The Wisconsin Regional Primate Research Center will host the 18th Annual Symposium on Nonhuman Primate Models for AIDS Oct. 4-7, 2000, at the Monona Terrace Convention Center in Madison, Wisconsin, http://www.primate.wisc.edu/aids2000/.

The conference, which the WRPRC last hosted in 1993, serves an important role in the exchange of information on AIDS-related research using the nonhuman primate model. The symposium annually attracts approximately 300 scientists from the United States and abroad. It is funded in part by the National Center for Research Resources?National Institutes of Health.

Five sessions will focus on primate research using SIV, HIV-2, HIV-1, SHIV and other primate retroviruses. 

The scientific program chair is David Watkins.  Andrew McMichael (Oxford University) will deliver the keynote address. Topics will include pathogenesis (chaired by Christopher Miller, California RPRC), immunology (Norman Letvin, Beth Israel Deaconess Medical Center), vaccines/therapeutics (John Shiver, Merck Research Laboratories), and virology (Ronald Desrosiers, New England RPRC).

A special session, Resource Development, will be chaired by Neal Nathanson, Office of AIDS Research. This will include updates on tetramers (John Altman, Emory University), intracellular staining (Louis Picker, Oregon RPRC), genetics (Jeff Rogers, Southwest Foundation for Biomedical Research), MHC class I (David Watkins, WRPRC), MHC class II (Ronald Bontrop, Biomedical Primate Research Center, Netherlands), lymphocyte depletion (Keith Reimann, Beth Israel Hospital), and R. Dee Schramm (in vitro fertilization, WRPRC). 

The conference coordinator is Edi Chan, phone, (608) 263-3500; fax, (608) 263-4031, e-mail, chan@primate.wisc.edu.
 

New fact sheets describe species, primate models for womens health, aging

The Primate Center now has five fact sheets available to help meet requests for information from the public. Already, these fact sheets have been distributed at a conference on women’s health issues in Milwaukee, to school groups visiting the WRPRC, to participants at conferences attended by staff, and through other venues.

The two-sided fact sheets are available by contacting either Jordana Lenon at the WRPRC (608-263-7024, jlenon@primate.wisc.edu), or Kathy Kaplan (301-435-0885, ospio@ncrr.nih.gov) through the NIH-NCRR Office of Science Policy.
 

• What is the Primate Research Center?
• Rhesus Macaque, Macaca mulatta
• Common Marmoset, Callithrix jacchus
• Primate Models of Aging
• Primate Models for Women's Health

Field notes—
Muriqui monkeys may be unique among social primates

Male muriqui monkeys live in highly social groups--multi-male and multi-female. Yet they do not show elevated levels of testosterone during the breeding season as do males of other social nonhuman primate species, a recently completed 19-month field study in Brazil has revealed.

These findings, by Drs. Toni Ziegler and Karen Strier of the University of Wisconsin-Madison, substantiate that testosterone surges among the males of nonhuman primate species living in highly social groups may not always be related directly to the onset of breeding, but rather to the increased competition for females.

Strier’s longterm field study in Minas Gerais, Brazil, has demonstrated that the endangered muriquis are a highly nonaggressive species. Yet, Ziegler and Strier still believed these animals might show testosterone surges during the breeding season just as do male mouse lemurs, rhesus, squirrel and many other monkeys.

When analysis of six males’ feces collected during the fall breeding season revealed no upswings in testosterone compared with samples taken during the rest of year, the researchers knew they had revealed an interesting characteristic of this elusive species. 

The muriqui research may lead to further studies on how basic temperament affects testosterone levels, aggression and breeding in other primate species.

This basic biological finding is even more remarkable when one considers that the researchers did not even have to touch the animals or disrupt the colony in any way during the entire study period. The fecal steroid assay techniques developed at the Wisconsin Regional Primate Research Center and used for this study also show promise for helping researchers learn more about the breeding and behavior of other endangered monkeys. Conservationists who have a better understanding of the populations they are trying to preserve can develop new ways to promote the protection and perpetuation of these populations, both in captivity and in the wild. This work is critical as habitats and populations continue to shrink for many nonhuman primate populations.

References:
Strier, K.B., T.E. Ziegler, and D. Wittwer. 1999. Seasonal and social correlates of fecal testosterone and cortisol levels in wild male muriquis (Brachyteles arachnoides). Hormones and Behavior. Apr;35(2):125-34.

Strier, K.B. 1999. Faces in the Forest: The Endangered Muriqui Monkeys of Brazil.  Harvard University Press, Cambridge, Mass.
 

Tasty treat

Sense of taste in primates is highly developed. Rhesus monkeys, like humans, chimpanzees and other primates, show a preference for sweet taste. Recent studies by Vicktoria Danilova, Ph.D., have revealed strong relationships between the activity in different types of taste fibers and the gustatory (taste) behavior in rhesus monkeys and marmosets. For example, animals always preferred solutions which in electrophysiological experiments stimulated only the taste fibers predominantly responsive to sweeteners.

Reference:
Danilova V, Hellekant G, Roberts T. 1999. Gustatory responses of common marmoset to compounds sweet in humans: conditional taste aversion test. Chemical Senses, 24:584.

Read more on this research and the "Taste-o-matic."
 

WRPRC Research Highlight—Clues found to mystery of SIV/HIV variability

WRPRC scientists have discovered new evidence explaining why retroviruses such as HIV in people and SIV in rhesus monkeys are so variable and difficult for the body’s immune system to target and kill.

The finding, reported in the November issue of the scientific journal Nature Medicine (see abstract page 3), is another step toward the development of effective vaccines to prevent AIDS. David Watkins, Ph.D., and two graduate students, David Evans and David O’Connor, conducted the research at the Primate Center.

A key finding: Killer cells called cytotoxic T lymphocyte cells (CTLs) likely play a greater role than previously thought in controlling infection in both humans and monkeys, says Watkins.

Two important arms of the immune system that respond to infection are CTLs and antibodies,” Watkins explains. “However, the antibody response does not fully develop until much later. By contrast, the peak of the CTL response coincides with early control of virus replication.”

Within a month after infection, he says, enormous replication takes place. The virus infects and then copies itself within host cells, turning the host cells into “virus factories.” CTLs recognize these infected cells and destroy them, limiting viral spread. Unfortunately, although a strong CTL response arises early, it ultimately fails to prevent progression to AIDS. Previous research has implied that HIV escapes the CTL response by replacing specific amino acids within regions of its own proteins that would normally be recognized by CTLs. The researchers tracked 10 of these regions, called epitopes, during the course of disease progression in rhesus monkeys. All 10 epitopes accumulated amino acid replacements. Many of the replacements either reduced or eliminated the CTLs’ ability to kill virus-infected cells.

“This supports the CTL escape hypothesis and underscores the importance of these killer cells in controlling viral replication,”  Watkins says.

Further characterization of CTLs and the epitopes they recognize is critical to designing effective vaccines, he added. The WRPRC is now developing a colony of genetically defined rhesus monkeys for more controlled AIDS research.

The Nature Medicine study represents collaboration between Watkins and Alessandro Sette at Epimmune, Inc., of San Diego, Calif. The work also involved the Laboratory of Genetics and Department of Pathology and Laboratory Medicine at UW-Madison, Biomedical Primate Research Centre-TNO in the Netherlands, and the Institute of Molecular Evolutionary Genetics at Pennsylvania State University.
 

Just published

Center scientists and affiliates publish frequently in peer-reviewed scientific journals. Following is just a small 
sampling of recent abstracts from these publications, reprinted here with  permission.

Evans DT, O'Connor DH, Jing P, Dzuris JL, Sidney J, da Silva J, Allen TM, Horton H, Venham JE, Rudersdorf RA, Vogel T, Pauza CD, Bontrop RE, DeMars R, Sette A, Hughes AL, Watkins DI. 1999. Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immuno-deficiency virus Env and Nef. Nature Medicine. Nov;5(11):1270-6.

Cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus arise early after infection, but ultimately fail to prevent progression to AIDS. Human immunodeficiency virus may evade the CTL response by accumulating amino-acid replacements within CTL epitopes. We studied 10 CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques. All 10 of these CTL epitopes accumulated amino-acid replacements and showed evidence of positive selection by the time the macaques died. Many of the amino-acid replacements in these epitopes reduced or eliminated major histocompatibility complex class I binding and/or CTL recognition. These findings strongly support the CTL ‘escape’ hypothesis. 

* * *

Keen KL, Burich AJ, Mitsushima D, Kasuya E, Terasawa E. 1999. Effects of pulsatile infusion of the GABA(A) receptor blocker bicuculline on the onset of puberty in female rhesus
monkeys. Endocrinology. Nov;140(11):5257-66.

In order to test the hypothesis that GABA is an inhibitory neurotransmitter restricting the release of LHRH before puberty, we examined the effects of pulsatile infusion of the GABA(A) receptor blocker, bicuculline, on the timing of puberty. Eleven female monkeys at 14-15 months of age were implanted with a stainless steel cannula into the base of the third ventricle above the median eminence. Five mon-keys received bicuculline infusion every 2 h at a dose of 1 microM with a gradual increase to 100 microM in 10 microl using a portable infusion pump. The remaining 6 monkeys received similar infusions of saline. An additional 11 colony monkeys without cannula implantation were used for controls. Results indicate that bicuculline infusion advances the timing of puberty. The age of menarche (17.8+/-0.5 months) in the bicuculline infusion animals was significantly earlier than that in the saline controls (28.2+/-2.3, P < 0.001) as well as in colony controls (30.6+/-0.9, P < 0.001). The age of first ovulation (30.5+/-3.3 months) in bicuculline-treated animals was much younger (P < 0.001) than that in both controls (44.8+/-1.8 and 44.7+/-1.2, respectively). Bicuculline also accelerated the growth curve. These results suggest that the reduction of tonic GABA inhibition of LHRH neurons advances the onset of puberty. 

* * *

Eisner JR, Dumesic DA, Kemnitz JW, Abbott DH. 2000. Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys. J. Clinical Endocrinol Metab. 85(3):1206-10.

This study determined whether timing of prenatal androgen excess resulted in differential impairment of insulin-glucose homeostasis in adult female rhesus monkeys. Ten female rhesus monkeys exposed to testosterone propionate starting on gestational day 40 (early treated), 9 females exposed to testosterone propionate starting between gestational days 100-115 (late treated), and 15 control females were studied. The modified minimal animal model was used to examine various measures derived from an iv glucose tolerance test, with regression analysis performed between these variables and body mass index. In addition, the disposition index (DI) and the hyperbolic relationship between insulin sensitivity (SI) and acute insulin response to glucose were examined. Early treated females demonstrated impaired pancreatic ß-cell function, as shown by diminished DI and decreased percentile ranking for the hyperbolic relationship between SI  and acute insulin response to glucose. In contrast, late treated females exhibited both an increase in DI and a negative relationship between body mass index and SI. These results suggest that prenatal androgen excess in female rhesus monkeys, regardless of gestational timing, perturbs insulin-glucose homeodynamics, with androgen excess in early and late gestation impairing pancreatic ß-cell function and altering insulin sensitivity, respectively.
 

Gleanings

New grants
Dee Schramm, Ph.D., received a Developmental Award from Great Lakes CFAR (Center for AIDS Research). The grant is for producing genetically identical MHC-defined monkeys by blastomere separation (embryo splitting). Use of MHC-defined monkeys enhances efforts to conduct more controlled SIV research.

Jon Ramsey, Ph.D., is the principal investigator on a one-year NIH-NIA grant entitled, “Dietary Restriction and Regional Energy Expenditure.”

Ted Golos, Ph.D., has received a new five-year NIH grant to study interactions of placental MHC class I molecules with uterine natural killer cell receptors in the rhesus monkey.

David Watkins, Ph.D., is principal investigator and Helen Horton, Ph.D., is co-investigator on a three-year NIH-NIAID grant entitled, “Quantification of T-Cell Responses in Vaccinated Macaques.”

A $10.9 million NIH mind-body grant will fund the establishment of the Center for the Study of Mind-Body Interaction, directed by Richard Davidson, Ph.D. (Psychiatry Dept.) The grant is administered by the HealthEmotions Research Institute, directed by Ned Kalin, M.D., and Steve Shelton.

Ned Kalin, M.D., received a five-year grant, “Fearful temperament points to vulnerability,” from the National Insitute of Mental Health for in collaboration with John Berard, Ph.D., Caribbean Primate Research Center-Cayo Santiago, and Steve Shelton. The team is studying the biology and behavior of free-ranging rhesus monkeys to predict their reactivity to the naturally occurring stress of leaving their natal group.

Wendy Garland Saltzman, Ph.D., is the principal investigator on a four-year, $874,000, grant from the National Institute of Mental Health-NIH entitled, “Mechanisms of Psychosocial Suppression of Cortisol.” Along with David Abbott, Ph.D., and Ian Bird, Ph.D. (Dept. of Ob/Gyn), Dr. Saltzman will look at the hormonal, cellular, and molecular mechanisms of adrenocortical suppression in subordinate female marmosets.

Promotions
Jen Haegele, from Lab Animal Technician 1 to Lab Animal Technician 2.

Bruce Pape, from Mechanician Journey to Instrument Maker Journey in the General Shop.
Appointments
Amy Usborne, D.V.M. (Pathology Unit), became a Diplomate of the American College of Veterinary Pathology by passing her board examination on Sept. 22-23 in Ames, IA.

Iris Bolton, D.V.M., (Animal Services) who began at the WRPRC in June, became a licensed veterinarian in Wisconsin in November. She was previously a primate medicine resident at the California Regional Primate Research Center in Davis, California.

David Watkins, Ph.D.,  has been appointed to serve a three-year term as a member of the National Institutes of Health’s AIDS and Related Research Study Section 2, Center for Scientific Review. This is the study section responsible for reviewing the majority of AIDS-related immunology RO1 grant applications.

Richard Atkinson, M.D., recently accepted the position as Editor of the International Journal of Obesity (for North America). This will be a 5-year term, renewable appointment.

In the news
Drs. Toni Ziegler, Charles Snowdon, and Jeffrey French were featured in an Oct. 11, 1999, Washington Post article, “For tamarins, it takes a village.” 

Steve Shelton, distinguished researcher, Psychiatry Department, was recently featured on the Discovery Channel on-line for his research into the chemical basis for rhesus monkey emotions and the similarity to humans. The article is entitled “That Human Feeling."

James Thomson, V.M.D., Ph.D., and Neal First, Ph.D., were featured in a Dec. 19 Capital Times special segment, “Leaders for a new Millennium.” 

WRPRC Director Joseph Kemnitz, Ph.D., was interviewed for USA Today’s Dec. 8 cover story, “Violence escalates over animal research.” 

Rick Weindruch, Ph.D., and Ricki Colman, Ph.D., appeared on the Scientific American Frontiers program, “Never Say Die,” with Alan Alda Jan. 25 on PBS. Dr. Weindruch was interviewed, among other scientists nationwide, for his research into aging and life extension. 

Dr. Weindruch and Thomas Prolla, Ph.D., were mentioned in Signals, the online magazine of biotech nology industry analysis, in an article entitled, “Essence de vie.” 

James Thomson, V.M.D., Ph.D., was quoted in The New York Times Magazine Jan. 30 for his embryonic stem cell research with both monkeys and humans.

Joseph Kemnitz, Ph.D., and Christopher Coe, Ph.D., provided comments in a story on biomedical research and animal rights violence in the February 2000 issue of Scientific American. 

An article in the February 2000 issue of Lab Animal, “Open the Doors to the Public to Promote Support,” mentions the WRPRC. 

New staff
Darrel B. Florence, D.V.M., M.Sc., joined our staff as Research Animal Veterinarian and Associate Director for Animal Services March 6. A native of Southwestern Alberta, Canada, Dr. Florence was recently Director of Animal Resources at Atlantic Veterinary College, University of Prince Edward Island, Canada. He previously spent five years at the California Regional Primate Research Center at UC-Davis.  He will be responsible for ensuring that all animals at the WRPRC receive appropriate care and husbandry, and are used in research in accordance with all applicable guidelines, legislation and regulations. 

Lia Bauer, associate research specialist, Sept.1 (Pathology Unit).
Sarah Peeks, animal technician, June 6 (Animal Services).
Dagna Solveig Sheerar, associate research specialist, Sept. 1 (Immunology and Virology Core).
Rao Zhou, research assistant, Sept. 1 (Abbott lab).
Ren-He Xu, M.D., Ph.D., senior scientist, Oct. 4 (Thomson lab).
Megan Sosa, animal caretaker, Oct. 11 (Animal Services).
Katie Tietz, associate research specialist, Dec. 1 (Kalin/Shelton lab).
Steven A. Busch, program assistant 2, Jan. 18. 
The lab of David Watkins, Ph.D., has welcomed a number of new staff since last fall:
Lorenzo Mortara, Ph.D., research associate; Max Liebl, associate research specialist; Ed Dunphy, associate researcher; Barry McClernon, associate research specialist; Donald Carter, associate research specialist; ShuNing Zhan, research specialist; Jason Weinfurther, associate research specialist. 

Departures
Julie Vanderloop, veterinary technician, who has worked at the center since May 1993, departed Oct. 31 to  pursue a career in canine training.

Etsuko Kasuya, a postdoctoral fellow who began working at the Primate Center in May 1996, left Dr. Terasawa’s lab to assume a scientist position in the Department of Physiology, at the National Institute of Animal Industry, Tsukuba, Japan, Oct 1. She will study brain function in domestic animals.

Scott Paffenroth, program assistant, departed Nov. 18 to accept a position as Digital Dept. supervisor at Best Buy West in Madison.
 

Dr. Bavister accepts endowed chair in
New Orleans

Barry Bavister, Ph.D., has accepted an endowed chair as the Freeport-MacMoran Professor of Conservation Biology at the University of New Orleans. He plans to resign his UW-Madison faculty position June 1, 2000. The chair is accom-panied by a joint research appointment at the Audubon Institute, Center for Research of En-dangered Species in New Orleans. Bavister will also be working closely with the Tulane Primate Center and other institutions in Louisiana.

“This is a unique opportunity to extend my embryology work into species conservation, to work closely with other senior investigators in this research, and to help build a new Ph.D. program in Conservation Biology,” Bavister said.

Bavister will continue to serve as director of the ERP Program until the end of the spring semester. A professor in the Department of Animal Health and Biomedical Sciences, he has been a reproduction researcher at the UW-Madison and associated with the WRPRC for more than 20 years. His studies have largely addressed the regulatory mechanisms of sperm and egg maturation, sperm-egg interactions, fertilization, and preimplantation embryo development, using monkeys, hamsters, cattle, and cats. In 1984, his lab produced the world’s first “test tube” rhesus monkey, Petri. See also: UW profile of Dr. Bavister’s work.