Biochemistry, Biophysics, and Structural Biology Commons^™

A Chimeric Nucleobase - Phenylazo Derivative As An Intrinsic Nucleobase Quencher, Gyeongsu Park, Timothy Martin-Chan, Amer El Samm, Robert H.E. Hudson

Western Research Forum

Molecular beacons are important bioanalytical probes which are most often

constructed from a single-stranded oligonucleotide which has been labeled at

opposite termini with a fluorophore and a quencher. When the fluorophore and

quencher are in close proximity, no fluorescence is observed due to FRET

(Fluorescence Resonance Energy Transfer). DABCYL (4-dimethylaminoazobenzene-

4'-carboxylic acid) has been used as a quencher in the molecular beacon to absorbs

excitation energy from a fluorophore and to dissipate the energy as heat. However,

DABCYL is unable to form a base-pair and is conventionally placed as an overhanging

residue. This produces a derivative wherein the chromophore has …

Role Of Pu.1 And C/Ebpα In Remodelling The Interleukin (Il)-1Β Enhancer-Promoter Interaction, Woohyun Cho, Soon-Duck Ha, Sung Ouk Kim

Western Research Forum

Background: IL-1b is a potent inflammatory cytokine promptly expressed in activated myeloid immune cells. Among various transcription factors, PU.1 and CCAAT/enhancer-binding protein alpha (C/EBPa) play a key role in the lineage commitment of myeloid cells. To date, however, the exact mechanisms by which these lineage-determining transcription factors employ to regulate the expression of myeloid-specific genes remains elusive; thus, this study explores the role of PU.1 and C/EBPa in remodelling the chromatin conformation that allows ample production of IL-1b.

Methods: To examine the mechanism of these lineage-determining transcription factors, production of IL-1b and enhancer-promoter interactions were analyzed in non-myeloid B16-BL6 cells …

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …

Maternal Protein Restriction (Mpr): A Risk Factor For Acute Respiratory Distress Syndrome (Ards), Reza Khazaee

Western Research Forum

Background: Acute respiratory distress syndrome (ARDS) is defined as severe lung dysfunction. The lung impairments in ARDS result from alterations to pulmonary surfactant; a lipid-protein mixture coating the inside of the lung and maintains the lungs’ ability to expand easily. Due to a lack of effective pharmacological therapies mortality associated with ARDS is over 30%. Our research focuses on risk factors that indicate a susceptibility to the disease, which could provide new and early therapeutic options. One such potential risk factor is Maternal Protein Restriction (MPR). MPR is defined by low birth weight and contributes to a variety of adult-onset …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

Valued readers, it is with a heavy heart that I inform you that this is the last issue of Killi-Data News. The good news is that we will be back as Killifish Research Review. The dissolution of Killi-Data International created a prob- lem: how can the newsletter of a defunct organization live on without that organization? But other additional problems were building in the background. The first issue numbered 15 pages. The previous issue was 28 pages. The number of killifish related papers is increasing while time on our end (the editorial team) is running out. It takes a lot …

Killi-Data News (Fall), Tyrone Genade

Killifish Research Review

Many interesting papers have been published over the last three months. The large volume of papers coupled with the start of the new college semester (and the workload it brings) delayed this issue of Killi-Data News. But better late than never—or so I hope! In this issue Richard van der Laan provides an insightful review of the recent Aphanius papers as to their taxonomic implications and questions. The systematic issues he raises show the importance of the Molecular project: we need to get more samples of the various cyprinodontiforme families to resolve unsettled systematic and taxonomic issues. In the Next …

Killi-Data News (Summer), Tyrone Genade

Killifish Research Review

Over the last three months several interesting and exciting pa- pers have been published. By now most of you have heard the Nothobranchius fish poo news emanating from the Valenzano lab. That paper is reviewed and certainly has repercussions for the health of our captive fish. Polaçik et al have published interesting data with ramifications as to how we breed and incubate annual killifish. The big news in this issue is the paper from the Reznick lab which Jean Huber reviews. The contents of that paper goes to the heart of the question of just what a killifish is. The …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

This is the fourth edition, and concluding issue of the first volume, of Killi-Data News and I am happy that it has been well received by readers. At 25 pages this issue is a bit thin- ner than the last but this is because we agreed to make the cut-off for submissions the 1 st of December so we could get this edition out by the New Year. This is an exciting edition full of new species descrip- tions and analyses that will keep taxonomists busy for years to come. Costa has given us two molecular phylogenies on Melanorivulus as …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

Characterization Of Metabolic Networks In Differentiated Cd4+ T Cells, Bailee Lichter

Honors Program: Senior Projects (Public)

CD4+ T cells play a critical role in the immune system and protecting the body from infection. Cell differentiation of T-cells leads to the specialization of the immune system and has been determined to have plasticity. Differentiation of the CD4+ T cells depends on cytokines present in the environment, concentration of antigens, types of antigen – presenting cells (APCs), and costimulatory molecules (Luckheeram, 2012). Commonly known differentiated T-cells include the T-helper 1 (Th1) and the T-helper 2 (Th2) cells. Upon CD4+ T cell activation, the cells undergo metabolic changes that allow for cell growth and division. By characterizing the metabolic …

Thermodynamics In Large Hairpin Polyamide-Dna Interactions, Yang Song

Dissertations

Human papillomavirus (HPV) is a common sexually transmitted virus responsible for cervical cancers, and its infection is currently incurable. Only a few vaccines against high-risk HPV strains are available. Hairpin polyamides (PAs) in different sizes (8-20 units long) bind DNA in different lengths. They have been shown to have different anti-HPV activities in cell culture.

The interaction between PA and DNA is stabilized by two types of molecular forces: attractive and repulsive forces. Attractive forces include hydrogen bonds, van der Waals contacts and electrostatic forces between PA and DNA. Repulsive forces include the hydrophobic effect, which forces the PA out …

Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson

Honors Program: Senior Projects (Public)

Copy number variations (CNVs) are large insertions, deletions, and duplications in the genome that vary between individuals in a species. These variations are known to impact a broad range of phenotypes from molecular-level traits to higher-order clinical phenotypes. CNVs have been linked to complex traits in humans such as autism, attention deficit hyperactivity disorder, nervous system disorders, and early-onset extreme obesity. In this study, whole-genome sequence was obtained from 72 founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska. This included 24 boars (12 Duroc and 12 Landrace) and …

Assessment Of A Single Decoupling Alchemical Approach For The Calculation Of The Absolute Binding Free Energies Of Protein-Peptide Complexes, Denise Kilburg, Emilio Gallicchio

Publications and Research

The computational modeling of peptide inhibitors to target protein-protein binding interfaces is growing in interest as these are often too large, too shallow, and too feature-less for conventional small molecule compounds. Here, we present a rare successful application of an alchemical binding free energy method for the calculation of converged absolute binding free energies of a series of protein-peptide complexes. Specifically, we report the binding free energies of a series of cyclic peptides derived from the LEDGF/p75 protein to the integrase receptor of the HIV1 virus. The simulations recapitulate the effect of mutations relative to the wild-type binding motif of …

Non-Methane Organic Gas Emissions From Biomass Burning: Identification, Quantification, And Emission Factors From Ptr-Tof During The Firex 2016 Laboratory Experiment, Abigail R. Koss, Kanako Sekimoto, Jessica B. Gilman, Vanessa Selimovic, Matthew M. Coggon, Kyle J. Zarzana, Bin Yuan, Brian M. Lerner, Steven S. Brown, Jose L. Jimenez, Jordan Krechmer, James M. Roberts, Carsten Warneke, Robert J. Yokelson, Joost De Gouw

Chemistry and Biochemistry Faculty Publications

Volatile and intermediate-volatility non-methane organic gases (NMOGs) released from biomass burning were measured during laboratory-simulated wildfires by proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF). We identified NMOG contributors to more than 150 PTR ion masses using gas chromatography (GC) pre-separation with electron ionization, H3O+ chemical ionization, and NO+ chemical ionization, an extensive literature review, and time series correlation, providing higher certainty for ion identifications than has been previously available. Our interpretation of the PTR-ToF mass spectrum accounts for nearly 90ĝ€-% of NMOG mass detected by PTR-ToF across all fuel types. The relative contributions of different NMOGs to individual exact ion masses are …

Structure Of Full-Length Human Trpm4, Jingjing Duan, Zongli Li, Jian Li, Ana Santa-Cruz, Silvia Sanchez-Martinez, Jin Zhang, David E. Clapham

Molecular and Cellular Biochemistry Faculty Publications

Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na⁺-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist …

Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona

UNO Student Research and Creative Activity Fair

Smoothened receptor (SMO) is a protein that in humans, is encoded by the SMO gene. A systemic mutation in its binding pocket helps predict the sensitivity of mutant proteins to different drugs. Known as a GPCR-like receptor, it is a component of the hedgehog signaling pathway; a pathway involved in body patterning and the regulation of adult stem cells. An uncontrolled or inappropriate activation of the Hedgehog pathway drives tumor progression in cancers and a number of birth defects. To achieve these goals, the molecular modeling software MOE was used to build small molecules and drug molecules like Vismodegib and …

Investigating The Genetic Structure Of Northern Long-Eared Bats In Nebraska, Jonathan Korbitz

UNO Student Research and Creative Activity Fair

Abstract:

The northern long-eared bat (Myotis septentrionalis) is one of many species of hibernating bats in North America affected by a recently discovered fungal disease called white-nose syndrome (WNS). Northern long-eared bats seem to be extremely susceptible to the disease with mass fatalities occurring among populations in eastern North America. Researchers in the eastern distribution of this species have performed mtDNA analysis to identify the population structure of the species; however, genetic analysis has yet to be done in western parts of its distribution. The goal of this study is to create a better understanding of the genetic …

Bpwrapper: Bioperl-Based Sequence And Tree Utilities For Rapid Prototyping Of Bioinformatics Pipelines, Yözen Hernández, Rocky Bernstein, Pedro Pagan, Levy Vargas, William Mccaig, Girish Ramrattan, Saymon Akther, Amanda Larracuente, Lia Di, Filipe G. Vieira, Weigang Qiu

Publications and Research

Abstract:

Background: Automated bioinformatics workflows are more robust, easier to maintain, and results more reproducible when built with command-line utilities than with custom-coded scripts. Command-line utilities further benefit by relieving bioinformatics developers to learn the use of, or to interact directly with, biological software libraries. There is however a lack of command-line utilities that leverage popular Open Source biological software toolkits such as BioPerl (http://bioperl.org) to make many of the well-designed, robust, and routinely used biological classes available for a wider base of end users.

Results: Designed as standard utilities for UNIX-family operating systems, BpWrapper makes functionality of some of …

Evolution Of Echovirus 11 In A Chronically Infected Immunodeficient Patient., Majid Laassri, Tatiana Zagorodnyaya, Sharon Hassin-Baer, Rachel Handsher, Danit Sofer, Merav Weil, Konstantinos Karagiannis, Vahan Simonyan, Konstantin Chumakov, Lester Shulman

Biochemistry and Molecular Medicine Faculty Publications

Deep sequencing was used to determine complete nucleotide sequences of echovirus 11 (EV11) strains isolated from a chronically infected patient with CVID as well as from cases of acute enterovirus infection. Phylogenetic analysis showed that EV11 strains that circulated in Israel in 1980-90s could be divided into four clades. EV11 strains isolated from a chronically infected individual belonged to one of the four clades and over a period of 4 years accumulated mutations at a relatively constant rate. Extrapolation of mutations accumulation curve into the past suggested that the individual was infected with circulating EV11 in the first half of …

Aerosol Optical Properties And Trace Gas Emissions By Pax And Op-Ftir For Laboratory-Simulated Western Us Wildfires During Firex, Vanessa Selimovic, Robert J. Yokelson, Carsten Warneke, James M. Roberts, Joost De Gouw, James Reardon, David W.T. Griffith

Chemistry and Biochemistry Faculty Publications

Western wildfires have a major impact on air quality in the US. In the fall of 2016, 107 test fires were burned in the large-scale combustion facility at the US Forest Service Missoula Fire Sciences Laboratory as part of the Fire Influence on Regional and Global Environments Experiment (FIREX). Canopy, litter, duff, dead wood, and other fuel components were burned in combinations that represented realistic fuel complexes for several important western US coniferous and chaparral ecosystems including ponderosa pine, Douglas fir, Engelmann spruce, lodgepole pine, subalpine fir, chamise, and manzanita. In addition, dung, Indonesian peat, and individual coniferous ecosystem fuel …

Serum Tumour Necrosis Factor Alpha In Osteopenic And Osteoporotic Postmenopausal Females: A Cross-Sectional Study In Pakistan, Rafat Murad, Zahra Shezad, Saara Ahmed, Mussarat Ashraf, Murad Qadir, Rehana Rehman

Department of Biological & Biomedical Sciences

Objective: To compare biochemical parameters serum tumour necrosis factor alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D in postmenopausal women.
Methods: This cross-sectional study was carried out from June 2015 to July 2016 at Jinnah Medical and Dental College, Karachi, and comprised postmenopausal women. Bone mineral density done by dual energy X-ray absorptiometryscan categorised subjects by World Health Organisation classification into normal (T score > -1) osteopenic (T score between -1 and -2.5) and osteoporotic (T score < -2.5). Biochemical parameters like tumour necrosis alpha, calcium, magnesium, bone-specific alkaline phosphatase and vitamin D were measured by solid phase enzyme amplified sensitivity immunoassay method. SPSS 16 was used to analyse the data.
Results: Of the 146 women, 34(23%) were normal, 93(67%) were osteopenic and 19(13%) were osteoporotic. There was significant difference in mean body mass …

A Gender-Based Comparison In Health Behaviors And State Of Happiness Among University Students, Rehana Rehman, Amara Zafar, Aleena Mohib, Mukhtiar Baig

Department of Biological & Biomedical Sciences

Objective: The presence of good healthy behaviors among university students is imperative for their future life. This study aimed to compare positive health behaviors and state of happiness between the two genders of Bahria University (BU), Karachi, Pakistan.
Subjects and methods: This cross-sectional study was conducted at BU, Karachi, Pakistan. A total 813 students participated in this study. The healthquestionnaire, adapted from Health and Behavior Survey and the Subjective Happiness Scale, was used to assess self-reported happiness. The data were analyzed using IBM SPSS version 22.
Results: Overall self-reported health behaviors were found to be more prevalent in females as …

Circulating Pander Concentration Is Associated With Increased Hba1c And Fasting Blood Glucose In Type 2 Diabetic Subjects, Catherine B. Marelia, Melanie N. Kuehl, Tiffany A. Shemwell, Amy C. Alman, Brant R. Burkhardt

Molecular Biosciences Faculty Publications

Aim: PANcreatic-DERived factor (PANDER, FAM3B) is a novel hormone that regulates glucose levels via interaction with both the endocrine pancreas and liver. Prior studies examining PANDER were primarily conducted in murine models or in vitro but little is known regarding the circulating concentration of PANDER in humans, especially with regard to the association of type 2 diabetes (T2D) or overall glycemic regulation. To address this limitation, we performed a cross-sectional analysis of circulating serum PANDER concentration in association with other hormones that serve as either markers of insulin resistance (insulin and adiponectin) or to metabolic parameters of glycemic control such …

In Vitro Label Free Screening Of Chemotherapeutic Drugs Using Raman Micro-Spectroscopy: Towards A New Paradigm Of Spectralomics., Zeineb Farhane, Haq Nawaz, Franck Bonnier, Hugh Byrne

Articles

This overview groups some of the recent studies highlighting the potential application of Raman micro-spectroscopy as an analytical technique in preclinical development to predict drug mechanism of action and in clinical application as a companion diagnostic and in personalised therapy due to its capacity to predict cellular resistance and therefore to optimise chemotherapeutic treatment efficacy.

Notably, the anthracyclines, Doxorubicin and Actinomycin D, elicit similar spectroscopic signatures of subcellular interaction characteristic of the mode of action of intercalation. Although Cisplatin and Vincristine show markedly different signatures, at low exposure doses, their signatures at higher doses show marked similarities to those elicited …

Contribution Of Bulky <&Alpha>,<&Beta>-Dehydroamino Acids To The Proteolytic Stability Andenhanced Folding Of <&Beta>-Hairpins And Progress Towards The Total Synthesis Of Yaku<'>Amide A, Ankur Jalan

Theses and Dissertations

This dissertation primarily covers the impact of bulky ,-dehydroamino acids on the proteolytic stability and enhanced folding of -hairpins. It partly describes the progress towards the total synthesis of yakuamide A, a potent anticancer peptide with an IC50 value of 14 ng/mL against leukemia cells. Proteins and peptides are a very attractive source of potential medicinal agents as they can target various protein“protein interactions that are implicated in several diseases and disorders. The global sales of peptide drugs in 2013 were estimated to be about $28 billion and are constantly rising at an appreciable rate. However, peptide drugs have a …

Characterization Of The Roles Of Muscle-Synthesized Brain-Derived Neurotrophic Factor And Presynaptic Tyrosine Receptor Kinase B In Motor Neuron Axonal Transport, Luke A. Vanosdol

All NMU Master's Theses

Brain-derived neurotrophic factor (BDNF) is a small, diffusible protein essential for the development and function of neurons. It is synthesized by many types of tissue, including muscle. BDNF actions are mediated via binding to its receptor, tyrosine receptor kinase B (TrkB). The BDNF-TrkB complex is endocytosed into a specialized vesicle, which induces downstream signaling cascades locally in the dendrites, or, more often, is delivered to the cell soma via retrograde axonal transport, where it modulates gene expression. BDNF activation of TrkB is critical for the initiation of axonal transport, and this cellular process relies on the interaction of numerous adaptor …

Rescue Of Neocortical Circuit Deficits With Modified Bone Marrow-Derived Mesenchymal Stem Cells, Sb623, In A Rat Model Of Photothrombotic Stroke, Alexander Urry

Yale Day of Data

The following poster characterizes the effects of a novel stem cell line on treating the neural circuit deficits resulting from stroke.

Electron Transfer To Nitrogenase In Different Genomic And Metabolic Backgrounds, Saroj Poudel, Daniel R. Colman, Kathryn R. Fixen, Rhesa N. Ledbetter, Yanning Zheng, Natasha Pence, Lance C. Seefeldt, John W. Peters, Caroline S. Harwood, Eric S. Boyd

Chemistry and Biochemistry Faculty Publications

Nitrogenase catalyzes the reduction of dinitrogen (N₂) using low-potential electrons from ferredoxin (Fd) or flavodoxin (Fld) through an ATP-dependent process. Since its emergence in an anaerobic chemoautotroph, this oxygen (O₂)-sensitive enzyme complex has evolved to operate in a variety of genomic and metabolic backgrounds, including those of aerobes, anaerobes, chemotrophs, and phototrophs. However, whether pathways of electron delivery to nitrogenase are influenced by these different metabolic backgrounds is not well understood. Here, we report the distribution of homologs of Fds, Flds, and Fd-/Fld-reducing enzymes in 359 genomes of putative N₂ fixers (diazotrophs). Six distinct lineages …

Lafora Disease Offers A Unique Window Into Neuronal Glycogen Metabolism, Matthew S. Gentry, Joan J. Guinovart, Berge A. Minassian, Peter J. Roach, Jose M. Serratosa

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase.