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Roles Of Cellular Rna-Dependent Rna Polymerases In Endogenous Small Rna Pathways In Caenorhabditis Elegans: A Dissertation, Jessica J. Vasale 2010 University of Massachusetts Medical School

Roles Of Cellular Rna-Dependent Rna Polymerases In Endogenous Small Rna Pathways In Caenorhabditis Elegans: A Dissertation, Jessica J. Vasale

GSBS Dissertations and Theses

The RNA interference (RNAi) pathway in Caenorhabditis elegans is a two-step, small RNA-mediated silencing pathway. Unlike in other organisms, Dicer processing of double-stranded RNA into small interfering (si) RNAs is not sufficient in worms to induce gene silencing. The activity of cellular RNA-dependent RNA polymerase (RdRP) is necessary to synthesize a secondary pool of siRNAs, which interact with a unique class of Argonaute proteins to form the functional effector complexes that mediate silencing. The aims of this thesis were to: 1) characterize the role of RdRP family members in endogenous small RNA biogenesis; 2) identify the Argonaute proteins that interact ...


Molecular Mechanisms Of Neurite Complexity In The Drosophila Brain: A Dissertation, Lei Shi 2010 University of Massachusetts Medical School

Molecular Mechanisms Of Neurite Complexity In The Drosophila Brain: A Dissertation, Lei Shi

GSBS Dissertations and Theses

Development of functional neural circuits involves a series of complicated steps, including neurogenesis and neuronal morphogenesis. To understand the molecular mechasnims of neurite complexity, especially neurite branching/arborization, the Drosophila brain, especially MBNs (mushroom body neurons) and PNs (projection neurons) in olfactory circuitry, was used in this dissertation work as the model system to study how two molecules, Dscam and Kr-h1 affect neurite complexity in the Drosophilabrain.

For the Drosophila Dscam, through alternative splicing it could encode up to 152,064 distinct immunoglobulin/fibronectin type cell adhesion molecules. Each Dscam isoform is derived from one of the 19,008 ...


Rna Recognition By The Caenorhabditis Elegans Embryonic Determinants Mex-5 And Mex-3: A Dissertation, John M. Pagano Jr. 2010 University of Massachusetts Medical School

Rna Recognition By The Caenorhabditis Elegans Embryonic Determinants Mex-5 And Mex-3: A Dissertation, John M. Pagano Jr.

GSBS Dissertations and Theses

Post-transcriptional regulation of gene expression is a mechanism that governs developmental and cellular events in metazoans. In early embryogenesis, transcriptionally quiescent cells depend upon maternally supplied factors such as RNA binding proteins and RNA that control key decisions. Morphogen gradients form and in turn pattern the early embryo generating different cell types and spatial order. In the nematode Caenorhabditis elegans, the early embryo relies upon several RNA binding proteins that control mRNA stability, translation efficiency, and/or mRNA localization of cell fate determinants essential for proper development.

MEX-5 and MEX-3 are two conserved RNA-binding proteins required to pattern the anterior ...


Conservation Value Of Residential Open Space: Designation And Management Language Of Florida’S Land Development Regulations, Dara M. Wald 2010 University of Florida

Conservation Value Of Residential Open Space: Designation And Management Language Of Florida’S Land Development Regulations, Dara M. Wald

Dara Wald

The conservation value of open space depends upon the quantity and quality of the area protected, as well as how it is designed and managed. This study reports the results of a content analysis of Florida county Land Development Regulations. Codes were reviewed to determine the amount of open space required, how open space is protected during construction, the delegation of responsibilities, and the designation of funds for management. Definitions of open space varied dramatically across the state. Most county codes provided inadequate descriptions of management recommendations, which could lead to a decline in the conservation value of the protected ...


Calling On Science: Making “Alternatives” The New Gold Standard, Melvin E. Andersen 2010 The Hamner Institutes for Health Sciences

Calling On Science: Making “Alternatives” The New Gold Standard, Melvin E. Andersen

in Vitro Research Models Collection

All of life’s great journeys start with a goal in mind! The 2007 NAS report, Toxicity Testing in the 21st Century – A Vision and A Strategy, has proposed a clear goal. This report envisions a not-so-distant future where all routine toxicity testing for environmental agents will be conducted in human cells in vitro evaluating perturbations of cellular responses in a suite of toxicity pathway assays. Dose response modeling would utilize computational systems biology models of the circuitry underlying each toxicity pathway; in vitro to in vivo extrapolations would use pharmacokinetic models, ideally physiologically based pharmacokinetic models, to predict human ...


Exercise Does Not Increase Cyclooxygenase-2 Myocardial Levels In Young Or Senescent Hearts, John C. Quindry, Joel French, Karen L. Hamilton, Youngil Lee, Josh Selsby, Scott Powers 2010 University of Florida

Exercise Does Not Increase Cyclooxygenase-2 Myocardial Levels In Young Or Senescent Hearts, John C. Quindry, Joel French, Karen L. Hamilton, Youngil Lee, Josh Selsby, Scott Powers

Animal Science Publications

Increased myocardial cyclooxygenase-2 (COX-2) activity is essential for late phase ischemic preconditioning (IPC). Currently unknown is whether cardioprotection elicited by exercise also involves elevated myocardial COX-2 activity. This investigation tested whether aerobic exercise elevates myocardial COX-2 protein content or enzyme activity in young and senescent male Fisher 344 rats assigned to sedentary or cardioprotective endurance exercise treatments (3 consecutive days of treadmill exercise, 60 min/day @~70% VO2max). Assay of cardiac COX-2 protein content, catalytic activity, and inducible nitric oxide synthase (iNOS) protein content reveal that exercise did not alter COX-2 activity (PGE2, p = 0.866; PGF1α, p = 0.796 ...


A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann 2010 Humane Society International

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

Experimentation Collection

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 ...


Publication Bias In Reports Of Animal Stroke Studies Leads To Major Overstatement Of Efficacy, Emily Sena, H. Bart van der Worp, Philip M.W. Bath, David W. Howells, Malcolm Macleod 2010 University of Edinburgh

Publication Bias In Reports Of Animal Stroke Studies Leads To Major Overstatement Of Efficacy, Emily Sena, H. Bart Van Der Worp, Philip M.W. Bath, David W. Howells, Malcolm Macleod

Validation of Animal Experimentation Collection

The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst “experts” and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such “publication bias” in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach ...


Can Animal Models Of Disease Reliably Inform Human Studies?, H. Bart van der Worp, David W. Howells, Emily Sena, Michelle J. Porritt, Sarah Rewell, Victoria O'Collins, Malcolm Macleod 2010 Rudolf Magnus Institute of Neuroscience

Can Animal Models Of Disease Reliably Inform Human Studies?, H. Bart Van Der Worp, David W. Howells, Emily Sena, Michelle J. Porritt, Sarah Rewell, Victoria O'Collins, Malcolm Macleod

Validation of Animal Experimentation Collection

  • The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic.
  • Translational failure may be explained in part by methodological flaws in animal studies, leading to systematic bias and thereby to inadequate data and incorrect conclusions about efficacy.
  • Failures also result because of critical disparities, usually disease specific, between the animal models and the clinical trials testing the treatment strategy.
  • Systematic review and meta-analysis of animal studies may aid in the selection of the most ...


A View Of The Imd Pathway From The Rhim, Kamna Aggarwal 2010 University of Massachusetts Medical School

A View Of The Imd Pathway From The Rhim, Kamna Aggarwal

GSBS Dissertations and Theses

Innate immunity is the first line of defense against invading pathogens. It functions to eliminate pathogens and also to control infections. The innate immune response is also important for the development of pathogen-specific adaptive immune responses. As a result, the study of innate immune signaling pathways is crucial for understanding the interactions between host and pathogen. Unlike mammals, insects lack a classical adaptive immune response and rely mostly on innate immune responses.

Innate immune mechanisms have been widely studied in the fruit fly, Drosophila melanogaster. The genetic and molecular tools available in the Drosophila system make it an excellent model ...


Endogenous Small Rnas In The Drosophila Soma: A Dissertation, Megha Ghildiyal 2010 University of Massachusetts Medical School

Endogenous Small Rnas In The Drosophila Soma: A Dissertation, Megha Ghildiyal

GSBS Dissertations and Theses

Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNAs have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, modes of target regulation and in the biological pathways they regulate.

Historically, siRNAs were believed to arise only from exogenous double-stranded RNA triggers in organisms lacking RNA-dependent RNA polymerases. However, the discovery of endogenous siRNAs in flies expanded the biological significance of siRNAs beyond viral defense. By high throughput sequencing we identified Drosophila endosiRNAs as 21 nt small RNAs, bearing a 2´-O ...


Toxicity Testing In The 21st Century: A Vision And A Strategy, Daniel Krewski, Daniel Acosta Jr, Melvin Anderson, Henry Anderson, John C. Bailar III, Kim Boekelheide, Robert Brent, Gail Charnley, Vivian G. Cheung, Sidney Green Jr, Karl T. Kelsey, Nancy I. Kerkvliet, Abby A. Li, Lawrence McCray, Otto Meyer, Reid D. Patterson, William Pennie, Robert A. Scala, Gina M. Solomon, Martin Stephens, James Yager, Lauren Zeise 2010 University of Ottawa

Toxicity Testing In The 21st Century: A Vision And A Strategy, Daniel Krewski, Daniel Acosta Jr, Melvin Anderson, Henry Anderson, John C. Bailar Iii, Kim Boekelheide, Robert Brent, Gail Charnley, Vivian G. Cheung, Sidney Green Jr, Karl T. Kelsey, Nancy I. Kerkvliet, Abby A. Li, Lawrence Mccray, Otto Meyer, Reid D. Patterson, William Pennie, Robert A. Scala, Gina M. Solomon, Martin Stephens, James Yager, Lauren Zeise

Experimentation Collection

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational ...


Maintenance Of Visual Sensitivity In The Drosophila Eye: A Dissertation, Lina Ni 2010 University of Massachusetts Medical School Worcester

Maintenance Of Visual Sensitivity In The Drosophila Eye: A Dissertation, Lina Ni

GSBS Dissertations and Theses

High visual sensitivity is a common but important characteristic of animal eyes. It is especially critical for night vision. In animal eyes, photoreceptors are the first to receive the incoming rays of light and they convert the light signals to electrical signals before passing the information to interneurons in the eye and finally to the brain.

To function in dim light conditions, photoreceptors have developed high sensitivities to light. It is reported that both mammalian rod photoreceptors and Drosophilaphotoreceptors can detect single photons.

The high sensitivities of photoreceptors largely depend on a high content of rhodopsin, a light-stimulated G ...


Introduction: Knowing The Wild, Etienne S. Benson 2010 University of Pennsylvania

Introduction: Knowing The Wild, Etienne S. Benson

Departmental Papers (HSS)

The argument that wildlife conservation and the science that supports it are contentious and politicized is, of course, not new. American wildlife managers and biologists have been complaining about "biopolitics"—understood as political interference into decisions properly left to experts—since at least as far back as the 1930s, when they first established the journals, conferences, professional associations, degree programs, and financial supporters that allowed them to lay claim to the status of an autonomous, self-accrediting profession. Conservation activists have regularly protested the manipulation of policy by (other) special interests. New administrations in Washington have brought sudden reversals in supposedly ...


Dynamics Of The Rapsyn Scaffolding Protein At The Neuromuscular Junction Of Live Mice, Emile Bruneau, Mohammed Akaaboune 2010 University of Pennsylvania

Dynamics Of The Rapsyn Scaffolding Protein At The Neuromuscular Junction Of Live Mice, Emile Bruneau, Mohammed Akaaboune

Departmental Papers (ASC)

The efficacy of synaptic transmission depends on the maintenance of a high density of neurotransmitter receptors and their associated scaffold proteins in the postsynaptic membrane. While the dynamics of receptors has been extensively studied, the dynamics of the intracellular scaffold proteins that make up the postsynaptic density are largely unknown in vivo. Here, we focused on the dynamics of rapsyn, a protein required for the clustering and maintenance of acetylcholine receptor (AChR) density at postsynaptic sites. Using time-lapse imaging, we demonstrated that rapsyn is remarkably dynamic compared to AChRs at functional synapses, turning over 4–6 times more rapidly than ...


Quantifying Corn Nitrogen Deficiency And Application Rate With Active Canopy Sensors, J. E. Sawyer, D. W. Barker 2010 Iowa State University

Quantifying Corn Nitrogen Deficiency And Application Rate With Active Canopy Sensors, J. E. Sawyer, D. W. Barker

Agronomy Conference Proceedings and Presentations

Precision agriculture technologies are an integral part of many crop production operations. However, implementation for N application has lagged, primarily due to lack of a viable system for variable N rate decisions. Active canopy sensors have been developed as a tool to determine plant N stress deficiency and provide an on-the-go decision for implementing variable rate. Two general approaches could be implemented. One is to plan on conducting canopy sensing each year, with a reduced N rate applied preplant, at planting, or early sidedress and then sensing conducted at mid-vegetative growth to determine additional application need. A second is to ...


Toward Genuine Rodent Welfare: Response To Reviewer Comments, Jonathan P. Balcombe 2010 Independent Scientist and Author

Toward Genuine Rodent Welfare: Response To Reviewer Comments, Jonathan P. Balcombe

Laboratory Experiments Collection

I’m grateful to the editors for soliciting critiques of my commentary and for the opportunity to respond. Because one of the respondents (Patterson-Kane, 2010/this issue) does not take issue with the main points of my article, whereas the other (Blanchard, 2010/this issue) does, I focus my remarks here mostly on Blanchard’s critique.


Non-Invasive Methods Of Identifying And Tracking Wild Squid, Ruth A. Byrne, James B. Wood, Roland C. Anderson, Ulrike Griebel, Jennifer A. Mather 2010 Medical University of Vienna

Non-Invasive Methods Of Identifying And Tracking Wild Squid, Ruth A. Byrne, James B. Wood, Roland C. Anderson, Ulrike Griebel, Jennifer A. Mather

Morality and Ethics of Animal Experimentation Collection

The ability to identify individual free-living animals in the field is an important method for studying their behavior. Apart from invasive external or internal tags, which may cause injury or abnormal behavior, most cephalopods cannot be tagged, as their skin is too soft and delicate for tag retention. Additionally, cephalopods remove many types of tags. However, body markings have been successfully used as a non invasive method to identify individuals of many different species of animals, including whale sharks, grey whales, seals, and zebras. We developed methods to sex and individually identify Caribbean reef squid, Sepiotheuthis sepioidea. Males showed distinct ...


Laboratory Rodent Welfare: Thinking Outside The Cage, Jonathan P. Balcombe 2010 Independent Scientist and Author

Laboratory Rodent Welfare: Thinking Outside The Cage, Jonathan P. Balcombe

Laboratory Experiments Collection

This commentary presents the case against housing rats and mice in laboratory cages; the commentary bases its case on their sentience, natural history, and the varied detriments of laboratory conditions. The commentary gives 5 arguments to support this position: (a) rats and mice have a high degree of sentience and can suffer, (b) laboratory environments cause suffering, (c) rats and mice in the wild have discrete behavioral needs, (d) rats and mice bred for many generations in the laboratory retain these needs, and (e) these needs are not met in laboratory cages.


Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens 2010 The Humane Society of the United States

Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens

Laboratory Experiments Collection

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS’s animal care and use standards must report these incidents to the NIH’s OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The ...


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