Life Sciences Commons^™

Giants Among Micromorphs: Were Cincinnatian (Ordovician, Katian) Small Shelly Phosphatic Faunas Dwarfed?, Benjamin F. Dattilo, Rebecca L. Freeman, Winfried S. Peters, William P. Heimbrock, Bradley Deline, Anthony J. Martin, Jack W. Kallmeyer, Jesse Reeder, Anne Argast

Winfried S. Peters

Nilgai Antelope In Northern Mexico As A Possible Carrier For Cattle Fever Ticks And Babesia Bovis And Babesia Bigemina., E Cardenas-Canales, J. Alfonso Ortega-Santos, Tyler A. Campbell, Zeferino Garcia-Vaquez, Antonio Cantu-Covarrubias, Julio Figueroa-Millian, Randy W. Deyoung, David G. Hewitt, Fred Bryant

Fred B. Bryant

Of 20 blood samples from nilgais from Me´ xico, five were polymerase chain reaction-positive for Babesia bigemina and one for Babesia bovis. Positive samples had the expected 170 (B. bigemina) and 291 (B. bovis) base pairs and were identical to Gen-Bank B. bigemina accession S45366 and B. bovis M38218.

Characterizing The Performance And Behaviors Of Runners Using Twitter, Qian He, Emmanuel Agu, Diane Strong, Bengisu Tulu, Peder Pedersen

Emmanuel O. Agu

Running is a popular physical activity that improves physical and mental wellbeing. Unfortunately, up-to- date information about runners’ performance and psychological wellbeing is limited. Many questions remain unanswered, such as how far and how fast runners typically run, their preferred running times and frequencies, how long new runners persist before dropping out, and what factors cause runners to quit. Without hard data, establishing patterns of runner behavior and mitigating the challenges they face are difficult. Collecting data manually from large numbers of runners for research studies is costly and time consuming. Emerging Social Networking Services (SNS) and fitness tracking devices …

Disease Will Limit Future Food Supply From The Global Crustacean Fishery And Aquaculture Sectors, G. Stentiford, D. Neil, E. Peeler, J. Shields, H. Small, T. Flegel, J. Vlak, B. Jones, F. Morado, S. Moss, J. Lotz, Lyric Bartholomay, D. Behringer, C. Hauton, D. Lightner

Lyric Bartholomay

Seafood is a highly traded food commodity. Farmed and captured crustaceans contribute a significant proportion with annual production exceeding 10 M metric tonnes with first sale value of $40bn. The sector is dominated by farmed tropical marine shrimp, the fastest growing sector of the global aquaculture industry. It is significant in supporting rural livelihoods and alleviating poverty in producing nations within Asia and Latin America while forming an increasing contribution to aquatic food supply in more developed countries. Nations with marine borders often also support important marine fisheries for crustaceans that are regionally traded as live animals and commodity products. …

Forecasting Climate Change Impacts On The Distribution Of Wetland Habitat In The Midwestern United States, Heath Garris, Randall Mitchell, Lauchlan Fraser, Linda Barrett

Randall J. Mitchell

Shifting precipitation patterns brought on by climate change threaten to alter the future distribution of wetlands. We developed a set of models to understand the role climate plays in determining wetland formation on a landscape scale and to forecast changes in wetland distribution for the Midwestern United States. These models combined 35 climate variables with 21 geographic and anthropogenic factors thought to encapsulate other major drivers of wetland distribution for the Midwest. All models successfully recreated a majority of the variation in current wetland area within the Midwest, and showed that wetland area was significantly associated with climate, even when …

Effectiveness Of A Spontaneous Carvacrol Nanoemulsion Against Salmonella Enterica Enteritidis And Escherichia Coli O157:H7 On Contaminated Broccoli And Radish Seeds, Kyle Landry, Sean Micheli, David Julian Mcclements, Lynne Mclandsborough

Kyle S Landry

Forecasting Climate Change Impacts On The Distribution Of Wetland Habitat In The Midwestern United States, Heath Garris, Randall Mitchell, Lauchlan Fraser, Linda Barrett

Linda R. Barrett

Shifting precipitation patterns brought on by climate change threaten to alter the future distribution of wetlands. We developed a set of models to understand the role climate plays in determining wetland formation on a landscape scale and to forecast changes in wetland distribution for the Midwestern United States. These models combined 35 climate variables with 21 geographic and anthropogenic factors thought to encapsulate other major drivers of wetland distribution for the Midwest. All models successfully recreated a majority of the variation in current wetland area within the Midwest, and showed that wetland area was significantly associated with climate, even when …

Biocompatible Flavone-Based Fluorogenic Probes For Quick Wash-Free Mitochondria! Imaging In Living Cells, Bin Liu, Mickey Shah, Ge Zhang, Qin Liu, Yi Pang

Yi Pang

Mitochondria, vital organelles existing in almost all eukaryotic cells, play a crucial role in energy metabolism and apoptosis of aerobic organisms. In this work, we report two new flavone-based fluorescent probes, MC-Mito1 and MC-Mito2, for monitoring mitochondria in living cells. These two probes exhibit remarkably low toxicity, good cell permeability, and high specificity; these probes complement the existing library of mitochondrial imaging agents. The new dyes give nearly no background fluorescence, and their application does not require tedious postwashing after cell staining. The appreciable tolerance of MC-Mito2 encourages a broader range of biological applications for understanding the cell degeneration and …

A Single Molecular Probe For Multi-Analyte (Cr3+, Al3+ And Fe3+) Detection In Aqueous Medium And Its Biological Application, Junfeng Wang, Yingbo Li, Nikul Patel, Ge Zhang, Demin Zhou, Yi Pang

Yi Pang

An ESIPT based fluorescent sensor 1 was developed, which could selectively detect and differentiate trivalent metal ions Cr3+, Al3+ and Fe3+ in aqueous medium. The cell imaging experiments confirmed that 1 can be used for monitoring intracellular Cr3+ and Al3+ levels in living cells.

Structural Libraries Of Protein Models For Multiple Species To Understand Evolution Of The Renin-Angiotensin System, Jeremy Prokop, Victoria Petri, Mary Shimoyama, Ingrid Watanabe, Dulce Casarini, Thomas Peeper, Stephanie Bilinovich, Howard Jacob, Robson Santos, Almir Martins, Fabiano Araujo, Fernando Reis, Amy Milsted

Thomas C Leeper

The details of protein pathways at a structural level provides a bridge between genetics/molecular biology and physiology. The renin-angiotensin system is involved in many physiological pathways with informative structural details in multiple components. Few studies have been performed assessing structural knowledge across the system. This assessment allows use of bioinformatics tools to fill in missing structural voids. In this paper we detail known structures of the renin-angiotensin system and use computational approaches to estimate and model components that do not have their protein structures defined. With the subsequent large library of protein structures, we then created a species specific protein …

Biocompatible Flavone-Based Fluorogenic Probes For Quick Wash-Free Mitochondria! Imaging In Living Cells, Bin Liu, Mickey Shah, Ge Zhang, Qin Liu, Yi Pang

Ge Zhang

Mitochondria, vital organelles existing in almost all eukaryotic cells, play a crucial role in energy metabolism and apoptosis of aerobic organisms. In this work, we report two new flavone-based fluorescent probes, MC-Mito1 and MC-Mito2, for monitoring mitochondria in living cells. These two probes exhibit remarkably low toxicity, good cell permeability, and high specificity; these probes complement the existing library of mitochondrial imaging agents. The new dyes give nearly no background fluorescence, and their application does not require tedious postwashing after cell staining. The appreciable tolerance of MC-Mito2 encourages a broader range of biological applications for understanding the cell degeneration and …

A Single Molecular Probe For Multi-Analyte (Cr3+, Al3+ And Fe3+) Detection In Aqueous Medium And Its Biological Application, Junfeng Wang, Yingbo Li, Nikul Patel, Ge Zhang, Demin Zhou, Yi Pang

Ge Zhang

An ESIPT based fluorescent sensor 1 was developed, which could selectively detect and differentiate trivalent metal ions Cr3+, Al3+ and Fe3+ in aqueous medium. The cell imaging experiments confirmed that 1 can be used for monitoring intracellular Cr3+ and Al3+ levels in living cells.

Record Of Archaeal Activity At The Serpentinite-Hosted Lost City Hydrothermal Field, S. Méhay, G. Früh-Green, Susan Lang, S. Bernasconi, W. Brazelton, M. Schrenk, P. Schaeffer, P. Adam

Susan Q. Lang

No abstract provided.

Structure-Guided Design Of A High Affinity Inhibitor To Human Ctbp, Brendan Hilbert, Benjamin Morris, Keith Ellis, Janet Paulsen, Celia Schiffer, Steven Grossman, William Royer

Celia A. Schiffer

Oncogenic transcriptional coregulators C-terminal Binding Protein (CtBP) 1 and 2 possess regulatory d-isomer specific 2-hydroxyacid dehydrogenase (D2-HDH) domains that provide an attractive target for small molecule intervention. Findings that the CtBP substrate 4-methylthio 2-oxobutyric acid (MTOB) can interfere with CtBP oncogenic activity in cell culture and in mice confirm that such inhibitors could have therapeutic benefit. Recent crystal structures of CtBP 1 and 2 revealed that MTOB binds in an active site containing a dominant tryptophan and a hydrophilic cavity, neither of which are present in other D2-HDH family members. Here, we demonstrate the effectiveness of exploiting these active site …

Project-Based Collaborative Innovation For The Igeneration, James Gerry, Carl Heine

Carl Heine

Social media provides powerful opportunities to create new learning communities. Online, project-based activities reach today's iGen students in ways they learn best, maximizing interaction and individualization through the use of free Web technologies such as CoolHub.IMSA. Discover ways to use networing tools to transform teaching and learning at your school.

Water-Smart Growth: Integrating Water Management And Land Use Planning, Enjie Li

Enjie Li

Water and urban growth are inextricably interconnected, particularly in arid regions. Urban growth and water management have generated multi-dimensional conflicts. Growing cities that seek to quench their continuously increasing thirst with limited available water resources often have adverse impacts on the environment or region from which the water is drawn. Given that land use planning is an effective tool to control and manage urban growth and it has direct influence on urban water management, a holistic land-water planning approach is needed to cope with rapid growth and water scarcity in the arid western United States. However, this land-water planning approach …

The Large Intracellular Loop Of Hzip4 Is An Intrinsically Disordered Zinc Binding Domain, Robert Dempski, Elizabeth Bafaro, Sagar Antala, Tuong-Vi Nguyen, Stephen Dzul, Brian Doyon, Timothy Stemmler

Robert E. Dempski

The human (h) ZIP4 transporter is a plasma membrane protein which functions to increase the cytosolic concentration of zinc. hZIP4 transports zinc into intestinal cells and therefore has a central role in the absorption of dietary zinc. hZIP4 has eight transmembrane domains and encodes a large intracellular loop between transmembrane domains III and IV, M3M4. Previously, it has been postulated that this domain regulates hZIP4 levels in the plasma membrane in a zinc-dependent manner. The objective of this research was to examine the zinc binding properties of the large intracellular loop of hZIP4. Therefore, we have recombinantly expressed and purified …

Soil Denitrification Fluxes From Three Northeastern North American Forests Across A Range Of Nitrogen Deposition, Jennifer Morse, Jorge Durán, Fred Beall, Eric Enanga, Irena Creed, Ivan Fernandez, Peter Groffman

Ivan J. Fernandez

In northern forests, large amounts of missing N that dominate N balances at scales ranging from small watersheds to large regional drainage basins may be related to N-gas production by soil microbes. We measured denitrification rates in forest soils in northeastern North America along a N deposition gradient to determine whether N-gas fluxes were a significant fate for atmospheric N inputs and whether denitrification rates were correlated with N availability, soil O2 status, or forest type. We quantified N2 and N2O fluxes in the laboratory with an intact-core method and monitored soil O2, temperature and moisture in three forests differing …

Books And Our Human Stories, Paul Benson

Paul H. Benson

An essay on the impact of the works in the Imprints and Impressions: Milestones in Human Progress, an exhibition of rare books from the collection of Stuart Rose. Exhibition was held Sept. 29-Nov. 9, 2014, at the University of Dayton.

Structural Basis And Distal Effects Of Gag Substrate Coevolution In Drug Resistance To Hiv-1 Protease, Aysegul Ozen, Kuan-Hung Lin, Nese Yilmaz, Celia Schiffer

Celia A. Schiffer

Drug resistance mutations in response to HIV-1 protease inhibitors are selected not only in the drug target but elsewhere in the viral genome, especially at the protease cleavage sites in the precursor protein Gag. To understand the molecular basis of this protease-substrate coevolution, we solved the crystal structures of drug resistant I50V/A71V HIV-1 protease with p1-p6 substrates bearing coevolved mutations. Analyses of the protease-substrate interactions reveal that compensatory coevolved mutations in the substrate do not restore interactions lost due to protease mutations, but instead establish other interactions that are not restricted to the site of mutation. Mutation of a substrate …

Structural Analysis Of Asunaprevir Resistance In Hcv Ns3/4a Protease, Djade Soumana, Akbar Ali, Celia Schiffer

Celia A. Schiffer

Asunaprevir (ASV), an isoquinoline-based competitive inhibitor targeting the hepatitis C virus (HCV) NS3/4A protease, is very potent in vivo. However, the potency is significantly compromised by the drug resistance mutations R155K and D168A. In this study three crystal structures of ASV and an analogue were determined to analyze the structural basis of drug resistance susceptibility. These structures revealed that ASV makes extensive contacts with Arg155 outside the substrate envelope. Arg155 in turn is stabilized by Asp168, and thus when either residue is mutated, the enzyme's interaction with ASV's P2* isoquinoline is disrupted. Adding a P1-P3 macrocycle to ASV enhances the …

Improving The Resistance Profile Of Hepatitis C Ns3/4a Inhibitors: Dynamic Substrate Envelope Guided Design, Aysegul Ozen, Woody Sherman, Celia Schiffer

Celia A. Schiffer

Drug resistance is a principal concern in the treatment of quickly evolving diseases. The viral protease NS3/4A is a primary drug target for the hepatitis C virus (HCV) and is known to evolve resistance mutations in response to drug therapy. At the molecular level, drug resistance reflects a subtle change in the balance of molecular recognition by NS3/4A; the drug resistant protease variants are no longer effectively inhibited by the competitive active site inhibitors but can still process the natural substrates with enough efficiency for viral survival. In previous works we have developed the "substrate envelope" hypothesis, which posits that …

Efficient Computation Of Small-Molecule Configurational Binding Entropy And Free Energy Changes By Ensemble Enumeration, Nathaniel Silver, Bracken King, Madhavi Nalam, Hong Cao, Akbar Ali, G. S. Kiran Kumar Reddy, Tariq Rana, Celia Schiffer, Bruce Tidor

Celia A. Schiffer

Here we present a novel, end-point method using the dead-end-elimination and A* algorithms to efficiently and accurately calculate the change in free energy, enthalpy, and configurational entropy of binding for ligand-receptor association reactions. We apply the new approach to the binding of a series of human immunodeficiency virus (HIV-1) protease inhibitors to examine the effect ensemble reranking has on relative accuracy as well as to evaluate the role of the absolute and relative ligand configurational entropy losses upon binding in affinity differences for structurally related inhibitors. Our results suggest that most thermodynamic parameters can be estimated using only a small …

Drug Resistance Conferred By Mutations Outside The Active Site Through Alterations In The Dynamic And Structural Ensemble Of Hiv-1 Protease, Debra Ragland, Ellen Nalivaika, Madhavi Nalam, Kristina Prachanronarong, Hong Cao, Rajintha Bandaranayake, Yufeng Cai, Nese Yilmaz, Celia Schiffer

Celia A. Schiffer

HIV-1 protease inhibitors are part of the highly active antiretroviral therapy effectively used in the treatment of HIV infection and AIDS. Darunavir (DRV) is the most potent of these inhibitors, soliciting drug resistance only when a complex combination of mutations occur both inside and outside the protease active site. With few exceptions, the role of mutations outside the active site in conferring resistance remains largely elusive. Through a series of DRV-protease complex crystal structures, inhibition assays, and molecular dynamics simulations, we find that single and double site mutations outside the active site often associated with DRV resistance alter the structure …

Testing The Substrate-Envelope Hypothesis With Designed Pairs Of Compounds, Yang Shen, Michael Altman, Akbar Ali, Madhavi Nalam, Hong Cao, Tariq Rana, Celia Schiffer, Bruce Tidor

Celia A. Schiffer

Acquired resistance to therapeutic agents is a significant barrier to the development of clinically effective treatments for diseases in which evolution occurs on clinical time scales, frequently arising from target mutations. We previously reported a general strategy to design effective inhibitors for rapidly mutating enzyme targets, which we demonstrated for HIV-1 protease inhibition [Altman et al. J. Am. Chem. Soc. 2008, 130, 6099-6113]. Specifically, we developed a computational inverse design procedure with the added constraint that designed inhibitors bind entirely inside the substrate envelope, a consensus volume occupied by natural substrates. The rationale for the substrate-envelope constraint is that it …

Development Of A Novel Screening Strategy Designed To Discover A New Class Of Hiv Drugs, Nancy Cheng, Sook-Kyung Lee, P. Donover, Mel Reichman, Celia Schiffer, Emily Hull-Ryde, Ronald Swanstrom, William Janzen

Celia A. Schiffer

Current antiretroviral treatments target multiple pathways important for human immunodeficiency virus (HIV) multiplication, including viral entry, synthesis and integration of the DNA provirus, and the processing of viral polyprotein precursors. However, HIV is becoming increasingly resistant to these "combination therapies." Recent findings show that inhibition of HIV Gag protein cleavage into its two structural proteins, matrix (MA) and capsid (CA), has a devastating effect on viral production, revealing a potential new target class for HIV treatment. Unlike the widely used HIV protease inhibitors, this new class of inhibitor would target the substrate, not the protease enzyme itself. This approach offers …

Crystal Structures Of Human Ctbp In Complex With Substrate Mtob Reveal Active Site Features Useful For Inhibitor Design, Brendan Hilbert, Steven Grossman, Celia Schiffer, William Royer

Celia A. Schiffer

The oncogenic corepressors C-terminal Binding Protein (CtBP) 1 and 2 harbor regulatory d-isomer specific 2-hydroxyacid dehydrogenase (d2-HDH) domains. 4-Methylthio 2-oxobutyric acid (MTOB) exhibits substrate inhibition and can interfere with CtBP oncogenic activity in cell culture and mice. Crystal structures of human CtBP1 and CtBP2 in complex with MTOB and NAD(+) revealed two key features: a conserved tryptophan that likely contributes to substrate specificity and a hydrophilic cavity that links MTOB with an NAD(+) phosphate. Neither feature is present in other d2-HDH enzymes. These structures thus offer key opportunities for the development of highly selective anti-neoplastic CtBP inhibitors. Elsevier B.V. All …

Drug Resistance Mutations Alter Dynamics Of Inhibitor-Bound Hiv-1 Protease, Yufeng Cai, Wazo Myint, Janet Paulsen, Celia Schiffer, Rieko Ishima, Nese Yilmaz

Celia A. Schiffer

Under the selective pressure of therapy, HIV-1 protease mutants resistant to inhibitors evolve to confer drug resistance. Such mutations can impact both the dynamics and structures of the bound and unbound forms of the enzyme. Flap+ is a multidrug-resistant variant of HIV-1 protease with a combination of primary and secondary resistance mutations (L10I, G48V, I54V, V82A) and a strikingly altered thermodynamic profile for darunavir (DRV) binding relative to the wild-type protease. We elucidated the impact of these mutations on protein dynamics in the DRV-bound state using molecular dynamics simulations and NMR relaxation experiments. Both methods concur in that the conformational …

The Role Of Histidine Residues In The Specificity Of The Human Zinc Transporter Hzip4, Robert Dempski, Sagar Antala, Elizabeth Bafaro

Robert E. Dempski

ZIP transporters, named after the zinc regulated (Zrt) and iron regulated (Irt) transport proteins, are essential for zinc and iron translocation across cellular membranes. These proteins function to increase the cytosolic concentration of transition metals. While both zinc and iron are essential micronutrients which are required for the structure and/or function of hundreds of cellular proteins, the molecular mechanism of ZIP transporters is not well understood. Complicating mechanistic studies is the observation that the concentration of free zinc and iron is nano to picomolar.

Effectiveness Of A Novel Spontaneous Carvacrol Nanoemulsion Against Salmonella Enterica Enteritidis And Escherichia Coli O157:H7 On Contaminated Mung Bean And Alfalfa Seeds, Kyle Landry, Yuhua Chang, David Julian Mcclements, Lynne Mclandsborough

Kyle S Landry