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Mouse Label-Retaining Cells Are Molecularly And Functionally Distinct From Reserve Intestinal Stem Cells, Ning Li, Angela Nakauka-Ddamba, John Tobias, Shane T. Jensen, Christopher J. Lengner 2016 University of Pennsylvania

Mouse Label-Retaining Cells Are Molecularly And Functionally Distinct From Reserve Intestinal Stem Cells, Ning Li, Angela Nakauka-Ddamba, John Tobias, Shane T. Jensen, Christopher J. Lengner

Statistics Papers

BACKGROUND & AIMS: Intestinal homeostasis and regeneration after injury are controlled by 2 different types of cells: slow cycling, injury-resistant reserve intestinal stem cells (ISCs) and actively proliferative ISCs. Putative reserve ISCs have been identified using a variety of methods, including CreER insertions at Hopx or Bmi1 loci in mice and DNA label retention. Label-retaining cells (LRCs) include dormant stem cells in several tissues; in the intestine, LRCs appear to share some properties with reserve ISCs, which can be marked by reporter alleles. We investigated the relationships between these populations.

METHODS: Studies were performed in Lgr5-EGFP-IRESCreERT2, Bmi1-CreERT2, Hopx-CreERT2, and TRE-H2BGFP::Hopx-CreERT2::lox-stop-lox-tdTomato mice. Intestinal epithelial cell populations were purified; we compared reporter allele-marked reserve ISCs and several LRC populations (marked by H2B-GFP retention) using histologic flow cytometry and functional and single-cell gene expression assays.

RESULTS: LRCs were dynamic and their cellular composition changed with time. Short-term LRCs had properties of secretory progenitor cells undergoing commitment to the Paneth or enteroendocrine lineages, while retaining ...


Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan 2016 The Humane Society of the United States

Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Martin Stephens, Ph.D.

While most people recognize that biomedical scientists are searching for knowledge that will improve the health of humans and animals, the image of someone deliberately causing harm to an animal in order to produce data that may lead to some future benefit has always prompted an uncomfortable reaction outside the laboratory. However, proponents of animal research have usually justified the practice by reference to greater benefits (new knowledge and medical treatments) over lesser costs (in animal suffering and death). Given that one of the costs of animal research is the suffering experienced by the animals, the goal of eliminating distress ...


Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens 2016 Tufts University

Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens

Martin Stephens, Ph.D.

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation. This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress ...


Unrelieved Pain And Distress In Animals: An Analysis Of Usda Data On Experimental Procedures, Martin Stephens, Philip Mendoza, Adrianna Weaver, Tamara Hamilton 2016 The Humane Society of the United States

Unrelieved Pain And Distress In Animals: An Analysis Of Usda Data On Experimental Procedures, Martin Stephens, Philip Mendoza, Adrianna Weaver, Tamara Hamilton

Martin Stephens, Ph.D.

Pain and distress are core issues in the field of animal experimentation and in the controversy that surrounds it. We sought to add to the empirical base of the literature on pain and distress by examining government data on experimental procedures that caused unrelieved pain and distress (UPAD) in animals. Of the species regulated by the U.S. Department of Agriculture (USDA), most of the approximately 100,000 animals subjected to UP AD during the year analyzed (1992) were guinea pigs and hamsters. Most of these animals were used in industry laboratories for various testing procedures, primarily vaccine potency testing ...


The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan 2016 The Humane Society of the United States

The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Martin Stephens, Ph.D.

While the attention given to preventing, assessing, and alleviating pain in research animals has increased noticeably in recent decades, much remains to be done both in terms of implementing best practices and conducting studies to answer outstanding questions. In contrast, the attention to distress (particularly non-pain induced distress) has shown no comparable increase. There are many reasons for this discrepancy, including the conceptual untidiness of the distress concept, the paucity of pharmacological treatments for distress, and perceived lack of regulatory emphasis on distress. These are challenges that need to be addressed and overcome. This book is intended to help meet ...


Chimpanzees In Laboratories: Distribution And Types Of Research, Martin L. Stephens 2016 The Humane Society of the United States

Chimpanzees In Laboratories: Distribution And Types Of Research, Martin L. Stephens

Martin Stephens, Ph.D.

This review presents the results of an informal 1993 survey of the distribution of chimpanzees (Pan troglodytes) in the world's laboratories, and the types of research conducted on them. Based on the available information, there are over 2200 chimpanzees in.laboratories, most of which are located in several US facilities. Europe apparently has less than 200 chimpanzees housed in two facilities. Worldwide, an estimated 80% of the chimpanzees in laboratories are used in studies on AIDS and hepatitis. It is concluded that, if Europe terminated its use of chimpanzees in research, for either financial, moral or political reasons, the ...


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 2016 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

Martin Stephens, Ph.D.

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 ...


A Holistic Approach To Taking Research Animal Suffering Seriously, Martin Stephens, Kathleen Conlee 2016 The Humane Society of the United States

A Holistic Approach To Taking Research Animal Suffering Seriously, Martin Stephens, Kathleen Conlee

Martin Stephens, Ph.D.

It is widely agreed, and often legally required, that distress and pain in research animals should be minimized--for the sake of animal welfare, ethical obligation, and public concern, as well as scientific quality. As testimony to the importance of distress and pain to stakeholders interested in research animals, many countries compile and publish annual statistics documenting overall patterns and trends on distress and pain in research animals. We argue for a holistic approach to minimizing research animal suffering, with all relevant parties sharing in this responsibility. Researchers, laboratory personnel, oversight committees, and facility administrators are central to day-to-day animal care ...


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 2016 Charles River Laboratories Foundation

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

Martin Stephens, Ph.D.

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 Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. de Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars 2016 Radboud University

The Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. De Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars

Martin Stephens, Ph.D.

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also amoral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic ...


Telonicher Marine Laboratory, HSU Telonicher Marine Laboratory 2016 Humboldt State University

Telonicher Marine Laboratory, Hsu Telonicher Marine Laboratory

Newsletters

No abstract provided.


Of Mice And Men, Bernard E. Rollin 2016 Colorado State University

Of Mice And Men, Bernard E. Rollin

Bernard Rollin, Ph.D.

No abstract provided.


Overcoming Ideology: Why It Is Necessary To Create A Culture In Which The Ethical Review Of Protocols Can Flourish, Bernard E. Rollin 2016 Colorado State University

Overcoming Ideology: Why It Is Necessary To Create A Culture In Which The Ethical Review Of Protocols Can Flourish, Bernard E. Rollin

Bernard Rollin, Ph.D.

My objective in this commentary is to describe and discuss a major threat to the continued thriving of science in our society, which is all the more insidious because it is largely unrecognized by those in the scientific community who are in a position to rectify the problem. Astute people in that community are well aware of many threats to science that include but are not limited to the following: appalling public scientific illiteracy; the unfortunate resurgence of “magic thinking”—reflected in turn in the reappearance of Creationism, which is hostile to evolution—and the billions of dollars spent on ...


Animal Research: A Moral Science, Bernard E. Rollin 2016 Colorado State University

Animal Research: A Moral Science, Bernard E. Rollin

Bernard Rollin, Ph.D.

No abstract provided.


Toxicology And New Social Ethics For Animals, Bernard E. Rollin 2016 Colorado State University

Toxicology And New Social Ethics For Animals, Bernard E. Rollin

Bernard Rollin, Ph.D.

The issue of animal treatment has emerged as a major social concern over the past three decades. This ramified in a new ethic for animal treatment that goes beyond concern about cruelty and attempts to eliminate animal pain and suffering, whatever its source. This is evidenced by laws governing animal research in many countries. Insofar as toxicology can entail significant and prolonged animal suffering, it is at loggerheads with this new ethic. Ways are suggested for the toxicological community to put itself in harmony with the ethic and thereby preserve its autonomy.


The Moral Status Of Invasive Animal Research, Bernard E. Rollin 2016 Selected Works

The Moral Status Of Invasive Animal Research, Bernard E. Rollin

Bernard Rollin, Ph.D.

No abstract provided.


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 2016 Charles River Laboratories Foundation

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

David Fraser, Ph.D.

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.


Single-Cell Transcriptional Analysis Of Normal, Aberrant, And Malignant Hematopoiesis In Zebrafish, Finola E. Moore, Elaine G. Garcia, Riadh Lobbardi, Esha Jain, Qin Tang, John C. Moore, Mauricio Cortes, Aleksey Molodtsov, Melissa Kasheta, Christina C. Luo, Amaris J. Garcia, Ravi Mylvaganam, Jeffrey A. Yoder, Jessica S. Blackburn, Ruslan I. Sadreyev, Craig J. Ceol, Trista E. North, David M. Langenau 2016 Massachusetts General Hospital

Single-Cell Transcriptional Analysis Of Normal, Aberrant, And Malignant Hematopoiesis In Zebrafish, Finola E. Moore, Elaine G. Garcia, Riadh Lobbardi, Esha Jain, Qin Tang, John C. Moore, Mauricio Cortes, Aleksey Molodtsov, Melissa Kasheta, Christina C. Luo, Amaris J. Garcia, Ravi Mylvaganam, Jeffrey A. Yoder, Jessica S. Blackburn, Ruslan I. Sadreyev, Craig J. Ceol, Trista E. North, David M. Langenau

Molecular and Cellular Biochemistry Faculty Publications

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4+ cell type, representing a putative cytotoxic T/NK cell. Our platform ...


Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

Animal tests yield misleading results.


The Beginning Of The End For Chimpanzee Experiments?, Andrew Knight 2016 Animal Consultants International

The Beginning Of The End For Chimpanzee Experiments?, Andrew Knight

Andrew Knight, Ph.D.

The advanced sensory, psychological and social abilities of chimpanzees confer upon them a profound ability to suffer when born into unnatural captive environments, or captured from the wild – as many older research chimpanzees once were – and when subsequently subjected to confinement, social disruption, and involuntary participation in potentially harmful biomedical research. Justifications for such research depend primarily on the important contributions advocates claim it has made toward medical advancements. However, a recent large-scale systematic review indicates that invasive chimpanzee experiments rarely provide benefits in excess of their profound animal welfare, bioethical and financial costs. The approval of large numbers of ...


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