of soil erosion, and providing habitat for fresh water invertebrates. Despite their importance many sedges are still poorly known, such as the woodland sedges in Carex section Laxiflorae, which is …

Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi

Dissertations, Theses, and Capstone Projects

Trypanosome lytic factors (TLFs) are primate-specific antimicrobial protein complexes that lyse African trypanosome parasites by delivering the channel-forming toxin APOL1 to the invading microorganisms. Human serum contains two TLFs that are delivered to the parasite by separate mechanisms, only one of which has been characterized. TLF1 is endocytosed by a receptor that is typically blocked by other serum factors in vivo, suggesting that TLF2 is the more relevant lytic factor in the context of trypanosome immunity. TLF2 is non-covalently associated with polyclonal immunoglobulin M (IgM) antibodies, which we report here to be involved in the uptake mechanism. The TLF2-IgMs …

Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty

Dissertations

The Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) compromises multiple copies of three enzymes - 2-oxoglutarate dehydrogenase (E1o), dihydrolipoyl succinyltransferase (E2o), and dihydrolipoyl dehydrogenase (E3). OGDHc is found in the Krebs cycle and catalyzes the formation of the all-important succinyl-Coenzyme A (succinyl-CoA). OGDHc was engineered to understand the catalytic mechanism and optimized for chemical synthetic goals.

Succinyl-CoA formation takes place within the catalytic domain of E2o via a transesterification reaction. The succinyl group from the thiol ester of S8-succinyldihydrolipoyl-E2o is transferred to the thiol group of CoA. Mechanistic studies were designed to investigate enzymatic transthioesterification. His375 and Asp374 was shown to …

Anisotropic Singlet Fission In Single Crystalline Hexacene, Dezheng Sun, Gang-Hua Deng, Bolei Xu, Enshi Xu, Xia Li, Yajing Wu, Yuqin Qian, Yu Zhong, Colin Nuckolls, Avetik R. Harutyunyan, Hai-Lung Dai, Gugang Chen, Hanning Chen, Yi Rao

Chemistry and Biochemistry Faculty Publications

Singlet fission is known to improve solar energy utilization by circumventing the Shockley-Queisser limit. The two essential steps of singlet fission are the formation of a correlated triplet pair and its subsequent quantum decoherence. However, the mechanisms of the triplet pair formation and decoherence still remain elusive. Here we examined both essential steps in single crystalline hexacene and discovered remarkable anisotropy of the overall singlet fission rate along different crystal axes. Since the triplet pair formation emerges on the same timescale along both crystal axes, the quantum decoherence is likely responsible for the directional anisotropy. The distinct quantum decoherence rates …

Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin

Publications and Research

The mitochondrial permeability transition pore (MPTP) has resisted molecular identification. The original model of the MPTP that proposed the adenine nucleotide translocator (ANT) as the inner membrane pore-forming component was challenged when mitochondria from Ant1/2 double null mouse liver still had MPTP activity. Because mice express three Ant genes, we reinvestigated whether the ANTs comprise the MPTP. Liver mitochondria from Ant1, Ant2, and Ant4 deficient mice were highly refractory to Ca2+-induced MPTP formation, and when also given cyclosporine A (CsA), the MPTP was completely inhibited. Moreover, liver mitochondria from mice with quadruple deletion of Ant1, Ant2, Ant4, and Ppif (cyclophilin …

Spectroscopic Description Of The E1 State Of Mo Nitrogenase Based On Mo And Fe X‑Ray Absorption And MöSsbauer Studies, Casey Van Stappen, Roman Davydov, Zhi-Yong Yang, Ruixi Fan, Yisong Guo, Eckhard Bill, Lance C. Seefeldt, Brian M. Hoffman, Serena Debeer

Chemistry and Biochemistry Faculty Publications

Mo nitrogenase (N2ase) utilizes a two-component protein system, the catalytic MoFe and its electron-transfer partner FeP, to reduce atmospheric dinitrogen (N₂) to ammonia (NH₃). The FeMo cofactor contained in the MoFe protein serves as the catalytic center for this reaction and has long inspired model chemistry oriented toward activating N₂. This field of chemistry has relied heavily on the detailed characterization of how Mo N2ase accomplishes this feat. Understanding the reaction mechanism of Mo N2ase itself has presented one of the most challenging problems in bioinorganic chemistry because of the ephemeral nature of its …

An Exploration Of Protein And Dna Components In Fingerprint Residue, Ashley Borrego

Student Theses

The main focus of this project was to investigate the protein and DNA components in both sebaceous and eccrine fingerprints. This study investigated the relative content of DNA and proteins in eccrine fingerprints to sebaceous fingerprints. All volunteers were instructed to wash and dry their hands prior to depositing parallel thumbprints. Twenty volunteers were instructed to touch their face to produce sebaceous prints, and 5 volunteers were instructed to wear gloves over a heat source to produce sweaty or eccrine prints. Microscopy was used to score the cellular debris of the right fingerprint on a scale of 1-4 based on …

Trophic Upgrading And Mobilization Of Wax Esters In Microzooplankton, Keyana Roohani, Brad A. Haubrich, Kai-Lou Yue, Nigel D'Souza, Amanda Mantalbano, Tatiana Rynearson, Susanne Menden-Deuer, Christopher Reid

Science and Technology Department Faculty Journal Articles

Heterotrophic protists play pivotal roles in aquatic ecosystems by transferring matter and energy, including lipids, from primary producers to higher trophic predators. Using Oxyrrhis marina as a model organism, changes to the non-saponifiable protist lipids were investigated under satiation and starvation conditions. During active feeding on the alga Cryptomonas sp., the O. marina hexane soluble non-saponifiable fraction lipid profile reflected its food source with the observed presence of long chain mono-unsaturated fatty alcohols up to C25:1. Evidence of trophic upgrading in O. marina was observed with long chain mono-unsaturated fatty alcohol accumulation of up to C35:1. To the best of …