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Full-Text Articles in Pharmacology, Toxicology and Environmental Health

Implementing A Community-Based Social Marketing Project To Improve Agricultural Worker Health, Joan D. Flocks, Leslie Clarke, Stan Albrecht, Carol Bryant, Paul Monaghan, Holly Baker Apr 2016

Implementing A Community-Based Social Marketing Project To Improve Agricultural Worker Health, Joan D. Flocks, Leslie Clarke, Stan Albrecht, Carol Bryant, Paul Monaghan, Holly Baker

Joan D. Flocks

The Together for Agricultural Safety project is a community-based social marketing project working to reduce the adverse health effects of pesticide exposure among fernery and nursery workers in Florida. In 3 years, the collaboration between university and community researchers has embodied many of the principles of community-based research while completing multiple stages of formative data collection required for a social marketing project. This hybrid approach to developing a health intervention for a minority community has been successful in its early stages because the community partners are organized, empowered, and motivated to execute research activities with the assistance of academic partners. …


Pesticide Policy And Farmworker Health, Joan D. Flocks Apr 2016

Pesticide Policy And Farmworker Health, Joan D. Flocks

Joan D. Flocks

Although data on the carcinogenicity of agricultural pesticides are still being generated and are thus incomplete, research such as the Agricultural Health Study indicates that populations with increased, regular exposure to pesticides have high rates of a variety of cancers (National Institutes of Health & Environmental Protection Agency 2008). Policies that regulate toxins such as pesticides are envisioned by the public to be empirical and objective, but toxins are socially produced and their regulation is just as often based on political and economic factors as it is on science (Luke 2000). This does not bode well for farm- workers who …


The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer Jan 2016

The Ssdna Mutator Apobec3a Is Regulated By Cooperative Dimerization, Markus-Frederik Bohn, Shivender Shandilya, Tania Silvas, Ellen Nalivaika, Takahide Kouno, Brian Kelch, Sean Ryder, Nese Yilmaz, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

Deaminase activity mediated by the human APOBEC3 family of proteins contributes to genomic instability and cancer. APOBEC3A is by far the most active in this family and can cause rapid cell death when overexpressed, but in general how the activity of APOBEC3s is regulated on a molecular level is unclear. In this study, the biochemical and structural basis of APOBEC3A substrate binding and specificity is elucidated. We find that specific binding of single-stranded DNA is regulated by the cooperative dimerization of APOBEC3A. The crystal structure elucidates this homodimer as a symmetric domain swap of the N-terminal residues. This dimer interface …


Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo Jan 2016

Structure Of The Vif-Binding Domain Of The Antiviral Enzyme Apobec3g, Takahide Kouno, Elizabeth Luengas, Megumi Shigematsu, Shivender Shandilya, Jingying Zhang, Luan Chen, Mayuko Hara, Celia Schiffer, Reuben Harris, Hiroshi Matsuo

Celia A. Schiffer

The human APOBEC3G (A3G) DNA cytosine deaminase restricts and hypermutates DNA-based parasites including HIV-1. The viral infectivity factor (Vif) prevents restriction by triggering A3G degradation. Although the structure of the A3G catalytic domain is known, the structure of the N-terminal Vif-binding domain has proven more elusive. Here, we used evolution- and structure-guided mutagenesis to solubilize the Vif-binding domain of A3G, thus permitting structural determination by NMR spectroscopy. A smaller zinc-coordinating pocket and altered helical packing distinguish the structure from previous catalytic-domain structures and help to explain the reported inactivity of this domain. This soluble A3G N-terminal domain is bound by …


Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick Jan 2016

Simultaneously Targeting The Ns3 Protease And Helicase Activities For More Effective Hepatitis C Virus Therapy, Jean Ndjomou, M Corby, Noreena Sweeney, Alicia Hanson, Cihan Aydin, Akbar Ali, Celia Schiffer, Kelin Li, Kevin Frankowski, Frank Schoenen, David Frick

Celia A. Schiffer

This study examines the specificity and mechanism of action of a recently reported hepatitis C virus (HCV) nonstructural protein 3 (NS3) helicase-protease inhibitor (HPI), and the interaction of HPI with the NS3 protease inhibitors telaprevir, boceprevir, danoprevir, and grazoprevir. HPI most effectively reduced cellular levels of subgenomic genotype 4a replicons, followed by genotypes 3a and 1b replicons. HPI had no effect on HCV genotype 2a or dengue virus replicon levels. Resistance evolved more slowly to HPI than telaprevir, and HPI inhibited telaprevir-resistant replicons. Molecular modeling and analysis of the ability of HPI to inhibit peptide hydrolysis catalyzed by a variety …


Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco Jan 2016

Structural Basis For Mutation-Induced Destabilization Of Profilin 1 In Als, Sivakumar Boopathy, Tania Silvas, Maeve Tischbein, Silvia Jansen, Shivender Shandilya, Jill Zitzewitz, John Landers, Bruce Goode, Celia Schiffer, Daryl Bosco

Celia A. Schiffer

Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the …


Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler Jan 2016

Inhibition Of Apobec3g Activity Impedes Double-Stranded Dna Repair, Ponnandy Prabhu, Shivender Shandilya, Elena Britan-Rosich, Adi Nagler, Celia Schiffer, Moshe Kotler

Celia A. Schiffer

The cellular cytidine deaminase APOBEC3G (A3G) was first described as an anti-HIV-1 restriction factor, acting by directly deaminating reverse transcripts of the viral genome. HIV-1 Vif neutralizes the activity of A3G, primarily by mediating degradation of A3G to establish effective infection in host target cells. Lymphoma cells, which express high amounts of A3G, can restrict Vif-deficient HIV-1. Interestingly, these cells are more stable in the face of treatments that result in double-stranded DNA damage, such as ionizing radiation and chemotherapies. Previously, we showed that the Vif-derived peptide (Vif25-39) efficiently inhibits A3G deamination, and increases the sensitivity of lymphoma cells to …


Rediii: A Pipeline For Automated Structure Solution, Markus-Frederik Bohn, Celia Schiffer Jan 2016

Rediii: A Pipeline For Automated Structure Solution, Markus-Frederik Bohn, Celia Schiffer

Celia A. Schiffer

High-throughput crystallographic approaches require integrated software solutions to minimize the need for manual effort. REdiii is a system that allows fully automated crystallographic structure solution by integrating existing crystallographic software into an adaptive and partly autonomous workflow engine. The program can be initiated after collecting the first frame of diffraction data and is able to perform processing, molecular-replacement phasing, chain tracing, ligand fitting and refinement without further user intervention. Preset values for each software component allow efficient progress with high-quality data and known parameters. The adaptive workflow engine can determine whether some parameters require modifications and choose alternative software strategies …


Modulation Of Hiv Protease Flexibility By The T80n Mutation, Hao Zhou, Shangyang Li, John Badger, Ellen Nalivaika, Yufeng Cai, Jennifer Foulkes-Murzycki, Celia Schiffer, Lee Makowski Jan 2016

Modulation Of Hiv Protease Flexibility By The T80n Mutation, Hao Zhou, Shangyang Li, John Badger, Ellen Nalivaika, Yufeng Cai, Jennifer Foulkes-Murzycki, Celia Schiffer, Lee Makowski

Celia A. Schiffer

The flexibility of HIV protease (HIVp) plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80, which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the …


A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro, Marc Potempa, Ellen Nalivaika, Debra Ragland, Sook-Kyung Lee, Celia Schiffer, Ronald Swanstrom Jan 2016

A Direct Interaction With Rna Dramatically Enhances The Catalytic Activity Of The Hiv-1 Protease In Vitro, Marc Potempa, Ellen Nalivaika, Debra Ragland, Sook-Kyung Lee, Celia Schiffer, Ronald Swanstrom

Celia A. Schiffer

Though the steps of human immunodeficiency virus type 1 (HIV-1) virion maturation are well documented, the mechanisms regulating the proteolysis of the Gag and Gag-Pro-Pol polyproteins by the HIV-1 protease (PR) remain obscure. One proposed mechanism argues that the maturation intermediate p15NC must interact with RNA for efficient cleavage by the PR. We investigated this phenomenon and found that processing of multiple substrates by the HIV-1 PR was enhanced in the presence of RNA. The acceleration of proteolysis occurred independently from the substrate's ability to interact with nucleic acid, indicating that a direct interaction between substrate and RNA is not …


A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon Jan 2016

A Balance Between Inhibitor Binding And Substrate Processing Confers Influenza Drug Resistance, Li Jiang, Ping Liu, Claudia Bank, Nicholas Renzette, Kristina Prachanronarong, L. Yilmaz, Daniel Caffrey, Konstantin Zeldovich, Celia Schiffer, Timothy Kowalik, Jeffrey Jensen, Robert Finberg, Jennifer Wang, Daniel Bolon

Celia A. Schiffer

The therapeutic benefits of the neuraminidase (NA) inhibitor oseltamivir are dampened by the emergence of drug resistance mutations in influenza A virus (IAV). To investigate the mechanistic features that underlie resistance, we developed an approach to quantify the effects of all possible single-nucleotide substitutions introduced into important regions of NA. We determined the experimental fitness effects of 450 nucleotide mutations encoding positions both surrounding the active site and at more distant sites in an N1 strain of IAV in the presence and absence of oseltamivir. NA mutations previously known to confer oseltamivir resistance in N1 strains, including H275Y and N295S, …


Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer Jan 2016

Structural And Thermodynamic Effects Of Macrocyclization In Hcv Ns3/4a Inhibitor Mk-5172, Djade Soumana, Nese Yilmaz, Kristina Prachanronarong, Cihan Aydin, Akbar Ali, Celia Schiffer

Celia A. Schiffer

Recent advances in direct-acting antivirals against Hepatitis C Virus (HCV) have led to the development of potent inhibitors, including MK-5172, that target the viral NS3/4A protease with relatively low susceptibility to resistance. MK-5172 has a P2-P4 macrocycle and a unique binding mode among current protease inhibitors where the P2 quinoxaline packs against the catalytic residues H57 and D81. However, the effect of macrocyclization on this binding mode is not clear, as is the relation between macrocyclization, thermodynamic stabilization, and susceptibility to the resistance mutation A156T. We have determined high-resolution crystal structures of linear and P1-P3 macrocyclic analogs of MK-5172 bound …


Our Chemical Selves : Gender, Toxics, And Environmental Health, Dayna Scott Oct 2015

Our Chemical Selves : Gender, Toxics, And Environmental Health, Dayna Scott

Dayna N. Scott

Everyday exposures to chemicals found in homes, schools, and workplaces are having devastating consequences on human health. These toxic exposures derive from common personal care products and cosmetics, household cleaners, pharmaceuticals, furniture, the food we eat, the water we drink, and even the air we breathe. Our Chemical Selves examines the impact of toxics on the long-term health of Canadians. Written by leading researchers in science, law, and public policy, the chapters in this collection reveal that while exposures to chemicals are pervasive and widespread, people from low-income, racialized, and Indigenous communities face a far greater risk of exposure. At …


Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski Apr 2014

Role Of Gluk1 Kainate Receptors In Seizures, Epileptic Discharges, And Epileptogenesis, Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, Michael A. Rogawski

Michael A. Rogawski

Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 …


An Evaluation Of Mercury Concentrations In Three Brands Of Canned Tuna, Shawn Gerstenberger, Adam Martinson, Joanna Kramer Mar 2014

An Evaluation Of Mercury Concentrations In Three Brands Of Canned Tuna, Shawn Gerstenberger, Adam Martinson, Joanna Kramer

Shawn Gerstenberger

There is widespread concern over the presence of Hg in fish consumed by humans. While studies have been focused on determining the Hg concentration in sport fish and some commercial fish, little attention has been directed to canned tuna; it is widely held that concentrations are low. In the present study, the amount of Hg present in canned tuna purchased in Las Vegas, Nevada, USA, was examined, and the brand, temporal variation, type, and packaging medium impacts on Hg concentrations in tuna were explored. A significant (p < 0.001) brand difference was noted: Brand 3 contained higher Hg concentrations ($\bar x$ …


Imagining Possibilities For Healthy Appalachian Communities In An Emerging Postindustrial Landscape, Brian Hoey Jan 2014

Imagining Possibilities For Healthy Appalachian Communities In An Emerging Postindustrial Landscape, Brian Hoey

Brian A. Hoey, Ph.D.

This paper explores how community might be re-imagined to promote incipient social and economic agendas born increasingly of broad-minded citizen initiatives within the Appalachian region aimed at what is generally understood as “development,” but of a form distinct from the prevailing models of a more industrial age. I would like to ask whether a city like Huntington, West Virginia can emerge as a progressive example of what we might term postindustrial, urban regeneration and perhaps what we might call community healing—specifically through grassroots movement now finding local governmental support in collective attempts to transform this place from one defined primarily …


Ecosystems And Human Health:Toxicology And Environmental Hazards, Richard Philp Mar 2013

Ecosystems And Human Health:Toxicology And Environmental Hazards, Richard Philp

Richard B. Philp

This is a teaching text covering the toxicology of pollutants such as heavy metals and persistent organic pollutants, pesticides, as well as of animal and plant venoms and toxins. Environmental disasters are discussed and updated. There numerous case studies and each chapter has a self-evaluation quizz. See also www.amazon.com/Ecosystems-Human-Health-Toxicology-Environmental/dp/146656721


The Effects Of Water And Habitat Quality On Amphibian Assemblages In Two Midwest Watersheds, Abel Castaneda, Mark Jordan Nov 2012

The Effects Of Water And Habitat Quality On Amphibian Assemblages In Two Midwest Watersheds, Abel Castaneda, Mark Jordan

Mark A. Jordan

No abstract provided.


Pyocyanin-Induced Toxicity In A549 Respiratory Cells Is Causally Linked To Oxidative Stress, Lee Gloyne, Gary Grant, Anthony Perkins, Katie Powell, Catherine Mcdermott, Peter Johnson, Gregory Anderson, Milton Kiefel, Shailendra Anoopkumar-Dukie Nov 2012

Pyocyanin-Induced Toxicity In A549 Respiratory Cells Is Causally Linked To Oxidative Stress, Lee Gloyne, Gary Grant, Anthony Perkins, Katie Powell, Catherine Mcdermott, Peter Johnson, Gregory Anderson, Milton Kiefel, Shailendra Anoopkumar-Dukie

Catherine M. McDermott

Pyocyanin, a virulence factor produced by Pseudomonas aeruginosa, has many damaging effects on mammalian cells. Several lines of evidence suggest that this damage is primarily mediated by its ability to generate ROS and deplete host antioxidant defence mechanisms. However, a causal role for oxidative stress has not yet been demonstrated conclusively. Parallel measures of ROS production, antioxidant levels and cytotoxicity provide convincing evidence that pyocyanin-induced cytotoxicity in A549 respiratory cells is mediated by acute ROS production and subsequent oxidative stress. Pyocyanin increased ROS levels in A549 cells as measured by the fluorescent H2O2 probes Amplex Red and DCFH-DA. These effects …


A Cluster-Based Approach For Biological Hypothesis Testing And Its Application, Ahmed Mustafa Jun 2012

A Cluster-Based Approach For Biological Hypothesis Testing And Its Application, Ahmed Mustafa

Ahmed Mustafa Dr.

No abstract provided.


Preface, Richard B. Philp Apr 2012

Preface, Richard B. Philp

Richard B. Philp

Corporate greed, political corruption and callous disregard for workers and the public have led to environmental crises like the Gulf oil spill of 2010, the ongoing controversy over gas fracking and the Halliburton loophole which allows drilling right next to people's water supply, the Alberta tar sands, and repeated mine accidents where safety rules have been disregarded. Our insatiable thirst for energy has led to drilling in ever more difficult and environmentally fragile environments. New technologies may offer some hope of mitigating the damage we cause to the environment.


Environmental Issues For The Twenty-First Century And Their Impact On Human Health, Richard Philp Feb 2012

Environmental Issues For The Twenty-First Century And Their Impact On Human Health, Richard Philp

Richard B. Philp

This e-book documents environmental hazards from disasters such as the Gulf oil spill, from pollution resulting from resource exploitation, from contamination of the marine environment and from climate change including the role of human source greenhouse gases. Pollution from the electronic industry is a recent and serious threat to human and environmental health. The final chapter offers some means of preventing or reversing these hazards. Now available on Amazon


Effects Of Capsaicin Supplemented Feed On The Growth And Immune Response Of Coho Salmon, Oncorhynchus Kisutch., Ahmed Mustafa, Paul Mccain, Devin Carr Dec 2011

Effects Of Capsaicin Supplemented Feed On The Growth And Immune Response Of Coho Salmon, Oncorhynchus Kisutch., Ahmed Mustafa, Paul Mccain, Devin Carr

Ahmed Mustafa Dr.

No abstract provided.


Effects Of Vitamin C On Expression Of Stress Genes In Tilapia, Oreochromis Niloticus., Ahmed Mustafa, Sharif Hayat, Jessica Eash Dec 2011

Effects Of Vitamin C On Expression Of Stress Genes In Tilapia, Oreochromis Niloticus., Ahmed Mustafa, Sharif Hayat, Jessica Eash

Ahmed Mustafa Dr.

No abstract provided.


Survey Of Antibiotic Resistant Bacteria In Fish Gut Collected From Selected Sites., Ahmed Mustafa, Hasina Karki, Arlis Lamaster, Bob Gillespie, Shree Dhawale Dec 2011

Survey Of Antibiotic Resistant Bacteria In Fish Gut Collected From Selected Sites., Ahmed Mustafa, Hasina Karki, Arlis Lamaster, Bob Gillespie, Shree Dhawale

Ahmed Mustafa Dr.

No abstract provided.


Effects Of Capsaicin Supplemented Feed On The Growth And Immune Response Of Tilapia, Oreochromis Niloticus, Ahmed Mustafa, Paul Mccain, Devin Carr Dec 2011

Effects Of Capsaicin Supplemented Feed On The Growth And Immune Response Of Tilapia, Oreochromis Niloticus, Ahmed Mustafa, Paul Mccain, Devin Carr

Ahmed Mustafa Dr.

No abstract provided.


Psychology (Addiction: Biology, Psychology And Society), Ahmed Mustafa, Sharon Morgillo, Shree Dhawale Dec 2011

Psychology (Addiction: Biology, Psychology And Society), Ahmed Mustafa, Sharon Morgillo, Shree Dhawale

Ahmed Mustafa Dr.

No abstract provided.


Environmental Issues For The 21st Century And Their Impact On Human Health, Richard B. Philp Dec 2011

Environmental Issues For The 21st Century And Their Impact On Human Health, Richard B. Philp

Richard B. Philp

This book (see contents attached) is now available from the author on CD


Effects Of Indian Herbs On The Modulation Of Stress And Immune Response In Tilapia., Ahmed Mustafa, Brittany Byerley, Paul Mccain Dec 2010

Effects Of Indian Herbs On The Modulation Of Stress And Immune Response In Tilapia., Ahmed Mustafa, Brittany Byerley, Paul Mccain

Ahmed Mustafa Dr.

No abstract provided.


Effects Of Dietary Supplementation Of The Acidifier Vitoxal-Mionix On Growth, Survival, Immune Response And Gut Microbiota Of The Pacific White Shrimp, Litopenaeus Vannamei, Ahmed Mustafa, Davies Anuta, Alehandro Buentello, Susmita Patnaik, Addison Lawrence, Michaele Hume, Delbert Gatlin, Maurice Kemp Dec 2010

Effects Of Dietary Supplementation Of The Acidifier Vitoxal-Mionix On Growth, Survival, Immune Response And Gut Microbiota Of The Pacific White Shrimp, Litopenaeus Vannamei, Ahmed Mustafa, Davies Anuta, Alehandro Buentello, Susmita Patnaik, Addison Lawrence, Michaele Hume, Delbert Gatlin, Maurice Kemp

Ahmed Mustafa Dr.

No abstract provided.