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2014

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Articles 1 - 30 of 99

Full-Text Articles in Organisms

A Single Vertebrate Dna Virus Protein Disarms Invertebrate Immunity To Rna Virus Infection, Don B. Gammon, Sophie Duraffour, Daniel K. Rozelle, Heidi Hehnly, Rita Sharma, Michael E. Sparks, Cara C. West, Ying Chen, James J. Moresco, Graciela Andrei, John H. Connor, Darryl Conte Jr., Dawn E. Gundersen-Rindal, William L. Marshall, John R. Yates, Neal S. Silverman, Craig C. Mello Dec 2014

A Single Vertebrate Dna Virus Protein Disarms Invertebrate Immunity To Rna Virus Infection, Don B. Gammon, Sophie Duraffour, Daniel K. Rozelle, Heidi Hehnly, Rita Sharma, Michael E. Sparks, Cara C. West, Ying Chen, James J. Moresco, Graciela Andrei, John H. Connor, Darryl Conte Jr., Dawn E. Gundersen-Rindal, William L. Marshall, John R. Yates, Neal S. Silverman, Craig C. Mello

Neal Silverman

Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-kappaB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells …


Examining The Regulatory Value Of Multi-Route Mammalian Acute Systemic Toxicity Studies, Troy Seidle, Pilar Prieto, Anna Bulgheroni Dec 2014

Examining The Regulatory Value Of Multi-Route Mammalian Acute Systemic Toxicity Studies, Troy Seidle, Pilar Prieto, Anna Bulgheroni

Troy Seidle, PhD

Regulatory information requirements for pesticides call for submission of acute systemic toxicity data for up to three different exposure routes (oral, dermal, inhalation) for both active ingredients and formulated products. Similar multi-route testing is required in the European Union and elsewhere for industrial chemicals. To determine the value of acute toxicity testing by more than one route, oral-dermal and oralinhalation concordances among regulatory classifications were examined for large data sets of chemicals and pesticide active ingredients. Across all sectors examined, oral acute toxicity classifications for pure active substances were more severe than those derived from dermal data in more than …


An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle Dec 2014

An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle

Troy Seidle, PhD

Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines …


The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung Dec 2014

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Troy Seidle, PhD

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …


A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann Dec 2014

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Troy Seidle, PhD

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …


Humane Society International’S Global Campaign To End Animal Testing, Troy Seidle Dec 2014

Humane Society International’S Global Campaign To End Animal Testing, Troy Seidle

Troy Seidle, PhD

The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 …


The Fine-Scale Habitat Use Of Risso’S Dolphins Off Bardsey Island, Cardigan Bay (Uk), Marijke N. De Boer, Sonja Eisfeld, Mark P. Simmonds Dec 2014

The Fine-Scale Habitat Use Of Risso’S Dolphins Off Bardsey Island, Cardigan Bay (Uk), Marijke N. De Boer, Sonja Eisfeld, Mark P. Simmonds

Mark P. Simmonds, OBE

The main objectives of this study were (1) to estimate the population size of Risso’s dolphins off Bardsey Island using mark-recapture techniques (De Boer et al., 2013); and (2) to study habitat-use in relation to fine-scale oceanographic features. This work provides preliminary information on the habitat-use of Risso’s dolphins and will benefit future studies, along with the development of effective conservation measures for this species throughout the region.


Photo-Identification Methods Reveal Seasonal And Long-Term Site-Fidelity Of Risso’S Dolphins (Grampus Griseus) In Shallow Waters (Cardigan Bay, Wales), Marijke N. De Boer, Josephine Clark, Mardik F. Leopold, Mark P. Simmonds, Peter J.H. Reijnders Dec 2014

Photo-Identification Methods Reveal Seasonal And Long-Term Site-Fidelity Of Risso’S Dolphins (Grampus Griseus) In Shallow Waters (Cardigan Bay, Wales), Marijke N. De Boer, Josephine Clark, Mardik F. Leopold, Mark P. Simmonds, Peter J.H. Reijnders

Mark P. Simmonds, OBE

A photo-identification study on Risso’s dolphins was carried out off Bardsey Island in Wales (July to September, 1997-2007). Their local abundance was estimated using two different analytical techniques: 1) mark-recapture of well-marked dolphins using a “closed-population” model; and 2) a census technique based on the total number of iden-tified individual dolphins sighted over the study period. The mark-recapture estimates of 121 (left sides; 64 - 178, 95% CI; CV 0.24) and 145 dolphins (right sides; 78 - 213, 95% CI; CV 0.24) closely matched the census technique estimates (population size of 90 - 151). It was found that the dolphins …


Cetaceans And Marine Debris: The Great Unknown, Mark Peter Simmonds Dec 2014

Cetaceans And Marine Debris: The Great Unknown, Mark Peter Simmonds

Mark P. Simmonds, OBE

Plastics and other marine debris have been found in the gastrointestinal tracts of cetaceans, including instances where large quantities of material have been found that are likely to cause impairment to digestive processes and other examples, where other morbidity and even death have resulted. In some instances, debris may have been ingested as a result of the stranding process and, in others, it may have been ingested when feeding. Those species that are suction or “ram” feeders may be most at risk. There is also evidence of entanglement of cetaceans in marine debris. However, it is usually difficult to distinguish …


Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong Dec 2014

Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong

Katherine A. Fitzgerald

Enterohemorrhagic Escherichia coli (EHEC) is an extracellular pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. The proinflammatory cytokine, interleukin-1beta, has been linked to hemolytic uremic syndrome. Here we identify the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome as an essential mediator of EHEC-induced IL-1beta. Whereas EHEC-specific virulence factors were dispensable for NLRP3 activation, bacterial nucleic acids such as RNA:DNA hybrids and RNA gained cytosolic access and mediated inflammasome-dependent responses. Consistent with a direct role for RNA:DNA hybrids in inflammasome activation, delivery of synthetic EHEC RNA:DNA hybrids into the cytosol triggered NLRP3-dependent responses, …


Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli Dec 2014

Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli

Katherine A. Fitzgerald

Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1beta. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-gamma-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1beta expression required a second stimulation with LPS and was also dependent on IFN-gamma-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1beta upon a second …


Response Of Soil Nitrification To The Veterinary Pharmaceuticals Monensin, Ivermectin And Zinc Bacitracin, Magda A. Konopka Dec 2014

Response Of Soil Nitrification To The Veterinary Pharmaceuticals Monensin, Ivermectin And Zinc Bacitracin, Magda A. Konopka

Electronic Thesis and Dissertation Repository

Pharmaceutical residues can reach agricultural land through amendment with animal or human waste. Since 2010, a series of replicated plots received annual applications of ivermectin, monensin and zinc bacitracin, either singly or in a mixture, at 0.1 mg/kg and 10 mg/kg concentrations. I collected soil samples before and after the fourth annual application of pharmaceuticals and assayed them for functional changes and amoA gene abundance, a gene needed for ammonia oxidation. In 2013, I exposed the soils to 100 mg/kg in a laboratory experiment which resulted in acceleration of nitrification. Under 10 mg/kg treatments in the field the abundance of …


Increasing Compliance Of Personal Protective Equipment S Election And Use For Isolation Precautions Among Rns & Nas On A Med-Surg Unit, Megan R. Alsmeyer Dec 2014

Increasing Compliance Of Personal Protective Equipment S Election And Use For Isolation Precautions Among Rns & Nas On A Med-Surg Unit, Megan R. Alsmeyer

Master's Projects and Capstones

Background: Due to the high potential of transferring infectious diseases and/or organisms among patients, themselves, and the community, healthcare workers (HCWs) must be knowledgeable and confident in selecting the appropriate type of personal protective equipment (PPE), and the use in technique when putting on (donning) and removing (doffing) PPE based on the level of isolation precautions required for the patient being cared for.

Project Purpose: The purpose of this project is to determine whether assessing the knowledge and actual practice with observing, and utilizing an innovative approach of video and educational tools to isolation precautions would improve the consistency of …


Report Of The Working Group On Animal Distress In The Laboratory, Marilyn Brown, Larry Carbone, Kathleen Conlee, Marian Dawkins, Ian J. Duncan, David Fraser, Gilly Griffin, Victoria A. Hampshire, Lesley A. Lambert, Joy A. Mench, David Morton, Jon Richmond, Bernard E. Rollin, Andrew N. Rowan, Martin L. Stephens, Hanno Würbel Dec 2014

Report Of The Working Group On Animal Distress In The Laboratory, Marilyn Brown, Larry Carbone, Kathleen Conlee, Marian Dawkins, Ian J. Duncan, David Fraser, Gilly Griffin, Victoria A. Hampshire, Lesley A. Lambert, Joy A. Mench, David Morton, Jon Richmond, Bernard E. Rollin, Andrew N. Rowan, Martin L. Stephens, Hanno Würbel

Andrew N. Rowan, DPhil

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and often measures that alleviate one do not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining ‘distress,’ propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.


The Three Rs: The Way Forward, Michael Balls, Alan M. Goldberg, Julia H. Fentem, Caren L. Broadhead, Rex L. Burch, Michael F.W. Festing, John M. Frazier, Coenraad F.M. Hendriksen, Margaret Jennings, Margot D.O. Van Der Kamp, David B. Morton, Andrew N. Rowan, Claire Russell, William M.S. Russell, Horst Spielmann, Martin Stephens, William S. Stokes, Donald W. Straughan, James D. Yager, Joanne Zurlo, Bert F.M. Van Zutphen Dec 2014

The Three Rs: The Way Forward, Michael Balls, Alan M. Goldberg, Julia H. Fentem, Caren L. Broadhead, Rex L. Burch, Michael F.W. Festing, John M. Frazier, Coenraad F.M. Hendriksen, Margaret Jennings, Margot D.O. Van Der Kamp, David B. Morton, Andrew N. Rowan, Claire Russell, William M.S. Russell, Horst Spielmann, Martin Stephens, William S. Stokes, Donald W. Straughan, James D. Yager, Joanne Zurlo, Bert F.M. Van Zutphen

Andrew N. Rowan, DPhil

This is the report of the eleventh of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM), which was established in 1991 by the European Commission. ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well-informed about the state-of-the-art of non-animal test …


First Proof Of Concept Of Sustainable Metabolite Production From High Solids Fermentation Of Lignocellulosic Biomass Using A Bacterial Co-Culture And Cycling Flush System, Wanying Yao, Sue E. Nokes Dec 2014

First Proof Of Concept Of Sustainable Metabolite Production From High Solids Fermentation Of Lignocellulosic Biomass Using A Bacterial Co-Culture And Cycling Flush System, Wanying Yao, Sue E. Nokes

Biosystems and Agricultural Engineering Faculty Publications

To improve the lignocellulose conversion for ABE in high solids fermentation, this study explored the feasibility of cycling the process through the cellulolytic or/and solventogenic phases via intermittent flushing of the fermentation media. Five different flushing strategies (varying medium ingredients, inoculum supplement and cycling through phases) were investigated. Flushing regularly throughout the cellulolytic phase is necessary because re-incubation at 65 °C significantly improved glucose availability by at least 6-fold. The solvents accumulation was increased by 4-fold using corn stover (3-fold using miscanthus) over that produced by flushing only through the solventogenic phase. In addition, cycling process was simplified by re-incubating …


Characterization Of A Novel Fungal-Specific Gene, Fug1, In Fusarium Verticillioides, John Byron Ridenour Dec 2014

Characterization Of A Novel Fungal-Specific Gene, Fug1, In Fusarium Verticillioides, John Byron Ridenour

Graduate Theses and Dissertations

Filamentous fungi are responsible for numerous plant and animal diseases. The filamentous ascomycete Fusarium verticillioides is a globally important pathogen of maize, capable of causing severe yield reductions and economic losses. Also of substantial concern is the contamination of infected kernels with fumonisins, toxic secondary metabolites linked to toxicoses in humans and livestock. The number of sequenced fungal genomes is rapidly increasing. However, functional characterization of fungal genes has not progressed at a comparable rate. In pathogenic fungi, uncharacterized genes represent a source for novel virulence factors or anti-fungal targets. Therefore, to fully understand the genetic mechanisms underlying fungal pathogenesis, …


Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui Dec 2014

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …


Hiv Drug Resistance Among Infants And Children In South Africa: How Efficient Is Genotypic Testing?, Ellen Hendrix Dec 2014

Hiv Drug Resistance Among Infants And Children In South Africa: How Efficient Is Genotypic Testing?, Ellen Hendrix

Independent Study Project (ISP) Collection

Background: South Africa has the largest prevalence of HIV infection. This epidemic impacts adults as well as the pediatric population. The presence of drug-resistant mutations to antiretroviral therapies among infants and children is on the rise. Few studies have been conducted on this topic. Objective: The study aims to determine whether drug resistance testing in the form of genotypic testing is cost-effective when deciding whether to switch to a new HIV antiretroviral therapy following drug failure. Method: An interactive research approach is taken by collecting primary data from experts in this field. Secondary sources including guidelines from the World Health …


Carbon Dioxide For Euthanasia: Concerns Regarding Pain And Distress, With Special Reference To Mice And Rats, Kathleen Conlee, Martin Stephens, Andrew N. Rowan, Lesley A. King Nov 2014

Carbon Dioxide For Euthanasia: Concerns Regarding Pain And Distress, With Special Reference To Mice And Rats, Kathleen Conlee, Martin Stephens, Andrew N. Rowan, Lesley A. King

Andrew N. Rowan, DPhil

Carbon dioxide (CO2) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO2 flow rate and final concentration, presence …


Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan Nov 2014

Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan

Andrew N. Rowan, DPhil

Approaches and challenges to refining and reducing animal use in regulatory testing are reviewed. Regulatory testing accounts for the majority of animals reported in the most painful and/or distressful categories in the United States and Canada. Refinements in testing, including the use of humane endpoints, are of increasing concern. Traditional approaches to reduction (e.g., improving experimental design) are being supplemented with complementary approaches, such as the use of tier testing to eliminate some chemicals prior to in vivo testing. Technological advances in telemetry and noninvasive techniques will help decrease either the demand for animals in testing or animal suffering. Further …


A Vision Becoming Reality, Gill Langley Nov 2014

A Vision Becoming Reality, Gill Langley

Gill Langley, PhD

Non-animal science in toxicology and health research has been progressing for decades, but only now is it being seen widely as advanced science. The emergence of novel human biology-based tools and models, combined with legislative and regulatory change, a 21st century concept for toxicology, continuing failures in the drug pipeline, and systematic critiques of animal models, have created a pivotal moment of change. The leading edge is starting to become the norm. Humans and other animals are likely to benefit as a result.


Estimates For Worldwide Laboratory Animal Use In 2005, Katy Taylor, Nicky Gordon, Gill Langley, Wendy Higgins Nov 2014

Estimates For Worldwide Laboratory Animal Use In 2005, Katy Taylor, Nicky Gordon, Gill Langley, Wendy Higgins

Gill Langley, PhD

Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs (replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and unsubstantiated, ranging from 28–100 million. We collated data for 37 countries that …


Volunteer Studies In Pain Research — Opportunities And Challenges To Replace Animal Experiments: The Report And Recommendations Of A Focus On Alternatives Workshop, C. K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey Nov 2014

Volunteer Studies In Pain Research — Opportunities And Challenges To Replace Animal Experiments: The Report And Recommendations Of A Focus On Alternatives Workshop, C. K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey

Gill Langley, PhD

Despite considerable research, effective and safe treatments for human pain disorders remain elusive. Understanding the biology of different human pain conditions and researching effective treatments continue to be dominated by animal models, some of which are of limited value. British and European legislation demands that non-animal approaches should be considered before embarking on research using experimental animals. Recent scientific and technical developments, particularly in human neuroimaging, offer the potential to replace some animal procedures in the study of human pain. A group of pain research experts from academia and industry met with the aim of exploring creatively the tools, strategies …


Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley Nov 2014

Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley

Gill Langley, PhD

Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …


The Validity Of Animal Experiments In Medical Research, Gill Langley Nov 2014

The Validity Of Animal Experiments In Medical Research, Gill Langley

Gill Langley, PhD

Other animals, such as mice, rats, rabbits, dogs and monkeys, are widely used as surrogates for humans in fundamental medical research. This involves creating disorders in animals by chemical, surgical or genetic means, with the aim of mimicking selected aspects of human illnesses. It is a truism that any model or surrogate is not identical to the target being modelled. So, in medical research, experiments using animals or cell cultures or even healthy volunteers instead of patients (being the target population with the target illness) will inevitably have limitations, although these will be greater or lesser depending on the model.


Characterization And Quantification Of The Fungal Microbiome In Serial Samples From Individuals With Cystic Fibrosis, Sven D. Willger, Sharon L. Grim, Emily L. Dolben, Anna Shipunova, Thomas H. Hampton, Hillary G. Morrison, Laura M. Filkins, George A. O'Toole, Lisa A. Moulton, Alix Ashare, Mitchell L. Sogin, Deborah A. Hogan Nov 2014

Characterization And Quantification Of The Fungal Microbiome In Serial Samples From Individuals With Cystic Fibrosis, Sven D. Willger, Sharon L. Grim, Emily L. Dolben, Anna Shipunova, Thomas H. Hampton, Hillary G. Morrison, Laura M. Filkins, George A. O'Toole, Lisa A. Moulton, Alix Ashare, Mitchell L. Sogin, Deborah A. Hogan

Dartmouth Scholarship

Background: Human-associated microbial communities include fungi, but we understand little about which fungal species are present, their relative and absolute abundances, and how antimicrobial therapy impacts fungal communities. The disease cystic fibrosis (CF) often involves chronic airway colonization by bacteria and fungi, and these infections cause irreversible lung damage. Fungi are detected more frequently in CF sputum samples upon initiation of antimicrobial therapy, and several studies have implicated the detection of fungi in sputum with worse outcomes. Thus, a more complete understanding of fungi in CF is required. Results: We characterized the fungi and bacteria in expectorated sputa from six …


Chlorovirus Atcv-1 Is Part Of The Human Oropharyngeal Virome And Is Associated With Changes In Cognitive Functions In Humans And Mice, Robert H. Yolken, Lorraine Jones-Brando, David D. Dunigan, Geetha Kannan, Faith Dickerson, Emily Severance, Sarven Sabunciyan, C. Conover Talbot Jr., Emese Prandovszky, James R. Gurnon, Irina V. Agarkova, Flora Leister, Kristin L. Gressitt, Ou Chen, Bryan Deuber, Fangrui Ma, Mikhail V. Pletnikov, James L. Van Etten Nov 2014

Chlorovirus Atcv-1 Is Part Of The Human Oropharyngeal Virome And Is Associated With Changes In Cognitive Functions In Humans And Mice, Robert H. Yolken, Lorraine Jones-Brando, David D. Dunigan, Geetha Kannan, Faith Dickerson, Emily Severance, Sarven Sabunciyan, C. Conover Talbot Jr., Emese Prandovszky, James R. Gurnon, Irina V. Agarkova, Flora Leister, Kristin L. Gressitt, Ou Chen, Bryan Deuber, Fangrui Ma, Mikhail V. Pletnikov, James L. Van Etten

James Van Etten Publications

Chloroviruses (family Phycodnaviridae) are large DNA viruses known to infect certain eukaryotic green algae and have not been previously shown to infect humans or to be part of the human virome. We unexpectedly found sequences homologous to the chlorovirus Acanthocystis turfacea chlorella virus 1 (ATCV-1) in a metagenomic analysis of DNA extracted from human oropharyngeal samples. These samples were obtained by throat swabs of adults without a psychiatric disorder or serious physical illness who were participating in a study that included measures of cognitive functioning. The presence of ATCV-1 DNA was confirmed by quantitative PCR with ATCV-1 DNA being …


A Unique Mri Presentation Of Fungal Infection In The Brain, Muhammad Bilal Salman Khan, Saad Shafqat, Ather Enam Nov 2014

A Unique Mri Presentation Of Fungal Infection In The Brain, Muhammad Bilal Salman Khan, Saad Shafqat, Ather Enam

Section of Neurology

Fungal infections of CNS are common in certain geographic locations. MRI with or without contrast is a useful prediagnostic tool. However, the findings may sometimes be misleading. In this case report, the authors present unusual imaging findings in the MRI of fungal infection in an immunocompetent host, whereby hyper-intense signals were seen on T2-weighted images and patchy post-contrast enhancement was observed with surrounding edema. These findings were suggestive of a neoplastic lesion but it was identified as aspergillosis on subsequent histopathology. This unusual MRI finding of CNS highlights the need to consider fungal infection as a differential diagnosis of all …


Targeting The Small- And Intermediate Conductance Ca2+- Activated Potassium Channels: The Drug Binding Pocket At The Channel/Calmodulin Interface, Meng Cui, Guangrong Qin, Kunqian Yu, M. Scott Bowers, Miao Zhang Oct 2014

Targeting The Small- And Intermediate Conductance Ca2+- Activated Potassium Channels: The Drug Binding Pocket At The Channel/Calmodulin Interface, Meng Cui, Guangrong Qin, Kunqian Yu, M. Scott Bowers, Miao Zhang

Pharmacy Faculty Articles and Research

The small- and intermediate-conductance Ca 2+ -activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca 2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca 2+ -binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been …