DOCSLIB.ORG

Strategies for Improving Animal Models for Regenerative Medicine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Strategies for Improving Animal Models for Regenerative Medicine View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Cell Stem Cell Forum Strategies for Improving Animal Models for Regenerative Medicine Jose Cibelli,1 Marina E. Emborg,2 Darwin J. Prockop,3 Michael Roberts,4 Gerald Schatten,5 Mahendra Rao,6 John Harding,7 and Oleg Mirochnitchenko7,* 1Michigan State University, Cellular Reprogramming Laboratory, Department of Animal Science, B270 Anthony Hall, East Lansing, MI 48824, USA 2University of Wisconsin-Madison, Department of Medical Physics and Wisconsin National Primate Research Center, 1223 Capitol Court, Madison, WI 53715, USA 3Texas A&M Health Science Center, College of Medicine Institute for Regenerative Medicine at Scott and White, Department of Medicine, 5701 Airport Road, Module C, Temple, TX 76502, USA 4University of Missouri, 240b C.S. Bond Life Sciences Center, 1201 East Rollins Street, Columbia, MO 65211-7310, USA 5University of Pittsburgh, Department of Cell Biology and Physiology, S362 Biomedical Science Towers, 3500 Terrace Street, Pittsburgh, PA 15261, USA 6Center for Regenerative Medicine, National Institutes of Health, 50 South Drive, Suite 1140, Bethesda, MD 20892, USA 7Division of Comparative Medicine/ORIP/DPCPSI/OD, National Institutes of Health, 6701 Democracy Boulevard, Suite 943/950, Bethesda, MD 20892, USA *Correspondence: [email protected] http://dx.doi.org/10.1016/j.stem.2013.01.004 The field of regenerative medicine is moving toward translation to clinical practice. However, there are still knowledge gaps and safety concerns regarding stem cell-based therapies. Improving large animal models and methods for transplantation, engraftment, and imaging should help address these issues, facilitating eventual use of stem cells in the clinic. Introduction to cancer and renal failure. They are examples of a large animal model In this Forum, we discuss the current relatively obese and hypertensive due to currently being used to study human status, challenges, and major directions the constant access to food. In compar- genetic diseases (review in Kuzmuk and for future development of animal models ison to humans, mice have small body Schook, 2011). Even without genetic to facilitate the use of stem cells in size, short lifespan, and substantially modification, minipigs and full-size regenerative medicine. The variety of different physiology. Significant progress breeds have been widely used for stem cell sources and a wide spectrum has been made in the creation and use studying infectious diseases, cardiovas- of potential applications make the devel- of humanized mice. There are, how- cular disease and atherosclerosis, wound opment of universal recommendations ever, disadvantages to using the current healing, digestive processes, diabetes, and guiding principles very challenging, strains, including complications in repro- ophthalmology, and some cancers, as yet certain common themes and ducing standard chimeras, limitations well as providing organs for xenotrans- possible solutions are emerging that in choices of human cell types that can plantation. The value of pigs as biomed- can increase the predictive validity of be used for xenotransplantation, residual ical models has been enhanced over the animal models for regenerative medicine. host immunoreactivity, and problems last decade by targeting specific genomic This report is based on discussions that with translating conditioning regiments sites for modification. Swine disease took place at a recent NIH workshop between species. The evolutionary dis- models created by targeted genetic engi- on this topic (http://dpcpsi.nih.gov/orip/ tance between donor and recipient neering include those for cystic fibrosis, documents/summary_of_the_improving_ animals will also affect the survival of Alzheimer’s and Huntington’s disease, animal_models.pdf). transplanted stem cells due to species retinitis pigmentosa, hyperlipoproteine- differences in trophic properties of mia, and muscular dystrophy. Recently, Animal Models for Stem Cell-Based tissues. creation of humanized pigs has been re- Regenerative Medicine: Mice Larger animal species, which were crit- ported (Suzuki et al., 2012), as well as versus Large Animal Models ical for developing hematopoietic stem improved preclinical disease models suit- The discovery of mouse embryonic stem cell therapies, often have an enhanced able for testing stem cell therapies in pigs cells (ESCs) in 1981 revolutionized the ability to predict clinical efficacy relative (Giraud et al., 2011; McCall et al., 2012). study of developmental biology, and to mice. The utilization of large animal Most of this work has been enhanced mice are now used extensively to study models is expected to increase and, through access to the swine genome stem cell biology. However, there are limi- therefore, further development of large sequence and the use of inbred tations to their application as models for animal stem cell technologies will also minipigs (http://www.nsrrc.missouri.edu/ regenerative medicine. Mouse models be required. It will be critical to select strainavail.asp). Work in swine will do not reproduce in full certain human the large animal that is most appropriate complement nonhuman primate research disease conditions. For example, labora- for each potential therapy in humans. for neurological treatments when ana- tory mice are insulin resistant and prone The pig has emerged as one of the best lyzing recovery of fine motor skills or Cell Stem Cell 12, March 7, 2013 ª2013 Elsevier Inc. 271 Cell Stem Cell Forum impact on cognitive function. This related to safety, efficiency, and differen- certain cellular abnormalities of the corre- would be facilitated by equivalent tiation potential. sponding cells from patients with various advances in primate transgenesis, like Several problems remain before the Mendelian disorders. The ability to model the recent monkey models of Hunting- potential of nonrodent animal iPSCs can low-penetrance phenotypes, late-onset ton’s disease. be realized. Cell lines must be character- disorders, and genetically complex disor- Major challenges remain, however, for ized in more detail, chimerism tested, ders, however, remains to be proved. using large animals in stem cell research. and reprogramming increased in effi- Animal model systems may help solve For example, there is limited availability ciency and speed in order to enhance some of these problems because trans- of species-specific reagents, such as genome integrity. Cell surface markers plantation experiments can be performed antibodies and growth factors, and can be inconsistent among various lines using the animal as a host. The use of fully annotated expression microarrays. and cell populations may be heteroge- allogeneic iPSCs in animal model systems Authenticated ESCs have been difficult neous, probably reflecting different or xenotransplantation of human stem to generate from large domestic species, stages of reprogramming. Efficient deri- cells in immunocompromised or human- such as dog, swine, cattle, sheep, and vation of animal iPSC lines requires ized animals should facilitate analysis of goats. This has been obviated in part by further development of technologies for disease phenotypes that require cellular creation of induced pluripotent stem cells generating the cells, preferentially avoid- interactions in the tissues. Animal iPSCs (iPSCs) from these species by standard ing gene integration and potential risks can have certain advantages for testing reprogramming technologies. There is of tumorigenesis. hypotheses regarding the influence of a lack of centralized resources where An important aspect of animal studies is environmental or epigenetic components cells can be characterized and stored, the ability to test immune responses to of disease first identified in cell culture. reagents made available, and databases iPSCs and their derivatives. A number of The effects of exposures and genomic maintained for the wider biomedical animal studies have reported that iPSCs modifications can be tested at the level community. If these barriers can be over- can form teratomas and other types of of the tissue, organ, and the whole animal, come, well-characterized large animal tumors in immunodeficient, allogeneic, preserving interactions among distinct stem cells can provide an appropriate syngeneic, and xenogeneic recipients cell types in vivo. Use of animal systems choice of animal models for particular due to the inability of the host to re- also facilitates experimental design by human disease conditions and medical ject teratoma-inducing cells. The innate providing controls with matching genetic applications. These studies will comple- immune system appears capable of background, age, gender, and exposure ment the use of mice, leading to more dealing with small numbers of undifferen- history. comprehensive studies that can then be tiated iPSCs that might be present in applied to humans. grafts, despite efforts to eliminate them. Improving Stem Cell The ability of adaptive and innate immune Transplantation: Engraftment and Animal Induced Pluripotent Stem reactions to weaken engraftment of syn- Imaging Cells as Emerging Models for geneic stem cell transplants is another Two different approaches can be taken Human Therapeutic Applications important aspect of the host reaction for stem cell-based therapies. The first is The field of stem cell research experi- that can affect the efficiency of cell transplantation, in which stem cells, or enced
Load more

Recommended publications
  • Centrosome Detection in Sea Urchin Eggs with a Monoclonal
    Proc. Nati. Acad. Sci. USA Vol. 84, pp. 8488-8492, December 1987 Cell Biology Centrosome detection in sea urchin eggs with a monoclonal antibody against Drosophila intermediate filament proteins: Characterization of stages of the division cycle of centrosomes (cytoskeleton/fertilization/microtubules/mitosis) HEIDE SCHATTEN*, MARIKA WALTERt, DANIEL MAZIAt, HARALD BIESSMANNt, NEIDHARD PAWELETZ§, GE2RARD COFFE*, AND GERALD SCHATTEN* *Integrated Microscopy Resource for Biomedical Research, University of Wisconsin, 1117 West Johnson Street, Madison, WI 53706; tCenter for Developmental Biology, University of California, Irvine, CA 92717; tHopkins Marine Station, Department of Biological Sciences, Stanford University, Pacific Grove, CA 93950; and 1lnstitute for Cell and Tumor Biology, German Cancer Research Center, D-6900 Heidelberg, Federal Republic of Germany Contributed by Daniel Mazia, August 27, 1987 ABSTRACT A mouse monoclonal antibody generated Most all of the previous immunocytochemical work on against DrosophUa intermediate filament proteins (designated centrosomes has used an autoimmune serum from a patient Ah6/5/9 and referred to herein as Ah6) is found to cross-react suffering from CREST (calcinosis, Raynaud phenomenon, specifically with centrosomes in sea urchin eggs and with a esophageal dysmotility, sclerodactyly, telangiectasia) scle- 68-kDa antigen in eggs and isolated mitotic apparatus. When roderma (6-10). However, the inability to use this serum for preparations stained with Ah6 are counterstained with a immunoblotting precluded
    [Show full text]
  • Bioelectric Responses at Fertilization: Separation of the Events Associated
    Gamete Research 5:363-377 (1982) Bioelectric Responses at Fertilization: Separation of the Events Associated With Insemination From Those Due to the Cortical Reaction in Sea Urchin, Lytechinus variegatus Dieter Hulser and Gerald Schatten Department of Biological Science, The Florida State University, Tallahassee The bioelectric responses at fertilization of the sea urchin Lytechinus variegatus are a com- plex series of membrane potential and resistance changes that occur concomitant with ga- mete fusion, ionic fluxes, and the cortical granule discharge. This work attempts to separate the electrical effects of sperm-egg interactions from those of the cortical reactions. Two ap- proaches were taken to discern the electrical events associated with insemination, distinct from cortical granule discharge: 1) fertilization of eggs treated with 3% urethane, 10 mM procaine, or 10 mM nicotine, to prevent the cortical reaction and 2) refertilization of fertil- ized eggs (denuded with 1 mM aminotriazole containing 1 mg/ml soybean trypsin inhibitor). Cortical granule discharge in the absence of sperm incorporation was investigated by artifi- cial activation with 5 pM A23187 or by fertilization in the presence of 10 pM cytochalasin D, which prevents incorporation. These results are consistent with a model in which the sperm-egg interaction triggers both a rapid (50-400 msec), but minor (= 10 mV), electrical transient that leads to an action potential and then both the Na+-dependent fast block to polyspermy and the late block re- sulting from the secretion of the cortical granules. Key words: fertilization, sea urchin, bioelectric response, secretion, motility INTRODUCTION At fertilization the sea urchin egg undergoes a complex series of electrical changes in membrane potential and resistance.
    [Show full text]
  • Fraudulent Human Embryonic Stem Cell Research in South Korea: Lessons Learned
    Accountability in Research, 13:101–109, 2006 Copyright © Taylor & Francis Group, LLC ISSN: 0898-9621 print DOI: 10.1080/08989620600634193 GACR0898-96211545-5815Accountability in Research:Research Policies and Quality Assurance, Vol. 13, No. 01, February 2006: pp. 0–0 Commentary FRAUDULENT HUMAN EMBRYONIC STEM CELL RESEARCH IN SOUTH KOREA: LESSONS LEARNED Commentary:D. B. Resnik et Korean al. Stem Cell Fraud DAVID B. RESNIK , JD, PHD National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA ADIL E. SHAMOO, PHD Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, USA SHELDON KRIMSKY, PHD Department of Urban & Environmental Policy & Planning, Tufts University, Boston, Massachusetts, USA Now that most of the smoke has cleared from the South Korean human embryonic stem cell fraud, it is time to reflect on some lessons that one can learn from this scandal. First, a brief review of events will help to set the stage. In June 2005, Seoul University investigator Woo Suk Hwang and 24 co-authors published what appeared to be a ground- breaking paper in Science in which they claimed to have estab- lished eleven embryonic stem cell lines containing nuclear DNA from somatic cells of research subjects (Hwang et al., 2005). In March 2004, Hwang’s research team had published another apparently important paper in which they claimed to have estab- lished one cell line with the nuclear DNA from a research subject (Hwang et al 2004). If these two papers had been valid, they would have represented a significant step forward in human embryonic stem cell research, since they would have demon- strated the feasibility of a technique known as therapeutic Editor’s note: Although this piece is not related to the topic of this issue, we felt it was important to comment on the recent events in South Korea.
    [Show full text]
  • 1 Are We Ready for Genome Editing in Human Embryos for CLINICAL
    Are we ready for genome editing in human embryos FOR CLINICAL PURPOSES? Joyce C Harper and Gerald Schatten Joyce C Harper, Professor of Reproductive Science, Institute for Women’s Health, University College Londona Gerald Schatten, Professor of Ob-Gyn-Repro Sci, Cell Biology and Bioengineering, University of Pittsburgh School of Medicineb aInstitute for Women’s Health, University College London, 86-96 Chenies Mews, London, WC1E 6HX, UK, 0044 7880 795791, [email protected] (Corresponding author) b204 Craft Avenue Pittsburgh, PA 15213 412/641-2403 [phone] 412/641-6342 [fax] [email protected] [email protected] Abstract Perhaps the two most significant pioneering biomedical discoveries with immediate clinical implications during the past forty years have been the advent of assisted reproductive technologies (ART) and the genetics revolution. ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection and preimplantation genetic testing, has resulted in the birth of more than 8 million children, and the pioneer of IVF, Professor Bob Edwards, was awarded the 2010 Nobel Prize. The genetics revolution has resulted in our genomes being sequenced and many of the molecular mechanisms understood, and technologies for genomic editing have been developed. With the combination of nearly routine ART protocols for healthy conceptions together with almost error- free, inexpensive and simple methods for genetic modification, the question “Are we ready for genome editing in human embryos FOR CLINICAL PURPOSES?” was debated at the 5th Congress on Controversies in Preconception, Preimplantation and Prenatal Genetic Diagnosis, in collaboration with the Ovarian Club Meeting, in November 2018 in Paris. The co-authors each presented scientific, medical and bioethical backgrounds, and the debate was chaired by Professor Alan Handyside.
    [Show full text]
  • IVF) Versus Intracytoplasmic Sperm Injection (ICSI) Calvin R
    www.nature.com/scientificreports OPEN Fertilization and Cleavage Axes Difer In Primates Conceived By Conventional (IVF) Versus Intracytoplasmic Sperm Injection (ICSI) Calvin R. Simerly1, Diana Takahashi2, Ethan Jacoby3, Carlos Castro1, Carrie Hartnett1, Laura Hewitson4, Christopher Navara5 & Gerald Schatten 1* With nearly ten million babies conceived globally, using assisted reproductive technologies, fundamental questions remain; e.g., How do the sperm and egg DNA unite? Does ICSI have consequences that IVF does not? Here, pronuclear and mitotic events in nonhuman primate zygotes leading to the establishment of polarity are investigated by multidimensional time-lapse video microscopy and immunocytochemistry. Multiplane videos after ICSI show atypical sperm head displacement beneath the oocyte cortex and eccentric para-tangential pronuclear alignment compared to IVF zygotes. Neither fertilization procedure generates incorporation cones. At frst interphase, apposed pronuclei align obliquely to the animal-vegetal axis after ICSI, with asymmetric furrows assembling from the male pronucleus. Furrows form within 30° of the animal pole, but typically, not through the ICSI injection site. Membrane fow drives polar bodies and the ICSI site into the furrow. Mitotic spindle imaging suggests para-tangential pronuclear orientation, which initiates random spindle axes and minimal spindle:cortex interactions. Parthenogenetic pronuclei drift centripetally and assemble astral spindles lacking cortical interactions, leading to random furrows through the animal pole. Conversely, androgenotes display cortex-only pronuclear interactions mimicking ICSI. First cleavage axis determination in primates involves dynamic cortex-microtubule interactions among male pronuclei, centrosomal microtubules, and the animal pole, but not the ICSI site. With perhaps ten million ART babies now, fundamental problems regarding the mechanisms of fertilization and the onset of early development remain.
    [Show full text]
  • Embryogenesis and Blastocyst Development After Somatic Cell Nuclear Transfer in Nonhuman Primates: Overcoming Defects Caused by Meiotic Spindle Extraction$
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Developmental Biology 276 (2004) 237–252 www.elsevier.com/locate/ydbio Embryogenesis and blastocyst development after somatic cell nuclear transfer in nonhuman primates: overcoming defects caused by meiotic spindle extraction$ Calvin Simerlya,b,1, Christopher Navaraa,b,1, Sang Hwan Hyuna,b,1, Byeong Chun Leec, Sung Keun Kangc, Saverio Capuanoa,b, Gabriella Gosmana,b, Tanja Dominko2, Kowit-Yu Chonga,b, Duane Comptond, Woo Suk Hwangc, Gerald Schattena,b,* aDepartment of Obstetrics-Gynecology-Reproductive Sciences, Pittsburgh Development Center, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA 15213, USA bDepartment of Cell Biology-Physiology, Pittsburgh Development Center, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, 204 Craft Avenue, Pittsburgh, PA 15213, USA cDepartment of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea dDepartment of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA Received for publication 13 August 2004, revised 28 September 2004, accepted 12 October 2004 Abstract Therapeutic cloning or nuclear transfer for stem cells (NTSC) seeks to overcome immune rejection through the development of embryonic stem cells (ES cells) derived from cloned blastocysts. The successful derivation of a human embryonic stem cell (hESC) line from blastocysts generated by somatic cell nuclear transfer (SCNT) provides proof-of-principle for btherapeutic cloning,Q though immune matching of the differentiated NT-hES remains to be established. Here, in nonhuman primates (NHPs; rhesus and cynomologus macaques), the strategies used with human SCNT improve NHP-SCNT development significantly.
    [Show full text]
  • Status of the Implementation of the Federal Stem Cell Research Policy
    S. HRG. 107–874 STATUS OF THE IMPLEMENTATION OF THE FEDERAL STEM CELL RESEARCH POLICY HEARING BEFORE A SUBCOMMITTEE OF THE COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE ONE HUNDRED SEVENTH CONGRESS SECOND SESSION SPECIAL HEARING SEPTEMBER 25, 2002—WASHINGTON, DC Printed for the use of the Committee on Appropriations ( Available via the World Wide Web: http://www.access.gpo.gov/congress/senate U.S. GOVERNMENT PRINTING OFFICE 85–408 PDF WASHINGTON : 2003 For sale by the Superintendent of Documents, U.S. Government Printing Office Internet: bookstore.gpo.gov Phone: toll free (866) 512–1800; DC area (202) 512–1800 Fax: (202) 512–2250 Mail: Stop SSOP, Washington, DC 20402–0001 COMMITTEE ON APPROPRIATIONS ROBERT C. BYRD, West Virginia, Chairman DANIEL K. INOUYE, Hawaii TED STEVENS, Alaska ERNEST F. HOLLINGS, South Carolina THAD COCHRAN, Mississippi PATRICK J. LEAHY, Vermont ARLEN SPECTER, Pennsylvania TOM HARKIN, Iowa PETE V. DOMENICI, New Mexico BARBARA A. MIKULSKI, Maryland CHRISTOPHER S. BOND, Missouri HARRY REID, Nevada MITCH MCCONNELL, Kentucky HERB KOHL, Wisconsin CONRAD BURNS, Montana PATTY MURRAY, Washington RICHARD C. SHELBY, Alabama BYRON L. DORGAN, North Dakota JUDD GREGG, New Hampshire DIANNE FEINSTEIN, California ROBERT F. BENNETT, Utah RICHARD J. DURBIN, Illinois BEN NIGHTHORSE CAMPBELL, Colorado TIM JOHNSON, South Dakota LARRY CRAIG, Idaho MARY L. LANDRIEU, Louisiana KAY BAILEY HUTCHISON, Texas JACK REED, Rhode Island MIKE DEWINE, Ohio TERRENCE E. SAUVAIN, Staff Director CHARLES KIEFFER, Deputy Staff Director STEVEN J. CORTESE, Minority Staff Director LISA SUTHERLAND, Minority Deputy Staff Director SUBCOMMITTEE ON DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND RELATED AGENCIES TOM HARKIN, Iowa, Chairman ERNEST F.
    [Show full text]
  • The Egg and the Sperm: How Science Has Constructed a Romance Based on Stereotypical Male- Female Roles Author(S): Emily Martin Reviewed Work(S): Source: Signs, Vol
    The Egg and the Sperm: How Science Has Constructed a Romance Based on Stereotypical Male- Female Roles Author(s): Emily Martin Reviewed work(s): Source: Signs, Vol. 16, No. 3 (Spring, 1991), pp. 485-501 Published by: The University of Chicago Press Stable URL: http://www.jstor.org/stable/3174586 . Accessed: 06/04/2012 21:00 Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. The University of Chicago Press is collaborating with JSTOR to digitize, preserve and extend access to Signs. http://www.jstor.org THE EGG AND THE SPERM:HOW SCIENCEHAS CONSTRUCTED A ROMANCEBASED ON STEREOTYPICAL MALE-FEMALEROLES EMILYMARTIN The theory of the human body is always a part of a world- picture.... The theory of the human body is always a part of a fantasy. [JAMESHILLMAN, The Myth of Analysis]' As an anthropologist, I am intrigued by the possibility that culture shapes how biological scientists describe what they discover about the naturalworld. If this were so, we would be learning about more than the natural world in high school biology class; we would be learning about cultural beliefs and practices as if they were part of nature.
    [Show full text]
  • Making Matters of Fraud: Sociomaterial Technology in the Case of Hwang
    HOS0010.1177/0073275320921687History of SciencePark 921687research-article2020 Article HOS History of Science 2020, Vol. 58(4) 393 –416 Making matters of fraud: © The Author(s) 2020 Sociomaterial technology Article reuse guidelines: sagepub.com/journals-permissions in the case of Hwang and https://doi.org/10.1177/0073275320921687DOI: 10.1177/0073275320921687 Schatten journals.sagepub.com/home/hos Buhm Soon Park Graduate School of Science, Technology, and Policy, Korea Advanced Institute of Science and Technology (KAIST), Republic of Korea Abstract This paper revisits the “Hwang case,” which shook Korean society and the world of stem cell research in 2005 with the fraudulent claim of creating patient-specific embryonic stem cells. My goal is to overcome a human-centered, Korea-oriented narrative, by illustrating how materials can have an integral role in the construction and judgment of fraud. To this end, I pay attention to Woo Suk Hwang’s lab at Seoul National University as a whole, including human and nonhuman agents, that functioned as what I call sociomaterial technology, and Gerald P. Schatten at the University of Pittsburgh, Hwang’s collaborator, who played a crucial role in demonstrating the potency of this technology to the members of the scientific community. By recasting the whole event as the “case of Hwang and Schatten,” I argue that fraud is, like all knowledge claims, a sociotechnical construct, and that matters of fraud are locally judged. Fraud leaves its mark on materials, but I show that material evidence alone never
    [Show full text]
  • 16.2 News 768-769 MH
    Vol 439|16 February 2006 NEWS After budget cuts, this US space scientists rage picture of a mission to find earth-like planets is unlikely over axed projects to become a reality. Proposed cuts to NASA’s science budget have Scientists appreciate that NASA’s adminis- unleashed a storm of anger from US astro- trator, Mike Griffin, is struggling to balance nomers and planetary researchers, who say the his books. Griffin explained during the budget reductions would cause irreparable harm and press conference that the science cuts were drive young people from the field. necessary to pay for shuttle flights required to Under a NASA budget unveiled on 6 Febru- complete the International Space Station. “It’s ary (see Nature439,644; 2006), growth in what we needed to do,” he said regretfully. science spending between 2007 and 2010 But Jonathan Lunine, a planetary scientist at would be slashed by 17%. The budget proposed the University of Arizona, Tucson, sums up by President George W. Bush has yet to be the view of many when he says he finds it approved by Congress, but many planned pro- “puzzling and frustrating” that NASA would jects — from planet searches to a Mars sample divert money from science, widely considered return, as well as scores of individual research its most productive enterprise, to keep the grants — are likely to be scrapped (see ‘Some aged space shuttles flying. “It seems that NASA cuts proposed at NASA’). is trying to capitalize on its failures rather than Planetary scientist Alan Boss of the Carn- its successes,” says Lunine.
    [Show full text]
  • Curriculum Vitae
    Charles A. Easley, Ph.D. Department of Environmental Health Science University of Georgia College of Public Health Regenerative Bioscience Center 425 River Rd. Animal Dairy Sciences Bldg RM 450 Athens, GA 30602 Email: [email protected] Telephone: (706)542-2725 Education 2008 Virginia Commonwealth University, Richmond, Virginia Ph.D., Biochemistry 2005 Virginia Commonwealth University, Richmond, Virginia M.S., Biology 2002 College of William and Mary, Williamsburg, Virginia B.S., Biology Positions 2016-present Assistant Professor, Tenure Track, Department of Environmental Health Science, University of Georgia College of Public Health, Athens, GA 2015-2016 Assistant Professor, Research Track, Department of Cell Biology Emory University School of Medicine, Atlanta, GA 2012-2015 Instructor, Department of Cell Biology Emory University School of Medicine, Atlanta, GA 2012-2015 Faculty Supervisor, Laboratory of Translational Cell Biology Emory University School of Medicine, Atlanta, GA Research Training 2008-2012 Postdoctoral Fellow, Magee Womens Research Institute, University of Pittsburgh Pittsburgh, PA, with Prof. Gerald Schatten 2004-2008 Graduate Student, Virginia Commonwealth University Richmond, VA, with Prof. Robert Tombes Awards and Fellowships 2013 Cell Press Cell Reports Best of 2012, paper of the year 2011 L50 NIH Educational Loan Repayment Program in Contraception and Infertility (Easley, C. A.) Utilizing Induced Pluripotent Stem Cells to Restore Fertility in Sterile Primates: A Model for Re-establishing Male Fertility Following Rigorous
    [Show full text]
  • Microtubule Configurations During Fertilization, Mitosis, and Early Development in the Mouse and the Requirement for Egg Microtu
    Proc. Natl. Acad. Sci. USA Vol. 82, pp. 4152-4156, June 1985 Cell Biology Microtubule configurations during fertilization, mitosis, and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization (centrioles/cytoskeleton/embryogenesis/maternal inheritafice/microtubule organizing centers) GERALD SCHATTEN, CALVIN SIMERLY, AND HEIDE SCHATTEN Department of Biological Science, Florida State University, Tallahassee, FL 32306-3050 Communicated by Daniel Mazia, February 26, 1985 ABSTRACT Microtubules forming within the mouse egg MATERIALS AND METHODS during fertilization are required for the movements leading to the union of the sperm and egg nuclei (male and female pronu- Virgin CD-1 mice (Charles River Breeding Laboratories) clei, respectively). In the unfertilized oocyte, microtubules are were superovulated with 10 international units of pregnant predominantly found in the arrested meiotic spindle. At the mare serum followed 48 hr later with 10 international units of time for sperm incorporation, a dozen cytoplasmic asters as- human chorionic gonadotropin (10) and introduced to experi- semble, often associated with the pronuclei. As the pronuclei enced males. After mating, fertilized oocytes were collected move to the egg center, these asters enlarge into a dense array. (11, 12) and maintained at 370C in 114 mM NaCl/3.2 mM At the end of first interphase, the dense array disassembles KCl/2 mM CaCl2/0.5 mM MgCl2/2 mM NaHCO3/0.4 mM and is replaced by sheaths of microtubules surrounding the NaH2PO4/5 mM glucose/10 mM sodium lactate/0.1 mM so- adjacent pronuclei. Syngamy (pronuclear fusion) is not ob- dium pyruvate/10 mM Hepes/100 units of penicillin G per served; rather the adjacent paternal and maternal chromo- ml/10 ,ug ofphenol red per ml/2 mg ofbovine serum albumin some sets first meet at metaphase.
    [Show full text]