Digital Commons Network^™

Ubiquitin-Specific Peptidase 10 (Usp10) Deubiquitinates And Stabilizes Muts Homolog 2 (Msh2) To Regulate Cellular Sensitivity To Dna Damage, Mu Zhang, Chen Hu, Dan Tong, Shengyan Xiang, Kendra Williams, Wenlong Bai, Guo-Min Li, Gerold Bepler, Xiaohong Zhang

Toxicology and Cancer Biology Faculty Publications

MSH2 is a key DNA mismatch repair protein, which plays an important role in genomic stability. In addition to its DNA repair function, MSH2 serves as a sensor for DNA base analogs-provoked DNA replication errors and binds to various DNA damage-induced adducts to trigger cell cycle arrest or apoptosis. Loss or depletion of MSH2 from cells renders resistance to certain DNA-damaging agents. Therefore, the level of MSH2 determines DNA damage response. Previous studies showed that the level of MSH2 protein is modulated by the ubiquitin-proteasome pathway, and histone deacetylase 6 (HDAC6) serves as an ubiquitin E3 ligase. However, the deubiquitinating …

Comparison Of Protein Phosphatase Inhibition Assay With Lc-Ms/Ms For Diagnosis Of Microcystin Toxicosis In Veterinary Cases, Caroline E. Moore, Jeanette Juan, Yanping Lin, Cynthia L. Gaskill, Birgit Puschner

Veterinary Diagnostic Laboratory Faculty Publications

Microcystins are acute hepatotoxins of increasing global concern in drinking and recreational waters and are a major health risk to humans and animals. Produced by cyanobacteria, microcystins inhibit serine/threonine protein phosphatase 1 (PP1). A cost-effective PP1 assay using p-nitrophenyl phosphate was developed to quickly assess water and rumen content samples. Significant inhibition was determined via a linear model, which compared increasing volumes of sample to the log-transformed ratio of the exposed rate over the control rate of PP1 activity. To test the usefulness of this model in diagnostic case investigations, samples from two veterinary cases were tested. In August …

P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A Brekken, Craig W. Vander Kooi, Arthur M. Mercurio

Molecular and Cellular Biochemistry Faculty Publications

Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTEN^pc−/− transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases the …

A Colletotrichum Graminicola Mutant Deficient In The Establishment Of Biotrophy Reveals Early Transcriptional Events In The Maize Anthracnose Disease Interaction, Maria F. Torres, Noushin Ghaffari, Ester A. S. Buiate, Neil Moore, Scott Schwartz, Charles D. Johnson, Lisa J. Vaillancourt

Plant Pathology Faculty Publications

Background: Colletotrichum graminicola is a hemibiotrophic fungal pathogen that causes maize anthracnose disease. It progresses through three recognizable phases of pathogenic development in planta: melanized appressoria on the host surface prior to penetration; biotrophy, characterized by intracellular colonization of living host cells; and necrotrophy, characterized by host cell death and symptom development. A “Mixed Effects” Generalized Linear Model (GLM) was developed and applied to an existing Illumina transcriptome dataset, substantially increasing the statistical power of the analysis of C. graminicola gene expression during infection and colonization. Additionally, the in planta transcriptome of the wild-type was compared with that of …

Data Publication With The Structural Biology Data Grid Supports Live Analysis, Peter A. Meyer, Stephanie Socias, Jason Key, Elizabeth Ransey, Emily C. Tjon, Alejandro Buschiazzo, Ming Lei, Chris Botka, James Withrow, David Neau, Kanagalaghatta Rajashankar, Karen S. Anderson, Richard H. Baxter, Stephen C. Blacklow, Titus J. Boggon, Alexandre M. J. J. Bonvin, Dominika Borek, Tom J. Brett, Amedeo Caflisch, Chung-I Chang, Walter J. Chazin, Kevin D. Corbett, Michael S. Cosgrove, Sean Crosson, Sirano Dhe-Paganon, Enrico Di Cera, Catherine L. Drennan, Michael J. Eck, Brandt F. Eichman, Qing R. Fan, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the …

Autocrine Epiregulin Activates Egfr Pathway For Lung Metastasis Via Emt In Salivary Adenoid Cystic Carcinoma, Shuli Liu, Dongxia Ye, Dongliang Xu, Yueling Liao, Ling Zhang, Liu Liu, Wenwen Yu, Yanan Wang, Yue He, Jingzhou Hu, Wenzheng Guo, Tong Wang, Beibei Sun, Hongyong Song, Huijing Yin, Jingyi Liu, Yadi Wu, Hanguang Zhu, Binhua P. Zhou, Jiong Deng, Zhiyuan Zhang

Markey Cancer Center Faculty Publications

Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, …

Mitigation Of Ergot Vasoconstriction By Clover Isoflavones In Goats (Capra Hircus), Glen E. Aiken, Michael D. Flythe, Isabelle A. Kagan, Huihua Ji, Lowell P. Bush

Kentucky Tobacco Research and Development Center Faculty Publications

Ergot alkaloids produced by a fungal endophyte (Epichloë coenophiala; formerly Neotyphodium coenophialum) that infects tall fescue (Lolium arundinaceum) can induce persistent constriction of the vasculature in ruminants, hindering their capability to thermo-regulate core body temperature. There is evidence that isoflavones produced by legumes can relax the vasculature, which suggests that they could relieve ergot alkaloid-induced vasoconstriction and mitigate the vulnerability to severe heat stress in ruminants that graze tall fescue. To test if isoflavones can relieve alkaloid-induced vasoconstriction, two pen experiments were conducted with rumen-fistulated goats (Capra hircus) to determine with ultrasonograpy if …

Cell-Free And Cell-Based Approaches To Explore The Roles Of Host Membranes And Lipids In The Formation Of Viral Replication Compartment Induced By Tombusviruses, Peter D. Nagy, Judit Pogany, Kai Xu

Plant Pathology Faculty Publications

Plant positive strand RNA viruses are intracellular infectious agents that take advantage of cellular lipids and membranes to support replication and protect viral RNA from degradation by host antiviral responses. In this review, we discuss how Tomato bushy stunt virus (TBSV) co-opts lipid transfer proteins and modulates lipid metabolism and transport to facilitate the assembly of the membrane-bound viral replicase complexes within intricate replication compartments. Identification and characterization of the proviral roles of specific lipids and proteins involved in lipid metabolism based on results from yeast (Saccharomyces cerevisiae) model host and cell-free approaches are discussed. The review also …

Biopolymeric Mucin And Synthetic Polymer Analogs: Their Structure, Function And Role In Biomedical Applications, Sundar Prasanth Authimoolam, Thomas D. Dziubla

Chemical and Materials Engineering Faculty Publications

Mucin networks are viscoelastic fibrillar aggregates formed through the complex self-association of biopolymeric glycoprotein chains. The networks form a lubricious, hydrated protective shield along epithelial regions within the human body. The critical role played by mucin networks in impacting the transport properties of biofunctional molecules (e.g., biogenic molecules, probes, nanoparticles), and its effect on bioavailability are well described in the literature. An alternate perspective is provided in this paper, presenting mucin’s complex network structure, and its interdependent functional characteristics in human physiology. We highlight the recent advances that were achieved through the use of mucin in diverse areas of bioengineering …

Transcriptional Profile Of Immediate Response To Ionizing Radiation Exposure, Eric C. Rouchka, Robert M. Flight, Brigitte H. Fasciotto, Rosendo Estrada, John W. Eaton, Phani K. Patibandla, Sabine J. Waigel, Dazhuo Li, John K. Kirtley, Palaniappan Sethu, Robert S. Keynton

Molecular and Cellular Biochemistry Faculty Publications

Astronauts participating in long duration space missions are likely to be exposed to ionizing radiation associated with highly energetic and charged heavy particles. Previously proposed gene biomarkers for radiation exposure include phosphorylated H2A Histone Family, Member X (γH2AX), Tumor Protein 53 (TP53), and Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A). However, transcripts of these genes may not be the most suitable biomarkers for radiation exposure due to a lack of sensitivity or specificity. As part of a larger effort to develop lab-on-a-chip methods for detecting radiation exposure events using blood samples, we designed a dose–course microarray study in order to determine coding …

Trail Planning, Jayoung Koo

Agriculture and Natural Resources Publications

There are two general ways to begin a trail project in a community. The first method is for the community (client) to hire design or planning professionals such as landscape architects, urban planners or engineers to lead a trail project on behalf of the community. The second way involves a grass roots approach where a community gets the project started and develops the conceptual ideas on their own and then later brings in professionals during the design phase. Regardless of the approach for the initial phase, professionals need to be involved to eventually construct the trail(s) but how much of …

Genetically Engineered Crops: Emerging Opportunities, Paul C. Vincelli

Agriculture and Natural Resources Publications

Biotechnology is “any technological application that uses biological systems, living organisms, or derivatives thereof, to make or modify products or processes for specific use.” This definition encompasses many, many applications, including traditional ones such as fermentation of alcoholic beverages.

In certain biotech crops, their genetic material (DNA) has been purposefully manipulated in the laboratory. These genetically engineered crops are often called “GMOs,” an acronym for “genetically modified organisms.” These GMOs are the focus of this publication.

Plant Diseases [2016], Kimberly Leonberger, Kelly Jackson, Robbie Smith, Nicole Ward Gauthier

Agriculture and Natural Resources Publications

Anyone who has ever planted a garden knows not only the rewards of beautiful flowers, fruit, and/ or vegetables, but also the disappointment when plants become diseased or damaged. Many factors cause plants to exhibit poor vigor, changes in appearance, or even death. Both abiotic (non-living) and biotic (living) factors can negatively impact plant heath. Disorders that result from non-living factors (such as nutrient deficiencies, over/under watering, temperature stress, and chemical damage) are discussed in subsequent chapters. This chapter focuses on those living organisms that cause disease: fungi, water molds, bacteria, viruses, nematodes, phytoplasmas, and parasitic plants.

Biological Nanomotors With A Revolution, Linear, Or Rotation Motion Mechanism, Peixuan Guo, Hiroyuki Noji, Christopher M. Yengo, Zhengyi Zhao, Ian Grainge

Nanobiotechnology Center Faculty Publications

The ubiquitous biological nanomotors were classified into two categories in the past: linear and rotation motors. In 2013, a third type of biomotor, revolution without rotation (http://rnanano.osu.edu/movie.html), was discovered and found to be widespread among bacteria, eukaryotic viruses, and double-stranded DNA (dsDNA) bacteriophages. This review focuses on recent findings about various aspects of motors, including chirality, stoichiometry, channel size, entropy, conformational change, and energy usage rate, in a variety of well-studied motors, including F_oF₁ ATPase, helicases, viral dsDNA-packaging motors, bacterial chromosome translocases, myosin, kinesin, and dynein. In particular, dsDNA translocases are used to illustrate how …

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

Myonuclear Transcription Is Responsive To Mechanical Load And Dna Content But Uncoupled From Cell Size During Hypertrophy, Tyler J. Kirby, Rooshil M. Patel, Timothy S. Mcclintock, Esther E. Dupont-Versteegden, Charlotte A. Peterson, John J. Mccarthy

Physiology Faculty Publications

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number …

Application Of Recycled Media And Algae-Based Anaerobic Digestate In Scenedesmus Cultivation, Xinyi E, Czarena Crofcheck, Mark Crocker

Biosystems and Agricultural Engineering Faculty Publications

To make large-algae cultivation systems sustainable, commercial fertilizer inputs should be minimized. One means of achieving this is to maximize the recycle of nutrients used in algae cultivation. In addition to recycling nutrient-containing water from algae harvesting and dewatering, after harvesting algal biomass can be used as a substrate for anaerobic digestion, which can then generate mineralized nutrients to be used for further cultivation. In this study, the effect of recycling media and using mineralized nutrients during Scenedesmus cultivation was investigated. The recycled media proved to be able to support cell growth with nutrient replenishment, and it could be recycled …

Unexpected Reaction Pathway For Butyrylcholinesterase-Catalyzed Inactivation Of "Hunger Hormone" Ghrelin, Jianzhuang Yao, Yaxia Yuan, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-step reaction pathway and the single-step acylation process is rate-determining. The free energy barrier (18.8 kcal/mol) calculated for the rate-determining step is reasonably close to the experimentally-derived free energy barrier (~19.4 kcal/mol), suggesting that the obtained mechanistic insights are reasonable. The single-step reaction pathway for the acylation is remarkably different from the well-known two-step acylation reaction pathway for numerous ester hydrolysis reactions …

Structures Of Eccb1 And Eccd1 From The Core Complex Of The Mycobacterial Esx-1 Type Vii Secretion System, Jonathan Mark Wagner, Sum Chan, Timothy J. Evans, Sara Kahng, Jennifer Kim, Mark A. Arbing, David Eisenberg, Konstantin V. Korotkov

Molecular and Cellular Biochemistry Faculty Publications

Background: The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system.

Results: This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB₁ and EccD₁. The periplasmic domain of EccB₁ consists of 4 repeat domains and a central domain, which together form a quasi …

Role Of Flippases In Protein Glycosylation In The Endoplasmic Reticulum, Jeffrey S. Rush

Molecular and Cellular Biochemistry Faculty Publications

Glycosylation is essential to the synthesis, folding, and function of glycoproteins in eukaryotes. Proteins are co- and posttranslationally modified by a variety of glycans in the endoplasmic reticulum (ER); modifications include C- and O-mannosylation, N-glycosylation, and the addition of glycosylphosphatidylinositol membrane anchors. Protein glycosylation in the ER of eukaryotes involves enzymatic steps on both the cytosolic and lumenal surfaces of the ER membrane. The glycans are first assembled as precursor glycolipids, on the cytosolic surface of the ER, which are tethered to the membrane by attachment to a long-chain polyisoprenyl phosphate (dolichol) containing a reduced α-isoprene. The lipid-anchored building blocks …

Involvement Of Parp1 In The Regulation Of Alternative Splicing, Elena Matveeva, John Maiorano, Qingyang Zhang, Abdallah M. Eteleeb, Paolo Convertini, Jing Chen, Vittoria Infantino, Stefan Stamm, Jiping Wang, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Specialized chromatin structures such as nucleosomes with specific histone modifications decorate exons in eukaryotic genomes, suggesting a functional connection between chromatin organization and the regulation of pre-mRNA splicing. Through profiling the functional location of Poly (ADP) ribose polymerase, we observed that it is associated with the nucleosomes at exon/intron boundaries of specific genes, suggestive of a role for this enzyme in alternative splicing. Poly (ADP) ribose polymerase has previously been implicated in the PARylation of splicing factors as well as regulation of the histone modification H3K4me3, a mark critical for co-transcriptional splicing. In light of these studies, we hypothesized that …

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …

A Specialist Herbivore Pest Adaptation To Xenobiotics Through Up-Regulation Of Multiple Cytochrome P450s, Fang Zhu, Timothy W. Moural, David R. Nelson, Subba R. Palli

Entomology Faculty Publications

The adaptation of herbivorous insects to their host plants is hypothesized to be intimately associated with their ubiquitous development of resistance to synthetic pesticides. However, not much is known about the mechanisms underlying the relationship between detoxification of plant toxins and synthetic pesticides. To address this knowledge gap, we used specialist pest Colorado potato beetle (CPB) and its host plant, potato, as a model system. Next-generation sequencing (454 pyrosequencing) was performed to reveal the CPB transcriptome. Differential expression patterns of cytochrome P450 complement (CYPome) were analyzed between the susceptible (S) and imidacloprid resistant (R) beetles. We also evaluated the global …

Pi(4)P Promotes Phosphorylation And Conformational Change Of Smoothened Through Interaction With Its C-Terminal Tail, Kai Jiang, Yajuan Liu, Junkai Fan, Jie Zhang, Xiang-An Li, B. Mark Evers, Haining Zhu, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc-Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an …

Targeting An Essential Gtpase Obg For The Development Of Broad-Spectrum Antibiotics, Josephine A. Bonventre, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti-gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from …

Stable Isotope Resolved Metabolomics Studies In Ex Vivo Tissue Slices, Teresa W-M Fan, Andrew N. Lane, Richard M. Higashi

Toxicology and Cancer Biology Faculty Publications

An important component of this methodology is to assess the role of the tumor microenvironment on tumor growth and survival. To tackle this problem, we have adapted the original approach of Warburg (Warburg, 1923), by combining thin tissue slices with Stable Isotope Resolved Metabolomics (SIRM) to determine detailed metabolic activity of human tissues. SIRM enables the tracing of metabolic transformations of source molecules such as glucose or glutamine over defined time periods, and is a requirement for detailed pathway tracing and flux analysis. In our approach, we maintain freshly resected tissue slices (both cancerous and non- cancerous from the same …

The Significance Of A Common Idiotype (1f7) On Antibodies Against Human Immune Deficiency Virus Type 1 And Hepatitis C Virus, Sybille Muller, Matthew S. Parsons, Heinz Kohler, Michael Grant

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In this review, we trace the concept and potential functional role of regulatory idiotypes in the immune response to human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus, and hepatitis C virus (HCV). A major idiotype involved in these viral infections is recognized and defined by a murine monoclonal antibody (1F7). Antibodies expressing the idiotype defined by 1F7 are dominant in HIV-1 infection and are also found on many broadly neutralizing antibodies against HIV-1. This regulatory idiotypic axis offers opportunities for exploitation in vaccine development for HIV-1, HCV, and other chronic viral infections.

Development And Pilot-Testing Of A Patient Decision Aid For Left Ventricular Assist Device Placement, Kristin Kostick, Estevan D. Delgado, Lidija A. Wilhelms, Courtenay R. Bruce, Jerry D. Estep, Matthias Loebe, Charles Minard, Jennifer S. Blumenthal-Barby

The VAD Journal

Objectives: This paper describes the development methodology and pilot-testing of a decision aid for Left Ventricular Assist Device (LVAD) placement, combining traditional needs-assessment with a novel user-centered approach.

Background: Studies indicate suboptimal patient understanding of the capabilities, lifestyle implications, and risks of LVAD therapy.

Methods and Results: We developed the decision aid in line with the Ottawa Decision Support Framework (ODSF) and the International Patient Decision Aids Standards (IPDAS) for ensuring quality, patient-centered content. Structured interviews were conducted with patients, caregivers, candidates for LVAD treatment, and expert clinicians (n=71) to generate content based on patient values and …

Optogenetic Stimulation Of Drosophila Heart Rate At Different Temperatures And Ca2+ Concentrations, Yuechen Zhu, Henry Uradu, Zana R. Majeed, Robin L. Cooper

Biology Faculty Publications

Optogenetics is a revolutionary technique that enables noninvasive activation of electrically excitable cells. In mammals, heart rate has traditionally been modulated with pharmacological agents or direct stimulation of cardiac tissue with electrodes. However, implanted wires have been known to cause physical damage and damage from electrical currents. Here, we describe a proof of concept to optically drive cardiac function in a model organism, Drosophila melanogaster. We expressed the light sensitive channelrhodopsin protein ChR2.XXL in larval Drosophila hearts and examined light‐induced activation of cardiac tissue. After demonstrating optical stimulation of larval heart rate, the approach was tested at low temperature …

Unique Features Of A Global Human Ectoparasite Identified Through Sequencing Of The Bed Bug Genome, Joshua B. Benoit, Zach N. Adelman, Klaus Reinhardt, Amanda Dolan, Monica Poelchau, Emily C. Jennings, Elise M. Szuter, Richard W. Hagan, Hemant Gujar, Jayendra Nath Shukla, Fang Zhu, M. Mohan, David R. Nelson, Andrew J. Rosendale, Christian Derst, Valentina Resnik, Sebastian Wernig, Pamela Menegazzi, Christian Wegener, Nicolai Peschel, Jacob M. Hendershot, Wolfgang Blenau, Reinhard Predel, Paul R. Johnston, Panagiotis Ioannidis, Robert M. Waterhouse, Ralf Nauen, Corinna Schorn, Mark-Christoph Ott, Frank Maiwald, Subba R. Palli

Entomology Faculty Publications

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome …