Biochemistry, Biophysics, and Structural Biology Commons^™

Development And Application Of Quassiclassical Direct Dynamics Program For Organic And Organometallic Reactions, Nathan Wohlgemuth, Dan Ess

Journal of Undergraduate Research

Organic and organometallic reactions are generally assumed to follow statistical mechanical models of reactivity and selectivity that correspond to transition state theory. However, in recent years there have been several organic reactions that have been shown to be controlled by post-transition state reaction dynamics. While some direct dynamics programs are available (VENUS, ProgDyn, etc.) they are generally difficult to use and have little documentation. To overcome this problem, we created a molecular dynamics software suite (called DynSuite) that interfaces with the electronic structure program Gaussian 09. We used this software to perform known examples of direct dynamics simulations for organic …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

The Effects Of Intrauterine Growth Restriction (Iugr) On The Pulmonary Surfactant And Lung Injury, Reza Khazaee

Western Research Forum

The Effects of Intrauterine Growth Restriction (IUGR) on the Pulmonary Surfactant and Lung Injury

Khazaee R¹, McCaig LA², Hardy D¹, Yamashita CM², Veldhuizen, RAW²

Department of Physiology and Pharmacology¹, Western University, London, ON, Canada. Lawson Health Research Institute², London, ON, Canada

Background: Acute respiratory distress syndrome (ARDS) is defined as severe lung dysfunction that occurs after an insult to the lung such as an infection. The lung dysfunction in ARDS is due to alterations to surfactant, a lipid-protein mixture coats the inside of the lung and …

Editorial: Platelet Secretion, Brian Storrie, Sidney W. Whiteheart

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.

Molecular Regulation Of Stem Cell Behavior During Tissue Repair And Cancer Formation, Nestor J. Oviedo

Science Seminar Series

Oviedo will be presenting his work on identifying the mechanisms of adult stem cell fate determination based on their topographical location in the adult body. Understanding stem cell fate determination is crucial because tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. Despite its critical implications for stem cell biology, carcinogenesis and regenerative medicine, this physiological phenomenon has remained overlooked. Recent findings from his group provide intriguing evidence implying DNA repair mechanisms and cellular signaling through post-translational modifications regulate stem cell fate decision depending on their topographical location in the adult body. We …

Aberrant Coordination Geometries Discovered In The Most Abundant Metalloproteins, Sen Yao, Robert M. Flight, Eric C. Rouchka, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metalloproteins bind and utilize metal ions for a variety of biological purposes. Due to the ubiquity of metalloprotein involvement throughout these processes across all domains of life, how proteins coordinate metal ions for different biochemical functions is of great relevance to understanding the implementation of these biological processes. Toward these ends, we have improved our methodology for structurally and functionally characterizing metal binding sites in metalloproteins. Our new ligand detection method is statistically much more robust, producing estimated false positive and false negative rates of ∼0.11% and ∼1.2%, respectively. Additional improvements expand both the range of metal ions and their …

Patterns Of Morphological And Molecular Evolution In The Antillean Tree Bat, Ardops Nichollsi (Chiroptera: Phyllostomidae), Roxanne J. Larsen, Peter A. Larsen, Caleb D. Phillips, Hugh H. Genoways, Gary G. Kwiecinski, Scott C. Pedersen, Carleton J. Phillips, Robert J. Baker

University of Nebraska State Museum: Mammalogy Papers

Species endemic to oceanic islands offer unique insights into the mechanisms underlying evolution and have served as model systems for decades. Often these species show phenotypic variation that is correlated with the ecosystems in which they occur and such correlations may be a product of genetic drift, natural selection, and/or environmental factors. We explore the morphologic and genetic variation within Ardops nichollsi, a species of phyllostomid bat endemic to the Lesser Antillean islands. Ardops nichollsi is an ideal taxon to investigate the tempo of evolution in Chiroptera, as it: is a recently derived genus in the family Phyllostomidae; contains …

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

UNO Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: …

Session C-1: Modeling Stem Activities Into Classroom Practice, Sowmya Anjur

Professional Learning Day

Students understand concepts better when they have had a chance to work hands on with relevant material. Examples will be presented from my classroom where difficult concepts have been modeled into simple experiments with considerable success in enhancing student understanding. Special focus will be given to selected topics that students seem to have the most difficulty grasping. The objective is to enable students to transfer their understanding to solve complex problems with considerable ease and apply their understanding to real world scenarios on assessments. Suggestions will also be provided for implementation of various concepts into the high school classroom.

Zhx2 (Zinc Fingers And Homeoboxes 2) Regulates Major Urinary Protein Gene Expression In The Mouse Liver, Jieyun Jiang, Kate Townsend Creasy, Justin Purnell, Martha L. Peterson, Brett T. Spear

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as …

Pdip46 Is Involved In Replication Timing Control, Hsiao H. Chao, Hong Zhao, Sufang Zhang

NYMC Faculty Posters

No abstract provided.

Challenges Of Conducting Animal Based Research And Teaching In Medical Colleges Of Karachi, Pakistan, Muhammad Ulusyar Khan, Faiq Amin, Fazal Manzoor Arain

Department of Biological & Biomedical Sciences

No abstract provided.

Development Of Ad Like Symptoms Following Co-Administration Of Alcl3 And D-Gal In Rats: A Neurochemical, Biochemical And Behavioural Study, Laraib Liaquat, Saara Muddasir, Sadia Adir, Zehra Batool, Saima Khaliq, Saiqa Tabassum, Shaista Emad, Syeda Madiha, Sidrah Shahzad, Saida Haider

Department of Biological & Biomedical Sciences

Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with neurochemical and neurobehavioural alterations. Aluminium (Al) is considered as a contributing factor in the etiology of several neurodegenerative disorders like AD. D-galactose (D-gal) is a physiological nutrient but over supply induces some neurochemical and biochemical changes that exacerbate natural aging process. In this study, we aimed to develop AD animal model by co-administration of Al and D-gal in rats. Male albino Wistar rats were intraperitoneally injected with AlCl₃ and D-gal at a dose of 150mg/kg and 300mg/kg respectively for one week. After one week rats were subjected to behavioural …

Soluble Transferrin Receptor, Ferritin Index In Pakistani Population, Faiza Alam, Nabeel Ashraf, Ramsha Kashif, Hashaam Arshad, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

Inflammation affects the reliability of ferritin. The serum level of transferrin receptor protein (sTfR) represents true demand of iron in the body. This study attempts to identify levels of sTfR and correlate the trends of sTfR/ferritin index with BMI in the population of Karachi. 132 gender matched volunteers between the ages of 20-60 years were recruited for this cross-sectional study. BMI was calculated using the formula: (weight in kg / height in m2). Following groups were made according to South Asian criteria of BMI; Group A: normal weight (18.0-22.9 kg/m2), Group B: overweight (23.0-24.9 kg/m2), Group C: obese ( > 25.0 …

Smug2 Dna Glycosylase From Pedobacter Heparinus As A New Subfamily In Udg Superfamily, Panjiao Pang, Ye Yang, Jing Li, Zhong Wang, Weiguo Cao, Wei Xie

Publications

Base deamination is a common type of DNA damage that occurs in all organisms. DNA repair mechanisms are essential to maintain genome integrity, in which the base excision repair (BER) pathway plays a major role in the removal of base damage. In the BER pathway, the uracil DNA glycosylase superfamily is responsible for excising the deaminated bases from DNA and generates apurinic/apyrimidinic (AP) sites. Using bioinformatics tools, we identified a family 3 SMUG1-like DNA glycoyslase from Pedobacter heparinus (named Phe SMUG2), which displays catalytic activities towards DNA containing uracil or hypoxanthine/xanthine. Phylogenetic analyses show that SMUG2 enzymes are closely related …

The Role Of Estrogen In Mouse Gastric Stem Cell Homeostasis, Aysha Mohamed Yusuf Alkaabi

Theses

To maintain cellular homeostasis, the epithelial lining of the stomach wall continuously fluctuates between cellular proliferation, differentiation, and apoptosis. A key player in this process is the gastric stem cell (GSC). GSCs are located in the isthmus region of the corpus gastric gland and have the potential to proliferate and differentiate. Although several pathways have been identified to regulate stem cell role in several body tissues, little is known about controlling GSC homeostasis. This project aims to study the role of estrogen (E2) in GSC homeostasis using the well-established mouse gastric epithelial progenitor (mGEP) cell line. Our data showed that …

Quantitative Limits On Small Molecule Transport Via The Electropermeome - Measuring And Modeling Single Nanosecond Perturbations, Esin B. Sözer, Zachary A. Levine, P. Thomas Vernier

Bioelectrics Publications

The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical parameters in existing models must be replaced with physics- and biology-based terms anchored in experimental observations. We report here absolute values for the uptake of YO-PRO-1, a small-molecule fluorescent indicator of membrane integrity, into cells after a single electric pulse lasting only 6 ns. We correlate these measured values, based on fluorescence microphotometry of hundreds of individual cells, with a diffusion-based geometric analysis of pore-mediated …

Pneb193-Derived Suicide Plasmids For Gene Deletion And Protein Expression In The Methane-Producing Archaeon, Methanosarcina Acetivorans, Mitchell T. Shea, Mary E. Walter, Nikolas Duszenko, Anne-Lise Ducluzeau, Jared Aldridge, Shannon K. King, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Gene deletion and protein expression are cornerstone procedures for studying metabolism in any organism, including methane-producing archaea (methanogens). Methanogens produce coenzymes and cofactors not found in most bacteria, therefore it is sometimes necessary to express and purify methanogen proteins from the natural host. Protein expression in the native organism is also useful when studying post-translational modifications and their effect on gene expression or enzyme activity. We have created several new suicide plasmids to complement existing genetic tools for use in the methanogen, Methanosarcina acetivorans. The new plasmids are derived from the commercially available E. coli plasmid, pNEB193, and cannot replicate …

Isokinetic Dynamometry And 1rm Tests Produce Conflicting Results For Assessing Alterations In Muscle Strength, Paulo Gentil, Fabricio Boscolo Del Vecchio, Antonio Paoli, Brad J. Schoenfeld, Martim Bottaro

Publications and Research

The purpose of this study was to compare strength gains in the lower limbs, assessed by one maximum repetition (1RM) and isokinetic peak torque (PT), in young men undergoing a resistance training (RT) program. Twenty-seven young men performed resistance training twice a week for 11 weeks. Training involved two exercises for the lower body, two for the upper body and one for the midsection performed with three sets of 8-12 repetitions to momentary muscle failure. Before and after the training period, participants performed the 1RM test in the 45° leg press and knee extension PT in isokinetic dynamometry. The Pearson …

Epigenomic Reprogramming In Inorganic Arsenic-Mediated Gene Expression Patterns During Carcinogenesis, Meredith Eckstein, Rebekah Eleazer, Matthew Rea, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Arsenic is a ubiquitous metalloid that is not mutagenic but is carcinogenic. The mechanism(s) by which arsenic causes cancer remain unknown. To date, several mechanisms have been proposed, including the arsenic-induced generation of reactive oxygen species (ROS). However, it is also becoming evident that inorganic arsenic (iAs) may exert its carcinogenic effects by changing the epigenome, and thereby modifying chromatin structure and dynamics. These epigenetic changes alter the accessibility of gene regulatory factors to DNA, resulting in specific changes in gene expression both at the levels of transcription initiation and gene splicing. In this review, we discuss recent literature reports …

Characterization And Analysis Of Real-Time Capillary Convective Pcr Toward Commercialization, Xianbo Qiu, Shiyin Zhang, Lanju Mei, Di Wu, Ke Li, Shengxiang Ge, Xiangzhong Ye, Ningshao Xia, Michael G. Mauk

Mechanical & Aerospace Engineering Faculty Publications

Almost all the reported capillary convective polymerase chain reaction (CCPCR) systems to date are still limited to research use stemming from unresolved issues related to repeatability, reliability, convenience, and sensitivity. To move CCPCR technology forward toward commercialization, a couple of critical strategies and innovations are discussed here. First, single- and dual-end heating strategies are analyzed and compared between each other. Especially, different solutions for dual-end heating are proposed and discussed, and the heat transfer and fluid flow inside the capillary tube with an optimized dual-end heating strategy are analyzed and modeled. Second, real-time CCPCR is implemented with light-emitting diode and …

Foxo3 Increases Mir-34a To Cause Palmitate-Induced Cholangiocyte Lipoapoptosis, Sathish Kumar Natarajan, Bailey A. Stringham, Ashley M. Mohr, Cody J. Wehrkamp, Sizhao Lu, Mary Anne Phillippi, Duygu Dee Harrison-Findik, Justin L. Mott

School of Veterinary and Biomedical Sciences: Faculty Publications

Nonalcoholic steatohepatitis (NASH) patients have elevated plasma saturated free fatty acid levels. These toxic fatty acids can induce liver cell death and our recent results demonstrated that the biliary epithelium may be susceptible to lipotoxicity. Here, we explored the molecular mechanisms of cholangiocyte lipoapoptosis in cell culture and in an animal model of NASH. Treatment of cholangiocytes with palmitate (PA) showed increased caspase 3/7 activity and increased levels of cleaved poly (ADP-ribose) polymerase and cleaved caspase 3, demonstrating cholangiocyte lipoapoptosis. Interestingly, treatment with PA significantly increased the levels of microRNA miR-34a, a pro-apoptotic microRNA known to be elevated in NASH. …

Ticks Elicit Variable Fibrinogenolytic Activities Upon Feeding On Hosts With Different Immune Backgrounds, Ashish Vora, Vikas Taank, John F. Anderson, Durland Fish, Daniel E. Sonenshine, John D. Catravas, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ticks secrete several anti-hemostatic factors in their saliva to suppress the host innate and acquired immune defenses against infestations. Using Ixodes scapularis ticks and age-matched mice purchased from two independent commercial vendors with two different immune backgrounds as a model, we show that ticks fed on immunodeficient animals demonstrate decreased fibrinogenolytic activity in comparison to ticks fed on immunocompetent animals. Reduced levels of D-dimer (fibrin degradation product) were evident in ticks fed on immunodeficient animals in comparison to ticks fed on immunocompetent animals. Increased engorgement weights were noted for ticks fed on immunodeficient animals in comparison to ticks fed on …

The Mirnaome Of Catharanthus Roseus: Identification, Expression Analysis, And Potential Roles Of Micrornas In Regulation Of Terpenoid Indole Alkaloid Biosynthesis, Ethan M. Shen, Sanjay Kumar Singh, Jayadri S. Ghosh, Barunava Patra, Priyanka Paul, Ling Yuan, Sitakanta Pattanaik

Plant and Soil Sciences Faculty Publications

MicroRNAs (miRNAs) regulate numerous crucial biological processes in plants. However, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including Catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (TIAs). Using small RNA-sequencing, we identified 181 conserved and 173 novel miRNAs (cro-miRNAs) in C. roseus seedlings. Genome-wide expression analysis revealed that a set of cro-miRNAs are differentially regulated in response to methyl jasmonate (MeJA). In silico target prediction identified 519 potential cro-miRNA targets that include several auxin response factors (ARFs). The presence of cleaved transcripts of miRNA-targeted ARFs in C. roseus …

Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …

Hendra Virus Fusion Protein Transmembrane Domain Contributes To Pre-Fusion Protein Stability, Stacy Webb, Tamas Nagy, Hunter Moseley, Michael G. Fried, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains …

Bioaccumulation Of Metallic Trace Elements And Antioxidant Enzyme Activities In Apfelbeckia Insculpta (L. Koch, 1867) (Diplopoda: Callipodida) From The Cave Hadži-Prodanova Pećina (Serbia), Jelena Vranković, Slavica Borković-Mitić, Bojan Ilić, Milanka Radulović, Slaviša Milošević, Slobodan Makarov, Bojan Mitić

International Journal of Speleology

The concentration of 10 metallic trace elements or MTE (Cu, Fe, Zn, Mn, As, Hg, Pb, Cd, Ni, and Cr) was measured in specimens of the troglophilic millipede Apfelbeckia insculpta (L. Koch, 1867) and sediment of the cave Hadži-Prodanova Pećina in western Serbia. Some MTE, like Fe and Mn, displayed much higher concentrations compared to other elements, both in the sediment and in the body of A. insculpta. On the other hand, estimation of the bioaccumulation factor (BAF) in both males and females of A. insculpta showed values greater than 1 for xenobiotic elements compared to those that are essential. …

Oled Loki As A Catalyst For Tertiary Amine And Hydroxamate Glycosylation, Ryan R. Hughes, Khaled A. Shaaban, Jianjun Zhang, Hongnan Cao, George N. Phillips Jr., Jon S. Thorson

Center for Pharmaceutical Research and Innovation Faculty Publications

We describe the ability of an engineered glycosyltransferase (OleD Loki) to catalyze the N‐glycosylation of tertiary‐amine‐containing drugs and trichostatin hydroxamate glycosyl ester formation. As such, this study highlights the first bacterial model catalyst for tertiary‐amine N‐glycosylation and further expands the substrate scope and synthetic potential of engineered OleDs. In addition, this work could open the door to the discovery of similar capabilities among other permissive bacterial glycosyltransferases.

Dual-Functional-Tag-Facilitated Protein Labeling And Immobilization, Xinyi Zhang, Wei Lu, Kevin Kwan, Dibakar Bhattacharyya, Yinan Wei

Chemistry Faculty Publications

An important strategy in the construction of biomimetic membranes and devices is to use natural proteins as the functional components for incorporation in a polymeric or nanocomposite matrix. Toward this goal, an important step is to immobilize proteins with high efficiency and precision without disrupting the protein function. Here, we developed a dual-functional tag containing histidine and the non-natural amino acid azidohomoalanine (AHA). AHA is metabolically incorporated into the protein, taking advantage of the Met-tRNA and Met-tRNA synthetase. Histidine in the tag can facilitate metal-affinity purification, whereas AHA can react with an alkyne-functionalized probe or surface via well-established click chemistry. …

The Association Of Serum Levels Of Brain-Derived Neurotrophic Factor With The Occurrence Of And Recovery From Delirium In Older Medical Inpatients, John Williams, Karen Finn, Vincent Melvin, David Meagher, Geraldine Mccarthy, Dimitrios Adamis

Department of Biological Sciences Publications

Limited studies of the association between BDNF levels and delirium have given inconclusive results. This prospective, longitudinal study examined the relationship between BDNF levels and the occurrence of and recovery from delirium. Participants were assessed twice weekly using MoCA, DRS-R98, and APACHE II scales. BDNF levels were estimated using an ELISA method. Delirium was defined with DRS-R98 (score > 16) and recovery from delirium as ≥2 consecutive assessments without delirium prior to discharge. We identified no difference in BDNF levels between those with and without delirium. Excluding those who never developed delirium (), we examined the association of BDNF levels and …