Biochemistry Commons^™

Curcumin Potentiates The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Eslam El Nebrisi, Lina T. Al Kury, Keun-Hang Susan Yang, Petrilla Jayaprakash, Frank Christopher Howarth, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Effects of curcumin, a biologically active ingredient of turmeric, were tested on the Ca²⁺transients induced by the activation of α₇ subunit of the human nicotinic acetylcholine (α₇nACh) receptor expressed in SH-EP1 cells. Curcumin caused a significant potentiation of choline (1 mM)-induced Ca²⁺ transients with an EC₅₀ value of 133 nM. The potentiating effect of curcumin was not observed in Ca²⁺ transients induced by high K⁺ (60 mM) containing solutions or activation of α₄β₂ nACh receptors and the extent of curcumin potentiation was not altered in the presence of …

Analysis For Science Librarians Of The 2017 Nobel Prize In Physiology Or Medicine: The Life And Work Of Jeffrey C. Hall, Michael Rosbash, And Michael W. Young, Neyda V. Gilman

Library Scholarship

Jeffrey C. Hall, Michael Rosbash, and Michael W. Young are the 2017 Nobel Prize in Physiology or Medicine Laureates, having earned the award for their “discoveries of molecular mechanisms controlling the circadian rhythm.” They identified the genes involved in the circadian rhythm mechanism and explained how all of the different pieces of the mechanism work together. These discoveries explain how the biological cycles of Earth’s organisms correspond to the rotation of the planet, acting as an inner clock. Their research also provides further opportunities to continue learning about the role of circadian rhythm and its relationship to human health (Nobelprize.org …

The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A. Valeriote, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

Our quest to isolate and characterize natural products with in vitro solid tumor selectivity is driven by access to repositories of Indo-Pacific sponge extracts. In this project an extract of a species of Haplosclerida sponge obtained from the US NCI Natural Products Repository displayed, by in vitro disk diffusion assay (DDA) and IC

Audiobook Of A World From Dust, Ben Mcfarland

Faculty Open Access Books

A World From Dust is a popular science book about the chemical sequence behind the evolution of creation.

It’s about how geology, biology, and chemistry worked together over billions of years, providing a hidden order under the random flow of genes and lava and water.

It’s about the chemical job that each element takes up in life, and how that job is predictable from its place on the periodic table.

It can be told as the story of many elements: how iron and sulfur gave a spark of life; how manganese was a key for oxygen; and how copper and …

Examination Of Orthologous Genes (Mrub_2518 And B3728, Mrub_2519 And B3727, Mrub_2520 And B3726, Mrub_2521 And B3725) Responsible For Abc Phosphate Transporters In Two Species M. Ruber And E. Coli, Margaret Meyer, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes b3725, b3726, b3727, b3728 and Mrub_2518, Mrub_2519, Mrub_2520 and Mrub_2521 (KEGG map number 02010). We predict that these genes encode the components of a Phosphate ABC transporter: Orthologous genes Mrub_2518 (DNA coordinates 2565359..2566438) and b3728 encodes the periplasmic phosphate binding component; Orthologous genes Mrub_2519 (DNA coordinates 2566499..2567485) and b3727, and Mrub_2520 (DNA coordinates 2567496..2568326) and b3726 encode for the two transmembrane proteins; Orthologous genes Mrub_2521 (DNA coordinates 2568338..2569159) and b3725 encode for the ATP binding protein within the cytoplasm. Within the two species, M. ruber and E. coli, …

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted to …

Mrub_1675, Mrub_1676, Mrub_1677, And Mrub_1679 Genes Are Orthologs Of B_3458, B_3457, B_3456, And B_3454 Genes In E. Coli, Respectively, Coding For Abc Transporters. Mrub_1678 And B_3455, Though Perform Similar Tasks, Are Not Orthologous, Ravi Patel, Alaina Hofmann, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1675, Mrub_1676, Mrub_1677, and Mrub_1679 (KEGG map number 02010). We predict these genes encode components of a Branched chain amino acid (ABC) transporter: Mrub_1675 (DNA coordinates 1711022..1712185 on the reverse strand) encodes the permease component, Mrub_1676 (DNA coordinates 1712313..1713170) encodes for the NBD (aka nucleotide binding domain), Mrub_1677 (DNA coordinates 1713167..1714075 on the reverse strand) encodes the NBD (aka nucleotide binding domain), Mrub_1678 (DNA coordinates 1713167..1714075 on the reverse strand) encodes the TMD (aka transmembrane domain) and Mrub_1679 (DNA coordinates 1714781..1715485 on the reverse strand) encodes …

Adp-Ribosylation Factor-Like 2 (Arl2) Regulates Cilia Stability And Development Of Outer Segments In Rod Photoreceptor Neurons, Zachary C. Wright, Yuriy Loskutov, Daniel Murphy, Peter Stoilov, Elena Pugacheva, Andrew F.X. Goldberg, Visvanathan Ramamurthy

Faculty & Staff Scholarship

Photoreceptor cells are specialized neurons with a sensory cilium carrying an elaborate membrane structure, the outer segment (OS). Inherited mutations in genes involved in ciliogenesis frequently result in OS malformation and blindness. ADP-ribosylation factor-like 2 (ARL2) has recently been implicated in OS formation through its association with Binder of ARL2 (BART or ARL2BP), a protein linked to inherited blinding disease. To test the role of ARL2 in vision we created a transgenic mouse model expressing a tagged-dominant active form of human ARL2 (ARL2-Q70L) under a rod-specific promoter. Transgenic ARL2-Q70L animals exhibit reduced photoreceptor cell function as early as post-natal day …

Structural Basis For The Second Step Of Group Ii Intron Splicing, Russell T. Chan, Jessica K. Peters, Aaron R. Robart, Timothy Wiryaman, Kanagalaghatta R. Rajashankar, Navtej Toor

Faculty & Staff Scholarship

The group II intron and the spliceosome share a common active site architecture and are thought to be evolutionarily related. Here we report the 3.7 Å crystal structure of a eukaryotic group II intron in the lariat-3′ exon form, immediately preceding the second step of splicing, analogous to the spliceosomal P complex. This structure reveals the location of the intact 3′ splice site within the catalytic core of the group II intron. The 3′-OH of the 5′ exon is positioned in close proximity to the 3′ splice site for nucleophilic attack and exon ligation. The active site undergoes conformational rearrangements …

Could A Common Mechanism Of Protein Degradation Impairment Underlie Many Neurodegenerative Diseases?, David M. Smith

Faculty & Staff Scholarship

At the cellular level, many neurodegenerative diseases (NDs), often considered proteinopathies, are characterized by the accumulation of misfolded and damaged proteins into large insoluble aggregates. Prominent species that accumulate early and play fundamental roles in disease pathogenesis are amyloid β (Aβ) and tau in Alzheimer disease, α-synuclein (α-syn) in Parkinson disease, and polyQ-expanded huntingtin (Htt) in Huntington disease. Although significant efforts have focused on how the cell deals with these protein aggregates, why is it that these misfolded proteins are not degraded normally in the first place? A vast body of literature supports the notion that the cell’s protein degradation …

Seastar: Systematic Evaluation Of Alternative Transcription Start Sites In Rna, Zhiyi Qin, Peter Stoilov, Xuegong Zhang, Yi Xing

Faculty & Staff Scholarship

Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5′ Untrans- lated Regions (5′UTRs) and N-terminal coding se- quences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to iden- tify the 5′ ends of transcripts. We developed a compu- tational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and com- pares alternative first exon usage across multiple bi- ological conditions. The exons inferred by SEASTAR coincide with transcription start sites identified di- rectly by CAGE experiments and bear epigenetic hall- marks of active promoters. To …

Graphene Nanoplatelets-Sericin Surface-Modified Gum Alloy For Improved Biological Response, Valentina Mitran, Valentina Dinca, Raluca Ion, Vasile D. Cojocaru, Patricia Neacsu, Cerasela Zoica Dinu, Laurentiu Rusen, Simona Brajnicov, Anca Bonciu, Maria Dinescu, Doina Raducanu, Ioan Dan

Faculty & Staff Scholarship

In this study a “Gum Metal” titanium-based alloy, Ti-31.7Nb-6.21Zr-1.4Fe-0.16O, was synthesized by melting and characterized in order to evaluate its potential for biomedical applications. The results showed that the newly developed alloy presents a very high strength, high plasticity and a low Young's modulus relative to titanium alloys currently used in medicine. For further bone implant applications, the newly synthesized alloy was surface modified with graphene nanoplatelets (GNP), sericin (SS) and graphene nanoplatelets/sericine (GNP–SS) composite films via Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The characterization of each specimen was monitored by scanning electron microscopy (SEM), atomic force microscopy (AFM), …

A Functional Signature Ontology (Fusion) Screen Detects An Ampk Inhibitor With Selective Toxicity Toward Human Colon Tumor Cells, Binita Das, Beth K. Neilsen, Kurt W. Fisher, Drew Gehring, Youcai Hu, Deanna J. Volle, Hyun Seok Kim, Jamie L. Mccall, David L. Kelly, John B. Macmillian, Michael A. White, Robert E. Lewis

Faculty & Staff Scholarship

AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing α and regulatory β and γ subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKα1 expression is relatively consistent across colon cancer cell lines, AMPKα1 depletion does not induce cell death. Conversely, AMPKα2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. …

Farnesylation Of The Transducin G Protein Gamma Subunit Is A Prerequisite For Its Ciliary Targeting In Rod Photoreceptors, Celine Brooks, Joseph Murphy, Marycharmain Belcastro, Daniel Heller, Saravanan Kolandaivelu, Oleg Kisselev, Maxim Sokolov

Faculty & Staff Scholarship

Primary cilia are microtubule-based organelles, which protrude from the plasma membrane and receive a wide range of extracellular signals. Various cilia use G protein-coupled receptors (GPCRs) for the detection of these signals. For instance, vertebrate rod photoreceptors use their cilia (also called outer segments) as antennae detecting photons by GPCR rhodopsin. Rhodopsin recognizes incoming light and activates its G protein, transducin, which is composed of three subunits α, β, and γ. Similar to all G protein γ subunits, the transducin Gγ1 subunit undergoes C-terminal prenylation resulting in the addition of an isoprenoid farnesyl; however, the significance of this posttranslational modification …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

Brønsted Acid Catalyzed Carbon-Carbon Bond Forming Reactions, Jiangyue Miao

Electronic Theses and Dissertations

The focus of this research project lies in the development of new methodology in the field of Brønsted acid catalysis enabling rapid synthesis of medicinally relevant compounds. It is foreseen that small molecule sulfonic acids evaluated in this research project will unveil new asymmetric carbon carbon bond forming reactions between substrates hitherto unexplored with Brønsted acid catalysis. It has been established that strong Brønsted acids, such as phosphoric acids, are capable of mediating highly selective transformations operating through unique mechanistic manifolds.

Specific focus for the sulfonic acid catalysts was geared towards asymmetric coupling reactions with synthetically useful precursors such as …

Tau Aggregation, Conformational Selection, And Inhibition, Michael R. Holden

Electronic Theses and Dissertations

Tau fibrils are a pathological hallmark of over 20 neurodegenerative disorders, including Alzheimer's disease. There currently is no cure for these diseases and treatments are limited. Once Tau fibrils form in the brain, they propagate down neuronal networks, and this spreading is linked to disease progression. Studying the behavior and structure of Tau monomer and Tau aggregates therefore may give insight into methods by which the spread of Tau fibrils can be inhibited. The structures of the Tau fibrils from different diseases are thought to vary, partially giving rise to the different disease phenotypes. Tau natively binds to microtubules by …

Progress Toward The Synthesis Of Novel Bacterial Topoisomerase Inhibitors Derived From Fluoroquinolones. N-1 Amine Derivatives, Luke Burroughs, Joshua Kuperus, Evamarie Medendorp, Michael Barbachyn

Summer Research

Bacterial resistance to current antibiotics is a growing problem across the globe. The CDC reported that the estimated minimum illnesses caused by antibiotic resistance in the year 2013 was over 2 million, resulting in about 23,000 deaths in the U.S. 1 In 2014, the Obama administration released an executive order mandating that research be conducted to identify solutions to the bacterial resistance problem, especially in Gram-negative bacteria. One antibiotic series that has shown some promise are the fluoroquinolones. Fluoroquinolones have been on the market for years, with a current reference example being moxifloxacin. Fluoroquinolones (FQs) work by targeting DNA gyrase …

A Conceptual Framework For Understanding The Biogeochemistry Of Dry Riverbeds Through The Lens Of Soil Science, Maria Isabel Arce, Clara Mendoza, Maria Almagro, Nuria Catalan, Anna M. Romani, Eugenia Marti, R. Gomez, Susana Bernal, Arnaud Foulquier, Michael Mutz, Rafael Marce, Annamaria Zoppini, Giulia Gionchetta, Gabriele Weigelhofer, R. Del Campo, Christopher T. Robinson, Alan Gilmer, Martin Rulik, Obrador Biel, Oleksandra Shumilova, Sanja Zlatanovic, Shai Arnon, Petr Baldrian, Gabriel Andreas Singer, Thibault Datry, Nikolaos Th Skoulikidis, Britta Tietjen, Daniel Von Schiller

Articles

Intermittent rivers and ephemeral streams (IRES) encompass fluvial ecosystems that eventually stop flowing and run dry at some point in space and time. During the dry phase, channels of IRES consist mainly of dry riverbeds (DRBs), prevalent yet widely unexplored ecotones between dry and wet phases that can strongly influence the biogeochemistry of fluvial networks. DRBs are often overlooked because they do not strictly belong to either domain of soil or freshwater science. Due to this dual character of DRBs, we suggest that concepts and knowledge from soil science can be used to expand the understanding of IRES biogeochemistry. Based …

Four Hapten Spacer Sites Modulating Class Specificity: Nondirectional Multianalyte Immunoassay For 31 Β-Agonists And Analogues., Lanteng Wang, Wenmeng Jiang, Xing Shen, Xiangmei Li, Xin-An Huang, Zhenlin Xu, Yuanming Sun, Shun-Wan Chan, Lingwen Zeng, Eremin Sergei Alexandrovich, Hongtao Lei

Faculty of Science & Technology (THEi)

Immunoassay methods are important for monitoring β-agonists illegally used for reducing animal fat deposition in livestock. However, there is no simultaneous screening surveillance immunoassay for detecting various β-agonist chemicals that are possibly present in food. In this study, through the use of an R-(−)-salbutamol derivative as the immunizing hapten, an antibody recognizing 31 β-agonists and analogues was generated for the first time. Three-dimensional quantitative structure–activity relationship (3D QSAR) revealed that strong steric and hydrophobic fields around the hapten spacer near C-2, as well as a chirality at C-1′, dominantly modulated the class specificity of the raised antibody. However, a hapten …