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Sample records for catheterized rhesus macaque

  1. Ambiguity aversion in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Benjamin eHayden

    2010-09-01

    Full Text Available People generally prefer risky options, which have fully specified outcome probabilities, to ambiguous options, which have unspecified probabilities. This preference, formalized in economics, is strong enough that people will reliably prefer a risky option to an ambiguous option with a greater expected value. Explanations for ambiguity aversion often invoke uniquely human faculties like language, self-justification, or a desire to avoid public embarrassment. Challenging these ideas, here we demonstrate that a preference for unambiguous options is shared with rhesus macaques. We trained four monkeys to choose between pairs of options that both offered explicitly cued probabilities of large and small juice outcomes. We then introduced occasional trials where one of the options was obscured and examined their resulting preferences; we ran humans in a parallel experiment on a nearly identical task. We found that monkeys reliably preferred risky options to ambiguous ones, even when this bias was costly, closely matching the behavior of humans in the analogous task. Notably, ambiguity aversion varied parametrically with the extent of ambiguity. As expected, ambiguity aversion gradually declined as monkeys learned the underlying probability distribution of rewards. These data indicate that ambiguity aversion reflects fundamental cognitive biases shared with other animals rather than uniquely human factors guiding decisions.

  2. Gene targeting in adult rhesus macaque fibroblasts

    Directory of Open Access Journals (Sweden)

    Wolf Don P

    2008-03-01

    Full Text Available Abstract Background Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology. Results A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term in vitro manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer. Conclusion The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.

  3. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Chang, Steve W. C.; Amy A. Winecoff; Platt, Michael L.

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that t...

  4. Vicarious Reinforcement in Rhesus Macaques (Macaca Mulatta)

    OpenAIRE

    Chang, Steve W. C.; Amy A. Winecoff; Platt, Michael L.

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this...

  5. Ulcerative cheilitis in a rhesus macaque.

    Science.gov (United States)

    Bailey, C C; Miller, A D

    2012-03-01

    A 2-year-old, female, simian immunodeficiency virus E543-infected rhesus macaque (Macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commissure. Histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and nondegenerate neutrophils and macrophages admixed with syncytial epithelial cells. Rare epithelial cells contained herpetic inclusion bodies. These cells stained positive for Human herpesvirus 1 via immunohistochemistry, and DNA sequencing confirmed the presence of closely related Macacine herpesvirus 1 (B virus).

  6. Evolutionary and biomedical insights from the rhesus macaque genome

    DEFF Research Database (Denmark)

    Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G

    2007-01-01

    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedi...

  7. Vicarious reinforcement in rhesus macaques (macaca mulatta).

    Science.gov (United States)

    Chang, Steve W C; Winecoff, Amy A; Platt, Michael L

    2011-01-01

    What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1) and/or rewards to another monkey (M2) with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in non-social control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

  8. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Steve W. C. Chang

    2011-03-01

    Full Text Available What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1 and/or rewards to another monkey (M2 with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in nonsocial control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

  9. Seed dispersal by rhesus macaques Macaca mulatta in Northern India.

    Science.gov (United States)

    Sengupta, Asmita; McConkey, Kim R; Radhakrishna, Sindhu

    2014-12-01

    Frugivorous primates are important seed dispersers and their absence from forest patches is predicted to be detrimental to tropical forest regeneration and recruitment. With the reduction of primate populations globally, ecologically resilient primate species, characterized by dietary flexibility and the ability to thrive in a variety of habitats, assume new importance as seed dispersers. The most widely distributed non-human primate, the rhesus macaque Macaca mulatta has been intensively studied but little is known about its role in maintaining ecosystem structure and functions. Due to their frugivorous diet, large group sizes, large home ranges and tolerance to disturbance, rhesus macaques may be effective seed dispersers. We studied seed dispersal by rhesus macaques at the Buxa Tiger Reserve, India, through a combination of behavioural observations and germination experiments. Rhesus macaques dispersed 84% of the 49 species they fed on either through spitting or defecation. Nearly 96% of the handled seeds were undamaged and 61% of the species for which germination tests were performed had enhanced germination. Almost 50% of the monitored seeds among those deposited in situ germinated and 22% established seedlings, suggesting that rhesus macaques are important seed dispersers in tropical forests. Due to their widespread distribution and large populations, rhesus macaques are perceived as common and are categorized as Least Concern on the IUCN Red List, effectively excluding them from any conservation plans. Based on the results of our study, we argue that rhesus macaques fulfill critical ecological functions in their habitat and that this parameter must be taken into consideration when they are reviewed for conservation priorities.

  10. Effect of sildenafil citrate on penile erection of rhesus macaques

    Institute of Scientific and Technical Information of China (English)

    Xun-BinHuang; Cheng-LiangXiong; Cheng-GaoYu; Jie-LingZhou; Ji-YunShen

    2004-01-01

    Aim: To examine the effect of sildenafil citrate on penile erection of male rhesus macaque. Methods:Twenty Macaca mulatta were divided into the sildenafil treated and the control groups of l0 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. Results: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in the sildenafil group. Conclusion: Sildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque. (Asian J Androl 2004 Sep; 6: 233-235)

  11. Evolutionary and biomedical insights from the rhesus macaque genome.

    Science.gov (United States)

    Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G; Bumgarner, Roger; Weinstock, George M; Mardis, Elaine R; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Wilson, Richard K; Batzer, Mark A; Bustamante, Carlos D; Eichler, Evan E; Hahn, Matthew W; Hardison, Ross C; Makova, Kateryna D; Miller, Webb; Milosavljevic, Aleksandar; Palermo, Robert E; Siepel, Adam; Sikela, James M; Attaway, Tony; Bell, Stephanie; Bernard, Kelly E; Buhay, Christian J; Chandrabose, Mimi N; Dao, Marvin; Davis, Clay; Delehaunty, Kimberly D; Ding, Yan; Dinh, Huyen H; Dugan-Rocha, Shannon; Fulton, Lucinda A; Gabisi, Ramatu Ayiesha; Garner, Toni T; Godfrey, Jennifer; Hawes, Alicia C; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N; Joshi, Vandita; Khan, Ziad Mohid; Kirkness, Ewen F; Cree, Andrew; Fowler, R Gerald; Lee, Sandra; Lewis, Lora R; Li, Zhangwan; Liu, Yih-Shin; Moore, Stephanie M; Muzny, Donna; Nazareth, Lynne V; Ngo, Dinh Ngoc; Okwuonu, Geoffrey O; Pai, Grace; Parker, David; Paul, Heidie A; Pfannkoch, Cynthia; Pohl, Craig S; Rogers, Yu-Hui; Ruiz, San Juana; Sabo, Aniko; Santibanez, Jireh; Schneider, Brian W; Smith, Scott M; Sodergren, Erica; Svatek, Amanda F; Utterback, Teresa R; Vattathil, Selina; Warren, Wesley; White, Courtney Sherell; Chinwalla, Asif T; Feng, Yucheng; Halpern, Aaron L; Hillier, Ladeana W; Huang, Xiaoqiu; Minx, Pat; Nelson, Joanne O; Pepin, Kymberlie H; Qin, Xiang; Sutton, Granger G; Venter, Eli; Walenz, Brian P; Wallis, John W; Worley, Kim C; Yang, Shiaw-Pyng; Jones, Steven M; Marra, Marco A; Rocchi, Mariano; Schein, Jacqueline E; Baertsch, Robert; Clarke, Laura; Csürös, Miklós; Glasscock, Jarret; Harris, R Alan; Havlak, Paul; Jackson, Andrew R; Jiang, Huaiyang; Liu, Yue; Messina, David N; Shen, Yufeng; Song, Henry Xing-Zhi; Wylie, Todd; Zhang, Lan; Birney, Ewan; Han, Kyudong; Konkel, Miriam K; Lee, Jungnam; Smit, Arian F A; Ullmer, Brygg; Wang, Hui; Xing, Jinchuan; Burhans, Richard; Cheng, Ze; Karro, John E; Ma, Jian; Raney, Brian; She, Xinwei; Cox, Michael J; Demuth, Jeffery P; Dumas, Laura J; Han, Sang-Gook; Hopkins, Janet; Karimpour-Fard, Anis; Kim, Young H; Pollack, Jonathan R; Vinar, Tomas; Addo-Quaye, Charles; Degenhardt, Jeremiah; Denby, Alexandra; Hubisz, Melissa J; Indap, Amit; Kosiol, Carolin; Lahn, Bruce T; Lawson, Heather A; Marklein, Alison; Nielsen, Rasmus; Vallender, Eric J; Clark, Andrew G; Ferguson, Betsy; Hernandez, Ryan D; Hirani, Kashif; Kehrer-Sawatzki, Hildegard; Kolb, Jessica; Patil, Shobha; Pu, Ling-Ling; Ren, Yanru; Smith, David Glenn; Wheeler, David A; Schenck, Ian; Ball, Edward V; Chen, Rui; Cooper, David N; Giardine, Belinda; Hsu, Fan; Kent, W James; Lesk, Arthur; Nelson, David L; O'brien, William E; Prüfer, Kay; Stenson, Peter D; Wallace, James C; Ke, Hui; Liu, Xiao-Ming; Wang, Peng; Xiang, Andy Peng; Yang, Fan; Barber, Galt P; Haussler, David; Karolchik, Donna; Kern, Andy D; Kuhn, Robert M; Smith, Kayla E; Zwieg, Ann S

    2007-04-13

    The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

  12. Color-detection thresholds in rhesus macaque monkeys and humans

    OpenAIRE

    Gagin, Galina; Bohon, Kaitlin S.; Butensky, Adam; Gates, Monica A.; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L.; Qu, Jane; Stoughton, Cleo M.; Swanbeck, Sonja N.; Conway, Bevil R.

    2014-01-01

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection...

  13. Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

    Science.gov (United States)

    Newman, Christina M.; Mohr, Emma L.; Gellerup, Dane D.; Breitbach, Meghan E.; Buechler, Connor R.; Rasheed, Mustafa N.; Mohns, Mariel S.; Weiler, Andrea M.; Barry, Gabrielle L.; Weisgrau, Kim L.; Eudailey, Josh A.; Rakasz, Eva G.; Vosler, Logan J.; Post, Jennifer; Capuano, Saverio; Golos, Thaddeus G.; Permar, Sallie R.; Osorio, Jorge E.; Friedrich, Thomas C.; O’Connor, Shelby L.; O’Connor, David H.

    2016-01-01

    Background Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV. Methodology/Principal Findings Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form. Conclusions/Significance An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection

  14. Ranking Network of a Captive Rhesus Macaque Society: A Sophisticated Corporative Kingdom

    NARCIS (Netherlands)

    Hsieh, F.; McAssey, M.P.; Beisner, B.; McCowan, B.

    2011-01-01

    We develop a three-step computing approach to explore a hierarchical ranking network for a society of captive rhesus macaques. The computed network is sufficiently informative to address the question: Is the ranking network for a rhesus macaque society more like a kingdom or a corporation? Our compu

  15. Demographic histories and patterns of linkage disequilibrium in Chinese and Indian rhesus macaques

    DEFF Research Database (Denmark)

    Hernandez, Ryan D; Hubisz, Melissa J; Wheeler, David A;

    2007-01-01

    To understand the demographic history of rhesus macaques (Macaca mulatta) and document the extent of linkage disequilibrium (LD) in the genome, we partially resequenced five Encyclopedia of DNA Elements regions in 9 Chinese and 38 captive-born Indian rhesus macaques. Population genetic analyses o...

  16. A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys, Cynomolgus Macaques, and Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Donald K. Nichols

    2012-10-01

    Full Text Available Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV Boniface in non-human primates (NHP belonging to three different species. Groups of cynomolgus macaques (cyno, rhesus macaques (rhesus, and African green monkeys (AGM were challenged with target doses of 50 or 500 plaque-forming units (pfu of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT and aspartate transaminase (AST concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.

  17. Disease Progression Patterns of SHIV-KB9 in Rhesus Macaques of Chinese Origin in Comparison with Indian Macaques

    Institute of Scientific and Technical Information of China (English)

    QIANG LIU; GUI-BO YANG; HUI ZHAO; QIANG WEI; HUI XING; CHUAN QIN; YI-MING SHAO

    2008-01-01

    To develop a model of SHIV-KB9/Chinese origin rhesus (Ch Rh) macaques for vaccine research and to compare the pathogenesis of SHIV-KB9 in Ch Rh macaques with that reported in Indian rhesus (had Rh) macaques. Methods Seven mamu-A*01 negative Ch Rh macaques were inoculated intravenously with 1-10000 MID of SHIV-KB9. The monkeys were monitored for viral load, CD4, CD8, SHIV-specific antibody and virus genetic variation. The results were compared with those previously observed in Ind Rh macaques. Results As compared to that observed in Ind Rh macaques, SHIV-KB9 in Ch Rh macaques displayed three identical disease progression patterns. However, the primary pattern was not identical between the two subspecies. The level of plasma viremia differed in SHIV-KB9-infected Ch Rh macaques which exhibited different outcomes from those in Ind Rh macaques. Generally, the values of viral load and the maintenance of CD4 T cells were associated with humoral responses. Otherwise, the viral genetic distances (divergence, diversity) were larger in animals (M419, M425) with their CD4T cells profoundly depleted. Conclusion The model of SHIV-KB9/Ch Rh macaques displays a relatively slow progression to AIDS compared with Ind Rh macaques, which may more accurately reflect the potential ofcandidate vaccines in humans.

  18. Assisted reproductive technologies in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Wolf Don P

    2004-06-01

    Full Text Available Abstract The assisted reproductive technologies (ARTs have been used in the production of rhesus monkey offspring at the Oregon National Primate Research Center (ONPRC and that experience is summarized here. Additionally these technologies serve as a source of oocytes/embryos for monozygotic twinning, embryonic stem (ES cell derivation and cloning. High fertilization efficiencies were realized with conventional insemination or following the use of intracytoplasmic sperm injection (ICSI and approximately 50% of the resulting embryos grew in vitro to blastocysts. Both fresh and frozen sperm were employed in fertilization by ICSI and the resulting embryos could be low temperature stored for subsequent thawing and transfer when a synchronized recipient female was available or after shipment to another facility. Following the transfer of up to 3 embryos, an overall pregnancy rate of 30% was achieved with increasing rates dependent upon the number of embryos transferred. Singleton pregnancy outcomes following the transfer of ART produced embryos were similar to those observed in a control group of animals in the timed mated breeding colony at ONPRC. ICSI produced embryos were used in efforts to create monozygotic twins by blastomere separation or blastocyst splitting. While pregnancies were achieved following the transfer of demi-embryos, only one was a twin and it was lost to spontaneous abortion. ICSI produced embryos have also served as the source of blastocysts for the derivation of embryonic stem cells. These pluripotent cells hold potential for cell based therapies and we consider the monkey an important translational model in which to evaluate safety, efficacy and feasibility of regenerative medicine approaches based on the transplantation of stem cell-derived progeny. Finally, efforts to produce genetically-identical monkeys by nuclear transfer have been briefly summarized.

  19. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    Science.gov (United States)

    Bimber, Benjamin N.; Reed, Jason S.; Uebelhoer, Luke S.; Bhusari, Amruta; Hammond, Katherine B.; Klug, Alex; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Streblow, Daniel N.; Picker, Louis J.; Früh, Klaus; Sacha, Jonah B.

    2016-01-01

    Cytomegaloviruses (CMV) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. Accordingly, full genome phylogenetic analysis of multiple new CMV field isolates derived from two closely related nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM), revealed distinct and tight lineage clustering according to the species of origin, with MCM CMV isolates mirroring the limited genetic diversity of their primate host that underwent a population bottleneck 400 years ago. Despite the ability of Rhesus CMV (RhCMV) laboratory strain 68–1 to replicate efficiently in MCM fibroblasts and potently inhibit antigen presentation to MCM T cells in vitro, RhCMV 68–1 failed to productively infect MCM in vivo, even in the absence of host CD8+ T and NK cells. In contrast, RhCMV clone 68–1.2, genetically repaired to express the homologues of the HCMV anti-apoptosis gene UL36 and epithelial cell tropism genes UL128 and UL130 absent in 68–1, efficiently infected MCM as evidenced by the induction of transgene-specific T cells and virus shedding. Recombinant variants of RhCMV 68–1 and 68–1.2 revealed that expression of either UL36 or UL128 together with UL130 enabled productive MCM infection, indicating that multiple layers of cross-species restriction operate even between closely related hosts. Cumulatively, these results implicate cell tropism and evasion of apoptosis as critical determinants of CMV transmission across primate species barriers, and extend the macaque model of human CMV infection and immunology to MCM, a nonhuman primate species with uniquely simplified host immunogenetics. PMID:27829026

  20. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

    Science.gov (United States)

    Guo, Ming; Xian, Qiao-Yang; Rao, Yan; Zhang, Jing; Wang, Yong; Huang, Zhi-Xiang; Wang, Xin; Bao, Rong; Zhou, Li; Liu, Jin-Biao; Tang, Zhi-Jiao; Guo, De-yin; Qin, Chuan; Li, Jie-Liang; Ho, Wen-Zhe

    2017-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pathological and microbiological findings. Chest X-rays showed that co-infected animals had disseminated lesions in both left and right lungs, while M.tb mono-infected animals displayed the lesions only in right lungs. Necropsy of co-infected animals revealed a disseminated M.tb infection not only in the lungs but also in the extrapulmonary organs including spleen, pancreas, liver, kidney, and heart. The bacterial counts in the lungs, the bronchial lymph nodes, and the extrapulmonary organs of co-infected animals were significantly higher than those of M.tb mono-infected animals. The mechanistic studies demonstrated that two of three co-infected animals had lower levels of M.tb specific IFN-γ and IL-22 in PBMCs than M.tb mono-infected animals. These findings suggest that Chinese rhesus macaque is a suitable and alternative non-human primate model for SIV/M.tb coinfection studies. The impairment of the specific anti-TB immunity is likely to be a contributor of SIV-mediated enhancement M.tb infection. PMID:28133458

  1. A simple multiplex polymerase chain reaction to determine ABO blood types of rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Premasuthan, A; Kanthaswamy, S; Satkoski, J; Smith, D G

    2011-06-01

    Rhesus macaques are the most common nonhuman primate model organism used in biomedical research. Their increasingly frequent use as subjects in studies involving transplantation requires that blood and other tissue antigens of donors and recipients be compatible. We report here an easy and rapid multiplex polymerase chain reaction (PCR) to determine the ABO blood group phenotypes of rhesus macaques that can be performed with only small amounts of DNA. We phenotyped 78 individuals and found this species to exhibit the A, B and AB phenotypes in frequencies that vary by geographic region. The probability of randomly pairing rhesus macaque donors and recipients that exhibit major ABO phenotype incompatibility is approximately 0.35 and 0.45 for Indian and Chinese rhesus macaques, respectively.

  2. Fitness-related patterns of genetic variation in rhesus macaques.

    Science.gov (United States)

    Blomquist, Gregory E

    2009-03-01

    The patterning of quantitative genetic descriptions of genetic and residual variation for 15 skeletal and six life history traits was explored in a semi-free-ranging group of rhesus macaques (Macaca mulatta Zimmerman 1780). I tested theoretical predictions that explain the magnitude of genetic and residual variation as a result of 1. strength of a trait's association with evolutionary fitness, or 2. developmental and physiological relationships among traits. I found skeletal traits had higher heritabilities and lower coefficients of residual variation than more developmentally and physiologically dependent life history traits. Total lifetime fertility had a modest heritability (0.336) in this population, and traits with stronger correlations to fitness had larger amounts of residual variance. Censoring records of poorly-performing individuals on lifetime fertility and lifespan substantially reduced their heritabilities. These results support models for the fitness-related patterning of genetic variation based on developmental and physiological relationships among traits rather than the action of selection eroding variation.

  3. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong;

    2011-01-01

    The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

  4. Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus Macaques

    Science.gov (United States)

    Ferrari, Pier Francesco; Paukner, Annika; Ruggiero, Angela; Darcey, Lisa; Unbehagen, Sarah; Suomi, Stephen J.

    2009-01-01

    The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the…

  5. Crossmodal integration of conspecific vocalizations in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Christa Payne

    Full Text Available Crossmodal integration of audio/visual information is vital for recognition, interpretation and appropriate reaction to social signals. Here we examined how rhesus macaques process bimodal species-specific vocalizations by eye tracking, using an unconstrained preferential looking paradigm. Six adult rhesus monkeys (3M, 3F were presented two side-by-side videos of unknown male conspecifics emitting different vocalizations, accompanied by the audio signal corresponding to one of the videos. The percentage of time animals looked to each video was used to assess crossmodal integration ability and the percentages of time spent looking at each of the six a priori ROIs (eyes, mouth, and rest of each video were used to characterize scanning patterns. Animals looked more to the congruent video, confirming reports that rhesus monkeys spontaneously integrate conspecific vocalizations. Scanning patterns showed that monkeys preferentially attended to the eyes and mouth of the stimuli, with subtle differences between males and females such that females showed a tendency to differentiate the eye and mouth regions more than males. These results were similar to studies in humans indicating that when asked to assess emotion-related aspects of visual speech, people preferentially attend to the eyes. Thus, the tendency for female monkeys to show a greater differentiation between the eye and mouth regions than males may indicate that female monkeys were slightly more sensitive to the socio-emotional content of complex signals than male monkeys. The current results emphasize the importance of considering both the sex of the observer and individual variability in passive viewing behavior in nonhuman primate research.

  6. Human-wildlife conflict: proximate predictors of aggression between humans and rhesus macaques in India.

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    Beisner, Brianne A; Heagerty, Allison; Seil, Shannon K; Balasubramaniam, Krishna N; Atwill, Edward R; Gupta, Brij K; Tyagi, Praveen C; Chauhan, Netrapal P S; Bonal, B S; Sinha, P R; McCowan, Brenda

    2015-02-01

    Macaques live in close contact with humans across South and Southeast Asia, and direct interaction is frequent. Aggressive contact is a concern in many locations, particularly among populations of rhesus and longtail macaques that co-inhabit urbanized cities and towns with humans. We investigated the proximate factors influencing the occurrence of macaque aggression toward humans as well as human aggression toward macaques to determine the extent to which human behavior elicits macaque aggression and vice versa. We conducted a 3-month study of four free-ranging populations of rhesus macaques in Dehradun, India from October-December 2012, using event sampling to record all instances of human-macaque interaction (N = 3120). Our results show that while human aggression was predicted by the potential for economic losses or damage, macaque aggression was influenced by aggressive or intimidating behavior by humans as well as recent rates of conspecific aggression. Further, adult female macaques participated in aggression more frequently than expected, whereas adult and subadult males participated as frequently as expected. Our analyses demonstrate that neither human nor macaque aggression is unprovoked. Rather, both humans and macaques are responding to one another's behavior. Mitigation of human-primate conflict, and indeed other types of human-wildlife conflict in such coupled systems, will require a holistic investigation of the ways in which each participant is responding to, and consequently altering, the behavior of the other.

  7. Diversity and molecular phylogeny of mitochondrial DNA of rhesus macaques (Macaca mulatta) in Bangladesh.

    Science.gov (United States)

    Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Kanthaswamy, Sree; Smith, David Glenn

    2014-11-01

    While studies of rhesus macaques (Macaca mulatta) in the eastern (e.g., China) and western (e.g., India) parts of their geographic range have revealed major genetic differences that warrant the recognition of two different subspecies, little is known about genetic characteristics of rhesus macaques in the transitional zone extending from eastern India and Bangladesh through the northern part of Indo-China, the probable original homeland of the species. We analyzed genetic variation of 762 base pairs of mitochondrial DNA from 86 fecal swab samples and 19 blood samples from 25 local populations of rhesus macaque in Bangladesh collected from January 2010 to August 2012. These sequences were compared with those of rhesus macaques from India, China, and Myanmar. Forty-six haplotypes defined by 200 (26%) polymorphic nucleotide sites were detected. Estimates of gene diversity, expected heterozygosity, and nucleotide diversity for the total population were 0.9599 ± 0.0097, 0.0193 ± 0.0582, and 0.0196 ± 0.0098, respectively. A mismatch distribution of paired nucleotide differences yielded a statistically significantly negative value of Tajima's D, reflecting a population that rapidly expanded after the terminal Pleistocene. Most haplotypes throughout regions of Bangladesh, including an isolated region in the southwestern area (Sundarbans), clustered with haplotypes assigned to the minor haplogroup Ind-2 from India reflecting an east to west dispersal of rhesus macaques to India. Haplotypes from the southeast region of Bangladesh formed a cluster with those from Myanmar, and represent the oldest rhesus macaque haplotypes of Bangladesh. These results are consistent with the hypothesis that rhesus macaques first entered Bangladesh from the southeast, probably from Indo-China, then dispersed westward throughout eastern and central India.

  8. Serum Cobalamin (Vitamin B12) Concentrations in Rhesus Macaques (Macaca mulatta) and Pigtailed Macaques (Macaca nemestrina) with Chronic Idiopathic Diarrhea.

    Science.gov (United States)

    Izzi, Jessica M; Beck, Sarah E; Adams, Robert J; Metcalf Pate, Kelly A; Hutchinson, Eric K

    2016-01-01

    Chronic diarrhea poses a significant threat to the health of NHP research colonies, and its primary etiology remains unclear. In macaques, the clinical presentation of intractable diarrhea and weight loss that are accompanied by inflammatory infiltrates within the gastrointestinal tract closely resembles inflammatory bowel disease of humans, dogs, and cats, in which low serum and tissue cobalamin (vitamin B12) levels are due to intestinal malabsorption. We therefore hypothesized that macaques with chronic idiopathic diarrhea (CID) have lower serum cobalamin concentrations than do healthy macaques. Here we measured serum cobalamin concentrations in both rhesus and pigtailed macaques with CID and compared them with those of healthy controls. Serum cobalamin levels were 2.5-fold lower in pigtailed macaques with CID than control animals but did not differ between rhesus macaques with CID and their controls. This finding supports the use of serum cobalamin concentration as an adjunct diagnostic tool in pigtailed macaques that present with clinical symptoms of chronic gastrointestinal disease. This use of serum vitamin B12 levels has implications for the future use of parenteral cobalamin supplementation to improve clinical outcomes in this species.

  9. Evidence that emotion mediates social attention in rhesus macaques.

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    Emily J Bethell

    Full Text Available BACKGROUND: Recent work on non-human primates indicates that the allocation of social attention is mediated by characteristics of the attending animal, such as social status and genotype, as well as by the value of the target to which attention is directed. Studies of humans indicate that an individual's emotion state also plays a crucial role in mediating their social attention; for example, individuals look for longer towards aggressive faces when they are feeling more anxious, and this bias leads to increased negative arousal and distraction from other ongoing tasks. To our knowledge, no studies have tested for an effect of emotion state on allocation of social attention in any non-human species. METHODOLOGY: We presented captive adult male rhesus macaques with pairs of adult male conspecific face images - one with an aggressive expression, one with a neutral expression - and recorded gaze towards these images. Each animal was tested twice, once during a putatively stressful condition (i.e. following a veterinary health check, and once during a neutral (or potentially positive condition (i.e. a period of environmental enrichment. Initial analyses revealed that behavioural indicators of anxiety and stress were significantly higher after the health check than during enrichment, indicating that the former caused a negative shift in emotional state. PRINCIPLE FINDINGS: The macaques showed initial vigilance for aggressive faces across both conditions, but subsequent responses differed between conditions. Following the health check, initial vigilance was followed by rapid and sustained avoidance of aggressive faces. By contrast, during the period of enrichment, the macaques showed sustained attention towards the same aggressive faces. CONCLUSIONS/SIGNIFICANCE: These data provide, to our knowledge, the first evidence that shifts in emotion state mediate social attention towards and away from facial cues of emotion in a non-human animal. This work

  10. Color-detection thresholds in rhesus macaque monkeys and humans.

    Science.gov (United States)

    Gagin, Galina; Bohon, Kaitlin S; Butensky, Adam; Gates, Monica A; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L; Qu, Jane; Stoughton, Cleo M; Swanbeck, Sonja N; Conway, Bevil R

    2014-07-15

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection thresholds from initial testing to plateau performance (“learning”) was similar for +L − M (red) colors and +M − L (bluish-green) colors. But the extent of learning was higher for +S (lavender) than for −S (yellow-lime); moreover, at plateau performance, the cone contrast at the detection threshold was higher for +S than for −S. These asymmetries may reflect differences in retinal circuitry for S-ON and S-OFF. At plateau performance, the two species also had similar detection thresholds for all colors, although monkeys had shorter reaction times than humans and slightly lower thresholds for colors that modulated L/M cones. We discuss whether these observations, together with previous work showing that monkeys have lower spatial acuity than humans, could be accounted for by selective pressures driving higher chromatic sensitivity at the cost of spatial acuity amongst monkeys, specifically for the more recently evolved L − M mechanism.

  11. Zika viral dynamics and shedding in rhesus and cynomolgus macaques

    Science.gov (United States)

    Osuna, Christa E; Lim, So-Yon; Deleage, Claire; Griffin, Bryan D; Stein, Derek; Schroeder, Lukas T; Omange, Robert Were; Best, Katharine; Luo, Ma; Hraber, Peter T; Andersen-Elyard, Hanne; Ojeda, Erwing Fabian Cardozo; Huang, Scott; Vanlandingham, Dana L; Higgs, Stephen; Perelson, Alan S; Estes, Jacob D; Safronetz, David; Lewis, Mark G; Whitney, James B

    2017-01-01

    Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection was cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans. PMID:27694931

  12. Maternal effects on offspring mortality in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Blomquist, Gregory E

    2013-03-01

    The genetics of primate life histories are poorly understood, but quantitative genetic patterns in other mammals suggest phenotypic differences among individuals early in life can be strongly affected by interactions with mothers or other caretakers. I used generalized linear mixed model extensions of complex pedigree quantitative genetic techniques to explore regression coefficients and variance components for infant and juvenile mortality rates across prereproductive age classes in the semifree ranging Cayo Santiago rhesus macaques. Using a large set of records (maximum n = 977 mothers, 6,240 offspring), strong maternal effects can be identified early in development but they rapidly "burn off" as offspring age and mothers become less consistent buffers from increasingly prominent environmental variation. The different ways behavioral ecologists and animal breeders have defined and studied maternal effects can be subsumed, and even blended, within the quantitative genetic framework. Regression coefficients identify loss of the mother, maternal age, and offspring age within their birth cohort as having significant maternal effects on offspring mortality, while variance components for maternal identity record significant maternal influence in the first month of life.

  13. Characterization of the Cag pathogenicity island in Helicobacter pylori from naturally infected rhesus macaques.

    Science.gov (United States)

    Skoog, Emma C; Deck, Samuel L; Entwistle, Hasan D; Hansen, Lori M; Solnick, Jay V

    2016-12-01

    Helicobacter pylori commonly infects the epithelial layer of the human stomach and in some individuals causes peptic ulcers, gastric adenocarcinoma or gastric lymphoma. Helicobacter pylori is a genetically diverse species, and the most important bacterial virulence factor that increases the risk of developing disease, versus asymptomatic colonization, is the cytotoxin associated gene pathogenicity island (cagPAI). Socially housed rhesus macaques are often naturally infected with H. pylori similar to that which colonizes humans, but little is known about the cagPAI. Here we show that H. pylori strains isolated from naturally infected rhesus macaques have a cagPAI very similar to that found in human clinical isolates, and like human isolates, it encodes a functional type IV secretion system. These results provide further support for the relevance of rhesus macaques as a valid experimental model for H. pylori infection in humans.

  14. Comparative pathology of rhesus macaque and common marmoset animal models with Middle East respiratory syndrome coronavirus

    Science.gov (United States)

    Yu, Pin; Xu, Yanfeng; Deng, Wei; Bao, Linlin; Huang, Lan; Xu, Yuhuan; Yao, Yanfeng; Qin, Chuan

    2017-01-01

    Middle East respiratory syndrome (MERS), which is caused by a newly discovered coronavirus (CoV), has recently emerged. It causes severe viral pneumonia and is associated with a high fatality rate. However, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with MERS-CoV are unknown. We describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal models of MERS-CoV infection. The main histopathological findings in the lungs of rhesus macaques and common marmosets were varying degrees of pulmonary lesions, including pneumonia, pulmonary oedema, haemorrhage, degeneration and necrosis of the pneumocytes and bronchial epithelial cells, and inflammatory cell infiltration. The characteristic inflammatory cells in the lungs of rhesus macaques and common marmosets were eosinophils and neutrophils, respectively. Based on these observations, the lungs of rhesus macaques and common marmosets appeared to develop chronic and acute pneumonia, respectively. MERS-CoV antigens and viral RNA were identified in type I and II pneumocytes, alveolar macrophages and bronchial epithelial cells, and ultrastructural observations showed that viral protein was found in type II pneumocytes and inflammatory cells in both species. Correspondingly, the entry receptor DDP4 was found in type I and II pneumocytes, bronchial epithelial cells, and alveolar macrophages. The rhesus macaque and common marmoset animal models of MERS-CoV can be used as a tool to mimic the oncome of MERS-CoV infections in humans. These models can help to provide a better understanding of the pathogenic process of this virus and to develop effective medications and prophylactic treatments. PMID:28234937

  15. Rhesus macaques (Macaca mulatta are natural hosts of specific Staphylococcus aureus lineages.

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

    Full Text Available Currently, there is no animal model known that mimics natural nasal colonization by Staphylococcus aureus in humans. We investigated whether rhesus macaques are natural nasal carriers of S. aureus. Nasal swabs were taken from 731 macaques. S. aureus isolates were typed by pulsed-field gel electrophoresis (PFGE, spa repeat sequencing and multi-locus sequence typing (MLST, and compared with human strains. Furthermore, the isolates were characterized by several PCRs. Thirty-nine percent of 731 macaques were positive for S. aureus. In general, the macaque S. aureus isolates differed from human strains as they formed separate PFGE clusters, 50% of the isolates were untypeable by agr genotyping, 17 new spa types were identified, which all belonged to new sequence types (STs. Furthermore, 66% of macaque isolates were negative for all superantigen genes. To determine S. aureus nasal colonization, three nasal swabs from 48 duo-housed macaques were taken during a 5 month period. In addition, sera were analyzed for immunoglobulin G and A levels directed against 40 staphylococcal proteins using a bead-based flow cytometry technique. Nineteen percent of the animals were negative for S. aureus, and 17% were three times positive. S. aureus strains were easily exchanged between macaques. The antibody response was less pronounced in macaques compared to humans, and nasal carrier status was not associated with differences in serum anti-staphylococcal antibody levels. In conclusion, rhesus macaques are natural hosts of S. aureus, carrying host-specific lineages. Our data indicate that rhesus macaques are useful as an autologous model for studying S. aureus nasal colonization and infection prevention.

  16. CYP1B1 is polymorphic in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Matsushita, Akinori; Yamazaki, Hiroshi

    2011-09-01

    Cytochrome P450 (CYP) 1B1 is involved in the metabolic activation of various procarcinogens, and some CYP1B1 genetic variants alter CYP1B1-dependent procarcinogen metabolism. Cynomolgus and rhesus macaques are frequently used in toxicity tests due to their evolutionary closeness to humans. In this study, we attempted to identify CYP1B1 genetic variants in 13 cynomolgus and 4 rhesus macaques. A total of 17 genetic variants were identified, including 8 non-synonymous genetic variants, indicating that, similar to humans, CYP1B1 is polymorphic in macaques. These CYP1B1 genetic variants could be the basis for understanding potential inter-animal differences in macaque CYP1B1-dependent metabolism of promutagens.

  17. Examining the species-specificity of rhesus macaque cytomegalovirus (RhCMV in cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Angie K Marsh

    Full Text Available Cytomegalovirus (CMV is a highly species-specific virus that has co-evolved with its host over millions of years and thus restricting cross-species infection. To examine the extent to which host restriction may prevent cross-species research between closely related non-human primates, we evaluated experimental infection of cynomolgus macaques with a recombinant rhesus macaque-derived CMV (RhCMV-eGFP. Twelve cynomolgus macaques were randomly allocated to three groups: one experimental group (RhCMV-eGFP and two control groups (UV-inactivated RhCMV-eGFP or media alone. The animals were given two subcutaneous inoculations at week 0 and week 8, and a subset of animals received an intravenous inoculation at week 23. No overt clinical or haematological changes were observed and PBMCs isolated from RhCMV-eGFP inoculated animals had comparable eGFP- and IE-1-specific cellular responses to the control animals. Following inoculation with RhCMV-eGFP, we were unable to detect evidence of infection in any blood or tissue samples up to 4 years post-inoculation, using sensitive viral co-culture, qPCR, and Western blot assays. Co-culture of urine and saliva samples demonstrated the presence of endogenous cynomolgus CMV (CyCMV cytopathic effect, however no concomitant eGFP expression was observed. The absence of detectable RhCMV-eGFP suggests that the CyCMV-seropositive cynomolgus macaques were not productively infected with RhCMV-eGFP under these inoculation conditions. In a continued effort to develop CMV as a viral vector for an HIV/SIV vaccine, these studies demonstrate that CMV is highly restricted to its host species and can be highly affected by laboratory cell culture. Consideration of the differences between lab-adapted and primary viruses with respect to species range and cell tropism should be a priority in evaluating CMV as vaccine vector for HIV or other pathogens at the preclinical development stage.

  18. Social rank and cortisol among female rhesus macaques (Macaca mulatta)

    Institute of Scientific and Technical Information of China (English)

    Dong-Dong QIN; Joshua Dominic Rizak; Xiao-Li FENG; Xun-Xun CHU; Shang-Chuan YANG; Chun-Lu LI; Long-Bao LV; Yuan-Ye MA; Xin-Tian HU

    2013-01-01

    In animal societies,some stressful events can lead to higher levels of physiological stress.Such stressors,like social rank,also predict an increased vulnerability to an array of diseases.However,the physiological relationship between social rank and stress varies between different species,as well as within groups of a single species.For example,dominant individuals are more socially stressed at times,while at other times it is the subordinate ones who experience this stress.Together,these variations make it difficult to assess disease vulnerability as connected to social interactions.In order to leam more about how physiological rank relationships vary between groups of a single species,cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups.In despotic groups,cortisol levels were found not to be correlated with social rank,but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies.Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals.These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology.The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.

  19. Characterization of single-nucleotide variation in Indian-origin rhesus macaques (Macaca mulatta

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    Wheeler David A

    2011-06-01

    Full Text Available Abstract Background Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies. Results We used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease. Conclusions Resequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs

  20. Percutaneous transhepatic portal catheterization guided by ultrasound technology for islet transplantation in rhesus monkey

    Institute of Scientific and Technical Information of China (English)

    FengGao; Shao-DongAi; ShengLiu; Wen-BinZeng; WeiWang

    2012-01-01

    BACKGROUND: Pig islet xenotransplantation has the potential to overcome the shortage of donated human islets for islet cell transplantation in type 1 diabetes. Testing in non-human primate models is necessary before clinical application in humans. Intraportal islet transplantation in monkeys is usually performed by surgical infusion during laparotomy or laparoscopy. In this paper, we describe a new method of percutaneous transhepatic portal catheterization (PTPC) as an alternative to current methods of islet transplantation in rhesus monkeys. METHODS: We performed ultrasound-guided PTPC in five adult rhesus monkeys weighing 7-8 kg, with portal vein catheterization confirmed by digital subtraction angiography. We monitored for complications in the thoracic and abdominal cavity. To evaluate the safety of ultrasound-guided PTPC, we recorded the changes in portal pressure throughout the microbead transplantation procedure. RESULTS:  Ultrasound-guided PTPC and infusion of 16 000 microbeads/kg body weight into the portal vein was successful in all five monkeys. Differences in the hepatobiliary anatomy of rhesus monkeys compared to humans led to a higher initial complication rate. The first monkey died of abdominal hemorrhage 10 hours post-transplantation. The second suffered from a mild pneumothorax but recovered fully after taking only conservative measures. After gaining experience with the first two monkeys, we decreased both the hepatic puncture time and the number of puncture attempts required, with the remaining three monkeys experiencing no complications. Portal pressures initially increased proportional to the number of transplanted microbeads but returned to pre-infusion levels at 30 minutes post-transplantation. The changes in portal pressures occurring during the procedure were not significantly different. CONCLUSIONS: Ultrasound-guided PTPC is an effective, convenient, and minimally invasive method suitable for use in non-human primate models of

  1. Forest seasonality shapes diet of limestone-living rhesus macaques at Nonggang, China.

    Science.gov (United States)

    Tang, Chuangbin; Huang, Libin; Huang, Zhonghao; Krzton, Ali; Lu, Changhu; Zhou, Qihai

    2016-01-01

    Limestone forests are an unusual habitat for primates, but little information is available for the genus Macaca in such habitats, making a comparative understanding of extant limestone primates' behavioral adaptation incomplete. We collected data on the diet of rhesus macaques (Macaca mulatta) in a limestone habitat at Nonggang Nature Reserve, southwestern Guangxi, China, and examined the effects of forest seasonality on their diet. Our results indicated that a total of 114 species of plants are consumed by macaques. Young leaves are a preferred food, accounting for 48.9 and 56.9% of the overall diets. One group significantly increased young leaf consumption in response to availability. Fruits contributed to only 27.3 and 28.7% of overall diet. The macaque diet varied according to season. They fed on more fruits in the rainy season. Consumption of mature leaves increased when the availability of young leaves and fruits declined in the dry season, indicating that mature leaves are a fallback food for macaques in a limestone habitat. Similar to sympatric Assamese macaques, Bonia saxatilis, a shrubby, karst-endemic bamboo was consumed by rhesus macaques throughout the year, and was the top food species through most of the year, suggesting that bamboo consumption represents a key factor in the macaque's dietary adaptation to limestone habitat.

  2. The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype

    DEFF Research Database (Denmark)

    Solomon, C.; Southwood, S.; Hoof, Ilka;

    2010-01-01

    macaque potentially being a more relevant model for AIDS outcomes than the Indian rhesus macaque, the Chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility complex (MHC) composition and function, reducing their greater utilization. In this study, we...... characterized a total of 50 unique Chinese rhesus macaques from several varying origins for their entire MHC class I allele composition and identified a total of 58 unique complete MHC class I sequences. Only nine of the sequences had been associated with Indian rhesus macaques, and 28/58 (48...... binding characteristics with the HLA-B7 supertype, the most frequent supertype in human populations. These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques....

  3. Human and rhesus macaque hematopoietic stem cells cannot be purified based only on SLAM family markers.

    Science.gov (United States)

    Larochelle, Andre; Savona, Michael; Wiggins, Michael; Anderson, Stephanie; Ichwan, Brian; Keyvanfar, Keyvan; Morrison, Sean J; Dunbar, Cynthia E

    2011-02-03

    Various combinations of antibodies directed to cell surface markers have been used to isolate human and rhesus macaque hematopoietic stem cells (HSCs). These protocols result in poor enrichment or require multiple complex steps. Recently, a simple phenotype for HSCs based on cell surface markers from the signaling lymphocyte activation molecule (SLAM) family of receptors has been reported in the mouse. We examined the possibility of using the SLAM markers to facilitate the isolation of highly enriched populations of HSCs in humans and rhesus macaques. We isolated SLAM (CD150(+)CD48(-)) and non-SLAM (not CD150(+)CD48(-)) cells from human umbilical cord blood CD34(+) cells as well as from human and rhesus macaque mobilized peripheral blood CD34(+) cells and compared their ability to form colonies in vitro and reconstitute immune-deficient (nonobese diabetic/severe combined immunodeficiency/interleukin-2 γc receptor(null), NSG) mice. We found that the CD34(+) SLAM population contributed equally or less to colony formation in vitro and to long-term reconstitution in NSG mice compared with the CD34(+) non-SLAM population. Thus, SLAM family markers do not permit the same degree of HSC enrichment in humans and rhesus macaques as in mice.

  4. Serotonin transporter genotype modulates social reward and punishment in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Karli K Watson

    Full Text Available BACKGROUND: Serotonin signaling influences social behavior in both human and nonhuman primates. In humans, variation upstream of the promoter region of the serotonin transporter gene (5-HTTLPR has recently been shown to influence both behavioral measures of social anxiety and amygdala response to social threats. Here we show that length polymorphisms in 5-HTTLPR predict social reward and punishment in rhesus macaques, a species in which 5-HTTLPR variation is analogous to that of humans. METHODOLOGY/PRINCIPAL FINDINGS: In contrast to monkeys with two copies of the long allele (L/L, monkeys with one copy of the short allele of this gene (S/L spent less time gazing at face than non-face images, less time looking in the eye region of faces, and had larger pupil diameters when gazing at photos of a high versus low status male macaques. Moreover, in a novel primed gambling task, presentation of photos of high status male macaques promoted risk-aversion in S/L monkeys but promoted risk-seeking in L/L monkeys. Finally, as measured by a "pay-per-view" task, S/L monkeys required juice payment to view photos of high status males, whereas L/L monkeys sacrificed fluid to see the same photos. CONCLUSIONS/SIGNIFICANCE: These data indicate that genetic variation in serotonin function contributes to social reward and punishment in rhesus macaques, and thus shapes social behavior in humans and rhesus macaques alike.

  5. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

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    Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

    2011-05-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

  6. Comparative analysis of genotypic diversity in Entamoeba nuttalli isolates from Tibetan macaques and rhesus macaques in China.

    Science.gov (United States)

    Guan, Yue; Feng, Meng; Cai, Junlong; Min, Xiangyang; Zhou, Xingyu; Xu, Qing; Tan, Ning; Cheng, Xunjia; Tachibana, Hiroshi

    2016-03-01

    We have recently demonstrated the potentially virulent species Entamoeba nuttalli as one of the highly prevalent parasites in rhesus macaques (Macaca mulatta) in Mount Long-hu and Gui-yang in China. Tibetan macaque (Macaca thibetana) is a unique species living in China. To evaluate the prevalence of Entamoeba species in wild Tibetan macaques, we obtained 89 stool samples in Mount E-mei of Si-chuan Province in China. PCR analysis detected E. nuttalli, Entamoeba coli, and Entamoeba polecki ST2 in 17%, 42%, and 66% of the samples, respectively, whereas Entamoeba histolytica and Entamoeba dispar were undetected. This study is the first to report on the detection of E. nuttalli from Tibetan macaques. Six E. nuttalli isolates were obtained, 18S rRNA gene and six tRNA-linked short tandem repeat (STR) loci of the isolates were sequenced. The Mantel test results gave an r value of 0.97 of relationships between geographical distance and genetic diversity of Chinese E. nuttalli populations, indicating a significant isolation-by-distance effect in Chinese E. nuttalli according to the tRNA-STR loci sequences. Structural analysis of E. nuttalli isolates based on tRNA-linked STR loci demonstrated three Chinese E. nuttalli populations with their respective features, but the Gui-yang population was located in the middle. In the distance-based NJ tree, E. nuttalli isolates were divided into five different branches, and E-mei isolates were attributed to an independent branch to distinguish them from Gui-yang and Long-hu isolates. Genetic analysis in this study provided clues of the genetic differences between E. nuttalli isolates from Tibetan macaques and rhesus macaques in China.

  7. Evolutionary interrogation of human biology in well-annotated genomic framework of rhesus macaque.

    Science.gov (United States)

    Zhang, Shi-Jian; Liu, Chu-Jun; Yu, Peng; Zhong, Xiaoming; Chen, Jia-Yu; Yang, Xinzhuang; Peng, Jiguang; Yan, Shouyu; Wang, Chenqu; Zhu, Xiaotong; Xiong, Jingwei; Zhang, Yong E; Tan, Bertrand Chin-Ming; Li, Chuan-Yun

    2014-05-01

    With genome sequence and composition highly analogous to human, rhesus macaque represents a unique reference for evolutionary studies of human biology. Here, we developed a comprehensive genomic framework of rhesus macaque, the RhesusBase2, for evolutionary interrogation of human genes and the associated regulations. A total of 1,667 next-generation sequencing (NGS) data sets were processed, integrated, and evaluated, generating 51.2 million new functional annotation records. With extensive NGS annotations, RhesusBase2 refined the fine-scale structures in 30% of the macaque Ensembl transcripts, reporting an accurate, up-to-date set of macaque gene models. On the basis of these annotations and accurate macaque gene models, we further developed an NGS-oriented Molecular Evolution Gateway to access and visualize macaque annotations in reference to human orthologous genes and associated regulations (www.rhesusbase.org/molEvo). We highlighted the application of this well-annotated genomic framework in generating hypothetical link of human-biased regulations to human-specific traits, by using mechanistic characterization of the DIEXF gene as an example that provides novel clues to the understanding of digestive system reduction in human evolution. On a global scale, we also identified a catalog of 9,295 human-biased regulatory events, which may represent novel elements that have a substantial impact on shaping human transcriptome and possibly underpin recent human phenotypic evolution. Taken together, we provide an NGS data-driven, information-rich framework that will broadly benefit genomics research in general and serves as an important resource for in-depth evolutionary studies of human biology.

  8. Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Parham Peter

    2011-06-01

    Full Text Available Abstract Background Human killer immunoglobulin-like receptors (KIRs play a critical role in governing the immune response to neoplastic and infectious disease. Rhesus macaques serve as important animal models for many human diseases in which KIRs are implicated; however, the study of KIR activity in this model is hindered by incomplete characterization of KIR genetics. Results Here we present a characterization of KIR genetics in rhesus macaques (Macaca mulatta. We conducted a survey of KIRs in this species, identifying 47 novel full-length KIR sequences. Using this expanded sequence library to build upon previous work, we present evidence supporting the existence of 22 Mamu-KIR genes, providing a framework within which to describe macaque KIRs. We also developed a novel pyrosequencing-based technique for KIR genotyping. This method provides both comprehensive KIR genotype and frequency estimates of transcript level, with implications for the study of KIRs in all species. Conclusions The results of this study significantly improve our understanding of macaque KIR genetic organization and diversity, with implications for the study of many human diseases that use macaques as a model. The ability to obtain comprehensive KIR genotypes is of basic importance for the study of KIRs, and can easily be adapted to other species. Together these findings both advance the field of macaque KIRs and facilitate future research into the role of KIRs in human disease.

  9. Ranking network of a captive rhesus macaque society: a sophisticated corporative kingdom.

    Science.gov (United States)

    Fushing, Hsieh; McAssey, Michael P; Beisner, Brianne; McCowan, Brenda

    2011-03-15

    We develop a three-step computing approach to explore a hierarchical ranking network for a society of captive rhesus macaques. The computed network is sufficiently informative to address the question: Is the ranking network for a rhesus macaque society more like a kingdom or a corporation? Our computations are based on a three-step approach. These steps are devised to deal with the tremendous challenges stemming from the transitivity of dominance as a necessary constraint on the ranking relations among all individual macaques, and the very high sampling heterogeneity in the behavioral conflict data. The first step simultaneously infers the ranking potentials among all network members, which requires accommodation of heterogeneous measurement error inherent in behavioral data. Our second step estimates the social rank for all individuals by minimizing the network-wide errors in the ranking potentials. The third step provides a way to compute confidence bounds for selected empirical features in the social ranking. We apply this approach to two sets of conflict data pertaining to two captive societies of adult rhesus macaques. The resultant ranking network for each society is found to be a sophisticated mixture of both a kingdom and a corporation. Also, for validation purposes, we reanalyze conflict data from twenty longhorn sheep and demonstrate that our three-step approach is capable of correctly computing a ranking network by eliminating all ranking error.

  10. Ranking network of a captive rhesus macaque society: a sophisticated corporative kingdom.

    Directory of Open Access Journals (Sweden)

    Hsieh Fushing

    Full Text Available We develop a three-step computing approach to explore a hierarchical ranking network for a society of captive rhesus macaques. The computed network is sufficiently informative to address the question: Is the ranking network for a rhesus macaque society more like a kingdom or a corporation? Our computations are based on a three-step approach. These steps are devised to deal with the tremendous challenges stemming from the transitivity of dominance as a necessary constraint on the ranking relations among all individual macaques, and the very high sampling heterogeneity in the behavioral conflict data. The first step simultaneously infers the ranking potentials among all network members, which requires accommodation of heterogeneous measurement error inherent in behavioral data. Our second step estimates the social rank for all individuals by minimizing the network-wide errors in the ranking potentials. The third step provides a way to compute confidence bounds for selected empirical features in the social ranking. We apply this approach to two sets of conflict data pertaining to two captive societies of adult rhesus macaques. The resultant ranking network for each society is found to be a sophisticated mixture of both a kingdom and a corporation. Also, for validation purposes, we reanalyze conflict data from twenty longhorn sheep and demonstrate that our three-step approach is capable of correctly computing a ranking network by eliminating all ranking error.

  11. High-density rhesus macaque oligonucleotide microarray design using early-stage rhesus genome sequence information and human genome annotations

    Directory of Open Access Journals (Sweden)

    Magness Charles L

    2007-01-01

    Full Text Available Abstract Background Until recently, few genomic reagents specific for non-human primate research have been available. To address this need, we have constructed a macaque-specific high-density oligonucleotide microarray by using highly fragmented low-pass sequence contigs from the rhesus genome project together with the detailed sequence and exon structure of the human genome. Using this method, we designed oligonucleotide probes to over 17,000 distinct rhesus/human gene orthologs and increased by four-fold the number of available genes relative to our first-generation expressed sequence tag (EST-derived array. Results We constructed a database containing 248,000 exon sequences from 23,000 human RefSeq genes and compared each human exon with its best matching sequence in the January 2005 version of the rhesus genome project list of 486,000 DNA contigs. Best matching rhesus exon sequences for each of the 23,000 human genes were then concatenated in the proper order and orientation to produce a rhesus "virtual transcriptome." Microarray probes were designed, one per gene, to the region closest to the 3' untranslated region (UTR of each rhesus virtual transcript. Each probe was compared to a composite rhesus/human transcript database to test for cross-hybridization potential yielding a final probe set representing 18,296 rhesus/human gene orthologs, including transcript variants, and over 17,000 distinct genes. We hybridized mRNA from rhesus brain and spleen to both the EST- and genome-derived microarrays. Besides four-fold greater gene coverage, the genome-derived array also showed greater mean signal intensities for genes present on both arrays. Genome-derived probes showed 99.4% identity when compared to 4,767 rhesus GenBank sequence tag site (STS sequences indicating that early stage low-pass versions of complex genomes are of sufficient quality to yield valuable functional genomic information when combined with finished genome information from

  12. Pyrosequencing as a method for SNP identification in the rhesus macaque (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Kanthaswamy S

    2008-05-01

    Full Text Available Abstract Background Rhesus macaques (Macaca mulatta are the primate most used for biomedical research, but phenotypic differences between Indian-origin and Chinese rhesus macaques have encouraged genetic methods for identifying genetic differences between these two populations. The completion of the rhesus genome has led to the identification of many single nucleotide polymorphisms (SNPs in this species. These single nucleotide polymorphisms have many advantages over the short tandem repeat (STR loci currently used to assay genetic variation. However, the number of currently identified polymorphisms is too small for whole genome analysis or studies of quantitative trait loci. To that end, we tested a combination of methods to identify large numbers of high-confidence SNPs, and screen those with high minor allele frequencies (MAF. Results By testing our previously reported single nucleotide polymorphisms, we identified a subset of high-confidence, high-MAF polymorphisms. Resequencing revealed a large number of regionally specific SNPs not identified through a single pyrosequencing run. By resequencing a pooled sample of four individuals, we reliably identified loci with a MAF of at least 12.5%. Finally, we found that when applied to a larger, geographically variable sample of rhesus, a large proportion of our loci were variable in both populations, and very few loci were ancestry informative. Despite this fact, the SNP loci were more effective at discriminating Indian and Chinese rhesus than STR loci. Conclusion Pyrosequencing and pooled resequencing are viable methods for the identification of high-MAF SNP loci in rhesus macaques. These SNP loci are appropriate for screening both the inter- and intra-population genetic variation.

  13. Laboratory rhesus macaque social housing and social changes: Implications for research.

    Science.gov (United States)

    Hannibal, Darcy L; Bliss-Moreau, Eliza; Vandeleest, Jessica; McCowan, Brenda; Capitanio, John

    2017-01-01

    Macaque species, specifically rhesus (Macaca mulatta), are the most common nonhuman primates (NHPs) used in biomedical research due to their suitability as a model of high priority diseases (e.g., HIV, obesity, cognitive aging), cost effective breeding and housing compared to most other NHPs, and close evolutionary relationship to humans. With this close evolutionary relationship, however, is a shared adaptation for a socially stimulating environment, without which both their welfare and suitability as a research model are compromised. While outdoor social group housing provides the best approximation of a social environment that matches the macaque behavioral biology in the wild, this is not always possible at all facilities, where animals may be housed indoors in small groups, in pairs, or alone. Further, animals may experience many housing changes in their lifetime depending on project needs, changes in social status, management needs, or health concerns. Here, we review the evidence for the physiological and health effects of social housing changes and the potential impacts on research outcomes for studies using macaques, particularly rhesus. We situate our review in the context of increasing regulatory pressure for research facilities to both house NHPs socially and mitigate trauma from social aggression. To meet these regulatory requirements and further refine the macaque model for research, significant advances must be made in our understanding and management of rhesus macaque social housing, particularly pair-housing since it is the most common social housing configuration for macaques while on research projects. Because most NHPs are adapted for sociality, a social context is likely important for improving repeatability, reproducibility, and external validity of primate biomedical research. Am. J. Primatol. 79:e22528, 2017. © 2016 Wiley Periodicals, Inc.

  14. Serologic host response to Helicobacter pylori and Campylobacter jejuni in socially housed Rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Kienesberger Sabine

    2012-08-01

    Full Text Available Abstract Background Helicobacter pylori are successful colonizers of the human gastric mucosa. Colonization increases the risk of peptic ulcer disease and adenocarcinoma. However, potential benefits of H. pylori colonization include protection against early-onset asthma and against gastrointestinal infections. Campylobacter jejuni are a leading cause of bacterial diarrhea and complications include Guillain-Barré syndrome. Here, we describe the development of reliable serological assays to detect antibodies against those two bacteria in Rhesus macaques and investigated their distribution within a social group of monkeys. Methods Two cohorts of monkeys were analyzed. The first cohort consisted of 30 monkeys and was used to establish an enzyme-linked immunosorbent assay (ELISA for H. pylori antibodies detection. To evaluate colonization of those macaques, stomach biopsies were collected and analyzed for the presence of H. pylori by histology and culture. C. jejuni ELISAs were established using human serum with known C. jejuni antibody status. Next, plasma samples of the 89 macaques (Cohort 2 were assayed for antibodies and then statistically analyzed. Results An H. pylori IgG ELISA, which was 100% specific and 93% sensitive, was established. In contrast, the IgA ELISA was only 82% specific and 61% sensitive. The CagA IgG assay was 100% sensitive and 61% of the macaques were positive. In cohort 2, 62% macaques were H. pylori sero-positive and 52% were CagA positive. The prevalence of H. pylori IgG and CagA IgG increased with monkey age as described for humans. Of the 89 macaques 52% showed IgG against C. jejuni but in contrast to H. pylori, the sero-prevalence was not associated with increasing age. However, there was a drop in the IgG (but not in IgA mean values between infant and juvenile macaques, similar to trends described in humans. Conclusions Rhesus macaques have widespread exposure to H. pylori and C. jejuni, reflecting their social

  15. Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques

    Science.gov (United States)

    Coffey, Lark L.; Pesavento, Patricia A.; Keesler, Rebekah I.; Singapuri, Anil; Watanabe, Jennifer; Watanabe, Rie; Yee, JoAnn; Bliss-Moreau, Eliza; Cruzen, Christina; Christe, Kari L.; Reader, J. Rachel; von Morgenland, Wilhelm; Gibbons, Anne M.; Allen, A. Mark; Linnen, Jeff; Gao, Kui; Delwart, Eric; Simmons, Graham; Stone, Mars; Lanteri, Marion; Bakkour, Sonia; Busch, Michael; Morrison, John

    2017-01-01

    Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants. PMID:28141843

  16. Physiological, Behavioral, and Scientific Impact of Different Fluid Control Protocols in the Rhesus Macaque (Macaca mulatta)

    Science.gov (United States)

    Bertrand, Henri; Mindus, Claire; Flecknell, Paul

    2016-01-01

    Abstract Rhesus macaques are an important model in behavioral neuroscience due to their advanced cognitive abilities. To motivate animals to engage in complex tasks, fluid rewards, in conjunction with fluid control protocols, are often used. The impact of these protocols on animal welfare is controversial. We compared two fluid control protocols against a protocol providing free access to water and evaluated the impacts on physiological states of hydration, behavioral measures of welfare, and scientific output. Blood physiology did not significantly differ between any of the protocols, and urine measures were indicative of well functioning, healthy kidneys. Changes in behaviors were limited, the main one being an increase in motivation to drink on the stricter fluid control protocol, and improved task performance early in the week. Overall, fluid control protocols had little measurable impact on the welfare of rhesus macaques while ensuring that scientific data of high quality could be obtained. PMID:27679812

  17. Characterization of an in vitro Rhesus Macaque Blood-Brain Barrier

    Science.gov (United States)

    MacLean, Andrew G.; Orandle, Marlene S.; MacKey, John; Williams, Kenneth C.; Alvarez, Xavier; Lackner, Andrew A.

    2013-01-01

    The blood-brain barrier has been modeled in vitro in a number of species, including rat, cow and human. Coculture of multiple cell types is required for the correct expression of tight junction proteins by microvascular brain endothelial cells (MBEC). Markers of inflammation, especially MHC-II, and cell adhesion molecules, such as VCAM-1, are not expressed on the luminal surface of the barrier under resting conditions. The rhesus macaque model has been used to study early events of HIV-neuropathogenesis in vivo, but a suitable in vitro model has not been available for detailed mechanistic studies. Here we describe an in vitro rhesus macaque blood-brain barrier (BBB) that utilizes autologous MBEC and astrocytes. We believe that this model is highly relevant for examining immunological events at the blood-brain barrier and demonstrate its potential usefulness for examining early events in AIDS neuropathogenesis. PMID:12458041

  18. Surrogate Mobility and Orientation Affect the Early Neurobehavioral Development of Infant Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    Amanda M Dettmer; Ruggerio, Angela M.; Novak, Melinda A.; Meyer, Jerrold S.; Suomi, Stephen J.

    2008-01-01

    A biological mother’s movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard...

  19. Auditory Rehabilitation in Rhesus Macaque Monkeys (Macaca mulatta) with Auditory Brainstem Implants

    Institute of Scientific and Technical Information of China (English)

    Zhen-Min Wang; Zhi-Jun Yang; Fu Zhao; Bo Wang; Xing-Chao Wang; Pei-Ran Qu; Pi-Nan Liu

    2015-01-01

    Background:The auditory brainstem implants (ABIs) have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients.The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device.This study aimed to establish an animal model of ABI in adult rhesus macaque monkey (Macaca mulatta).Methods:Six adult rhesus macaque monkeys (M.mulatta) were included.Under general anesthesia,a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid (RS) approach.The electrical auditory brainstem response (EABR) waves were tested to ensure the optimal implant site.After the operation,the EABR and computed tomography (CT) were used to test and verify the effectiveness via electrophysiology and anatomy,respectively.The subjects underwent behavioral observation for 6 months,and the postoperative EABR was tested every two weeks from the 1st month after implant surgery.Result:The implant surgery lasted an average of 5.2 h,and no monkey died or sacrificed.The averaged latencies of peaks Ⅰ,Ⅱ and Ⅳ were 1.27,2.34 and 3.98 ms,respectively in the ABR.One-peak EABR wave was elicited in the operation,and one-or two-peak waves were elicited during the postoperative period.The EABR wave latencies appeared to be constant under different stimulus intensities;however,the amplitudes increased as the stimulus increased within a certain scope.Conclusions:It is feasible and safe to implant ABIs in rhesus macaque monkeys (M.mulatta) through a modified suboccipital RS approach,and EABR and CT are valid tools for animal model establishment.In addition,this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.

  20. Positive reinforcement training as enrichment for singly housed rhesus macaques (Macaca mulatta)

    OpenAIRE

    Baker, KC; Bloomsmith, MA; Neu, K; Griffis, C; Maloney, M.

    2010-01-01

    Positive reinforcement training is one component of behavioural management employed to improve psychological well-being. There has been regulatory promotion to compensate for restricted social housing in part by providing human interaction to singly caged primates, implying an efficacy standard for evaluating human interaction. The effect of positive reinforcement training on the behaviour of 61 singly housed laboratory rhesus macaques (Macaca mulatta) was evaluated at two large primate facil...

  1. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

    Science.gov (United States)

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g. dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially-housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration (180 words). PMID:25488714

  2. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kelly, K R; Pypendop, B H; Christe, K L

    2015-08-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g., dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post-tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration.

  3. Training rhesus macaques for venipuncture using positive reinforcement techniques: a comparison with chimpanzees.

    Science.gov (United States)

    Coleman, Kristine; Pranger, Lindsay; Maier, Adriane; Lambeth, Susan P; Perlman, Jaine E; Thiele, Erica; Schapiro, Steven J

    2008-01-01

    As more emphasis is placed on enhancing the psychological well-being of nonhuman primates, many research facilities have started using positive reinforcement training (PRT) techniques to train primates to voluntarily participate in husbandry and research procedures. PRT increases the animal's control over its environment and desensitizes the animal to stressful stimuli. Blood draw is a common husbandry and research procedure that can be particularly stressful for nonhuman primate subjects. Although studies have demonstrated that chimpanzees can be trained for in-cage venipuncture using PRT only, fewer studies have demonstrated success using similar techniques to train macaques. It is often assumed that macaques cannot be trained in the same manner as apes. In this study, we compare PRT data from singly housed adult rhesus macaques (Macaca mulatta; n = 8) with data from group-housed adult chimpanzees (Pan troglodytes; n = 4). All subjects were trained to place an arm in a 'blood sleeve' and remain stationary for venipuncture. Both facilities used similar PRT techniques. We were able to obtain repeated blood samples from 75% of the macaques and all of the chimpanzees. The training time did not differ significantly between the 2 species. These data demonstrate that macaques can be trained for venipuncture in a manner similar to that used for chimpanzees.

  4. Enteric Ganglionitis in Rhesus Macaques Infected with Simian Immunodeficiency Virus▿

    OpenAIRE

    2007-01-01

    Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection that can occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight in...

  5. Enteric Ganglionitis in Rhesus Macaques Infected with Simian Immunodeficiency Virus▿

    Science.gov (United States)

    Orandle, Marlene S.; Veazey, Ronald S.; Lackner, Andrew A.

    2007-01-01

    Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection that can occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight into potential pathogenic mechanisms of GI disease. Ganglia from duodenum, ileum, and colon were examined in healthy and acutely infected macaques by using a combination of routine histology, double-label immunofluorescence and in situ hybridization. Evaluation of tissues from infected macaques showed progressive infiltration of myenteric ganglia by CD3+ T cells and IBA1+ macrophages beginning as early as 8 days postinfection. Quantitative image analysis revealed that the severity of myenteric ganglionitis increased with time after SIV infection and, in general, was more severe in ganglia from the small intestine than in ganglia from the colon. Despite an abundance of inflammatory cells in myenteric ganglia during acute infection, the ENS was not a target for virus infection. This study provides evidence that the ENS may be playing a role in the pathogenesis of GI disease and enteropathy in HIV-infected people. PMID:17392357

  6. Intrauterine administration of CDB-2914 (Ulipristal) suppresses the endometrium of rhesus macaques

    Science.gov (United States)

    Brenner, Robert M.; Slayden, Ov D.; Nath, Anita; Tsong, YY; Sitruk-Ware, Regine

    2010-01-01

    Background Ulipristal (CDB-2914; UPA) is a progesterone receptor modulator with contraceptive potential. To test its effects when delivered by an intrauterine system (IUS), we prepared control and UPA-filled IUS and evaluated their effects in rhesus macaques. Study Design Short lengths of Silastic tubing either empty (n=3), or containing UPA (n=5), were inserted into the uteri of 8 ovariectomized macaques. Animals were cycled by sequential treatment with estradiol and progesterone. After 3.5 cycles, the uterus was removed. Results During treatment, animals with an empty IUS menstruated for a mean total of 11.66 ± 0.88 days while UPA-IUS treated animals bled for only 1 ± 0.45 days. Indices of endometrial proliferation were significantly reduced by UPA-IUS treatment. The UPA exposed endometria were atrophied with some glandular cysts while the blank controls displayed a proliferative morphology without cysts. Androgen receptors were more intensely stained in the glands of the UPA-IUS treated endometria than in the blank-IUS treated controls. Conclusions In rhesus macaques, a UPA-IUS induced endometrial atrophy and amenorrhea. The work provides proof of principle that an IUS can deliver effective intrauterine concentrations of Ulipristal. PMID:20227552

  7. Comparison of noncontact infrared thermometry and 3 commercial subcutaneous temperature transponding microchips with rectal thermometry in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Brunell, Marla K

    2012-07-01

    This study compared a noncontact infrared laser thermometer and 3 different brands of subcutaneous temperature transponding microchips with rectal thermometry in 50 rhesus macaques (Macaca mulatta). The data were analyzed by using intraclass correlation coefficients and limits of agreement. In addition, the technical capabilities and practicality of the thermometers in the clinical setting were reviewed. None of the alternative techniques investigated was equivalent to rectal thermometry in rhesus macaques. Temperatures obtained by using microchips had higher correlation and agreed more closely with rectal temperatures than did those obtained by the noncontact infrared method. However, transponding microchips did not yield consistent results. Due to difficulty in positioning nonsedated macaques in their homecage, subcutaneous microchips were not practical in the clinical setting. Furthermore, pair-housed macaques may be able to break or remove microchips from their cagemates.

  8. Interleukin-8 and interleukin-10, brain volume and microstructure, and the influence of calorie restriction in old rhesus macaques

    OpenAIRE

    Willette, A.A.; Coe, C.L.; Birdsill, A. C.; Bendlin, B. B.; Colman, R.J.; Alexander, A.L.; Allison, D. B.; Weindruch, R.H.; Johnson, S.C.

    2013-01-01

    Higher systemic levels of the proinflammatory cytokine interleukin-6 (IL-6) were found to be associated with lower gray matter volume and tissue density in old rhesus macaques. This association between IL-6, and these brain indices were attenuated by long-term 30 % calorie restriction (CR). To extend these findings, the current analysis determined if a CR diet in 27 aged rhesus monkeys compared to 17 normally fed controls reduced circulating levels of another proinflammatory cytokine, interle...

  9. Social relevance drives viewing behavior independent of low-level salience in rhesus macaques

    Directory of Open Access Journals (Sweden)

    James Andrew Solyst

    2014-11-01

    Full Text Available Quantifying attention to social stimuli during the viewing of complex social scenes with eye tracking has proven to be a sensitive method in the diagnosis of autism spectrum disorders years before average clinical diagnosis. Rhesus macaques provide an ideal model for understanding the mechanisms underlying social viewing behavior, but to date no comparable behavioral task has been developed for use in monkeys. Using a novel scene-viewing task, we monitored the gaze of three rhesus macaques while they freely viewed well-controlled composed social scenes and analyzed the time spent viewing objects and monkeys. In each of six behavioral sessions, monkeys viewed a set of 90 images (540 unique scenes with each image presented twice. In two-thirds of the repeated scenes, either a monkey or an object was replaced with a novel item (manipulated scenes. When viewing a repeated scene, monkeys made longer fixations and shorter saccades, shifting from a rapid orienting to global scene contents to a more local analysis of fewer items. In addition to this repetition effect, in manipulated scenes, monkeys demonstrated robust memory by spending more time viewing the replaced items. By analyzing attention to specific scene content, we found that monkeys strongly preferred to view conspecifics and that this was not related to their salience in terms of low-level image features. A model-free analysis of viewing statistics found that monkeys that were viewed earlier and longer had direct gaze and redder sex skin around their face and rump, two important visual social cues. These data provide a quantification of viewing strategy, memory and social preferences in rhesus macaques viewing complex social scenes, and they provide an important baseline with which to compare to the effects of therapeutics aimed at enhancing social cognition.

  10. Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

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    Guang Tian

    Full Text Available In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270 and SV2 (200 µg F1 and 100 µg rV270 subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

  11. Dietary omega-3 fatty acids modulate large-scale systems organization in the rhesus macaque brain.

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    Grayson, David S; Kroenke, Christopher D; Neuringer, Martha; Fair, Damien A

    2014-02-01

    Omega-3 fatty acids are essential for healthy brain and retinal development and have been implicated in a variety of neurodevelopmental disorders. This study used resting-state functional connectivity MRI to define the large-scale organization of the rhesus macaque brain and changes associated with differences in lifetime ω-3 fatty acid intake. Monkeys fed docosahexaenoic acid, the long-chain ω-3 fatty acid abundant in neural membranes, had cortical modular organization resembling the healthy human brain. In contrast, those with low levels of dietary ω-3 fatty acids had decreased functional connectivity within the early visual pathway and throughout higher-order associational cortex and showed impairment of distributed cortical networks. Our findings illustrate the similarity in modular cortical organization between the healthy human and macaque brain and support the notion that ω-3 fatty acids play a crucial role in developing and/or maintaining distributed, large-scale brain systems, including those essential for normal cognitive function.

  12. IgG Binding Characteristics of Rhesus Macaque FcγR.

    Science.gov (United States)

    Chan, Ying N; Boesch, Austin W; Osei-Owusu, Nana Y; Emileh, Ali; Crowley, Andrew R; Cocklin, Sarah L; Finstad, Samantha L; Linde, Caitlyn H; Howell, Rebecca A; Zentner, Isaac; Cocklin, Simon; Miles, Adam R; Eckman, Joshua W; Alter, Galit; Schmitz, Joern E; Ackerman, Margaret E

    2016-10-01

    Indian rhesus macaques (Macaca mulatta) are routinely used in preclinical studies to evaluate therapeutic Abs and candidate vaccines. The efficacy of these interventions in many cases is known to rely heavily on the ability of Abs to interact with a set of Ab FcγR expressed on innate immune cells. Yet, despite their presumed functional importance, M. mulatta Ab receptors are largely uncharacterized, posing a fundamental limit to ensuring accurate interpretation and translation of results from studies in this model. In this article, we describe the binding characteristics of the most prevalent allotypic variants of M. mulatta FcγR for binding to both human and M. mulatta IgG of varying subclasses. The resulting determination of the affinity, specificity, and glycan sensitivity of these receptors promises to be useful in designing and evaluating studies of candidate vaccines and therapeutic Abs in this key animal model and exposes significant evolutionary divergence between humans and macaques.

  13. Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992-2014).

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    Reader, J Rachel; Canfield, Don R; Lane, Jennifer F; Kanthaswamy, Sreetharan; Ardeshir, Amir; Allen, A Mark; Tarara, Ross P

    2016-04-01

    Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease.

  14. Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta) at the California National Primate Research Center (1992–2014)

    Science.gov (United States)

    Reader, J Rachel; Canfield, Don R; Lane, Jennifer F; Kanthaswamy, Sreetharan; Ardeshir, Amir; Allen, A Mark; Tarara, Ross P

    2016-01-01

    Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease. PMID:27053572

  15. Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies.

    Science.gov (United States)

    Lee, Arthur S; Gutiérrez-Arcelus, María; Perry, George H; Vallender, Eric J; Johnson, Welkin E; Miller, Gregory M; Korbel, Jan O; Lee, Charles

    2008-04-15

    Copy number variants (CNVs) are heritable gains and losses of genomic DNA in normal individuals. While copy number variation is widely studied in humans, our knowledge of CNVs in other mammalian species is more limited. We have designed a custom array-based comparative genomic hybridization (aCGH) platform with 385 000 oligonucleotide probes based on the reference genome sequence of the rhesus macaque (Macaca mulatta), the most widely studied non-human primate in biomedical research. We used this platform to identify 123 CNVs among 10 unrelated macaque individuals, with 24% of the CNVs observed in multiple individuals. We found that segmental duplications were significantly enriched at macaque CNV loci. We also observed significant overlap between rhesus macaque and human CNVs, suggesting that certain genomic regions are prone to recurrent CNV formation and instability, even across a total of approximately 50 million years of primate evolution ( approximately 25 million years in each lineage). Furthermore, for eight of the CNVs that were observed in both humans and macaques, previous human studies have reported a relationship between copy number and gene expression or disease susceptibility. Therefore, the rhesus macaque offers an intriguing, non-human primate outbred model organism with which hypotheses concerning the specific functions of phenotypically relevant human CNVs can be tested.

  16. Characterization of an in vitro Rhesus Macaque Blood-Brain Barrier

    OpenAIRE

    2002-01-01

    The blood-brain barrier has been modeled in vitro in a number of species, including rat, cow and human. Coculture of multiple cell types is required for the correct expression of tight junction proteins by microvascular brain endothelial cells (MBEC). Markers of inflammation, especially MHC-II, and cell adhesion molecules, such as VCAM-1, are not expressed on the luminal surface of the barrier under resting conditions. The rhesus macaque model has been used to study early events of HIV-neurop...

  17. Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study.

    Science.gov (United States)

    Banajee, Kaikhushroo H; Embers, Monica E; Langohr, Ingeborg M; Doyle, Lara A; Hasenkampf, Nicole R; Macaluso, Kevin R

    2015-01-01

    Rickettsia parkeri is an emerging eschar-causing human pathogen in the spotted fever group of Rickettsia and is transmitted by the Gulf coast tick, Amblyomma maculatum. Tick saliva has been shown to alter both the cellular and humoral components of the innate and adaptive immune systems. However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined. We hypothesize that, by modifying the host immune response, tick feeding enhances infection and pathology of pathogenic spotted fever group Rickettsia sp. In order to assess this interaction in vivo, a pilot study was conducted using five rhesus macaques that were divided into three groups. One group was intradermally inoculated with low passage R. parkeri (Portsmouth strain) alone (n = 2) and another group was inoculated during infestation by adult, R. parkeri-free A. maculatum (n = 2). The final macaque was infested with ticks alone (tick feeding control group). Blood, lymph node and skin biopsies were collected at several time points post-inoculation/infestation to assess pathology and quantify rickettsial DNA. As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group. While eschars formed at all R. parkeri inoculation sites, larger and slower healing eschars were observed in the tick feeding plus R. parkeri group. Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group. This study indicates that rhesus macaques can be used to model R. parkeri rickettsiosis, and suggests that immunomodulatory factors

  18. Diverse Host Responses and Outcomes following Simian Immunodeficiency Virus SIVmac239 Infection in Sooty Mangabeys and Rhesus Macaques

    Science.gov (United States)

    Kaur, Amitinder; Grant, Robert M.; Means, Robert E.; McClure, Harold; Feinberg, Mark; Johnson, R. Paul

    1998-01-01

    Sooty mangabeys naturally infected with simian immunodeficiency virus (SIV) do not develop immunodeficiency despite the presence of viral loads of 105 to 107 RNA copies/ml. To investigate the basis of apathogenic SIV infection in sooty mangabeys, three sooty mangabeys and three rhesus macaques were inoculated intravenously with SIVmac239 and evaluated longitudinally for 1 year. SIVmac239 infection of sooty mangabeys resulted in 2- to 4-log-lower viral loads than in macaques and did not reproduce the high viral loads observed in natural SIVsmm infection. During acute SIV infection, polyclonal cytotoxic T-lymphocyte (CTL) activity coincident with decline in peak plasma viremia was observed in both macaques and mangabeys; 8 to 20 weeks later, CTL activity declined in the macaques but was sustained and broadly directed in the mangabeys. Neutralizing antibodies to SIVmac239 were detected in the macaques but not the mangabeys. Differences in expression of CD38 on CD8+ T lymphocytes or in the percentage of naive phenotype T cells expressing CD45RA and CD62L-selection did not correlate with development of AIDS in rhesus macaques. In macaques, the proportion of CD4+ T lymphocytes expressing CD25 declined during SIV infection, while in mangabeys, CD25-expressing CD4+ T lymphocytes increased. Longitudinal evaluation of cytokine secretion by flow cytometric analysis of unstimulated lymphocytes revealed elevation of interleukin-2 and gamma interferon in a macaque and only interleukin-10 in a concurrently infected mangabey during acute SIV infection. Differences in host responses following experimental SIVmac239 infection may be associated with the divergent outcome in sooty mangabeys and rhesus macaques. PMID:9811693

  19. Transepithelial transport and enzymatic detoxification of gluten in gluten-sensitive rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Michael T Bethune

    Full Text Available BACKGROUND AND AIMS: In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate. METHODS: Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten. RESULTS: Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA and anti-transglutaminase (IgG antibodies was observed during the EP-B2 treatment phase. CONCLUSIONS: Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data

  20. Familial periodontal disease in the Cayo Santiago rhesus macaques.

    Science.gov (United States)

    Gonzalez, Octavio A; Orraca, Luis; Kensler, Terry B; Gonzalez-Martinez, Janis; Maldonado, Elizabeth; Ebersole, Jeffrey L

    2016-01-01

    Substantial ongoing research continues to explore the contribution of genetics and environment to the onset, extent and severity of periodontal disease(s). Existing evidence supports that periodontal disease appears to have an increased prevalence in family units with a member having aggressive periodontitis. We have been using the nonhuman primate as a model of periodontal disease for over 25 years with these species demonstrating naturally occurring periodontal disease that increases with age. This report details our findings from evaluation of periodontal disease in skulls from 97 animals (5-31 years of age) derived from the skeletons of the rhesus monkeys (Macaca mulatta) on Cayo Santiago. Periodontal disease was evaluated by determining the distance from the base of the alveolar bone defect to the cemento-enamel junction on 1st/2nd premolars and 1st/2nd molars from all four quadrants. The results demonstrated an increasing extent and severity of periodontitis with aging across the population of animals beyond only compensatory eruption. Importantly, irrespective of age, extensive heterogeneity in disease expression was observed among the animals. Linking these variations to multi-generational matriarchal family units supported familial susceptibility of periodontitis. As the current generations of animals that are descendants from these matrilines are alive, studies can be conducted to explore an array of underlying factors that could account for susceptibility or resistance to periodontal disease.

  1. Detecting instability in animal social networks: genetic fragmentation is associated with social instability in rhesus macaques.

    Science.gov (United States)

    Beisner, Brianne A; Jackson, Megan E; Cameron, Ashley N; McCowan, Brenda

    2011-01-26

    The persistence of biological systems requires evolved mechanisms which promote stability. Cohesive primate social groups are one example of stable biological systems, which persist in spite of regular conflict. We suggest that genetic relatedness and its associated kinship structure are a potential source of stability in primate social groups as kinship structure is an important organizing principle in many animal societies. We investigated the effect of average genetic relatedness per matrilineal family on the stability of matrilineal grooming and agonistic interactions in 48 matrilines from seven captive groups of rhesus macaques. Matrilines with low average genetic relatedness show increased family-level instability such as: more sub-grouping in their matrilineal groom network, more frequent fighting with kin, and higher rates of wounding. Family-level instability in multiple matrilines within a group is further associated with group-level instability such as increased wounding. Stability appears to arise from the presence of clear matrilineal structure in the rhesus macaque group hierarchy, which is derived from cohesion among kin in their affiliative and agonistic interactions with each other. We conclude that genetic relatedness and kinship structure are an important source of group stability in animal societies, particularly when dominance and/or affilative interactions are typically governed by kinship.

  2. Prevalence of Entamoeba nuttalli infection in wild rhesus macaques in Nepal and characterization of the parasite isolates.

    Science.gov (United States)

    Tachibana, Hiroshi; Yanagi, Tetsuo; Lama, Chamala; Pandey, Kishor; Feng, Meng; Kobayashi, Seiki; Sherchand, Jeevan B

    2013-04-01

    We have recently resurrected the name Entamoeba nuttalli Castellani, 1908 for a potentially virulent ameba isolate, P19-061405, obtained from a rhesus macaque in Kathmandu, Nepal. The ameba was morphologically indistinguishable from Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii, but located phylogenetically between E. histolytica and E. dispar. To evaluate the prevalence of E. nuttalli infection in wild rhesus macaques, 112 fecal samples were collected in four locations of the Kathmandu Valley. PCR analysis of DNA extracted from the feces showed positive rates of E. nuttalli, E. dispar, E. histolytica and E. moshkovskii of 51%, 12%, 0% and 0%, respectively. A total of 14 E. nuttalli isolates were obtained from four locations, of which 6 were established as axenic cultures. The sequences of the serine-rich protein gene of E. nuttalli isolates differed among four locations although no differences were found in the composition of sequence motifs. Isoenzyme pattern was analyzed in 8 isolates obtained from three locations. In hexokinase, the mobility of the slower migrating band was located between E. histolytica and E. dispar regardless of the culture conditions. These results demonstrate that E. nuttalli is highly prevalent in wild rhesus macaques in Nepal. Rhesus macaques appear to be one of the natural hosts and heterogeneity of the serine-rich protein gene might be useful for geographical typing of isolates.

  3. Effects of maternal and infant characteristics on birth weight and gestation length in a colony of rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Hopper, Kelly J; Capozzi, Denise K; Newsome, Joseph T

    2008-12-01

    A retrospective study using maternal and birth statistics from an open, captive rhesus macaque colony was done to determine the effects of parity, exposure to simian retrovirus (SRV), housing, maternal parity, and maternal birth weight on infant birth weight, viability and gestation length. Retrospective colony statistics for a 23-y period indicated that birth weight, but not gestation length, differed between genders. Adjusted mean birth weights were higher in nonviable infants. Mothers positive for SRV had shorter gestations, but SRV exposure did not affect neonatal birth weights or viability. Infants born in cages had longer gestations than did those born in pens, but neither birth weight nor viability differed between these groups. Maternal birth weight did not correlate with infant birth weight but positively correlated with gestation length. Parity was correlated with birth weight and decreased viability. Increased parity of the mother was associated with higher birth weight of the infant. A transgenerational trend toward increasing birth weight was noted. The birth statistics of this colony were consistent with those of other macaque colonies. Unlike findings for humans, maternal birth weight had little predictive value for infant outcomes in rhesus macaques. Nonviable rhesus infants had higher birth weights, unlike their human counterparts, perhaps due to gestational diabetes occurring in a sedentary caged population. Similar to the situation for humans, multiparity had a protective effect on infant viability in rhesus macaques.

  4. Effects of the macrolide drug tylosin on chronic diarrhea in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Blackwood, Rebecca S; Tarara, Ross P; Christe, Kari L; Spinner, Abigail; Lerche, Nicholas W

    2008-02-01

    Diarrhea is the gastrointestinal disease most frequently encountered in captive rhesus macaques. The precise pathogenic mechanisms underlying chronic diarrhea in nonhuman primates are not well understood, but a persistent inflammatory component has been implicated strongly. This study evaluated the inflammatory changes in the colon of macaques with diarrhea and assessed the efficacy of a 10-d course of tylosin in a cohort of 21 animals with chronic diarrhea. Stool quality was evaluated daily, and fecal consistency was scored. Colonoscopies were performed; biopsy samples were characterized histologically and assayed for expression of TNFalpha mRNA. Blood samples collected pre-, mid-, and post-treatment were assayed for C-reactive protein (CRP). The results indicated that 63% of the animals receiving tylosin showed improvement in stool quality, compared with 10% in the sham-treated group. Histologically, 82% of animals in the tylosin-treated group had a reduction in the severity of colonic lesions post-treatment, compared with 40% of animals in the sham group. The amount of TNFalpha mRNA before treatment did not differ from that afterward in either tylosin- or sham-treated animals. CRP levels serially decreased in tylosin-treated monkeys; the average post-treatment CRP value for tylosin-treated animals was 11.96 +/- 3.86 microg/ml compared with 26.48 +/- 4.86 microg/ml for sham-treated controls. In conclusion, tylosin significantly improved the fecal consistency score, significantly decreased colonic inflammation, and significantly decreased serum CRP levels post-treatment in rhesus macaques with chronic diarrhea.

  5. An HSV-2 Trivalent Vaccine Is Immunogenic in Rhesus Macaques and Highly Efficacious in Guinea Pigs

    Science.gov (United States)

    Hook, Lauren M.; Shaw, Carolyn E.; Pahar, Bapi; Liu, David; Veazey, Ronald S.

    2017-01-01

    A genital herpes vaccine is urgently needed to prevent pain and suffering, reduce the incidence of neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital infection. We evaluated a trivalent HSV-2 subunit antigen vaccine administered with CpG and alum in rhesus macaques and guinea pigs. The vaccine contains glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent vaccine induced plasma and mucosa neutralizing antibodies, antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses. After intravaginal challenge, a self-limited vaginal infection of brief duration was detected by histopathology and immunohistochemistry in naïve, but not in trivalent immunized macaques. Vaccine efficacy was evaluated in female guinea pigs. Animals were mock immunized, or immunized with gD2, the trivalent vaccine or the trivalent vaccine followed by a booster dose of gD2 (trivalent + gD2). The trivalent and trivalent + gD2 groups were 97% and 99% efficacious, respectively in preventing genital lesions and both outperformed gD2 alone. As a marker of transmission risk, vaginal swabs were evaluated daily for HSV-2 DNA and replication competent virus between five and seven weeks after challenge. HSV-2 DNA shedding was reduced in all groups compared with mock. Shedding of replication competent virus occurred on fewer days in the trivalent than gD2 immunized animals while the trivalent + gD2 group had no shedding of replication competent virus. Overall, the trivalent group had genital lesions on < 1% days and shedding of replication competent virus on 0.2% days. The vaccine has outstanding potential for prevention of genital herpes in humans. PMID:28103319

  6. Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

    Directory of Open Access Journals (Sweden)

    Austin W. Boesch

    2016-12-01

    Full Text Available Antibodies raised in Indian rhesus macaques (Macaca mulatta, MM in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM IgG subclasses and how they may compare to human IgG subclasses. Here we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human FcγR and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies.

  7. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques

    Science.gov (United States)

    Gonzalez, Denise F.; Kieu, Hung T.; Castillo, Luis D.; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D.; Shacklett, Barbara L.; Barry, Peter A.; Sparger, Ellen E.

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease. PMID:28095513

  8. Effect of Uveal Melanocytes on Choroidal Morphology in Rhesus Macaques and Humans on Enhanced-Depth Imaging Optical Coherence Tomography

    Science.gov (United States)

    Yiu, Glenn; Vuong, Vivian S.; Oltjen, Sharon; Cunefare, David; Farsiu, Sina; Garzel, Laura; Roberts, Jeffrey; Thomasy, Sara M.

    2016-01-01

    Purpose To compare cross-sectional choroidal morphology in rhesus macaque and human eyes using enhanced-depth imaging optical coherence tomography (EDI-OCT) and histologic analysis. Methods Enhanced-depth imaging–OCT images from 25 rhesus macaque and 30 human eyes were evaluated for choriocapillaris and choroidal–scleral junction (CSJ) visibility in the central macula based on OCT reflectivity profiles, and compared with age-matched histologic sections. Semiautomated segmentation of the choriocapillaris and CSJ was used to measure choriocapillary and choroidal thickness, respectively. Multivariate regression was performed to determine the association of age, refractive error, and race with choriocapillaris and CSJ visibility. Results Rhesus macaques exhibit a distinct hyporeflective choriocapillaris layer on EDI-OCT, while the CSJ cannot be visualized. In contrast, humans show variable reflectivities of the choriocapillaris, with a distinct CSJ seen in many subjects. Histologic sections demonstrate large, darkly pigmented melanocytes that are densely distributed in the macaque choroid, while melanocytes in humans are smaller, less pigmented, and variably distributed. Optical coherence tomography reflectivity patterns of the choroid appear to correspond to the density, size, and pigmentation of choroidal melanocytes. Mean choriocapillary thickness was similar between the two species (19.3 ± 3.4 vs. 19.8 ± 3.4 μm, P = 0.615), but choroidal thickness may be lower in macaques than in humans (191.2 ± 43.0 vs. 266.8 ± 78.0 μm, P morphology on EDI-OCT in rhesus macaque and human eyes. Racial differences in pigmentation may affect choriocapillaris and CSJ visibility, and may influence the accuracy of choroidal thickness measurements. PMID:27792810

  9. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

    Science.gov (United States)

    Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

    2017-01-01

    As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1. Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection, and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG) on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues. PMID:28146109

  10. TRIMe7-CypA, an alternative splicing isoform of TRIMCyp in rhesus macaque, negatively modulates TRIM5α activity

    Energy Technology Data Exchange (ETDEWEB)

    Na, Lei [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Tang, Yan-Dong [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Biotechnology Institute of Southern Medical University, Guangzhou 510515 (China); Liu, Jian-Dong; Yu, Chang-Qing; Sun, Liu-Ke; Lin, Yue-Zhi; Wang, Xue-Feng [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Wang, Xiaojun, E-mail: xjw@hvri.ac.cn [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Zhou, Jian-Hua, E-mail: jianhua_uc@126.com [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Harbin Pharmaceutical Group Biovaccine Company, Harbin 150069 (China)

    2014-04-04

    Highlights: • TRIMe7-CypA expresses in rhesus and pig-tailed, but not long-tailed macaques. • TRIMe7-CypA does not show the restriction to a HIV-GFP report virus in vitro. • It acts as a negative modulator to TRIM5α likely by competitive inhibition. - Abstract: The existence of innate, host-specific restriction factors is a major obstacle to the development of nonhuman primate models for AIDS studies, and TRIM5α is one of the most important of these restriction factors. In recent years, a TRIM5 chimeric gene that was retrotransposed by a cyclophilin A (CypA) cDNA was identified in certain macaque species. The TRIM5α-CypA fusion protein, TRIMCyp, which was expressed in these monkeys, had lost its restriction ability toward HIV-1. We previously found that TRIMe7-CypA, an alternative splicing isoform of the TRIMCyp transcripts, was expressed in pig-tailed and rhesus macaques but absent in long-tailed macaques. In this study, the anti-HIV-1 activity of TRIMe7-CypA in the rhesus macaque (RhTRIMe7-CypA) was investigated. The over-expression of RhTRIMe7-CypA in CrFK, HeLa and HEK293T cells did not restrict the infection or replication of an HIV-1-GFP reporter virus in these cells. As a positive control, rhesus (rh)TRIM5α strongly inhibited the reporter virus. Intriguingly, the anti-HIV-1 activity of RhTRIM5α was significantly reduced in a dose-dependent manner by the co-repression of RhTRIMe7-CypA. Our data indicate that although the RhTRIMe7-CypA isoform does not appear to restrict HIV-1, it may act as a negative modulator of TRIM family proteins, presumably by competitive inhibition.

  11. Circulating natural killer and γδ T cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus

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    Juan D Rodas

    2009-07-01

    Full Text Available Rhesus macaques infected with the WE strain of lymphocytic choriomeningitis virus (LCMV-WE serve as a model for human infection with Lassa fever virus. To identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (PBMCs. Changes in CD3, CD4, CD8 and CD20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (NK and γδ T cells increased slightly on day 1 and then decreased significantly after two days. The NK subsets responsible for the decrease were primarily CD3-CD8+ or CD3-CD16+ and not the NKT (primarily CD3+CD56+ subset. Macaques infected with a non-virulent arenavirus, LCMV-Armstrong, showed a similar drop in circulating NK and γδ T cells, indicating that this is not a pathogenic event. V³9 T cells, representing the majority of circulating γδ T cells in rhesus macaques, displayed significant apoptosis when incubated with LCMV in cell culture; however, the low amount of cell death for virus-co-cultured NK cells was insufficient to account for the observed disappearance of this subset. Our observations in primates are similar to those seen in LCMV-infected mice, where decreased circulating NK cells were attributed to margination and cell death. Thus, the disappearance of these cells during acute hemorrhagic fever in rhesus macaques may be a cytokine-induced lymphopenia common to many virus infections.

  12. Host response dynamics following lethal infection of rhesus macaques with Zaire ebolavirus.

    Science.gov (United States)

    Ebihara, Hideki; Rockx, Barry; Marzi, Andrea; Feldmann, Friederike; Haddock, Elaine; Brining, Douglas; LaCasse, Rachel A; Gardner, Don; Feldmann, Heinz

    2011-11-01

    To gain further insight into the interdependent pathogenic processes in Ebola hemorrhagic fever (EHF), we have examined the dynamics of host responses in individual rhesus macaques infected with Zaire ebolavirus over the entire disease course. Examination of coagulation parameters revealed that decreased coagulation inhibitor activity triggered severe coagulopathy as indicated by prolonged coagulation times and decreased fibrinogen levels. This has been proposed as one of the significant mechanisms underlying disseminated intravascular coagulation in EHF patients. Furthermore, monitoring of expression levels for cytokines/chemokines suggested a mixed anti-inflammatory response syndrome (MARS), which indicates that a catastrophic uncontrolled immunological status contributes to the development of fatal hemorrhagic fever. These results highlight the pathological analogies between EHF and severe sepsis and not only contribute to our understanding of the pathogenic process, but will also help to establish novel postexposure treatment modalities.

  13. Phenotypic and Functional Characterization of Monoclonal Antibodies with Specificity for Rhesus Macaque CD200, CD200R and Mincle.

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    Siddappa N Byrareddy

    Full Text Available Lectin-like molecules and their receptors are cell surface molecules that have been shown to play a role in either facilitating infection or serving as transporters of HIV/SIV in vivo. The role of these lectin-like molecules in the pathogenesis of HIV/SIV infection continues to be defined. In efforts to gain further insight on the potential role of these lectin-like molecules, our laboratory generated monoclonal antibodies (mAb against the human analogs of rhesus macaque CD200, CD200R and Mincle, since the rhesus macaques are accepted as the most reliable animal model to study human HIV infection. The characterization of the cell lineages from the blood and various tissues of rhesus macaques that express these lectin-like molecules are described herein. Among the mononuclear cells, the cells of the myeloid lineage of rhesus macaques are the predominant cell lineages that express readily detectable levels of CD200, CD200R and Mincle that is similar to the expression of Siglec-1 and Siglec-3 reported by our laboratory earlier. Subset analysis revealed that a higher frequency of the CD14+/CD16- subset from normal rhesus macaques express CD200, CD200R and Mincle. Differences in the frequencies and density of expression of these molecules by the gated population of CD14+ cells from various tissues are noted with PBMC and bone marrow expressing the highest and the mononuclear cells isolated from the colon and ileum expressing the lowest levels. While a significant frequency of pDCs and mDCs express Siglec-1/Siglec-3, a much lower frequency expresses CD200, CD200R and Mincle in PBMCs from rhesus macaques. The mAb against CD200 and CD200R but not Mincle appear to inhibit the infection of macrophage tropic SIV/SHIV in vitro. We conclude that these mAbs may have potential to be used as adjunctive therapeutic agents to control/inhibit SIV/HIV infection.

  14. Bisphenol A exposure alters developmental gene expression in the fetal rhesus macaque uterus.

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    Kathryn C Calhoun

    Full Text Available Bisphenol A (BPA exposure results in numerous developmental and functional abnormalities in reproductive organs in rodent models, but limited data are available regarding BPA effects in the primate uterus. To determine if maternal oral BPA exposure affects fetal uterine development in a non-human primate model, pregnant rhesus macaques carrying female fetuses were exposed orally to 400 µg/kg BPA or vehicle control daily from gestation day (GD 50-100 or GD100-165. Fetal uteri were collected at the completion of treatment (GD100 or GD165; tissue histology, cell proliferation, and expression of estrogen receptor alpha (ERα and progesterone receptor (PR were compared to that of controls. Gene expression analysis was conducted using rhesus macaque microarrays. There were no significant differences in histology or in the percentage of cells expressing the proliferation marker Ki-67, ERα, or PR in BPA-exposed uteri compared to controls at GD100 or GD165. Minimal differences in gene expression were observed between BPA-exposed and control GD100 uteri. However, at GD165, BPA-exposed uteri had significant differences in gene expression compared to controls. Several of the altered genes, including HOXA13, WNT4, and WNT5A, are critical for reproductive organ development and/or adult function. We conclude that second or third trimester BPA exposure does not significantly affect fetal uterus development based on morphological, proliferation, and steroid hormone receptor assessments. However, differences in expression of key developmental genes after third trimester exposure suggest that BPA could alter transcriptional signals influencing uterine function later in life.

  15. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    Energy Technology Data Exchange (ETDEWEB)

    Herring, M.J.; Putney, L.F.; St George, J.A. [California National Primate Research Center, Davis, CA (United States); Avdalovic, M.V. [Department of Internal Medicine, Division of Pulmonary and Critical Care, University of California, Davis, CA (United States); Schelegle, E.S.; Miller, L.A. [California National Primate Research Center, Davis, CA (United States); Hyde, D.M., E-mail: dmhyde@ucdavis.edu [California National Primate Research Center, Davis, CA (United States)

    2015-02-15

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  16. Effect of combination antiretroviral therapy on Chinese rhesus macaques of simian immunodeficiency virus infection.

    Science.gov (United States)

    Ling, Binhua; Rogers, Linda; Johnson, Ann-Marie; Piatak, Michael; Lifson, Jeffrey; Veazey, Ronald S

    2013-11-01

    Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to CCR5(+)CD4(+) mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

  17. Ab initio identification of transcription start sites in the Rhesus macaque genome by histone modification and RNA-Seq

    OpenAIRE

    2011-01-01

    Rhesus macaque is a widely used primate model organism. Its genome annotations are however still largely comparative computational predictions derived mainly from human genes, which precludes studies on the macaque-specific genes, gene isoforms or their regulations. Here we took advantage of histone H3 lysine 4 trimethylation (H3K4me3)’s ability to mark transcription start sites (TSSs) and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures. We generated...

  18. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Chang, Steve W C; Barter, Joseph W; Ebitz, R Becket; Watson, Karli K; Platt, Michael L

    2012-01-17

    People attend not only to their own experiences, but also to the experiences of those around them. Such social awareness profoundly influences human behavior by enabling observational learning, as well as by motivating cooperation, charity, empathy, and spite. Oxytocin (OT), a neurosecretory hormone synthesized by hypothalamic neurons in the mammalian brain, can enhance affiliation or boost exclusion in different species in distinct contexts, belying any simple mechanistic neural model. Here we show that inhaled OT penetrates the CNS and subsequently enhances the sensitivity of rhesus macaques to rewards occurring to others as well as themselves. Roughly 2 h after inhaling OT, monkeys increased the frequency of prosocial choices associated with reward to another monkey when the alternative was to reward no one. OT also increased attention to the recipient monkey as well as the time it took to render such a decision. In contrast, within the first 2 h following inhalation, OT increased selfish choices associated with delivery of reward to self over a reward to the other monkey, without affecting attention or decision latency. Despite the differences in species typical social behavior, exogenous, inhaled OT causally promotes social donation behavior in rhesus monkeys, as it does in more egalitarian and monogamous ones, like prairie voles and humans, when there is no perceived cost to self. These findings potentially implicate shared neural mechanisms.

  19. Positive reinforcement training as enrichment for singly housed rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Baker, K C; Bloomsmith, M A; Neu, K; Griffis, C; Maloney, M

    2010-08-01

    Positive reinforcement training is one component of behavioural management employed to improve psychological well-being. There has been regulatory promotion to compensate for restricted social housing in part by providing human interaction to singly caged primates, implying an efficacy standard for evaluating human interaction. The effect of positive reinforcement training on the behaviour of 61 singly housed laboratory rhesus macaques (Macaca mulatta) was evaluated at two large primate facilities. Training involved body part presentation and basic control behaviours. Baseline data were compared to two treatment phases presented in varying order across individuals, six minutes per week of positive reinforcement training and six minutes per week of unstructured human interaction. While a MANOVA involving behavioural categories and study conditions across study subjects was significant, univariate ANOVAs found no effect of phase within any behavioural category. Categorising subjects according to rearing, housing facility, or baseline levels of abnormal behaviour did not reveal changes in behaviour with positive reinforcement training or human interaction. This study failed to detect, to any degree, the types of behavioural changes documented in the scientific literature to result from pairing singly housed monkeys. Implementing short durations of positive reinforcement training across large numbers of singly housed animals may not be the most effective manner for incorporating positive reinforcement training in the behavioural management of laboratory macaques. Rather, directing efforts toward individuals with specific behavioural, management, clinical, research or therapeutic needs may represent a more fruitful approach to improving psychological well-being with this technique.

  20. Efficacy of antibiotic-impregnated polymethylmethacrylate beads in a rhesus macaque (Macaca mulatta) with osteomyelitis.

    Science.gov (United States)

    Kelly, Kristi R; Kapatkin, Amy R; Zwingenberger, Allison L; Christe, Kari L

    2012-08-01

    Here we describe the successful surgical implementation of antibiotic-impregnated polymethylmethacrylate beads in a rhesus macaque (Macaca mulatta) with marked osteomyelitis. The macaque presented to the veterinary clinic with grossly contaminated bite wounds in the left ankle secondary to conspecific trauma. Radiographic findings were highly suggestive of osteomyelitis. Additional differential diagnoses included bony infarct, fracture, and cellulitis. In light of the location of the lesion and extensive tissue trauma, the animal had a poor prognosis. Systemic, broad-spectrum antibiotics were instituted. After 2 wk of care, lesions did not respond to empirical therapies. On consultation, a veterinary orthopedic surgeon at another facility recommended placement of antibiotic-impregnated polymethylmethacrylate beads at the sites of osteomyelitis. The animal underwent minor surgery in which beads were introduced into the wound. The monkey had a positive response to therapy. The animal regained full function and was returned to outdoor social housing. Veterinarians are encouraged to consider using antibiotic-impregnated polymethylmethacrylate beads when treating osteomyelitis in other nonhuman primates and in other traditional laboratory animal species.

  1. Manipulating the affiliative interactions of group-housed rhesus macaques using positive reinforcement training techniques.

    Science.gov (United States)

    Schapiro, S J; Perlman, J E; Boudreau, B A

    2001-11-01

    Social housing, whether continuous, intermittent, or partial contact, typically provides many captive primates with opportunities to express affiliative behaviors, important components of the species-typical behavioral repertoire. Positive reinforcement training techniques have been successfully employed to shape many behaviors important for achieving primate husbandry goals. The present study was conducted to determine whether positive reinforcement training techniques could also be employed to alter levels of affiliative interactions among group-housed rhesus macaques. Twenty-eight female rhesus were divided into high (n = 14) and low (n = 14) affiliators based on a median split of the amount of time they spent affiliating during the baseline phase of the study. During the subsequent training phase, half of the low affiliators (n = 7) were trained to increase their time spent affiliating, and half of the high affiliators (n = 7) were trained to decrease their time spent affiliating. Trained subjects were observed both during and outside of training sessions. Low affiliators significantly increased the amount of time they spent affiliating, but only during nontraining sessions. High affiliators on the other hand, significantly decreased the amount of time they spent affiliating, but only during training sessions. These data suggest that positive reinforcement techniques can be used to alter the affiliative behavior patterns of group-housed, female rhesus monkeys, although the two subgroups of subjects responded differently to the training process. Low affiliators changed their overall behavioral repertoire, while high affiliators responded to the reinforcement contingencies of training, altering their proximity patterns but not their overall behavior patterns. Thus, positive reinforcement training can be used not only as a means to promote species-typical or beneficial behavior patterns, but also as an important experimental manipulation to facilitate systematic

  2. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  3. Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

    Science.gov (United States)

    Gadad, Bharathi S; Li, Wenhao; Yazdani, Umar; Grady, Stephen; Johnson, Trevor; Hammond, Jacob; Gunn, Howard; Curtis, Britni; English, Chris; Yutuc, Vernon; Ferrier, Clayton; Sackett, Gene P; Marti, C Nathan; Young, Keith; Hewitson, Laura; German, Dwight C

    2015-10-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

  4. Sex-specific heritability of spontaneous lipid levels in an extended pedigree of Indian-origin rhesus macaques (Macaca mulatta.

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    Amanda Vinson

    Full Text Available The rhesus macaque is an important model for human atherosclerosis but genetic determinants of relevant phenotypes have not yet been investigated in this species. Because lipid levels are well-established and heritable risk factors for human atherosclerosis, our goal was to assess the heritability of lipoprotein cholesterol and triglyceride levels in a single, extended pedigree of 1,289 Indian-origin rhesus macaques. Additionally, because increasing evidence supports sex differences in the genetic architecture of lipid levels and lipid metabolism in humans and macaques, we also explored sex-specific heritability for all lipid measures investigated in this study. Using standard methods, we measured lipoprotein cholesterol and triglyceride levels from fasted plasma in a sample of 193 pedigreed rhesus macaques selected for membership in large, paternal half-sib cohorts, and maintained on a low-fat, low cholesterol chow diet. Employing a variance components approach, we found moderate heritability for total cholesterol (h²=0.257, P=0.032, LDL cholesterol (h²=0.252, P=0.030, and triglyceride levels (h²=0.197, P=0.034 in the full sample. However, stratification by sex (N=68 males, N=125 females revealed substantial sex-specific heritability for total cholesterol (0.644, P=0.004, females only, HDL cholesterol (0.843, P=0.0008, females only, VLDL cholesterol (0.482, P=0.018, males only, and triglyceride levels (0.705, P=0.001, males only that was obscured or absent when sexes were combined in the full sample. We conclude that genes contribute to spontaneous variation in circulating lipid levels in the Indian-origin rhesus macaque in a sex-specific manner, and that the rhesus macaque is likely to be a valuable model for sex-specific genetic effects on lipid risk factors for human atherosclerosis. These findings are a first-ever report of heritability for cholesterol levels in this species, and support the need for expanded analysis of these traits in

  5. X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Youjun [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Qi, Jianxun [Graduate School, Chinese Academy of Sciences, Beijing (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Zhang, Huimin; Wang, Jinzi [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Liu, Jinhua [College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Jiang, Fan [Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Gao, Feng, E-mail: gaofeng@im.ac.cn [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

    2006-01-01

    X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β{sub 2}m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides.

  6. The value of extended pedigrees for next-generation analysis of complex disease in the rhesus macaque.

    Science.gov (United States)

    Vinson, Amanda; Prongay, Kamm; Ferguson, Betsy

    2013-01-01

    Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease.

  7. Risk Factor Analysis May Provide Clues to Diarrhea Prevention in Outdoor-Housed Rhesus Macaques (Macaca mulatta)

    OpenAIRE

    PRONGAY, KAMM; Park, Byung; Murphy, Stephanie J.

    2013-01-01

    Seventy-five percent of rhesus macaques at national primate research centers are housed outside. Annually, 15–39% of these animals experience diarrhea and require veterinary treatment for dehydration, electrolyte imbalance, or weight loss. An estimated 21–33% of these patients will die or be euthanized. Many studies have explored the various infectious etiologies of non-human primate diarrhea. However, there is little published information on diarrhea incidence rates and risk factors in outdo...

  8. The UNC-Wisconsin Rhesus Macaque Neurodevelopment Database: A Structural MRI and DTI Database of Early Postnatal Development

    Science.gov (United States)

    Young, Jeffrey T.; Shi, Yundi; Niethammer, Marc; Grauer, Michael; Coe, Christopher L.; Lubach, Gabriele R.; Davis, Bradley; Budin, Francois; Knickmeyer, Rebecca C.; Alexander, Andrew L.; Styner, Martin A.

    2017-01-01

    Rhesus macaques are commonly used as a translational animal model in neuroimaging and neurodevelopmental research. In this report, we present longitudinal data from both structural and diffusion MRI images generated on a cohort of 34 typically developing monkeys from 2 weeks to 36 months of age. All images have been manually skull stripped and are being made freely available via an online repository for use by the research community. PMID:28210206

  9. Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children.

    Science.gov (United States)

    Zhang, Ying; Wang, Lichun; Liao, Yun; Liu, Longding; Ma, Kaili; Yang, Erxia; Wang, Jingjing; Che, Yanchun; Jiang, Li; Pu, Jing; Guo, Lei; Feng, Min; Liang, Yan; Cui, Wei; Yang, Huai; Li, Qihan

    2015-11-17

    During the development of enterovirus 71 (EV71) inactivated vaccine for preventing human hand, foot and mouth diseases (HFMD) by EV71 infection, an effective animal model is presumed to be significant and necessary. Our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of HFMD, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during EV71 infection. Although an immune response in terms of neutralizing antibody and T cell memory was observed in animals infected by the virus or stimulated by viral antigen, whether such a response could be considered as an indicator to justify the immune response in individuals vaccinated or infected in a pandemic needs to be investigated. Here, a comparative analysis of the neutralizing antibody response and IFN-γ-specific T cell response in vaccinated neonatal rhesus macaques and a human clinical trial with an EV71 inactivated vaccine was performed, and the results showed the identical tendency and increased level of neutralizing antibody and the IFN-γ-specific T cell response stimulated by the EV71 antigen peptide. Importantly, the clinical protective efficacy against virus infection by the elicited immune response in the immunized population compared with the placebo control and the up-modulated gene profile associated with immune activation were similar to those in infected macaques. Further safety verification of this vaccine in neonatal rhesus macaques and children confirmed the potential use of the macaque as a reliable model for the evaluation of an EV71 candidate vaccine.

  10. Ab initio identification of transcription start sites in the Rhesus macaque genome by histone modification and RNA-Seq.

    Science.gov (United States)

    Liu, Yi; Han, Dali; Han, Yixing; Yan, Zheng; Xie, Bin; Li, Jing; Qiao, Nan; Hu, Haiyang; Khaitovich, Philipp; Gao, Yuan; Han, Jing-Dong J

    2011-03-01

    Rhesus macaque is a widely used primate model organism. Its genome annotations are however still largely comparative computational predictions derived mainly from human genes, which precludes studies on the macaque-specific genes, gene isoforms or their regulations. Here we took advantage of histone H3 lysine 4 trimethylation (H3K4me3)'s ability to mark transcription start sites (TSSs) and the recently developed ChIP-Seq and RNA-Seq technology to survey the transcript structures. We generated 14,013,757 sequence tags by H3K4me3 ChIP-Seq and obtained 17,322,358 paired end reads for mRNA, and 10,698,419 short reads for sRNA from the macaque brain. By integrating these data with genomic sequence features and extending and improving a state-of-the-art TSS prediction algorithm, we ab initio predicted and verified 17,933 of previously electronically annotated TSSs at 500-bp resolution. We also predicted approximately 10,000 novel TSSs. These provide an important rich resource for close examination of the species-specific transcript structures and transcription regulations in the Rhesus macaque genome. Our approach exemplifies a relatively inexpensive way to generate a reasonably reliable TSS map for a large genome. It may serve as a guiding example for similar genome annotation efforts targeted at other model organisms.

  11. SHIV-162P3 infection of rhesus macaques given maraviroc gel vaginally does not involve resistant viruses.

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    Athe M N Tsibris

    Full Text Available Maraviroc (MVC gels are effective at protecting rhesus macaques from vaginal SHIV transmission, but breakthrough infections can occur. To determine the effects of a vaginal MVC gel on infecting SHIV populations in a macaque model, we analyzed plasma samples from three rhesus macaques that received a MVC vaginal gel (day 0 but became infected after high-dose SHIV-162P3 vaginal challenge. Two infected macaques that received a placebo gel served as controls. The infecting SHIV-162P3 stock had an overall mean genetic distance of 0.294±0.027%; limited entropy changes were noted across the envelope (gp160. No envelope mutations were observed consistently in viruses isolated from infected macaques at days 14-21, the time of first detectable viremia, nor selected at later time points, days 42-70. No statistically significant differences in MVC susceptibilities were observed between the SHIV inoculum (50% inhibitory concentration [IC(50] 1.87 nM and virus isolated from the three MVC-treated macaques (MVC IC(50 1.18 nM, 1.69 nM, and 1.53 nM, respectively. Highlighter plot analyses suggested that infection was established in each MVC-treated animal by one founder virus genotype. The expected Poisson distribution of pairwise Hamming Distance frequency counts was observed and a phylogenetic analysis did not identify infections with distinct lineages from the challenge stock. These data suggest that breakthrough infections most likely result from incomplete viral inhibition and not the selection of MVC-resistant variants.

  12. Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model.

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    Engelmann, Flora; Josset, Laurence; Girke, Thomas; Park, Byung; Barron, Alex; Dewane, Jesse; Hammarlund, Erika; Lewis, Anne; Axthelm, Michael K; Slifka, Mark K; Messaoudi, Ilhem

    2014-01-01

    Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure. Unvaccinated populations experience 20 to 50% fatality. Few studies have examined the pathophysiological changes that occur in humans during YFV infection due to the sporadic nature and remote locations of outbreaks. Rhesus macaques are highly susceptible to YFV infection, providing a robust animal model to investigate host-pathogen interactions. In this study, we characterized disease progression as well as alterations in immune system homeostasis, cytokine production and gene expression in rhesus macaques infected with the virulent YFV strain DakH1279 (YFV-DakH1279). Following infection, YFV-DakH1279 replicated to high titers resulting in viscerotropic disease with ∼72% mortality. Data presented in this manuscript demonstrate for the first time that lethal YFV infection results in profound lymphopenia that precedes the hallmark changes in liver enzymes and that although tissue damage was noted in liver, kidneys, and lymphoid tissues, viral antigen was only detected in the liver. These observations suggest that additional tissue damage could be due to indirect effects of viral replication. Indeed, circulating levels of several cytokines peaked shortly before euthanasia. Our study also includes the first description of YFV-DakH1279-induced changes in gene expression within peripheral blood mononuclear cells 3 days post-infection prior to any clinical signs. These data show that infection with wild type YFV-DakH1279 or live-attenuated vaccine strain YFV-17D, resulted in 765 and 46 differentially expressed genes (DEGs), respectively. DEGs detected after YFV-17D infection were mostly associated with innate immunity, whereas YFV-DakH1279 infection resulted in dysregulation of genes associated with the development of immune response, ion metabolism, and apoptosis. Therefore, WT-YFV infection

  13. Factors affecting aggression among females in captive groups of rhesus macaques (Macaca mulatta).

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    Beisner, Brianne A; Isbell, Lynne A

    2011-11-01

    Captive groups of primates often exhibit higher rates of aggression than wild, free-ranging groups. It is important to determine which factors influence aggression in captivity because aggression, particularly intense aggression, can be harmful to animal health and well-being. In this study, we investigated the effect of ground substrate as well as season, rank, age, and group size on rates of agonistic interactions per female in seven captive groups of rhesus macaques (n = 70 females, 1,723 focal samples) at the California National Primate Research Center. Agonistic interactions were divided into three categories: displacements, mild aggression, and intense aggression. Females living in enclosures with gravel substrate were 1.7 times more likely to be involved in intense aggression (e.g. chases and physical contact) than females living in enclosures with grass (Poisson regression model: P females were at least 1.3 times more likely to be involved in mild (e.g. threats and lunges) aggression than lower-ranking females (low rank: P = 0.03; mid rank: P = 0.001). Females of all ranks were 1.5-1.9 times more likely to be involved in both intense and mild aggression during the breeding season than other seasons. Age and group size did not affect rates of mild or intense aggression. These findings indicate that although some aggression appears to be natural and unavoidable, i.e. aggression during the breeding season, the well-being of captive macaques can be improved by developing grass substrate in outdoor enclosures.

  14. Factors increasing snake detection and perceived threat in captive rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Etting, Stephanie F; Isbell, Lynne A; Grote, Mark N

    2014-02-01

    The primary predators of primates are all ambush hunters, and yet felids, raptors, and snakes differ in aspects of their ecology that affect the evasive strategies of their primate prey. Felids and raptors can traverse long distances quickly, thus the urgency of threat they present increases as they come closer in proximity to primates. In contrast, snakes do not move rapidly over long distances, and so primates may be reasonably safe even at close distances provided snakes can be detected and monitored. We investigated the ability of captive rhesus macaques (Macaca mulatta) to detect snakes at distances ranging from 15 to 1.5 m. We also examined variation in intensity of perceived threat by applying a Hidden Markov Model to infer changes in underlying state from observable behaviors, that is, increased attention and mobbing. We found that the macaques often failed to detect snake models but that closer proximity improved snake detection, which is necessary before threat can be perceived. We also found that having only one individual in fairly close proximity (≤ 7.5 m) was sufficient to alert the rest of the group and so the chances of detection did not increase with increasing group size. Finally, we found that when the snakes were perceived, they did not elicit greater intensity of response with closer proximity. These results provide evidence that the threat from snakes is greatest when they are in proximity to primates but are unseen. When snakes are seen, however, distance appears not to affect primates' perceived risk, in contrast to their perceived risk from raptors and felids.

  15. In captive rhesus macaques, cervicovaginal inflammation is common but not associated with the stable polymicrobial microbiome.

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    Gregory Spear

    Full Text Available Vaginal inoculation of rhesus macaques (RM with simian immunodeficiency virus (SIV has been used to study the biology of HIV transmission. Although the results of vaginal SIV transmission experiments could be affected by vaginal inflammation, studies to date have been conducted without regard to levels of pre-existing genital inflammation present in RM. We collected cevicovaginal secretions (CVS from 33-36 RM during the mid menstrual cycle (day 10-20 at 2 time points approximately 8 months apart and characterized the mRNA and protein levels of inflammatory cytokines, chemokines and interferon-stimulated genes. There was extreme variability in the levels of inflammatory mediators (IFN-α, IFN-γ, IL-6, TNF, IL-1b, IP-10, MIG, IL-12 and IL-17. In most animals, the mRNA levels of the inflammatory mediators were similar in the 2 CVS samples collected 8 months apart, suggesting that genital inflammation is stable in a subset of captive female RM. At both time points the cervicovaginal microbiota had low levels of Lactobacillus and was relatively diverse with an average of 13 genera in the samples from the first time point (median 13, range 7-21 and an average of 11.5 genera in the samples from the second time point (median 11, range 5-20. Many of the macaques had similar microbiota in the samples collected 8 months apart. However, we found no correlation between specific bacterial genera and the mRNA or protein levels of the inflammatory mediators in the genital tract of RM in this study. It seems likely that results of published vaginal SIV transmission experiments in RM have been influenced by pre-existing inflammation in the animals used for the experiments.

  16. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques.

    Science.gov (United States)

    Falzarano, Darryl; de Wit, Emmie; Rasmussen, Angela L; Feldmann, Friederike; Okumura, Atsushi; Scott, Dana P; Brining, Doug; Bushmaker, Trenton; Martellaro, Cynthia; Baseler, Laura; Benecke, Arndt G; Katze, Michael G; Munster, Vincent J; Feldmann, Heinz

    2013-10-01

    The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. Therapeutic interventions have not been evaluated in vivo; thus, patient management relies exclusively on supportive care, which, given the high case-fatality rate, is not highly effective. The rhesus macaque is the only known model organism for MERS-CoV infection, developing an acute localized to widespread pneumonia with transient clinical disease that recapitulates mild to moderate human MERS-CoV cases. The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro; therefore, we initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to untreated, infected macaques, treated animals did not develop breathing abnormalities and showed no or very mild radiographic evidence of pneumonia. Moreover, treated animals showed lower levels of systemic (serum) and local (lung) proinflammatory markers, in addition to fewer viral genome copies, distinct gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic for other infections, IFN-α2b and ribavirin should be considered for the management of MERS-CoV cases.

  17. Depressive-like behavioural profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

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    Sandrine MJ Camus

    2014-02-01

    Full Text Available Background: To unravel the causes of major depressive disorder (MDD, the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored.Methods: Behavioural data (including body postures, orientations, gaze directions, inter-individual distances and locations in the cage were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys.Results: Consistent with our previous studies, we found depressive-like characteristics (e.g. inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles.Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a spontaneous model of depressive disorders.

  18. Depressive-like behavioral profiles in captive-bred single- and socially-housed rhesus and cynomolgus macaques: a species comparison

    Science.gov (United States)

    Camus, Sandrine M. J.; Rochais, Céline; Blois-Heulin, Catherine; Li, Qin; Hausberger, Martine; Bezard, Erwan

    2014-01-01

    Background: To unravel the causes of major depressive disorder (MDD), the third leading cause of disease burden around the world, ethological animal models have recently been proposed. Our previous studies highlighted a depressive-like profile among single- and socially-housed farm-bred cynomolgus macaques. Although phylogenetically close, cynomolgus and rhesus macaques, the two most commonly used macaque species in biomedical research, differ on several levels such as patterns of aggression, reconciliation, temperament, or dominance styles. The question of whether one captive macaque species was more vulnerable than another in the development of a pathological profile reminiscent of MDD symptoms was explored. Methods: Behavioral data (including body postures, orientations, gaze directions, inter-individual distances, and locations in the cage) were collected in farming conditions. Using an unbiased validated ethological scan-sampling method, followed by multiple correspondence and hierarchical clustering analyses, 40 single- and 35 socially-housed rhesus macaques were assessed. Independently, for each housing condition, inter-species comparisons were made with previously acquired data on farm-bred cynomolgus monkeys. Results: Consistent with our previous studies, we found depressive-like characteristics (e.g., inactivity, low level of investigation and maintenance, long time spent inactive while facing the wall) among single- and socially-housed rhesus macaques. Species-specificities were reported in non-depressive time budgets and in the prevalence of the pathological profiles. Conclusions: Our results suggest that rhesus may be more vulnerable to developing a despair-like state than cynomolgus macaques, both in single- and in social-housing conditions. Therefore, rhesus macaques are more suitable for use as a “spontaneous” model of depressive disorders. PMID:24600363

  19. The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

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    Yuan Qiaoping

    2012-06-01

    Full Text Available Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction in the macaque is more

  20. Positive Reinforcement Training Moderates Only High Levels of Abnormal Behavior in Singly Housed Rhesus Macaques

    Science.gov (United States)

    Baker, Kate C.; Bloomsmith, Mollie; Neu, Kimberly; Griffis, Caroline; Maloney, Margaret; Oettinger, Brooke; Schoof, Valérie A. M.; Martinez, Marni

    2010-01-01

    This study evaluated the application of positive reinforcement training (PRT) as an intervention for abnormal behaviors in singly housed laboratory rhesus macaques at 2 large primate facilities. Training involved basic control behaviors and body-part presentation. The study compared baseline behavioral data on 30 adult males and 33 adult females compared with 3 treatment phases presented in counterbalanced order: 6 min per week of PRT, 20 or 40 min per week of PRT, and 6 min per week of unstructured human interaction (HI). Within-subject parametric tests detected no main or interaction effects involving experimental phase. However, among a subset of subjects with levels of abnormal in the top quartile of the range (n = 15), abnormal behavior was reduced from 35% to 25% of samples with PRT but not with HI. These results suggest that short durations of PRT applied as enrichment for this species and in this context may not in itself be sufficient intervention for abnormal behavior because levels remained high. However, it may be appropriate as an adjunct to other interventions and may be best targeted to the most severely affected individuals. PMID:20183477

  1. Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

    Institute of Scientific and Technical Information of China (English)

    Houjun Xia; Hongliang Liu; Gaohong Zhang; Yongtang Zheng

    2009-01-01

    Dendritic cells (DCs) play a pivotal role in linking the innate immunity and acquired immunity in responses to pathogen. Non-human primates such as Chinese Rhesus Macaque (CRM) are the favorable models for preclinical study of potential therapeutic drugs, vaccines and mechanisms of human diseases. However, the phenotypicai characterization of monocyte-derived dendritic cells (MDDCs) from CRM has not been elucidated. Monocytes from CRM were cultured with GM-CSF and IL-4 in RPMI-1640. Six days later, these cells were differentiated with typical dendritical morphology. CDllc and DC-SIGN were highly expressed. The immature MDDCs expressed the low levels of CD25, CD80, CD83, moderate CD40, CD86, and high MHC. After stimulation, the mature MDDCs increased expression of mature molecules CD25 and CD83, co-stimulatory molecules such as CD80, CD86 and CD40, and kept a high level of MHC. The capacity of endocytosis decreased with maturation. The mature MDDCs have strong ability of inducing allogeneic T cell proliferation and producing IL-12. In conclusion, we have characterized the phenotype and ultimate function of MDDCs from CRM for the first time. Cellular & Molecular Immunology. 2009;6(3):159-165.

  2. Paternal relatedness and age proximity regulate social relationships among adult female rhesus macaques.

    Science.gov (United States)

    Widdig, A; Nürnberg, P; Krawczak, M; Streich, W J; Bercovitch, F B

    2001-11-20

    Kin selection promotes the evolution of social behavior that increases the survival and reproductive success of close relatives. Among primates, maternal kinship frequently coincides with a higher frequency of grooming and agonistic aiding, but the extent to which paternal kinship influences adult female social relationships has not yet been investigated. Here, we examine the effect of both maternal and paternal kinship, as well as age proximity, on affiliative interactions among semifree-ranging adult female rhesus macaques, Macaca mulatta. Kinship was assessed by using both microsatellites and DNA-fingerprinting. Our study confirms that the closest affiliative relationships characterize maternal half-sisters. We provide evidence that adult females are significantly more affiliative with paternal half-sisters than with nonkin. Furthermore, paternal kin discrimination was more pronounced among peers than among nonpeers, indicating that age proximity has an additional regulatory effect on affiliative interactions. We propose that kin discrimination among cercopithecine primates emerges from ontogenetic processes that involve phenotype matching based on shared behavioral traits, such as inherited personality profiles, rather than physiological or physical characteristics.

  3. Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues

    Science.gov (United States)

    Hirsch, Alec J.; Smith, Jessica L.; Parkins, Christopher J.; Kreklywich, Craig; DeFilippis, Victor R.; Denton, Michael; Smith, Patricia P.; Messer, William B.; Colgin, Lois M. A.; Ducore, Rebecca M.; Grigsby, Peta L.; Hennebold, Jon D.; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael K.; MacAllister, Rhonda; Nelson, Jay A.; Streblow, Daniel N.

    2017-01-01

    Zika virus (ZIKV), an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1–7 days post infection (dpi) that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission. PMID:28278237

  4. Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques.

    Science.gov (United States)

    Ewers, Evan C; Pratt, William D; Twenhafel, Nancy A; Shamblin, Joshua; Donnelly, Ginger; Esham, Heather; Wlazlowski, Carly; Johnson, Joshua C; Botto, Miriam; Hensley, Lisa E; Goff, Arthur J

    2016-03-30

    Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule-a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.

  5. Surrogate mobility and orientation affect the early neurobehavioral development of infant rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Dettmer, Amanda M; Ruggiero, Angela M; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2008-05-01

    A biological mother's movement appears necessary for optimal development in infant monkeys. However, nursery-reared monkeys are typically provided with inanimate surrogate mothers that move very little. The purpose of this study was to evaluate the effects of a novel, highly mobile surrogate mother on motor development, exploration, and reactions to novelty. Six infant rhesus macaques (Macaca mulatta) were reared on mobile hanging surrogates (MS) and compared to six infants reared on standard stationary rocking surrogates (RS) and to 9-15 infants reared with their biological mothers (MR) for early developmental outcome. We predicted that MS infants would develop more similarly to MR infants than RS infants. In neonatal assessments conducted at Day 30, both MS and MR infants showed more highly developed motor activity than RS infants on measures of grasping (p = .009), coordination (p = .038), spontaneous crawl (p = .009), and balance (p = .003). At 2-3 months of age, both MS and MR infants displayed higher levels of exploration in the home cage than RS infants (p = .016). In a novel situation in which only MS and RS infants were tested, MS infants spent less time near their surrogates in the first five minutes of the test session than RS infants (p = .05), indicating a higher level of comfort. Collectively, these results suggest that when nursery-rearing of infant monkeys is necessary, a mobile hanging surrogate may encourage more normative development of gross motor skills and exploratory behavior and may serve as a useful alternative to stationary or rocking surrogates.

  6. Lipopolysaccharide induces immune activation and SIV replication in rhesus macaques of Chinese origin.

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    Rong Bao

    Full Text Available BACKGROUND: Chronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We thus investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV-infected rhesus macaques of Chinese origin. METHODS: The animals were inoculated intravenously with SIVmac239. The levels of plasma viral load and host inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio and systemic immune activation markers were examined by flow cytometric analysis of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels were determined using biochemistry analyzer. The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL test. RESULTS: The animals inoculated with SIVmac239 became infected as evidenced by the increased plasma levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected animals induced a transient increase of plasma SIV RNA and immune activation, which was indicated by the elevated expression of the inflammatory cytokines and CD4+HLA-DR+ T cells in PBMCs. CONCLUSIONS: These data support the concept that LPS is a driving factor in systemic immune activation of HIV disease.

  7. Persistence of Borrelia burgdorferi in rhesus macaques following antibiotic treatment of disseminated infection.

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    Monica E Embers

    Full Text Available The persistence of symptoms in Lyme disease patients following antibiotic therapy, and their causes, continue to be a matter of intense controversy. The studies presented here explore antibiotic efficacy using nonhuman primates. Rhesus macaques were infected with B. burgdorferi and a portion received aggressive antibiotic therapy 4-6 months later. Multiple methods were utilized for detection of residual organisms, including the feeding of lab-reared ticks on monkeys (xenodiagnosis, culture, immunofluorescence and PCR. Antibody responses to the B. burgdorferi-specific C6 diagnostic peptide were measured longitudinally and declined in all treated animals. B. burgdorferi antigen, DNA and RNA were detected in the tissues of treated animals. Finally, small numbers of intact spirochetes were recovered by xenodiagnosis from treated monkeys. These results demonstrate that B. burgdorferi can withstand antibiotic treatment, administered post-dissemination, in a primate host. Though B. burgdorferi is not known to possess resistance mechanisms and is susceptible to the standard antibiotics (doxycycline, ceftriaxone in vitro, it appears to become tolerant post-dissemination in the primate host. This finding raises important questions about the pathogenicity of antibiotic-tolerant persisters and whether or not they can contribute to symptoms post-treatment.

  8. Immunoglobulin VH gene diversity and somatic hypermutation during SIV infection of rhesus macaques.

    Science.gov (United States)

    Guo, Kejun; Halemano, Kalani; Schmitt, Kimberly; Katuwal, Miki; Wang, Yaqiong; Harper, Michael S; Heilman, Karl J; Kuwata, Takeo; Stephens, Edward B; Santiago, Mario L

    2015-07-01

    B cell functional defects are associated with delayed neutralizing antibody development in pathogenic lentivirus infections. However, the timeframe for alterations in the antibody repertoire and somatic hypermutation (SHM) remains unclear. Here, we utilized the SIV/rhesus macaque (RM) model to investigate the dynamics of immunoglobulin V(H) gene diversity and SHM following infection. Three RMs were infected with SIVmac239, and V(H)1, V(H)3, and V(H)4 genes were amplified from peripheral blood at 0, 2, 6, 24, and 36 weeks postinfection for next-generation sequencing. Analysis of over 3.8 million sequences against currently available RM germline V(H) genes revealed a highly biased V(H) gene repertoire in outbred RMs. SIV infection did not significantly perturb the predominant IgG1 response, but overall immunoglobulin SHM declined during the course of SIV infection. Moreover, SHM at the AID deamination hotspot, WRC, rapidly decreased and was suppressed throughout SIV infection. In contrast, a transient increase in mutations at the APOBEC3G deamination hotspot, CCC, coincided with a spike in APOBEC3G expression during acute SIV infection. The results outline a timetable for altered V(H) gene repertoire and IgG SHM in the SIV/RM model and suggest a burst of APOBEC3G-mediated antibody SHM during acute SIV infection.

  9. Training pair-housed Rhesus macaques (Macaca mulatta) using a combination of negative and positive reinforcement.

    Science.gov (United States)

    Wergård, Eva-Marie; Temrin, Hans; Forkman, Björn; Spångberg, Mats; Fredlund, Hélène; Westlund, Karolina

    2015-04-01

    When training animals, time is sometimes a limiting factor hampering the use of positive reinforcement training (PRT) exclusively. The aim of this study was to evaluate the effects of a combination of negative and positive reinforcement training (NPRT). Twenty naïve female Rhesus macaques (Macaca mulatta) were trained in 30 sessions with either PRT (n=8) or NPRT (n=12) to respond to a signal, move into a selected cage section and accept confinement. In the NPRT-group a signal preceded the presentation of one or several novel, and thus aversive, stimuli. When the correct behaviour was performed, the novel stimulus was removed and treats were given. As the animal learned to perform the correct behaviour, the use of novel stimuli was decreased and finally phased out completely. None of the PRT-trained animals finished the task. Ten out of 12 monkeys in the NPRT-group succeeded to perform the task within the 30 training sessions, a significant difference from the PRT-group (p=0.0007). A modified approach test showed no significant difference between the groups (p=0.67) in how they reacted to the trainer. The results from this study suggest that carefully conducted NPRT can be an alternative training method to consider, especially when under a time constraint.

  10. The use of positive reinforcement training to reduce stereotypic behavior in rhesus macaques.

    Science.gov (United States)

    Coleman, Kristine; Maier, Adriane

    2010-05-01

    Stereotypic behavior is a pervasive problem for captive monkeys and other animals. Once this behavior pattern has started, it can be difficult to alleviate. We tested whether or not using positive reinforcement training (PRT) can reduce this undesired behavior. Subjects for this study were 11 adult, female rhesus macaques (Macaca mulatta) with a history of locomotor stereotypy (e.g., pacing, bouncing, and somersaulting). We assessed baseline levels of stereotypic behavior and then utilized PRT to train six animals to touch a target and accept venipuncture. The other five monkeys served as controls. We assessed stereotypic behavior 1 week a month for 4 months, on days in which the monkey was not trained. Trained animals showed a significant reduction in stereotypic behavior after 1 month of training, compared to control monkeys (Mann Whitney U=28.00, P=0.02). These group differences did not persist after the first month (Month 2: Mann Whitney U=19.50, P=0.40, Month 3: Mann Whitney U=17.0, P=0.71, Month 4: Mann Whitney U=17.00, P=0.72). Still, the majority of the trained monkeys (n=4) engaged in less stereotypic behavior at the end of the study compared to baseline. Thus, training may be an effective way to reduce stereotypic behavior, at least for some individuals.

  11. Positive reinforcement training in rhesus macaques-training progress as a result of training frequency.

    Science.gov (United States)

    Fernström, A-L; Fredlund, H; Spångberg, M; Westlund, K

    2009-05-01

    Positive reinforcement training (PRT) efficiency was examined as a function of training frequency in 33 pair- or triple-housed female rhesus macaques. The animals were trained three times a week, once a day or twice a day, using PRT and a clicker as a secondary reinforcer. All animals were trained on 30 sessions, with an average of 5 min per training session per animal. The behaviors, trained in succession, were Targeting (reliably touching and following a Target); Collaborating (dominant animals allowing subordinates to train while stationing); Box-training (accepting being enclosed in a small compartment while responding to Target training) and initial Injection training.Fulfilled criteria for Targeting were obtained in 32/33 animals in a median of nine training sessions. Collaboration was obtained in 27/33 animals in a median of 15 training sessions. However, only four animals completed Box-training during the 30 training sessions and started Injection training. When comparing training success in terms of number of training sessions, training twice a day was less efficient than the other two treatments. In terms of daily progress, our results suggest that from a management perspective, daily training is more conducive to quick training success than thrice weekly training. In addition, in this study no further advantages could be gained from training twice a day.

  12. Positive reinforcement training moderates only high levels of abnormal behavior in singly housed rhesus macaques.

    Science.gov (United States)

    Baker, Kate C; Bloomsmith, Mollie; Neu, Kimberly; Griffis, Caroline; Maloney, Margaret; Oettinger, Brooke; Schoof, Valerie A M; Martinez, Marni

    2009-01-01

    This study evaluated the application of positive reinforcement training (PRT) as an intervention for abnormal behaviors in singly housed laboratory rhesus macaques at 2 large primate facilities. Training involved basic control behaviors and body-part presentation. The study compared baseline behavioral data on 30 adult males and 33 adult females compared with 3 treatment phases presented in counterbalanced order: 6 min per week of PRT, 20 or 40 min per week of PRT, and 6 min per week of unstructured human interaction (HI). Within-subject parametric tests detected no main or interaction effects involving experimental phase. However, among a subset of subjects with levels of abnormal in the top quartile of the range (n = 15), abnormal behavior was reduced from 35% to 25% of samples with PRT but not with HI. These results suggest that short durations of PRT applied as enrichment for this species and in this context may not in itself be sufficient intervention for abnormal behavior because levels remained high. However, it may be appropriate as an adjunct to other interventions and may be best targeted to the most severely affected individuals.

  13. Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

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    Félicien Moukambi

    2015-12-01

    Full Text Available Follicular T helper cells (Tfh, a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies.

  14. Personality Traits in Rhesus Macaques (Macaca mulatta) Are Heritable but Do Not Predict Reproductive Output.

    Science.gov (United States)

    Brent, Lauren J N; Semple, Stuart; Maclarnon, Ann; Ruiz-Lambides, Angelina; Gonzalez-Martinez, Janis; Platt, Michael L

    2014-02-01

    There is growing evidence that behavioral tendencies, or "personalities," in animals are an important aspect of their biology, yet their evolutionary basis is poorly understood. Specifically, how individual variation in personality arises and is subsequently maintained by selection remains unclear. To address this gap, studies of personality require explicit incorporation of genetic information. Here, we explored the genetic basis of personality in rhesus macaques by determining the heritability of personality components and by examining the fitness consequences of those components. We collected observational data for 108 adult females living in three social groups in a free-ranging population via focal animal sampling. We applied principal component analysis to nine spontaneously occurring behaviors and identified six putative personality components, which we named Meek, Bold, Aggressive, Passive, Loner, and Nervous. All components were repeatable and heritable, with heritability estimates ranging from 0.14 to 0.35. We found no evidence of an association with reproductive output, measured either by infant survival or by interbirth interval, for any of the personality components. This finding suggests either that personality does not have fitness-related consequences in this population or that selection has acted to reduce fitness-associated variation in personality.

  15. The development of an instrument to measure global dimensions of maternal care in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    McCormack, K; Howell, B R; Guzman, D; Villongco, C; Pears, K; Kim, H; Gunnar, M R; Sanchez, M M

    2015-01-01

    One of the strongest predictors of healthy child development is the quality of maternal care. Although many measures of observation and self-report exist in humans to assess global aspects of maternal care, such qualitative measures are lacking in nonhuman primates. In this study, we developed an instrument to measure global aspects of maternal care in rhesus monkeys, with the goal of complementing the individual behavioral data collected using a well-established rhesus macaque ethogram during the first months postpartum. The 22 items of the instrument were adapted from human maternal sensitivity assessments and a maternal Q-sort instrument already published for macaques. The 22 items formed four dimensions with high levels of internal reliability that represented major constructs of maternal care: (1) Sensitivity/Responsivity, (2) Protectiveness, (3) Permissiveness, and (4) Irritability. These dimensions yielded high construct validity when correlated with mother-infant frequency and duration behavior that was collected from focal observations across the first 3 postnatal months. In addition, comparisons of two groups of mothers (Maltreating vs. Competent mothers) showed significant differences across the dimensions suggesting that this instrument has strong concurrent validity, even after controlling for focal observation variables that have been previously shown to significantly differentiate these groups. Our findings suggest that this Instrument of Macaque Maternal Care has the potential to capture global aspects of the mother-infant relationship that complement individual behaviors collected through focal observations.

  16. Adapting to Florida's riverine woodlands: the population status and feeding ecology of the Silver River rhesus macaques and their interface with humans.

    Science.gov (United States)

    Riley, Erin P; Wade, Tiffany W

    2016-04-01

    The study of primates living in novel environments represents an interesting context in which to examine patterns of behavioral and ecological flexibility. Our research focused on an understudied, anthropogenically introduced primate population living in Florida, USA: the Silver River rhesus macaques (Macaca mulatta). To better understand how this population has adapted to life in Florida's riparian woodlands, we collected data on the diet and size of the rhesus macaque population and its encounters with boaters along the Silver River from January to May 2013. Using scan sampling and all-occurrences sampling, we collected 166 h of diet data and 105 h of human-macaque encounter data, respectively. We confirmed previous reports that four social groups comprise the Silver River macaque population, totaling 118 individuals. The Silver River macaques predominantly consumed leaves and other vegetative plant parts (87.5 %), with ash trees serving as a staple food (66.5 % of feeding records). Although human-macaque encounters were frequent (80 % of 611 boats observed), only a small proportion of boats (11.5 %) provisioned the macaques. Motorized boats (e.g., pontoon and motor boats) were more likely to provision, while kayaks and canoes were more likely to move in close proximity of the macaques situated at the river's edge. Our results indicate that the Silver River macaques have adjusted to life in the New World by adopting a temperate-dwelling feeding strategy and by incorporating locally available foods (e.g., sedges) into their diet. They have also learned that the river's edge provides opportunities to receive provisions from boaters. However, because the rate of provisioning is low, these foods likely play a filler fallback role. Given that provisioning and direct contact between macaques and boaters are infrequent but proximity to the macaques is a concern, our findings have important implications for the management of the human-macaque interface along the

  17. Pathological findings and diagnostic implications of a rhesus macaque (Macacca mulatta) model of aerosol exposure to Burkholderia mallei (glanders).

    Science.gov (United States)

    Yingst, Samuel L; Facemire, Paul; Chuvala, Lara; Norwood, David; Wolcott, Mark; Huzella, Louis

    2015-06-01

    Burkholderia mallei is a Gram-negative bacillus that causes a pneumonic disease known as glanders in equids and humans, and a lymphatic infection known as farcy, primarily in equids. With the potential to infect humans by the respiratory route, aerosol exposure can result in severe, occasionally fatal, pneumonia. Today, glanders infections in humans are rare, likely due to less frequent contact with infected equids than in the past. Acutely ill humans often have non-specific clinical signs and in order to diagnose cases, especially in scenarios of multiple cases in an unexpected setting, rapid diagnostics for B. mallei may be critical. The pathogenesis of acute glanders in the rhesus macaque (Macaca mulatta) was studied as an initial effort to improve diagnostic methods. In the study described here, the diagnostic techniques of PCR, culture and histopathology were compared. The results indicated that PCR may provide rapid, non-invasive diagnosis of glanders in some cases. As expected, PCR results were positive in lung tissue in 11/12 acutely infected rhesus macaques, but more importantly in terms of diagnostic algorithm development, PCR results were frequently positive in non-invasive samples such as broncho-alveolar lavage or nasal swabs (7/12) and occasionally in blood (3/12). However, conventional bacterial culture failed to recover bacteria in many of these samples. The study showed that the clinical presentation of aerosol-exposed rhesus macaques is similar to descriptions of human glanders and that PCR has potential for rapid diagnosis of outbreaks, if not individual cases.

  18. Monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions.

    Directory of Open Access Journals (Sweden)

    Haifeng Song

    Full Text Available Natural killer (NK cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV infection is not well characterized. In this intravenous challenge study of MPXV infection in rhesus macaques (Macaca mulatta, we analyzed blood and lymph node NK cell changes in absolute cell numbers, cell proliferation, chemokine receptor expression, and cellular functions. Our results showed that the absolute number of total NK cells in the blood increased in response to MPXV infection at a magnitude of 23-fold, manifested by increases in CD56+, CD16+, CD16-CD56- double negative, and CD16+CD56+ double positive NK cell subsets. Similarly, the frequency and NK cell numbers in the lymph nodes also largely increased with the total NK cell number increasing 46.1-fold. NK cells both in the blood and lymph nodes massively proliferated in response to MPXV infection as measured by Ki67 expression. Chemokine receptor analysis revealed reduced expression of CXCR3, CCR7, and CCR6 on NK cells at early time points (days 2 and 4 after virus inoculation, followed by an increased expression of CXCR3 and CCR5 at later time points (days 7-8 of infection. In addition, MPXV infection impaired NK cell degranulation and ablated secretion of interferon-γ and tumor necrosis factor-α. Our data suggest a dynamic model by which NK cells respond to MPXV infection of rhesus macaques. Upon virus infection, NK cells proliferated robustly, resulting in massive increases in NK cell numbers. However, the migrating capacity of NK cells to tissues at early time points might be reduced, and the functions of cytotoxicity and cytokine secretion were largely compromised. Collectively, the data may explain, at least partially, the pathogenesis of MPXV infection in rhesus macaques.

  19. Risk factor analysis may provide clues to diarrhea prevention in outdoor-housed rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Prongay, Kamm; Park, Byung; Murphy, Stephanie J

    2013-08-01

    Seventy-five percent of rhesus macaques at national primate research centers are housed outside. Annually, 15-39% of these animals experience diarrhea and require veterinary treatment for dehydration, electrolyte imbalance, or weight loss. An estimated 21-33% of these patients will die or be euthanized. Many studies have explored the various infectious etiologies of non-human primate diarrhea. However, there is little published information on diarrhea incidence rates and risk factors in outdoor-housed rhesus macaques. Without this information, it is challenging to determine endemic and epidemic diarrhea levels, or to develop and evaluate mitigation strategies. Using electronic medical records, we conducted a retrospective cohort study to calculate diarrhea incidence rates for rhesus macaques (N = 3,181) housed in three different outdoor housing types (corrals, shelters, and temporary housing) at the Oregon National Primate Research Center between November 1, 2009 and October 31, 2010. With multiple logistic regression analysis, we determined the relative risk of housing type, sex, and age on development of diarrhea. Diarrhea incidence and mortality in our population was lower than many published ranges. Type of outdoor housing, age, and previous diarrhea episode were positively correlated with diarrhea risk. Younger animals in smaller shelters and temporary housing had a greater risk of acquiring diarrhea, with juvenile animals (0.7-3.9 years) having the highest mortality rate. Sex was not a risk factor, but adult females with diarrhea were more likely to develop life-threatening complications than adult males. We also constructed a predictive model for diarrhea-associated mortality using Classification and Regression Tree. Findings from this study will be used to develop and evaluate mitigation strategies in our outdoor-housed population and to provide a foundation for genetic susceptibility and immune function testing.

  20. Medicinal management of corneal opacity in free ranging rhesus macaques (Macaca mulatta of Shivalik hills in Western Himalayas, Northern India

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    V. Kumar

    2015-05-01

    Full Text Available Corneal opacification was diagnosed in 17 free ranging rhesus macaques during detailed ophthalmic examination as a part of clinical health examination, at the monkey rescue sterilization centre in Hamirpur Himachal Pradesh, India. The cornea was completely opaque permitting only a little vision with respect to the affected eye. Medical management with topical ciprofloxacin and prednisolone along with ketoprofen and vitamin A was instituted. The corneal lesions subsided completely within one week following treatment. The treatment protocol successfully eliminated the discomfort and intraocular lesions with no serious subsequent irritation due to the treatment in these animals.

  1. Transplantation of adult monkey neural stem cells into a contusion spinal cord injury model in rhesus macaque monkeys

    DEFF Research Database (Denmark)

    Nemati, Shiva Nemati; Jabbari, Reza; Hajinasrollah, Mostafa

    2014-01-01

    , therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. MATERIALS AND METHODS: In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model...... on Tarlov's scale and our established behavioral tests for monkeys. CONCLUSION: Our findings have indicated that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque monkeys. Additional studies are necessary to determine the im- provement mechanisms after cell transplantation....

  2. Facial paralysis and lymphocytic facial neuritis in a rhesus macaque (Macaca mulatta) positive for simian retrovirus type D2.

    Science.gov (United States)

    Hampton, Anna L; Colby, Lesley A; Bergin, Ingrid L

    2011-12-01

    Simian retrovirus type D (SRVD) is a naturally occurring betaretrovirus in nonhuman primates of the genus Macaca. Infection can lead to a variety of clinical, hematologic, and histopathologic abnormalities. We report an unusual clinical presentation of facial paralysis and histologic lymphocytic neuritis in an SRVD type 2 (SRVD2)-infected rhesus macaque (Macaca mulatta) with a catheter-associated vena caval thrombus, anemia, thrombocytopenia, and multisystemic lymphoid hyperplasia. At initial presentation, a right atrial mass was detected by echocardiography. The macaque was clinically asymptomatic but had persistent anemia, thrombocytopenia, hyperglobulinemia, and later neutropenia. It was seropositive for SRV and PCR-positive for SRVD 2. Approximately 1 mo after initial presentation, the macaque developed right facial paralysis and was euthanized. Histologic lesions included lymphoplasmacytic aggregates affecting multiple organs, consistent with SRV-related lymphoid hyperplasia. The right facial nerve showed lymphoplasmacytic inflammation. The nerve itself was negative immunohistochemically for SRV antigen, but antigen was present infrequently in pericapillary lymphoid cells within the facial nerve and abundantly within lymphoid aggregates in the adjacent parotid salivary gland, bone marrow, and soft tissue. Known neurotropic viruses could not be identified. Given the widespread inflammation in this macaque, particularly in the area surrounding the facial nerve, lymphocytic neuritis and facial paralysis likely were an indirect effect of SRV infection due to local extension of SRV-related inflammation in the surrounding tissue.

  3. Specific anti-glycan antibodies are sustained during and after parasite clearance in Schistosoma japonicum-infected rhesus macaques

    Science.gov (United States)

    Yang, Y. Y. Michelle; Li, Xiao Hong; Brzezicka, Katarzyna; Reichardt, Niels-Christian; Wilson, R. Alan; van Diepen, Angela

    2017-01-01

    Background Human immunity to Schistosoma infection requires many years of exposure, and multiple infections and treatments to develop. Unlike humans, rhesus macaques clear an established schistosome infection naturally at the same time acquiring immunity towards re-infection. In macaques, schistosome egg production decreases after 8 weeks post-infection and by week 22, physiological impairment of the worm caused by unclarified antibody-mediated processes is observed. Since strong antibody responses have been observed against schistosome glycan antigens in human and animal infections, we here investigate if anti-glycan antibodies are associated with immunity against schistosome infections in macaques. Methods We used a microarray containing a large repertoire of glycoprotein- and glycolipid-derived glycans from different schistosome life stages to analyse anti-glycan serum IgG and IgM from S. japonicum-infected macaques during the course of infection and self-cure. We also used an in vitro schistosomula assay to investigate whether macaque sera containing anti-glycan antibodies can kill schistosomula. Conclusions/significance Antibody responses towards schistosome glycans at week 4 post-infection were dominated by IgM while IgG was high at week 8. The profound increase in IgG was observed mainly for antibodies towards a large subset of glycans that contain (multi-)fucosylated terminal GalNAcβ1-4GlcNAc (LDN), and Galβ1-4(Fucα1–3)GlcNAc (LeX) motifs. In general, glycans with a higher degree of fucosylation gave rise to stronger antibody responses than non-fucosylated glycans. Interestingly, even though many IgG and IgM responses had declined by week 22 post-infection, IgG towards O-glycans with highly fucosylated LDN motifs remained. When incubating macaque serum with schistosomula in vitro, schistosomula death was positively correlated with the duration of infection of macaques; macaque serum taken 22 weeks post-infection caused most schistosomula to die

  4. Plasma cortisol responses to stress in lactating and nonlactating female rhesus macaques.

    Science.gov (United States)

    Maestripieri, Dario; Hoffman, Christy L; Fulks, Richelle; Gerald, Melissa S

    2008-01-01

    Lactating female rats without their pups exhibit lower HPA responsiveness to stress than nonlactating females. However, responsiveness to stress is similar when lactating females are tested with their pups and the stressor involves a potential threat to the offspring. This study constitutes the first comparison of stress responsiveness in lactating and nonlactating female nonhuman primates. Subjects were 53 multiparous female free-ranging rhesus macaques. Approximately half of the females were lactating and half were nonpregnant/nonlactating. Blood samples were obtained after capture and after overnight housing in an individual cage. Lactating females were tested with their infants. Lactating females had significantly higher plasma cortisol levels than nonlactating females on both days. Having or not having an infant was also a better predictor of plasma cortisol levels among all females than their age, dominance rank, group of origin, time of day at which the sample was obtained, and time elapsed since beginning of the sampling procedure or since anesthesia. Plasma cortisol levels of lactating females were not significantly correlated with post-partum stage or with the cortisol levels of their infants. Capture, handling, and individual housing in a cage are powerful psychological stressors for free-ranging primates. We suggest that the higher plasma cortisol levels exhibited by lactating females reflect greater responsiveness to stress associated with perception of risks to infants. Hyporesponsiveness to stress may not be a general characteristic of lactation in all mammalian species, but a short-term effect of infant suckling that is most apparent with stressors unrelated to the offspring.

  5. Does Male Care, Provided to Immature Individuals, Influence Immature Fitness in Rhesus Macaques?

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    Doreen Langos

    Full Text Available Among many mammals, maternal care strongly impacts infant survival; however, less is known about whether adult males also affect infant fitness. Paternal care is expected when providing care enhances offspring survival and reproduction, which likewise increases fathers' fitness. Males might also care for unrelated immature individuals to increase their mating probability with the immature individuals' mothers. Studies in multimale primate groups showed that sires enhance food access for offspring and provide protection in conflicts. Furthermore, fathers' presence during infancy has been suggested to accelerate offspring sexual maturation. However, no study has yet directly linked the degree of father-offspring bonds to offspring fitness in primates. We previously reported father-offspring affiliation in rhesus macaques, pronounced during early infancy and independent of mothers' presence. The present study aims at investigating whether affiliation with fathers or other males affects proxies of immature fitness (body mass gain, body fat and testis size. First, we combined behavioral, genetic and morphometric data from 55 subjects of one group. Second, using demographic and genetic data, we investigated for 92 individuals of the population whether mother- and father-offspring co-residence during immaturity influenced offspring lifetime reproductive success (LRS. Our results show that focal rank and higher amounts of affiliation with high-ranking males during infancy tend to positively impact body mass gain of female, but not male focal animals. In contrast, body mass gain of male focal individuals, but not females', appeared to be higher when affiliation of male immature individuals was evenly distributed across their adult male partners. Moreover, we found mothers', but not fathers', presence during immaturity to predict offspring LRS. Our results suggest that male-immature affiliation, but not father-offspring co-residence, potentially impacts

  6. Th1-skewed tissue responses to a mycolyl glycolipid in mycobacteria-infected rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Daisuke; Miyamoto, Ayumi; Hattori, Yuki; Komori, Takaya [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Nakamura, Takashi [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Igarashi, Tatsuhiko, E-mail: tigarash@virus.kyoto-u.ac.jp [Laboratory of Primate Model, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Harashima, Hideyoshi, E-mail: harasima@pharm.hokudai.ac.jp [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Sugita, Masahiko, E-mail: msugita@virus.kyoto-u.ac.jp [Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan)

    2013-11-08

    Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cell responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection.

  7. Comprehensive analysis and selection of anthrax vaccine adsorbed immune correlates of protection in rhesus macaques.

    Science.gov (United States)

    Chen, Ligong; Schiffer, Jarad M; Dalton, Shannon; Sabourin, Carol L; Niemuth, Nancy A; Plikaytis, Brian D; Quinn, Conrad P

    2014-11-01

    Humoral and cell-mediated immune correlates of protection (COP) for inhalation anthrax in a rhesus macaque (Macaca mulatta) model were determined. The immunological and survival data were from 114 vaccinated and 23 control animals exposed to Bacillus anthracis spores at 12, 30, or 52 months after the first vaccination. The vaccinated animals received a 3-dose intramuscular priming series (3-i.m.) of anthrax vaccine adsorbed (AVA) (BioThrax) at 0, 1, and 6 months. The immune responses were modulated by administering a range of vaccine dilutions. Together with the vaccine dilution dose and interval between the first vaccination and challenge, each of 80 immune response variables to anthrax toxin protective antigen (PA) at every available study time point was analyzed as a potential COP by logistic regression penalized by least absolute shrinkage and selection operator (LASSO) or elastic net. The anti-PA IgG level at the last available time point before challenge (last) and lymphocyte stimulation index (SI) at months 2 and 6 were identified consistently as a COP. Anti-PA IgG levels and lethal toxin neutralization activity (TNA) at months 6 and 7 (peak) and the frequency of gamma interferon (IFN-γ)-secreting cells at month 6 also had statistically significant positive correlations with survival. The ratio of interleukin 4 (IL-4) mRNA to IFN-γ mRNA at month 6 also had a statistically significant negative correlation with survival. TNA had lower accuracy as a COP than did anti-PA IgG response. Following the 3-i.m. priming with AVA, the anti-PA IgG responses at the time of exposure or at month 7 were practicable and accurate metrics for correlating vaccine-induced immunity with protection against inhalation anthrax.

  8. Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation.

    Science.gov (United States)

    Farese, Ann M; Hankey, Kim G; Cohen, Melanie Veirs; MacVittie, Thomas J

    2015-11-01

    Recovery from severe immunosuppression requires hematopoietic stem cell reconstitution and effective thymopoiesis to restore a functional immune cell repertoire. Herein, a model of immune cell reconstitution consequent to potentially lethal doses of irradiation is described, which may be valuable in evaluating potential medical countermeasures. Male rhesus macaques were total body irradiated by exposure to 6.00 Gy 250 kVp x-radiation (midline tissue dose, 0.13 Gy min), resulting in an approximate LD10/60 (n = 5/59). Animals received medical management, and hematopoietic and immune cell recovery was assessed (n ≤ 14) through 370 d post exposure. A subset of animals (n ≤ 8) was examined through 700 d. Myeloid recovery was assessed by neutrophil and platelet-related parameters. Lymphoid recovery was assessed by the absolute lymphocyte count and FACS-based phenotyping of B- and T-cell subsets. Recent thymic emigrants were identified by T cell receptor excision circle quantification. Severe neutropenia, lymphopenia, and thrombocytopenia resolved within 30 d. Total CD3+ cells μL required 60 d to reach values 60% of normal, followed by subsequent slow recovery to approximately normal by 180 d post irradiation. Recovery of CD3+4+ and CD3+8+ cell memory and naïve subsets were markedly different. Memory populations were ≥ 100% of normal by day 60, whereas naïve populations were only 57% normal at 180 d and never fully recovered to baseline post irradiation. Total (CD20+) B cells μL were within normal levels by 77 d post exposure. This animal model elucidates the variable T- and B-cell subset recovery kinetics after a potentially lethal dose of total-body irradiation that are dependent on marrow-derived stem and progenitor cell recovery, peripheral homeostatic expansion, and thymopoiesis.

  9. Electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins

    Directory of Open Access Journals (Sweden)

    Katarzyna eBozek

    2012-06-01

    Full Text Available Human immunodeficiency virus type 2 (HIV-2 and simian immunodeficiency virus isolated from a macaque monkey (SIVmac are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (SIVsm. Despite their close similarity in genome structure, HIV-2 and SIVmac show different sensitivities to TRIM5α, a host restriction factor against retroviruses. The replication of HIV-2 strains is potently restricted by rhesus (Rh monkey TRIM5α, while that of SIVmac strain 239 (SIVmac239 is not. Viral capsid protein is the determinant of this differential sensitivity to TRIM5α, as the HIV-2 mutant carrying SIVmac239 capsid protein evaded Rh TRIM5α-mediated restriction. However, the molecular determinants of this restriction mechanism are unknown. Electrostatic potential on the protein-binding site is one of the properties regulating protein-protein interactions. In this study, we investigated the electrostatic potential on the interaction surface of capsid protein of HIV-2 strain GH123 and SIVmac239. Although HIV-2 GH123 and SIVmac239 capsid proteins share more than 87% amino acid identity, we observed a large difference between the two molecules with the HIV-2 GH123 molecule having predominantly positive and SIVmac239 predominantly negative electrostatic potential on the surface of the loop between α-helices 4 and 5 (L4/5. As L4/5 is one of the major determinants of Rh TRIM5α sensitivity of these viruses, the present results suggest that the binding site of the Rh TRIM5α may show complementarity to the HIV-2 GH123 capsid surface charge distribution.

  10. Reproductive efficiency of captive Chinese- and Indian-origin rhesus macaque (Macaca mulatta) females.

    Science.gov (United States)

    Kubisch, H Michael; Falkenstein, Kathrine P; Deroche, Chelsea B; Franke, Donald E

    2012-02-01

    Reproductive and survival records (n=2,913) from 313 Chinese-origin and 365 Indian-derived rhesus macaques at the Tulane National Primate Research Center (TNPRC) spanning three generations were studied. Least-squares analysis of variance procedures were used to compare reproductive and infant survival traits while proportional hazards regression procedures were used to study female age at death, number of infants born per female, and time from last birth to death. Chinese females were older at first parturition than Indian females because they were older when placed with males, but the two subspecies had similar first postpartum birth interval (1st PPBI) and lifetime postpartum birth interval (LPPBI). Females that gave birth to stillborn infants had shorter first postpartum birth intervals (1st PPBI) than females giving birth to live infants. Postpartum birth intervals decreased in females from age 3 to 12 but then increased again with advancing age. Chinese infants had a greater survival rate than Indian infants at 30 days, 6 months, and 1 year of age. Five hundred and forty-three females (80.01%) had uncensored, or true records for age at death, number of infants born per female, and time from the birth until death whereas 135 females (19.91%) had censored records for these traits. Low- and high-uncensored observations for age at death were 3 and 26 years for Chinese, and 3 and 23 years for Indian females. Uncensored number of infants born per female ranged from 1 to 15 for Chinese females and 1 to 18 for Indian females. Each of these traits was significantly influenced by the origin×generation interaction in the proportional hazards regression analyses, indicating that probabilities associated with age at death, number of infants born per female, and time from last birth to death for Chinese and Indian females did not rank the same across generations.

  11. Mapping of a macular drusen susceptibility locus in rhesus macaques to the homologue of human chromosome 6q14-15.

    Science.gov (United States)

    Singh, Krishna K; Ristau, Steven; Dawson, William W; Krawczak, Michael; Schmidtke, Jörg

    2005-10-01

    Rhesus macaques (Macaca mulatta) are a natural model for retinal drusen formation. The present study aimed at clarifying whether chromosomal regions homologous to candidate genes for drusen formation and progression in humans are also associated with a drusen phenotype in rhesus macaques. Some 42 genetic markers from seven chromosomal regions implicated in macular degeneration syndromes in humans were tested for whether they identified homologous, polymorphic sequences in rhesus DNA. This was found to be the case for seven markers, all of which were subsequently screened for the presence of potentially disease-predisposing alleles in 52 randomly chosen adult animals from the Cayo Santiago population of rhesus macaques (Caribbean Primate Research Center, PR, USA). The high drusen prevalence expected in the Cayo Santiago colony was confirmed in our sample in that 38 animals were found to have drusen (73%). Logistic regression analysis revealed that some alleles of the rhesus homologue of anonymous human marker D6S1036 were consistently over-represented among affected animals. Of two candidate genes located in the respective region, allelic variation in one (IMPG1) showed strong association with drusen formation. We conclude that one or more genes located at the rhesus homologue of human 6q14-15 are likely to play a role in retinal drusen formation, a finding that represents a first step towards the identification of genetic factors implicated in macular drusen formation in rhesus macaques. This is an important tool for the separation of genetic and environmental factors which must occur before satisfactory management methods can be developed.

  12. Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans.

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    Ilhem Messaoudi

    2009-11-01

    Full Text Available Simian varicella virus (SVV, the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV. Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation.

  13. Brief communication: MaqFACS: A muscle-based facial movement coding system for the rhesus macaque.

    Science.gov (United States)

    Parr, L A; Waller, B M; Burrows, A M; Gothard, K M; Vick, S J

    2010-12-01

    Over 125 years ago, Charles Darwin (1872) suggested that the only way to fully understand the form and function of human facial expression was to make comparisons with other species. Nevertheless, it has been only recently that facial expressions in humans and related primate species have been compared using systematic, anatomically based techniques. Through this approach, large-scale evolutionary and phylogenetic analyses of facial expressions, including their homology, can now be addressed. Here, the development of a muscular-based system for measuring facial movement in rhesus macaques (Macaca mulatta) is described based on the well-known FACS (Facial Action Coding System) and ChimpFACS. These systems describe facial movement according to the action of the underlying facial musculature, which is highly conserved across primates. The coding systems are standardized; thus, their use is comparable across laboratories and study populations. In the development of MaqFACS, several species differences in the facial movement repertoire of rhesus macaques were observed in comparison with chimpanzees and humans, particularly with regard to brow movements, puckering of the lips, and ear movements. These differences do not seem to be the result of constraints imposed by morphological differences in the facial structure of these three species. It is more likely that they reflect unique specializations in the communicative repertoire of each species.

  14. A semi-automated pipeline for the segmentation of rhesus macaque hippocampus: validation across a wide age range.

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    Michael R Hunsaker

    Full Text Available This report outlines a neuroimaging pipeline that allows a robust, high-throughput, semi-automated, template-based protocol for segmenting the hippocampus in rhesus macaque (Macaca mulatta monkeys ranging from 1 week to 260 weeks of age. The semiautomated component of this approach minimizes user effort while concurrently maximizing the benefit of human expertise by requiring as few as 10 landmarks to be placed on images of each hippocampus to guide registration. Any systematic errors in the normalization process are corrected using a machine-learning algorithm that has been trained by comparing manual and automated segmentations to identify systematic errors. These methods result in high spatial overlap and reliability when compared with the results of manual tracing protocols. They also dramatically reduce the time to acquire data, an important consideration in large-scale neuroradiological studies involving hundreds of MRI scans. Importantly, other than the initial generation of the unbiased template, this approach requires only modest neuroanatomical training. It has been validated for high-throughput studies of rhesus macaque hippocampal anatomy across a broad age range.

  15. A semi-automated pipeline for the segmentation of rhesus macaque hippocampus: validation across a wide age range.

    Science.gov (United States)

    Hunsaker, Michael R; Amaral, David G

    2014-01-01

    This report outlines a neuroimaging pipeline that allows a robust, high-throughput, semi-automated, template-based protocol for segmenting the hippocampus in rhesus macaque (Macaca mulatta) monkeys ranging from 1 week to 260 weeks of age. The semiautomated component of this approach minimizes user effort while concurrently maximizing the benefit of human expertise by requiring as few as 10 landmarks to be placed on images of each hippocampus to guide registration. Any systematic errors in the normalization process are corrected using a machine-learning algorithm that has been trained by comparing manual and automated segmentations to identify systematic errors. These methods result in high spatial overlap and reliability when compared with the results of manual tracing protocols. They also dramatically reduce the time to acquire data, an important consideration in large-scale neuroradiological studies involving hundreds of MRI scans. Importantly, other than the initial generation of the unbiased template, this approach requires only modest neuroanatomical training. It has been validated for high-throughput studies of rhesus macaque hippocampal anatomy across a broad age range.

  16. κMicroarray analysis of relative gene expression stability for selection of internal reference genes in the rhesus macaque brain

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    Urbanski Henryk F

    2010-06-01

    Full Text Available Abstract Background Normalization of gene expression data refers to the comparison of expression values using reference standards that are consistent across all conditions of an experiment. In PCR studies, genes designated as "housekeeping genes" have been used as internal reference genes under the assumption that their expression is stable and independent of experimental conditions. However, verification of this assumption is rarely performed. Here we assess the use of gene microarray analysis to facilitate selection of internal reference sequences with higher expression stability across experimental conditions than can be expected using traditional selection methods. We recently demonstrated that relative gene expression from qRT-PCR data normalized using GAPDH, ALG9 and RPL13A expression values mirrored relative expression using quantile normalization in Robust Multichip Analysis (RMA on the Affymetrix® GeneChip® rhesus Macaque Genome Array. Having shown that qRT-PCR and Affymetrix® GeneChip® data from the same hormone replacement therapy (HRT study yielded concordant results, we used quantile-normalized gene microarray data to identify the most stably expressed among probe sets for prospective internal reference genes across three brain regions from the HRT study and an additional study of normally menstruating rhesus macaques (cycle study. Gene selection was limited to 575 previously published human "housekeeping" genes. Twelve animals were used per study, and three brain regions were analyzed from each animal. Gene expression stabilities were determined using geNorm, NormFinder and BestKeeper software packages. Results Sequences co-annotated for ribosomal protein S27a (RPS27A, and ubiquitin were among the most stably expressed under all conditions and selection criteria used for both studies. Higher annotation quality on the human GeneChip® facilitated more targeted analysis than could be accomplished using the rhesus GeneChip®. In

  17. Neonatal imitation predicts infant rhesus macaque (Macaca mulatta) social and anxiety-related behaviours at one year

    Science.gov (United States)

    Kaburu, Stefano S. K.; Paukner, Annika; Simpson, Elizabeth A.; Suomi, Stephen J.; Ferrari, Pier F.

    2016-01-01

    The identification of early markers that predict the development of specific social trajectories is critical to understand the developmental and neurobiological underpinnings of healthy social development. We investigated, in infant rhesus macaques (Macaca mulatta), whether newborns’ capacity to imitate facial gestures is a valid predictive marker for the emergence of social competencies later in development, at one year of age. Here we first assessed whether infant macaques (N = 126) imitate lipsmacking gestures (a macaque affiliative expression) performed by a human experimenter in their first week of life. We then collected data on infants’ social interactions (aggression, grooming, and play) and self-scratching (a proxy indicator of anxiety) at 11–14 months when infants were transferred into a new enclosure with a large social group. Our results show that neonatal imitators exhibit more dominant behaviours, are less anxious, and, for males only, spend more time in play at one year old. These findings suggest that neonatal imitation may be an early predictor of infant sociality and may help identify infants at risk of neurodevelopmental social deficits. PMID:27725768

  18. Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling.

    Science.gov (United States)

    Gaddini, Gino W; Grant, Kathleen A; Woodall, Andrew; Stull, Cara; Maddalozzo, Gianni F; Zhang, Bo; Turner, Russell T; Iwaniec, Urszula T

    2015-02-01

    Chronic heavy alcohol consumption is a risk factor for cortical bone fractures in males. The increase in fracture risk may be due, in part, to reduced bone quality. Intracortical (osteonal) bone remodeling is the principle mechanism for maintaining cortical bone quality. However, it is not clear how alcohol abuse impacts intracortical bone remodeling. This study investigated the effects of long-duration heavy alcohol consumption on intracortical bone remodeling in a non-human primate model. Following a 4-month induction period, male rhesus macaques (Macaca mulatta, n=21) were allowed to voluntarily self-administer water or alcohol (4% ethanol w/v) for 22h/d, 7 d/wk for 12months. Control monkeys (n=13) received water and an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3days prior to sacrifice for determination of active mineralization sites. Animals in the alcohol group consumed 2.7±0.2g alcohol/kg/d (mean±SE) during the 12months of self-administration, resulting in a mean daily blood alcohol concentration of 77±9mg/dl from samples taken at 7h after the start of a daily session. However, blood alcohol concentration varied widely from day to day, with peak levels exceeding 250mg/dl, modeling a binge-drinking pattern of alcohol consumption. The skeletal response to alcohol was determined by densitometry, microcomputed tomography and histomorphometry. Significant differences in tibial bone mineral content, bone mineral density, and cortical bone architecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and polar moment of inertia) in the tibial diaphysis were not detected with treatment. However, cortical porosity was lower (1.8±0.5 % versus 0.6±0.1 %, p=0.021) and labeled osteon density was lower (0.41±0.2/mm(2)versus 0.04±0.01/mm(2), premodeling. In concordance, plasma CTx was lower (2.5±0.3ng/ml versus 1.7±0.1ng/ml, p=0.028) in the alcohol group. These results suggest that

  19. Poor immune responses of newborn rhesus macaques to measles virus DNA vaccines expressing the hemagglutinin and fusion glycoproteins.

    Science.gov (United States)

    Polack, Fernando P; Lydy, Shari L; Lee, Sok-Hyong; Rota, Paul A; Bellini, William J; Adams, Robert J; Robinson, Harriet L; Griffin, Diane E

    2013-02-01

    A vaccine that would protect young infants against measles could facilitate elimination efforts and decrease morbidity and mortality in developing countries. However, immaturity of the immune system is an important obstacle to the development of such a vaccine. In this study, DNA vaccines expressing the measles virus (MeV) hemagglutinin (H) protein or H and fusion (F) proteins, previously shown to protect juvenile macaques, were used to immunize groups of 4 newborn rhesus macaques. Monkeys were inoculated intradermally with 200 μg of each DNA at birth and at 10 months of age. As controls, 2 newborn macaques were similarly vaccinated with DNA encoding the influenza virus H5, and 4 received one dose of the current live attenuated MeV vaccine (LAV) intramuscularly. All monkeys were monitored for development of MeV-specific neutralizing and binding IgG antibody and cytotoxic T lymphocyte (CTL) responses. These responses were poor compared to the responses induced by LAV. At 18 months of age, all monkeys were challenged intratracheally with a wild-type strain of MeV. Monkeys that received the DNA vaccine encoding H and F, but not H alone, were primed for an MeV-specific CD8(+) CTL response but not for production of antibody. LAV-vaccinated monkeys were protected from rash and viremia, while DNA-vaccinated monkeys developed rashes, similar to control monkeys, but had 10-fold lower levels of viremia. We conclude that vaccination of infant macaques with DNA encoding MeV H and F provided only partial protection from MeV infection.

  20. Limited impact of passive non-neutralizing antibody immunization in acute SIV infection on viremia control in rhesus macaques.

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    Taku Nakane

    Full Text Available BACKGROUND: Antiviral antibodies, especially those with neutralizing activity against the incoming strain, are potentially important immunological effectors to control human immunodeficiency virus (HIV infection. While neutralizing activity appears to be central in sterile protection against HIV infection, the entity of inhibitory mechanisms via HIV and simian immunodeficiency virus (SIV-specific antibodies remains elusive. The recent HIV vaccine trial RV144 and studies in nonhuman primate models have indicated controversial protective efficacy of HIV/SIV-specific non-neutralizing binding antibodies (non-NAbs. While reports on HIV-specific non-NAbs have demonstrated virus inhibitory activity in vitro, whether non-NAbs could also alter the pathogenic course of established SIV replication in vivo, likewise via neutralizing antibody (NAb administration, has been unclear. Here, we performed post-infection passive immunization of SIV-infected rhesus macaques with polyclonal SIV-specific, antibody-dependent cell-mediated viral inhibition (ADCVI-competent non-NAbs. METHODS AND FINDINGS: Ten lots of polyclonal immunoglobulin G (IgG were prepared from plasma of ten chronically SIVmac239-infected, NAb-negative rhesus macaques, respectively. Their binding capacity to whole SIVmac239 virions showed a propensity similar to ADCVI activity. A cocktail of three non-NAb lots showing high virion-binding capacity and ADCVI activity was administered to rhesus macaques at day 7 post-SIVmac239 challenge. This resulted in an infection course comparable with control animals, with no significant difference in set point plasma viral loads or immune parameters. CONCLUSIONS: Despite virus-specific suppressive activity of the non-NAbs having been observed in vitro, their passive immunization post-infection did not result in SIV control in vivo. Virion binding and ADCVI activity with lack of virus neutralizing activity were indicated to be insufficient for antibody

  1. Enhanced Th1/Th17 Functions of CD161+ CD8+ T Cells in Mucosal Tissues of Rhesus Macaques.

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    Namita Rout

    Full Text Available Expression of the C-type lectin-like receptor CD161 by human T cells is associated with type-17 responses, which play critical regulatory roles in immunity and inflammation at mucosal sites. However, the functions of CD161-expressing T cells in macaques, the pre-clinical model of several human diseases, remain unknown. This study examined the phenotypic and functional characteristics of CD161+ T cells in peripheral blood, mucosal tissues and lymph nodes of rhesus macaques. Majority of CD161-expressing T cells in peripheral blood and lung/intestinal mucosal tissues of rhesus macaques were found to be CD8+CD4- in phenotype. There was a significant enrichment of CD161+CD8+ T cells in the lungs and colonic mucosa (16.1%±6.6 and 16.8%±5.7 in comparison to peripheral blood (4.2%±1.2 and mesenteric lymph nodes (1.3%±0.8. Regardless of the tissue compartment, CD161+CD8+ T cells mainly comprised of γδ T cells and TCR Vα7.2+ MAIT cells (up to 80%, and displayed Th1 and Th17 cytokine responses to mitogen stimulation. Mucosal CD161+CD8+ T cells were characterized by very high expression of CD69, a recent activation marker that is preferentially expressed on tissue resident cells. Furthermore, lung and colonic mucosal CD161+CD8+ T cells showed enhanced IFN-γ, IL-17, and Perforin production in comparison to those in blood. Thus, macaque CD161+CD8+ T cells represent mucosal tissue-homing innate-like CD8+ T-cell populations with Th1/Th17 type cytokine and cytotoxic effector functions that can potentially enhance the recruitment of adaptive immune cells and control initial pathogen burden/dissemination in tissues. Analysis of their role in early immune responses to mucosal pathogens will be valuable in the design of vaccines and therapeutics.

  2. Exogenous IFN-alpha administration reduces influenza A virus replication in the lower respiratory tract of rhesus macaques.

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    Shannon R Matzinger

    Full Text Available To determine the role of innate immune responses in controlling influenza A virus replication, rhesus macaques (RM were administered pegylated IFN-alpha prior to virus challenge. Systemic and mucosal pegylated IFN-alpha administration induced expression of the interferon-stimulated genes (ISG MxA and OAS in the airways. RM treated with IFN-alpha 24 hours prior to influenza virus challenge had significantly lower peak vRNA levels in the trachea compared to untreated animals. In addition to blunting viral replication, IFN-alpha treatment minimized the weight loss and spike in body temperature after influenza infection of RM. These results confirm the importance of IFN-alpha induced innate immune responses in the rapid control of influenza A virus replication in primates.

  3. Detecting lineage-specific adaptive evolution of brain-expressed genes in human using rhesus macaque as outgroup

    DEFF Research Database (Denmark)

    Yu, Xiao-Jing; Zheng, Hong-Kun; Wang, Jun;

    2006-01-01

    Comparative genetic analysis between human and chimpanzee may detect genetic divergences responsible for human-specific characteristics. Previous studies have identified a series of genes that potentially underwent Darwinian positive selection during human evolution. However, without a closely...... related species as outgroup, it is difficult to identify human-lineage-specific changes, which is critical in delineating the biological uniqueness of humans. In this study, we conducted phylogeny-based analyses of 2633 human brain-expressed genes using rhesus macaque as the outgroup. We identified 47...... candidate genes showing strong evidence of positive selection in the human lineage. Genes with maximal expression in the brain showed a higher evolutionary rate in human than in chimpanzee. We observed that many immune-defense-related genes were under strong positive selection, and this trend was more...

  4. Response of Rhesus Macaques (Macaca mulatta) to the Body of a Group Member That Died from a Fatal Attack

    Science.gov (United States)

    Buhl, Jacqueline S.; Aure, Bonn; Ruiz-Lambides, Angelina; Gonzalez-Martinez, Janis; Platt, Michael L.; Brent, Lauren J. N.

    2013-01-01

    Among animals that form social bonds, the death of a conspecific may be a significant social event, representing the loss of an ally and resulting in disruptions to the dominance hierarchy. Despite this potential biological importance, we have only limited knowledge of animals' reactions to the death of a group member. This is particularly true of responses to dead adults, as most reports describe the responses of mothers to dead infants. Here, we describe in detail and provide video evidence of the behavioral responses of a group of free-ranging rhesus macaques (Macaca mulatta) immediately after the death of a mid-ranking adult male as a result of a fatal attack. High-ranking male members of the group, suspected to have carried out the attack, dragged and bit the dead body, exhibiting a rate of aggression 20 times greater than baseline levels. Lower-ranking individuals approached and inspected the body by looking closely, smelling, and grooming the fur. There was inconclusive evidence that these rhesus macaques found the death of a conspecific stressful: Levels of grooming between group members after the fatal attack were significantly higher than baseline levels, and higher than levels of grooming after nonfatal attacks. However, when grooming levels were adjusted based on the assumption that individuals positioned close to the body, i.e., those visible to researchers, were more likely to be engaged in grooming than those positioned farther away, this difference from baseline was no longer significant. The rate of self-directed behaviors after the fatal attack was also not different from baseline. Many of the behaviors we observed directed toward the body (aggression, inspection) have been previously reported in chimpanzees and geladas, and are similar to reactions sometimes displayed by humans. As such, this report represents a potentially valuable contribution the nascent field of nonhuman primate thanatology. PMID:23459587

  5. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

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    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Venzon, David [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Brocca-Cofano, Egidio; DiPasquale, Janet [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit [Advanced Bioscience Laboratories Inc., Rockville, MD 20850 (United States); Sui, Yongjun; Berzofsky, Jay A. [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Liu, Linda; Langermann, Solomon [Amplimmune Inc., Gaithersburg, MD 20878 (United States); Robert-Guroff, Marjorie, E-mail: guroffm@mail.nih.gov [Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-15

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

  6. Identification of rhesus macaque genital microbiota by 16S pyrosequencing shows similarities to human bacterial vaginosis: implications for use as an animal model for HIV vaginal infection.

    Science.gov (United States)

    Spear, Gregory T; Gilbert, Douglas; Sikaroodi, Masoumeh; Doyle, Lara; Green, Linda; Gillevet, Patrick M; Landay, Alan L; Veazey, Ronald S

    2010-02-01

    The composition of the lower genital tract microbiota in women is believed to affect the risk of sexually acquiring HIV. Since macaque genital microbiota could similarly impact vaginal infection with SIV we identified microbiota in 11 rhesus macaques using multitag pyrosequencing of the 16S rRNA gene. The microbiota was polymicrobial with a median of nine distinct bacterial taxa per macaque (range 3-16 taxa, each constituting 1% or more of the sequences). Taxa frequently found included Peptoniphilus, Sneathia, Porphyromonas, Mobiluncus, Atopobacter, Dialister, Thioreductor, Prevotella, and Streptococcus, many of which are also frequently found in women with bacterial vaginosis. Lactobacillus sequences (mostly L. johnsonii) were found in only four macaques but were not predominant in any (median of 0% of sequences, range 0-39%). All macaques were resampled 6 months after the first time point to determine the stability of the microbiota. The microbiota remained polymicrobial with a median of 10 taxa (range 6-18). Microbial patterns remained similar for six of the macaques, changed substantially in two, and had a mixed pattern in three. Significant sialidase enzyme activity, a marker of bacteria vaginosis in women, was detected in genital fluid from 9/11 and 8/11 macaques from the first and second time points, respectively. These results show that the macaque lower genital microbiota resembled a bacteria vaginosis-type microbiota in women and suggest that the microbiota of macaques in captivity promote rather than protect against vaginal infection with SIV. These results also suggest macaques could be used as an animal model to study some aspects of bacterial vaginosis.

  7. Effect of Carotenoid Supplemented Formula on Carotenoid Bioaccumulation in Tissues of Infant Rhesus Macaques: A Pilot Study Focused on Lutein

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    Sookyoung Jeon

    2017-01-01

    Full Text Available Lutein is the predominant carotenoid in the developing primate brain and retina, and may have important functional roles. However, its bioaccumulation pattern during early development is not understood. In this pilot study, we investigated whether carotenoid supplementation of infant formula enhanced lutein tissue deposition in infant rhesus macaques. Monkeys were initially breastfed; from 1 to 3 months of age they were fed either a formula supplemented with lutein, zeaxanthin, β-carotene and lycopene, or a control formula with low levels of these carotenoids, for 4 months (n = 2/group. All samples were analyzed by high pressure liquid chromatography (HPLC. Final serum lutein in the supplemented group was 5 times higher than in the unsupplemented group. All brain regions examined showed a selective increase in lutein deposition in the supplemented infants. Lutein differentially accumulated across brain regions, with highest amounts in occipital cortex in both groups. β-carotene accumulated, but zeaxanthin and lycopene were undetectable in any brain region. Supplemented infants had higher lutein concentrations in peripheral retina but not in macular retina. Among adipose sites, abdominal subcutaneous adipose tissue exhibited the highest lutein level and was 3-fold higher in the supplemented infants. The supplemented formula enhanced carotenoid deposition in several other tissues. In rhesus infants, increased intake of carotenoids from formula enhanced their deposition in serum and numerous tissues and selectively increased lutein in multiple brain regions.

  8. Effect of Carotenoid Supplemented Formula on Carotenoid Bioaccumulation in Tissues of Infant Rhesus Macaques: A Pilot Study Focused on Lutein

    Science.gov (United States)

    Jeon, Sookyoung; Neuringer, Martha; Johnson, Emily E.; Kuchan, Matthew J.; Pereira, Suzette L.; Johnson, Elizabeth J.; Erdman, John W.

    2017-01-01

    Lutein is the predominant carotenoid in the developing primate brain and retina, and may have important functional roles. However, its bioaccumulation pattern during early development is not understood. In this pilot study, we investigated whether carotenoid supplementation of infant formula enhanced lutein tissue deposition in infant rhesus macaques. Monkeys were initially breastfed; from 1 to 3 months of age they were fed either a formula supplemented with lutein, zeaxanthin, β-carotene and lycopene, or a control formula with low levels of these carotenoids, for 4 months (n = 2/group). All samples were analyzed by high pressure liquid chromatography (HPLC). Final serum lutein in the supplemented group was 5 times higher than in the unsupplemented group. All brain regions examined showed a selective increase in lutein deposition in the supplemented infants. Lutein differentially accumulated across brain regions, with highest amounts in occipital cortex in both groups. β-carotene accumulated, but zeaxanthin and lycopene were undetectable in any brain region. Supplemented infants had higher lutein concentrations in peripheral retina but not in macular retina. Among adipose sites, abdominal subcutaneous adipose tissue exhibited the highest lutein level and was 3-fold higher in the supplemented infants. The supplemented formula enhanced carotenoid deposition in several other tissues. In rhesus infants, increased intake of carotenoids from formula enhanced their deposition in serum and numerous tissues and selectively increased lutein in multiple brain regions. PMID:28075370

  9. Fasting induced kisspeptin signaling suppression is regulated by glutamate mediated cues in adult male rhesus macaque (Macaca mulatta).

    Science.gov (United States)

    Shamas, Shazia; Khan, Saeed-Ul-Hassan; Khan, Muhammad Yousaf; Shabbir, Nadia; Zubair, Hira; Shafqat, Saira; Wahab, Fazal; Shahab, Muhammad

    2015-08-01

    Kisspeptin signaling is suppressed by short term fasting. It has been reported that hypothalamic Kiss1 and Kiss1r mRNA expression decreased after 48h of fasting in male rhesus monkey. But the mechanism involved in the reduction of kisspeptin signaling after 48h of fasting is unknown. Recent studies have suggested the role of afferent excitatory and inhibitory pathways in the regulation of kisspeptin neurons. Therefore, this study was designed to observe the changes in the glutamate and GABA signaling during fed and 48h fasting states by performing immunofluorescence to examine the interaction of kisspeptin neurons with NR1 subunit of NMDA receptors and by performing SYBR green qRT-PCR to measure and quantify the levels of Kiss1, Kiss1r, NR1 and GAD67 mRNA in the POA and MBH of adult male rhesus macaque (Macaca mulatta) during 48h of fasting (n=2) and fed ad libitum (n=2). Plasma testosterone (pfasting. Our results clearly showed that expression of hypothalamic Kiss1, Kiss1r and NR1 mRNA was significantly (pfasting. These observations suggest that decreased kisspeptin signaling during fasting may occur due to reduction in glutamatergic inputs to kisspeptin neurons. Our results also suggest that fasting induced suppression of kisspeptin signaling is not mediated through GABAergic neurons.

  10. Low dose rectal inoculation of rhesus macaques by SIV smE660 or SIVmac251 recapitulates

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    Hraber, Peter [Los Alamos National Laboratory; Giorgi, Elena E [Los Alamos National Laboratory; Keele, Brandon [UNIV OF ALABAMA; Li, Hui [UNIV OF ALABAMA; Learn, Gerald [UNIV OF ALABAMA

    2008-01-01

    We recently developed a novel strategy to identify transmitted HIV-1 genomes in acutely infected humans using single-genome amplification and a model of random virus evolution. Here, we used this approach to determine the molecular features of simian immunodeficiency virus (SIV) transmission in 18 experimentally infected Indian rhesus macaques. Animals were inoculated intrarectally (i.r.) or intravenously (i.v.) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV-1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA 1--5 wk after infection. i.r. inoculation was followed by productive infection by one or a few viruses (median 1; range 1--5) that diversified randomly with near starlike phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or a few nucleotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder viruses. i.v. infection was >2,000-fold more efficient than i.r. infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV-1, and thus validate the SIV-macaque mucosal infection model for HIV-1 vaccine and microbicide research.

  11. Expression analysis of taste signal transduction molecules in the fungiform and circumvallate papillae of the rhesus macaque, Macaca mulatta.

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    Yoshiro Ishimaru

    Full Text Available The molecular mechanisms of the mammalian gustatory system have been examined in many studies using rodents as model organisms. In this study, we examined the mRNA expression of molecules involved in taste signal transduction in the fungiform papillae (FuP and circumvallate papillae (CvP of the rhesus macaque, Macaca mulatta, using in situ hybridization. TAS1R1, TAS1R2, TAS2Rs, and PKD1L3 were exclusively expressed in different subsets of taste receptor cells (TRCs in the FuP and CvP. This finding suggests that TRCs sensing different basic taste modalities are mutually segregated in macaque taste buds. Individual TAS2Rs exhibited a variety of expression patterns in terms of the apparent level of expression and the number of TRCs expressing these genes, as in the case of human TAS2Rs. GNAT3, but not GNA14, was expressed in TRCs of FuP, whereas GNA14 was expressed in a small population of TRCs of CvP, which were distinct from GNAT3- or TAS1R2-positive TRCs. These results demonstrate similarities and differences between primates and rodents in the expression profiles of genes involved in taste signal transduction.

  12. Effect of mating activity and dominance rank on male masturbation among free-ranging male rhesus macaques.

    Science.gov (United States)

    Dubuc, Constance; Coyne, Sean P; Maestripieri, Dario

    2013-11-01

    The adaptive function of male masturbation is still poorly understood, despite its high prevalence in humans and other animals. In non-human primates, male masturbation is most frequent among anthropoid monkeys and apes living in multimale-multifemale groups with a promiscuous mating system. In these species, male masturbation may be a non-functional by-product of high sexual arousal or be adaptive by providing advantages in terms of sperm competition or by decreasing the risk of sexually transmitted infections. We investigated the possible functional significance of male masturbation using behavioral data collected on 21 free-ranging male rhesus macaques (Macaca mulatta) at the peak of the mating season. We found some evidence that masturbation is linked to low mating opportunities: regardless of rank, males were most likely to be observed masturbating on days in which they were not observed mating, and lower-ranking males mated less and tended to masturbate more frequently than higher-ranking males. These results echo the findings obtained for two other species of macaques, but contrast those obtained in red colobus monkeys (Procolobus badius) and Cape ground squirrels (Xerus inauris). Interestingly, however, male masturbation events ended with ejaculation in only 15% of the observed masturbation time, suggesting that new hypotheses are needed to explain masturbation in this species. More studies are needed to establish whether male masturbation is adaptive and whether it serves similar or different functions in different sexually promiscuous species.

  13. Early involvement in friendships predicts later plasma concentrations of oxytocin and vasopressin in juvenile rhesus macaques (Macaca mulatta

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    Tamara Aliza Rachel Weinstein

    2014-08-01

    Full Text Available The neuropeptides oxytocin (OT and vasopressin (AVP are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques’ (Macaca mulatta friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center. Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay. Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject, multiplex friendships (friendships displayed in more than one behavioral domain, and total number of friendships. Females’ number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males’ plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual’s psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in

  14. Social buffering and contact transmission: network connections have beneficial and detrimental effects on Shigella infection risk among captive rhesus macaques

    Science.gov (United States)

    Beisner, Brianne; Vandeleest, Jessica; Atwill, Edward; McCowan, Brenda

    2016-01-01

    In social animals, group living may impact the risk of infectious disease acquisition in two ways. On the one hand, social connectedness puts individuals at greater risk or susceptibility for acquiring enteric pathogens via contact-mediated transmission. Yet conversely, in strongly bonded societies like humans and some nonhuman primates, having close connections and strong social ties of support can also socially buffer individuals against susceptibility or transmissibility of infectious agents. Using social network analyses, we assessed the potentially competing roles of contact-mediated transmission and social buffering on the risk of infection from an enteric bacterial pathogen (Shigella flexneri) among captive groups of rhesus macaques (Macaca mulatta). Our results indicate that, within two macaque groups, individuals possessing more direct and especially indirect connections in their grooming and huddling social networks were less susceptible to infection. These results are in sharp contrast to several previous studies that indicate that increased (direct) contact-mediated transmission facilitates infectious disease transmission, including our own findings in a third macaque group in which individuals central in their huddling network and/or which initiated more fights were more likely to be infected. In summary, our findings reveal that an individual’s social connections may increase or decrease its chances of acquiring infectious agents. They extend the applicability of the social buffering hypothesis, beyond just stress and immune-function-related health benefits, to the additional health outcome of infectious disease resistance. Finally, we speculate that the circumstances under which social buffering versus contact-mediated transmission may occur could depend on multiple factors, such as living condition, pathogen-specific transmission routes, and/or an overall social context such as a group’s social stability.

  15. Heterogeneity in Rhesus Macaque Complement Factor H Binding to Meningococcal Factor H Binding Protein (FHbp) Informs Selection of Primates To Assess Immunogenicity of FHbp-Based Vaccines

    OpenAIRE

    2014-01-01

    Neisseria meningitidis causes disease only in humans. An important mechanism underlying this host specificity is the ability of the organism to resist complement by recruiting the complement downregulator factor H (FH) to the bacterial surface. In previous studies, binding of FH to one of the major meningococcal FH ligands, factor H binding protein (FHbp), was reported to be specific for human FH. Here we report that sera from 23 of 73 rhesus macaques (32%) tested had high FH binding to FHbp....

  16. The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

    OpenAIRE

    2012-01-01

    Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta) is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in pop...

  17. Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in infected Indian rhesus macaques.

    Science.gov (United States)

    Mladinich, Katherine M; Piaskowski, Shari M; Rudersdorf, Richard; Eernisse, Christopher M; Weisgrau, Kim L; Martins, Mauricio A; Furlott, Jessica R; Partidos, Charalambos D; Brewoo, Joseph N; Osorio, Jorge E; Wilson, Nancy A; Rakasz, Eva G; Watkins, David I

    2012-02-01

    Every year, Dengue virus (DENV) infects approximately 100 million people. There are currently several vaccines undergoing clinical studies, but most target the induction of neutralizing antibodies. Unfortunately, DENV infection can be enhanced by subneutralizing levels of antibodies that bind virions and deliver them to cells of the myeloid lineage, thereby increasing viral replication (termed antibody-dependent enhancement [ADE]). T lymphocyte-based vaccines may offer an alternative that avoids ADE. The goal of our study was to describe the cellular immune response generated after primary DENV infection in Indian rhesus macaques. We infected eight rhesus macaques with 10⁵ plaque-forming units (PFU) of DENV serotype 2 (DENV2) New Guinea C (NGC) strain, and monitored viral load and the cellular immune response to the virus. Viral replication peaked at day 4 post-infection and was resolved by day 10. DENV-specific CD4+ and CD8+ T lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution of peak viremia. DENV-specific CD4+ cells expressed interferon-gamma (IFN-γ) along with tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), and macrophage inflammatory protein-1 beta (MIP-1β). In comparison, DENV-specific CD8+ cells expressed IFN-γ in addition to MIP-1β and TNF-α and were positive for the degranulation marker CD107a. Interestingly, a fraction of the DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be cytotoxic. Our results provide a more complete understanding of the cellular immune response during DENV infection in rhesus macaques and contribute to the development of rhesus macaques as an animal model for DENV vaccine and pathogenicity studies.

  18. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques

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    Bryan C. Au

    2016-02-01

    Full Text Available Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag-specific responses through direct injections of recombinant lentivectors (LVs that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis.

  19. Constitutive Release of IFNγ and IL2 from Peripheral Blood Mononuclear Cells of Rhesus Macaques (Macaca mulatta) Infected with Simian T-Lymphotropic Virus Type 1

    Science.gov (United States)

    Yee, JoAnn L; Montiel, Nestor A; Ardeshr, Amir; Lerche, Nicholas W

    2013-01-01

    Simian T-cell lymphotropic viruses (STLV), the nonhuman primate counterparts of human T-cell lymphotropic viruses (HTLV), are endemic in many populations of African and Asian monkeys and apes. Although an etiologic link between STLV1 infection and lymphoproliferative disorders such as malignant lymphomas has been suggested in some nonhuman primate species, most STLV infections are inapparent, and infected animals remain clinically healthy. The retroviral transactivator, tax, is well known to increase transcription of viral and cellular genes, resulting in altered cytokine profiles. This study compared the cytokine profiles of peripheral blood mononuclear cell (PBMC) cultures from 25 STLV1-seropositive rhesus macaques (Macaca mulatta) with those of age- and sex-matched seronegative controls. IFNγ, TNFα, IL10, and IL2 levels in unstimulated PBMC culture supernatants were measured at 24, 48, and 72 h by using enzyme immunoassays. IFNγ concentrations were found significantly higher in the supernatants of PBMC cultures of seropositive monkeys as compared with seronegative controls. In addition, although IL2 concentrations were not significantly elevated in the supernatants of PBMC cultures of all seropositive monkeys as compared with all seronegative controls, IL2 levels were increased in a subset of 5 pairs. Increased constitutive cytokine release occurred in the absence of spontaneous proliferation. The increased constitutive release of IFNγ and IL2 suggests that STLV1 alters immune functions in infected but clinically healthy rhesus macaques and further characterizes STLV1 infection of rhesus macaques as a potential model for human HTLV1 infection. PMID:24326227

  20. Molecular identification and characterization of Mycobacterium avium subspecies paratuberculosis in free living non-human primate (Rhesus macaques) from North India.

    Science.gov (United States)

    Singh, S V; Singh, A V; Singh, P K; Kumar, A; Singh, B

    2011-05-01

    In recent years, Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as major animal pathogen with significant zoonotic concerns, worldwide. MAP infection is endemic in domestic and wild ruminant population in India. However, information on MAP infection in free ranging animal species and non human primates is limited. Present study aimed to estimate the status of MAP infection in free living Rhesus macaques suffering with multiple clinical conditions (coughing and loose stool). A total of 25 stool samples were collected from six colonies of Rhesus macaques from Mathura region (North India) and screened for the presence of MAP, using microscopic examination and IS900 PCR, directly from stool samples. PCR positive DNA samples were further genotyped using IS1311 PCR-restriction enzyme analysis. Of the 25 stool samples, 10 (40.0%) and 2 (8.0%) were positive for MAP using microscopic examination and direct IS900 PCR, respectively. IS900 PCR positive DNA samples were genotyped as 'Indian Bison type', which is a major MAP genotype infecting domestic and wild ruminant species and human beings in India. Prevalence of MAP in Rhesus macaques (Indian monkeys) was moderately high and confirmed interspecies sharing of MAP between domestic livestock and non-human primates. Presence of MAP in non-human primates, support the etiological role of MAP in inflammatory bowel disease patients. Indian monkeys may serve as model for understanding the role of non-human primates in sustenance, transmission and pathogenesis of MAP infection.

  1. Evidence for Motor Planning in Monkeys: Rhesus Macaques Select Efficient Grips when Transporting Spoons

    Science.gov (United States)

    Nelson, Eliza L.; Berthier, Neil E.; Metevier, Christina M.; Novak, Melinda A.

    2011-01-01

    McCarty and colleagues (1999) developed the elevated spoon task to measure motor planning in human infants. In this task, a spoon containing food was placed on an elevated apparatus that supported both ends of the spoon. The handle was oriented to the left or right on different trials. We presented naive adult rhesus monkeys (Macaca mulatta) with…

  2. Simian virus 40 inhibits differentiation and maturation of rhesus macaque DC-SIGN+-dendritic cells

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    Changyong G

    2010-09-01

    Full Text Available Abstract Dendritic cells (DC are the initiators and modulators of the immune responses. Some species of pathogenic microorganisms have developed immune evasion strategies by controlling antigen presentation function of DC. Simian virus 40 (SV40 is a DNA tumor virus of rhesus monkey origin. It can induce cell transformation and tumorigenesis in many vertebrate species, but often causes no visible effects and persists as a latent infection in rhesus monkeys under natural conditions. To investigate the interaction between SV40 and rhesus monkey DC, rhesus monkey peripheral blood monocyte-derived DC were induced using recombinant human Interleukin-4 (rhIL-4 and infective SV40, the phenotype and function of DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN+ DC were analyzed by flow cytometry (FCM and mixed lymphocyte reaction (MLR. Results showed that SV40 can down-regulate the expression of CD83 and CD86 on DC and impair DC-induced activation of T cell proliferation. These findings suggest that SV40 might also cause immune suppression by influencing differentiation and maturation of DC.

  3. Acquisition of Helicobacter pylori Infection in Rhesus Macaques Is Most Consistent with Oral-Oral Transmission

    OpenAIRE

    Solnick, Jay V.; Fong, Julie; Hansen, Lori M.; Chang, Kikuko; Canfield, Don R.; Parsonnet, Julie

    2006-01-01

    Socially housed rhesus monkeys rapidly acquired Helicobacter pylori infection, although the organism was rarely cultivated from saliva, feces, or the environment. Since the concentrations of H. pylori in vomit were compatible with what is known about the infectious dose, our results are most consistent with an oral-oral means of transmission.

  4. Risk factors for stereotypic behavior and self-biting in rhesus macaques (Macaca mulatta): animal's history, current environment, and personality.

    Science.gov (United States)

    Gottlieb, Daniel H; Capitanio, John P; McCowan, Brenda

    2013-10-01

    Captive rhesus macaques sometimes exhibit undesirable abnormal behaviors, such as motor stereotypic behavior (MSB) and self-abuse. Many risk factors for these behaviors have been identified but the list is far from comprehensive, and large individual differences in rate of behavior expression remain. The goal of the current study was to determine which experiences predict expression of MSB and self-biting, and if individual differences in personality can account for additional variation in MSB expression. A risk factor analysis was performed utilizing data from over 4,000 rhesus monkeys at the California National Primate Research Center. Data were analyzed using model selection, with the best fitting models evaluated using Akaike Information Criterion. Results confirmed previous research that males exhibit more MSB and self-biting than females, MSB decreases with age, and indoor reared animals exhibit more MSB and self-biting than outdoor reared animals. Additionally, results indicated that animals exhibited less MSB and self-biting for each year spent outdoors; frequency of room moves and number of projects positively predicted MSB; pair separations positively predicted MSB and self-biting; pair housed animals expressed less MSB than single housed and grate paired animals; and that animals expressed more MSB and self-biting when in bottom rack cages, or cages near the room entrance. Based on these results we recommend limiting exposure to these risk factors when possible. Our results also demonstrated a relationship between personality and MSB expression, with animals low on gentle temperament, active in response to a human intruder, and high on novel object contact expressing more MSB. From these results we propose that an animal's MSB is related to its predisposition for an active personality, with active animals expressing higher rates of MSB.

  5. Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques.

    Science.gov (United States)

    Li, Hui; Wang, Shuyi; Kong, Rui; Ding, Wenge; Lee, Fang-Hua; Parker, Zahra; Kim, Eunlim; Learn, Gerald H; Hahn, Paul; Policicchio, Ben; Brocca-Cofano, Egidio; Deleage, Claire; Hao, Xingpei; Chuang, Gwo-Yu; Gorman, Jason; Gardner, Matthew; Lewis, Mark G; Hatziioannou, Theodora; Santra, Sampa; Apetrei, Cristian; Pandrea, Ivona; Alam, S Munir; Liao, Hua-Xin; Shen, Xiaoying; Tomaras, Georgia D; Farzan, Michael; Chertova, Elena; Keele, Brandon F; Estes, Jacob D; Lifson, Jeffrey D; Doms, Robert W; Montefiori, David C; Haynes, Barton F; Sodroski, Joseph G; Kwong, Peter D; Hahn, Beatrice H; Shaw, George M

    2016-06-14

    Most simian-human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding to rhesus CD4 (rhCD4) limits virus entry and replication and could be enhanced by substituting naturally occurring simian immunodeficiency virus Env residues at position 375, which resides at a critical location in the CD4-binding pocket and is under strong positive evolutionary pressure across the broad spectrum of primate lentiviruses. SHIVs containing primary or transmitted/founder HIV-1 subtype A, B, C, or D Envs with genotypic variants at residue 375 were constructed and analyzed in vitro and in vivo. Bulky hydrophobic or basic amino acids substituted for serine-375 enhanced Env affinity for rhCD4, virus entry into cells bearing rhCD4, and virus replication in primary rhCD4 T cells without appreciably affecting antigenicity or antibody-mediated neutralization sensitivity. Twenty-four RMs inoculated with subtype A, B, C, or D SHIVs all became productively infected with different Env375 variants-S, M, Y, H, W, or F-that were differentially selected in different Env backbones. Notably, SHIVs replicated persistently at titers comparable to HIV-1 in humans and elicited autologous neutralizing antibody responses typical of HIV-1. Seven animals succumbed to AIDS. These findings identify Env-rhCD4 binding as a critical determinant for productive SHIV infection in RMs and validate a novel and generalizable strategy for constructing SHIVs with Env glycoproteins of interest, including those that in humans elicit broadly neutralizing antibodies or bind particular Ig germ-line B-cell receptors.

  6. Heterogeneity in rhesus macaque complement factor H binding to meningococcal factor H binding protein (FHbp) informs selection of primates to assess immunogenicity of FHbp-based vaccines.

    Science.gov (United States)

    Beernink, Peter T; Shaughnessy, Jutamas; Stefek, Heather; Ram, Sanjay; Granoff, Dan M

    2014-11-01

    Neisseria meningitidis causes disease only in humans. An important mechanism underlying this host specificity is the ability of the organism to resist complement by recruiting the complement downregulator factor H (FH) to the bacterial surface. In previous studies, binding of FH to one of the major meningococcal FH ligands, factor H binding protein (FHbp), was reported to be specific for human FH. Here we report that sera from 23 of 73 rhesus macaques (32%) tested had high FH binding to FHbp. Similar to human FH, binding of macaque FH to the meningococcal cell surface inhibited the complement alternative pathway by decreasing deposition of C3b. FH contains 20 domains (or short consensus repeats), with domains 6 and 7 being responsible for binding of human FH to FHbp. DNA sequence analyses of FH domains 6 and 7 from macaques with high or low FH binding showed a polymorphism at residue 352 in domain 6, with Tyr being associated with high binding and His with low binding. A recombinant macaque FH 6,7/Fc fragment with Tyr352 showed higher binding to FHbp than the corresponding fragment with His352. In previous studies in human FH transgenic mice, binding of FH to FHbp vaccines decreased protective antibody responses, and mutant FHbp vaccines with decreased FH binding elicited serum antibodies with greater protective activity. Thus, macaques with high FH binding to FHbp represent an attractive nonhuman primate model to investigate further the effects of FH binding on the immunogenicity of FHbp vaccines.

  7. Adoptive Transfer of Engineered Rhesus Simian Immunodeficiency Virus-Specific CD8+ T Cells Reduces the Number of Transmitted/Founder Viruses Established in Rhesus Macaques.

    Science.gov (United States)

    Ayala, Victor I; Trivett, Matthew T; Barsov, Eugene V; Jain, Sumiti; Piatak, Michael; Trubey, Charles M; Alvord, W Gregory; Chertova, Elena; Roser, James D; Smedley, Jeremy; Komin, Alexander; Keele, Brandon F; Ohlen, Claes; Ott, David E

    2016-11-01

    AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4(+) T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively (P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus.

  8. Alzheimer's disease and methanol toxicity (part 2): lessons from four rhesus macaques (Macaca mulatta) chronically fed methanol.

    Science.gov (United States)

    Yang, Meifeng; Miao, Junye; Rizak, Joshua; Zhai, Rongwei; Wang, Zhengbo; Huma, Tanzeel; Li, Ting; Zheng, Na; Wu, Shihao; Zheng, Yingwei; Fan, Xiaona; Yang, Jianzhen; Wang, Jianhong; Yang, Shangchuan; Ma, Yuanye; Lü, Longbao; He, Rongqiao; Hu, Xintian

    2014-01-01

    A recently established link between formaldehyde, a methanol metabolite, and Alzheimer's disease (AD) pathology has provided a new impetus to investigate the chronic effects of methanol exposure. This paper expands this investigation to the non-human primate, rhesus macaque, through the chronic feeding of young male monkeys with 3% methanol ad libitum. Variable Spatial Delay Response Tasks of the monkeys found that the methanol feeding led to persistent memory decline in the monkeys that lasted 6 months beyond the feeding regimen. This change coincided with increases in tau protein phosphorylation at residues T181 and S396 in cerebrospinal fluid during feeding as well as with increases in tau phosphorylated aggregates and amyloid plaques in four brain regions postmortem: the frontal lobe, parietal lobe, temporal lobe, and the hippocampus. Tau phosphorylation in cerebrospinal fluid was found to be dependent on methanol feeding status, but phosphorylation changes in the brain were found to be persistent 6 months after the methanol feeding stopped. This suggested the methanol feeding caused long-lasting and persistent pathological changes that were related to AD development in the monkey. Most notably, the presence of amyloid plaque formations in the monkeys highlighted a marked difference in animal systems used in AD investigations, suggesting that the innate defenses in mice against methanol toxicity may have limited previous investigations into AD pathology. Nonetheless, these findings support a growing body of evidence that links methanol and its metabolite formaldehyde to AD pathology.

  9. Full genome sequence analysis of a novel adenovirus of rhesus macaque origin indicates a new simian adenovirus type and species

    Directory of Open Access Journals (Sweden)

    Daniel Malouli

    2014-09-01

    Full Text Available Multiple novel simian adenoviruses have been isolated over the past years and their potential to cross the species barrier and infect the human population is an ever present threat. Here we describe the isolation and full genome sequencing of a novel simian adenovirus (SAdV isolated from the urine of two independent, never co-housed, late stage simian immunodeficiency virus (SIV-infected rhesus macaques. The viral genome sequences revealed a novel type with a unique genome length, GC content, E3 region and DNA polymerase amino acid sequence that is sufficiently distinct from all currently known human- or simian adenovirus species to warrant classifying these isolates as a novel species of simian adenovirus. This new species, termed Simian mastadenovirus D (SAdV-D, displays the standard genome organization for the genus Mastadenovirus containing only one copy of the fiber gene which sets it apart from the old world monkey adenovirus species HAdV-G, SAdV-B and SAdV-C.

  10. Evaluation of the kappa-opioid receptor-selective tracer [{sup 11}C]GR103545 in awake rhesus macaques

    Energy Technology Data Exchange (ETDEWEB)

    Schoultz, Bent W. [University of Oslo, Department of Chemistry, Oslo (Norway); Hjornevik, Trine; Willoch, Frode [University of Oslo, Centre for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, Oslo (Norway); Akershus University Hospital, Department of Nuclear Medicine, Loerenskog (Norway); Marton, Janos [ABX Advanced Biochemical Compounds GmbH, Radeberg (Germany); Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro [Medical and Pharmacological Research Center Foundation, Basic Research Department, Hakui City, Ishikawa (Japan); Aarstad, Erik [University College of London, Institute of Nuclear Medicine, London (United Kingdom); Drzezga, Alexander [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Matsunari, Ichiro [Medical and Pharmacological Research Center Foundation, Clinical Research Department, Hakui City, Ishikawa (Japan); Henriksen, Gjermund [University of Oslo, Department of Chemistry, Oslo (Norway); Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

    2010-06-15

    The recent development in radiosynthesis of the {sup 11}C-carbamate function increases the potential of [{sup 11}C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor ({kappa}-OR) with PET. In the present study, [{sup 11}C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [{sup 11}C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [{sup 11}C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for {kappa}-OR (K{sub i} = 0.02 {+-}0.01 nM) with excellent selectivity over {mu}-OR (6 x 10{sup 2}-fold) and {delta}-OR (2 x 10{sup 4}-fold). PET imaging revealed a volume of distribution (V{sub T}) pattern consistent with the known distribution of {kappa}-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [{sup 11}C]GR103545 is selective for {kappa}-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

  11. A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae.

    Science.gov (United States)

    Denoël, Philippe; Philipp, Mario T; Doyle, Lara; Martin, Dale; Carletti, Georges; Poolman, Jan T

    2011-07-26

    Infections caused by Streptococcus pneumoniae are a major cause of mortality throughout the world. Protein-based pneumococcal vaccines are envisaged to replace or complement the current polysaccharide-based vaccines. In this context, detoxified pneumolysin (dPly) and pneumococcal histidine triad protein D (PhtD) are two potential candidates for incorporation into pneumococcal vaccines. In this study, the protective efficacy of a PhtD-dPly vaccine was evaluated in a rhesus macaque (Macaca mulatta) model of pneumonia. The animals were immunized twice with 10 μg of PhtD and 10 μg of dPly formulated in the Adjuvant System AS02 or with AS02 alone, before they were challenged with a 19F pneumococcal strain. The survival was significantly higher in the protein-vaccinated group and seemed to be linked to the capacity to greatly reduce bacterial load within the first week post-challenge. Vaccination elicited high concentrations of anti-PhtD and anti-Ply antibodies and a link was found between survival and antibody levels. In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies.

  12. Cytotoxic capacity of SIV-specific CD8(+ T cells against primary autologous targets correlates with immune control in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Daniel Mendoza

    2013-02-01

    Full Text Available Although the study of non-human primates has resulted in important advances for understanding HIV-specific immunity, a clear correlate of immune control over simian immunodeficiency virus (SIV replication has not been found to date. In this study, CD8(+ T-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (RM SIV infection model as has been suggested in chronic HIV infection. SIVmac251-infected human reverse transcriptase (hTERT-transduced CD4(+ T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4(+ T-cell elimination (ICE. Twenty-three SIV-infected rhesus macaques with widely varying plasma viral RNA levels were evaluated in a blinded fashion. Nineteen of 23 subjects (83% were correctly classified as long-term nonprogressor/elite controller (LTNP/EC, slow progressor, progressor or SIV-negative rhesus macaques based on measurements of ICE (weighted Kappa 0.75. LTNP/EC had higher median ICE than progressors (67.3% [22.0-91.7%] vs. 23.7% [0.0-58.0%], p = 0.002. In addition, significant correlations between ICE and viral load (r = -0.57, p = 0.01, and between granzyme B delivery and ICE (r = 0.89, p<0.001 were observed. Furthermore, the CD8(+ T cells of LTNP/EC exhibited higher per-cell cytotoxic capacity than those of progressors (p = 0.004. These findings support that greater lytic granule loading of virus-specific CD8(+ T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans. Therefore, such measurements appear to represent a correlate of control of viral replication in chronic SIV infection and their role as predictors of immunologic control in the vaccine setting should be evaluated.

  13. Social and nonsocial content differentially modulates visual attention and autonomic arousal in Rhesus macaques.

    Science.gov (United States)

    Machado, Christopher J; Bliss-Moreau, Eliza; Platt, Michael L; Amaral, David G

    2011-01-01

    The sophisticated analysis of gestures and vocalizations, including assessment of their emotional valence, helps group-living primates efficiently navigate their social environment. Deficits in social information processing and emotion regulation are important components of many human psychiatric illnesses, such as autism, schizophrenia and social anxiety disorder. Analyzing the neurobiology of social information processing and emotion regulation requires a multidisciplinary approach that benefits from comparative studies of humans and animal models. However, many questions remain regarding the relationship between visual attention and arousal while processing social stimuli. Using noninvasive infrared eye-tracking methods, we measured the visual social attention and physiological arousal (pupil diameter) of adult male rhesus monkeys (Macaca mulatta) as they watched social and nonsocial videos. We found that social videos, as compared to nonsocial videos, captured more visual attention, especially if the social signals depicted in the videos were directed towards the subject. Subject-directed social cues and nonsocial nature documentary footage, compared to videos showing conspecifics engaging in naturalistic social interactions, generated larger pupil diameters (indicating heightened sympathetic arousal). These findings indicate that rhesus monkeys will actively engage in watching videos of various kinds. Moreover, infrared eye tracking technology provides a mechanism for sensitively gauging the social interest of presented stimuli. Adult male rhesus monkeys' visual attention and physiological arousal do not always trend in the same direction, and are likely influenced by the content and novelty of a particular visual stimulus. This experiment creates a strong foundation for future experiments that will examine the neural network responsible for social information processing in nonhuman primates. Such studies may provide valuable information relevant to

  14. Early Predictors of Impaired Social Functioning in Male Rhesus Macaques (Macaca mulatta)

    Science.gov (United States)

    Del Rosso, Laura A.; Seil, Shannon K.; Calonder, Laura A.; Madrid, Jesus E.; Bone, Kyle J.; Sherr, Elliott H.; Garner, Joseph P.; Capitanio, John P.; Parker, Karen J.

    2016-01-01

    Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1–4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys’ motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets

  15. Social and nonsocial content differentially modulates visual attention and autonomic arousal in Rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Christopher J Machado

    Full Text Available The sophisticated analysis of gestures and vocalizations, including assessment of their emotional valence, helps group-living primates efficiently navigate their social environment. Deficits in social information processing and emotion regulation are important components of many human psychiatric illnesses, such as autism, schizophrenia and social anxiety disorder. Analyzing the neurobiology of social information processing and emotion regulation requires a multidisciplinary approach that benefits from comparative studies of humans and animal models. However, many questions remain regarding the relationship between visual attention and arousal while processing social stimuli. Using noninvasive infrared eye-tracking methods, we measured the visual social attention and physiological arousal (pupil diameter of adult male rhesus monkeys (Macaca mulatta as they watched social and nonsocial videos. We found that social videos, as compared to nonsocial videos, captured more visual attention, especially if the social signals depicted in the videos were directed towards the subject. Subject-directed social cues and nonsocial nature documentary footage, compared to videos showing conspecifics engaging in naturalistic social interactions, generated larger pupil diameters (indicating heightened sympathetic arousal. These findings indicate that rhesus monkeys will actively engage in watching videos of various kinds. Moreover, infrared eye tracking technology provides a mechanism for sensitively gauging the social interest of presented stimuli. Adult male rhesus monkeys' visual attention and physiological arousal do not always trend in the same direction, and are likely influenced by the content and novelty of a particular visual stimulus. This experiment creates a strong foundation for future experiments that will examine the neural network responsible for social information processing in nonhuman primates. Such studies may provide valuable information

  16. Peptide-binding motifs associated with MHC molecules common in Chinese rhesus macaques are analogous to those of human HLA supertypes and include HLA-B27-like alleles

    DEFF Research Database (Denmark)

    Mothé, Bianca R.; Southwood, Scott; Sidney, John

    2013-01-01

    that they may be a better model for HIV. Nevertheless, the specific mechanism(s) accounting for these kinetics remains unclear. The study of major histocompatibility complex (MHC) molecules, including their MHC/peptide-binding motifs, provides valuable information for measuring cellular immune responses...... in humans. All six alleles characterized in the present study were found to have specificities analogous to HLA supertype alleles. These data contribute to the concept that Chinese rhesus macaque MHC immunogenetics is more similar to HLA than their Indian rhesus macaque counterparts and thereby warrants...

  17. The efficacy of diazepam treatment for the management of acute wounding episodes in captive rhesus macaques.

    Science.gov (United States)

    Tiefenbacher, Stefan; Fahey, Michele A; Rowlett, James K; Meyer, Jerrold S; Pouliot, Amber L; Jones, Brenda M; Novak, Melinda A

    2005-08-01

    The spontaneous development of self-injurious behavior (SIB) in singly housed monkeys poses a challenge for their management and well-being in captivity. Relatively little information is available on effective treatments for SIB. This study examined the effects of diazepam (Valium) on self-wounding and other abnormal behaviors in eight individually housed male rhesus monkeys (Macaca mulatta). Each monkey's response to an anxiolytic dose of diazepam (1 mg/kg or greater orally) was compared with the animal's behavior during drug-free periods. When examined across all animals, treatment with diazepam did not significantly alter wounding frequency or rates of self-directed biting without wounding. However, closer examination of the data revealed that four of the animals showed significant decreases in self-biting and wounding frequency (positive responders, PR group), whereas the remaining monkeys showed a trend towards increased wounding frequency (negative responders, NR group). Subsequent examination of colony and veterinary records demonstrated that compared with NR monkeys, PR monkeys had spent significantly more years in individual cage housing and had experienced a greater number of minor veterinary procedures. PR animals also were significantly less likely to have a documented history of self-biting behavior. Our findings suggest that SIB is not a homogeneous disorder in rhesus monkeys; rather, distinct subtypes exist that require different treatment approaches.

  18. Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque.

    Science.gov (United States)

    Liao, Chenghong; Han, Qian; Ma, Yuanye; Su, Bing

    2016-09-30

    Degradation of visual function is a common phenomenon during aging and likely mediated by change in the impaired central visual pathway. Treatment with GABA or its agonist could recover the ability of visual neurons in the primary visual cortex of senescent macaques. However, little is known about how GABAergic system change is related to the aged degradation of visual function in nonhuman primate. With the use of quantitative PCR method, we measured the expression change of 24 GABA related genes in the primary visual cortex (Brodmann's 17) of different age groups. In this study, both of mRNA and protein of glutamic acid decarboxylase (GAD65) were measured by real-time RT-PCR and Western blot, respectively. Results revealed that the level of GAD65 message was not significantly altered, but the proteins were significantly decreased in the aged monkey. As GAD65 plays an important role in GABA synthesis, the down-regulation of GAD65 protein was likely the key factor leading to the observed GABA reduction in the primary visual cortex of the aged macaques. In addition, 7 of 14 GABA receptor genes were up-regulated and one GABA receptor gene was significantly reduced during aging process even after Banjamini correction for multiple comparisons (Pvisual dysfunctions and most of GABA receptor genes induce a clear indication of compensatory effect for the reduced GABA release in the healthy aged monkey cortex.

  19. Comparison of the Effects of Ketamine, Ketamine–Medetomidine, and Ketamine–Midazolam on Physiologic Parameters and Anesthesia-Induced Stress in Rhesus (Macaca mulatta) and Cynomolgus (Macaca fascicularis) Macaques

    OpenAIRE

    Lee, Vanessa K; Flynt, Kendall S; Haag, Lauren M; Taylor, Douglas K.

    2010-01-01

    This study compared the cardiovascular, respiratory, anesthetic, and glucocorticoid effects of ketamine alone with ketamine–medetomidine and ketamine–midazolam in rhesus and cynomolgus macaques. Macaques were given either intramuscular ketamine (10 mg/kg), intramuscular ketamine–medetomidine (3 mg/kg; 0.15 mg/kg), or oral midazolam (1 mg/kg) followed by intramuscular ketamine (8 mg/kg). The addition of medetomidine, but not midazolam, provided muscle relaxation and abolishment of reflexes tha...

  20. Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.

    Science.gov (United States)

    Johnson, Reed F; Dodd, Lori E; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A; Jett, Catherine; Bernbaum, John G; Ragland, Dan R; St Claire, Marisa; Byrum, Russell; Paragas, Jason; Blaney, Joseph E; Jahrling, Peter B

    2011-12-20

    Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens.

  1. Cloning and functional analysis of the rhesus macaque ABCG2 gene. Forced expression confers an SP phenotype among hematopoietic stem cell progeny in vivo.

    Science.gov (United States)

    Ueda, Takahiro; Brenner, Sebastian; Malech, Harry L; Langemeijer, Saskia M; Perl, Shira; Kirby, Martha; Phang, Oswald A; Krouse, Allen E; Donahue, Robert E; Kang, Elizabeth M; Tisdale, John F

    2005-01-14

    Hematopoietic cells can be highly enriched for repopulating ability based upon the efflux of the fluorescent Hoechst 33342 dye by sorting for SP (side population) cells, a phenotype attributed to expression of ABCG2, a member of the ABC transporter superfamily. Intriguingly, murine studies suggest that forced ABCG2 expression prevents hematopoietic differentiation. We cloned the full-length rhesus ABCG2 and introduced it into a retroviral vector. ABCG2-transduced human peripheral blood progenitor cells (PBPCs) acquired the SP phenotype but showed significantly reduced growth compared with control. Two rhesus macaques received autologous PBPCs split for transduction with the ABCG2 or control vectors. Marking levels were similar between fractions with no discrepancy between bone marrow and peripheral blood marking. Analysis for the SP phenotype among bone marrow and mature blood populations confirmed ABCG2 expression at levels predicted by vector copy number long term, demonstrating no block to differentiation in the large animal. In vitro studies showed selective protection against mitoxantrone among ABCG2-transduced rhesus PBPCs. Our results confirm the existence of rhesus ABCG2, establish its importance in conferring the SP phenotype, suggest no detrimental effect of its overexpression upon differentiation in vivo, and imply a potential role for its overexpression as an in vivo selection strategy for gene therapy applications.

  2. Molecular Analysis of a Novel Simian Virus 40 (SV40) Type in Rhesus Macaques and Evidence for Double Infections with the Classical SV40 Type▿†

    Science.gov (United States)

    Fagrouch, Zahra; Karremans, Kevin; Deuzing, Ilona; van Gessel, Sabine; Niphuis, Henk; Bogers, Willy; Verschoor, Ernst J.

    2011-01-01

    The incidence of simian virus 40 (SV40) infections in rhesus macaques infected with simian-human immunodeficiency viruses (SHIV) and in uninfected animals was determined using PCR. Rates varied from 5% in peripheral blood mononuclear cells of uninfected monkeys to 19.6% in SHIV-infected macaques. Much higher detection rates, up to 75%, were found in lymph nodes and spleen samples of SHIV-infected animals. Sequence analysis of PCR amplicons revealed that they form two genetic clusters, one containing the majority of known SV40 strains and the other formed by variants with 7% genetic difference. Based on this difference, we propose two SV40 types: “type 1” or “classical type” for the majority of SV40 strains and “type 2” for the novel SV40 variants. The genome of one variant, SV40-Ri257, was completely sequenced and analyzed. The agnogene of SV40-Ri257 extends into the VP2 open reading frame and encodes a typical agnoprotein fused to a C-terminal hydrophobic region. The transcriptional control region (TCR) of SV40-Ri257 is the least conserved region compared to type 1 viruses. Particularly, the 3′ end of the TCR, containing the early promoter and enhancer region, exhibits considerable variation. Further analysis of SHIV-infected macaques with type-specific PCRs revealed that the TCR of type 1 was completely conserved, whereas this region in type 2 varied considerably within the early enhancer region. We provide evidence here for the existence of a novel SV40 type in rhesus macaques and show that double infections with both types frequently occur. PMID:21307214

  3. Molecular analysis of a novel simian virus 40 (SV40) type in rhesus macaques and evidence for double infections with the classical SV40 type.

    Science.gov (United States)

    Fagrouch, Zahra; Karremans, Kevin; Deuzing, Ilona; van Gessel, Sabine; Niphuis, Henk; Bogers, Willy; Verschoor, Ernst J

    2011-04-01

    The incidence of simian virus 40 (SV40) infections in rhesus macaques infected with simian-human immunodeficiency viruses (SHIV) and in uninfected animals was determined using PCR. Rates varied from 5% in peripheral blood mononuclear cells of uninfected monkeys to 19.6% in SHIV-infected macaques. Much higher detection rates, up to 75%, were found in lymph nodes and spleen samples of SHIV-infected animals. Sequence analysis of PCR amplicons revealed that they form two genetic clusters, one containing the majority of known SV40 strains and the other formed by variants with 7% genetic difference. Based on this difference, we propose two SV40 types: "type 1" or "classical type" for the majority of SV40 strains and "type 2" for the novel SV40 variants. The genome of one variant, SV40-Ri257, was completely sequenced and analyzed. The agnogene of SV40-Ri257 extends into the VP2 open reading frame and encodes a typical agnoprotein fused to a C-terminal hydrophobic region. The transcriptional control region (TCR) of SV40-Ri257 is the least conserved region compared to type 1 viruses. Particularly, the 3' end of the TCR, containing the early promoter and enhancer region, exhibits considerable variation. Further analysis of SHIV-infected macaques with type-specific PCRs revealed that the TCR of type 1 was completely conserved, whereas this region in type 2 varied considerably within the early enhancer region. We provide evidence here for the existence of a novel SV40 type in rhesus macaques and show that double infections with both types frequently occur.

  4. [Cellular composition of the lymph nodes of monkeys (rhesus macaque) under normal and experimental conditions].

    Science.gov (United States)

    Rusina, A K

    1978-01-01

    By means of mathematical methods, quantitative and qualitative changes were studied in different structural components of the mesenteric (ileocecal) lymph nodes in normal monkeys (Macaca rhesus) and under per os administration of Salmonella typhi murium, streptomycin-dependent. Cellular composition was calculated in the cortical plateau, cortical (lymphoid) cords and in follicules. Average percent of every cell type was determined. Vaccine administration, was stated to inhibit cytopoiesis in the cortical plateau and in the follicules with light centers. An inverse correlation was noted between the content of small and medium size lymphocytes. Different reactivity of certain structural components in the lymph nodes was demonstrated. As a response to the vaccine administration, plasmocellular acidophilic and macrophagal reactions were most pronounced in the cortical (lymphoid) cords.

  5. Effects of early life adversity on cortisol/salivary alpha-amylase symmetry in free-ranging juvenile rhesus macaques.

    Science.gov (United States)

    Petrullo, Lauren A; Mandalaywala, Tara M; Parker, Karen J; Maestripieri, Dario; Higham, James P

    2016-11-01

    Early life adversity (ELA) affects physiological and behavioral development. One key component is the relationship between the developing Hypothalamic-Pituitary-Adrenal (HPA) axis and the Sympathetic Nervous System (SNS). Recent studies suggest a relationship between early life adversity and asymmetry in cortisol (a measure of HPA activation) and salivary alpha-amylase (sAA: a correlate of SNS activation) responses to stress among human children, but to our knowledge there have been no comparable studies in nonhumans. Here, we investigate the responses of these two analytes in "low stress" and "high stress" situations in free-ranging juvenile rhesus macaques (Macaca mulatta) on Cayo Santiago, Puerto Rico. Behavioral data on maternal maltreatment were collected during the first 3months of life to determine individual rates of ELA, and saliva samples were collected from subjects noninvasively during juvenility. Irrespective of ELA, salivary alpha-amylase levels were lower in low stress situations and higher in high stress situations. For cortisol however, high ELA subjects exhibited higher low stress concentrations and blunted acute responses during high stress situations compared to moderate and low ELA subjects. Cortisol and sAA values were positively correlated among low ELA subjects, suggesting symmetry, but were uncorrelated or negatively correlated among moderate and high ELA subjects, suggesting asymmetry in these individuals. These findings indicate dysregulation of the stress response among juveniles maltreated during infancy: specifically, attenuated cortisol reactivity coupled with typical sAA reactivity characterize the stress response profiles of juveniles exposed to higher rates of ELA during the first 3months of life.

  6. Effect of IL-7 therapy on naïve and memory T cell homeostasis in aged rhesus macaques

    Science.gov (United States)

    Okoye, Afam A.; Rohankhedkar, Mukta; Konfe, Audrie L.; Abana, Chike O.; Reyes, Matthew D.; Clock, Joseph A.; Duell, Derick M.; Sylwester, Andrew W.; Sammader, Partha; Legasse, Alfred W.; Park, Byung S.; Axthelm, Michael K.; Nikolich-Žugich, Janko; Picker, Louis J.

    2015-01-01

    Aging is associated with gradual deterioration of adaptive immune function, a hallmark of which is the profound loss of naïve T cells (TN) associated with decline in thymic output and export of new cells into the peripheral T cell pool. Since the lymphotropic cytokine IL-7 plays crucial roles in both development of TN in the thymus and TN homeostasis in the periphery, we sought to determine the extent to which therapeutic administration of IL-7 could reverse TN deficiency in aging rhesus macaques (RM), either by enhancement of the demonstrably reduced thymopoiesis or by peripheral TN expansion. Our results indicate that treatment of both adult (8–15 years) and old (>20 years) RM with recombinant simian IL-7 (rsIL-7) results in only transient increases in peripheral CD4+ and CD8+ TN numbers with no long-term benefit, even with repeated therapy. This transient effect was due to peripheral TN expansion and not enhanced thymic function, and appeared to be limited by induction of IL-7 non-responsiveness. However, rsIL-7 therapy had a more promising effect on the central memory T cell (TCM) population (both CD4+ and CD8+) in adult and old RM, doubling the numbers of these cells in circulation and maintaining this larger population long-term. IL-7 therapy didn't reduce TCR diversity of the memory T cell compartment, suggesting that rsIL-7-induced expansion was symmetrical. Thus, although rsIL-7 failed to counter age-associated TN loss, the ability of this therapy to expand clonotypically diverse CD4+ and CD8+ TCM populations might potentially improve adaptive immune responsiveness in the elderly. PMID:26416281

  7. Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

    Science.gov (United States)

    Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

    2016-08-01

    Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

  8. Social learning as a way to overcome choice-induced preferences? Insights from humans and rhesus macaques.

    Directory of Open Access Journals (Sweden)

    ELISABETTA eMONFARDINI

    2012-09-01

    Full Text Available Much theoretical attention is currently devoted to social learning. Yet, empirical studies formally comparing its effectiveness relative to individual learning are rare. Here, we focus on free choice, which is at the heart of individual reward-based learning, but absent in social learning. Choosing among two equally valued options is known to create a preference for the selected option in both humans and monkeys. We thus surmised that social learning should be more helpful when choice-induced preferences retard individual learning than when they optimize it. To test this prediction, the same task requiring to find which among two items concealed a reward was applied to rhesus macaques and humans. The initial trial was individual or social, rewarded or unrewarded. Learning was assessed on the second trial. Choice-induced preference strongly affected individual learning. Monkeys and humans performed much more poorly after an initial negative choice than after an initial positive choice. Comparison with social learning verified our prediction. For negative outcome, social learning surpassed or at least equaled individual learning in all subjects. For positive outcome, the predicted superiority of individual learning did occur in a majority of subjects (5/6 monkeys and 6/12 humans. A minority kept learning better socially though, perhaps due to a more dominant/aggressive attitude toward peers. Poor learning from errors due to over-valuation of personal choices is among the decision-making biases shared by humans and animals. The present study suggests that choice-immune social learning may help curbing this potentially harmful tendency. Learning from successes is an easier path. The present data suggest that whether one tends to walk it alone or with a peer's help might depend on the social dynamics within the actor/observer dyad.

  9. Alphavirus replicon-based adjuvants enhance the immunogenicity and effectiveness of Fluzone ® in rhesus macaques.

    Science.gov (United States)

    Carroll, Timothy D; Matzinger, Shannon R; Barro, Mario; Fritts, Linda; McChesney, Michael B; Miller, Christopher J; Johnston, Robert E

    2011-01-29

    Venezuelan equine encephalitis virus replicon particles (VRP) without a transgene (null VRP) have been used to adjuvant effective humoral [1], cellular [2], and mucosal [3] immune responses in mice. To assess the adjuvant activity of null VRP in the context of a licensed inactivated influenza virus vaccine, rhesus monkeys were immunized with Fluzone(®) alone or Fluzone(®) mixed with null VRP and then challenged with a human seasonal influenza isolate, A/Memphis/7/2001 (H1N1). Compared to Fluzone(®) alone, Fluzone(®)+null VRP immunized animals had stronger influenza-specific CD4(+) T cell responses (4.4 fold) with significantly higher levels of virus-specific IFN-γ (7.6 fold) and IL-2 (5.3 fold) producing CD4+ T cells. Fluzone(®)+null VRP immunized animals also had significantly higher plasma anti-influenza IgG (pVRP immunization was 1.2 log greater (pVRP immunized monkeys had a significantly lower level of viral replication (pVRP immunized monkeys immediately after challenge. There were significant inverse correlations between influenza RNA levels in tracheal lavages and plasma anti-influenza HI and IgG anti-influenza antibody titers prior to challenge. These results demonstrate that null VRP dramatically improve both the immunogenicity and protection elicited by a licensed inactivated influenza vaccine.

  10. The Peculiar Evolution of Apolipoprotein(a) in Human and Rhesus Macaque

    Science.gov (United States)

    Pesole, G.; Gerardi, A.; di-Jeso, F.; Saccone, C.

    1994-01-01

    Apo(a) is a low density lipoprotein homologous to plasminogen and has been shown to be involved in coronary atheroschlerosis. In the present paper we will try to analyze the interesting evolutionary pattern of Apo(a). The plasminogen gene contains 5 cysteine-rich sequences, called kringles, followed by a protease domain. Apo(a), probably arisen by duplication of an ancestral plasminogen gene, contains many tandemly repeated copies of a sequence domain similar to the fourth kringle of plasminogen, 37 in human and at least 10 in the partially sequenced gene of rhesus, and the protease domain. We have found that the upstream kringles of apo(a) undergo Molecular Drive-like processes that produce high intraspecies similarity, whereas the downstream kringles evolve in a molecular clock-like manner and show an high interspecies sequence similarity. The latter regions are obviously suitable for dating the duplication event by which Apo(a) arose from plasminogen, but only if they evolve at the same rate in the two genes. Thus, we propose a ``Molecular Clock Test'' for assessing whether the comparison of two paralogous genes (or gene regions) can give reliable information on the dating of their origin by duplication. Applying this test to the kringle-4 domain of apo(a) and plasminogen gene, we demonstrate that the separation between the two genes by duplication dates back at about 90 Mya immediately before the radiation of mammals. PMID:8138162

  11. Age-related neurochemical changes in the rhesus macaque inferior colliculus.

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    James eEngle

    2014-04-01

    Full Text Available Age-related hearing loss (ARHL is marked by audiometric hearing deficits that propagate along the auditory pathway. Neurochemical changes as a function of aging have also been identified in neurons along the auditory pathway in both rodents and carnivores, however, very little is known about how these neurochemicals change in the non-human primate. To examine how these compensatory neurochemical changes relate to normal aging and audiometric sensitivity along the auditory pathway, we collected auditory brainstem responses (ABRs and brain specimens from seven rhesus monkeys spanning in age from 15 to 35 years old, and examined the relationship between click evoked ABR thresholds and the ABR evoked pure tone average and changes in the number of parvalbumin and NADPH-diaphorase positive cells in the auditory midbrain. We found that the number of parvalbumin positive cells in the central nucleus and the surrounding cortex regions of the inferior colliculus were strongly correlated with advancing age and ABR pure tone average. We also found that the numbers of NADPHd positive cells in these same regions were not associated with normal aging or changes in the ABR thresholds. These findings suggest that the auditory midbrain undergoes an up-regulation of parvalbumin expressing neurons with aging that is related to changes in the processing of frequencies across the audiometric range.

  12. Daughter dearest: Sex-biased calcium in mother's milk among rhesus macaques.

    Science.gov (United States)

    Hinde, Katie; Foster, Alison B; Landis, Lauren M; Rendina, Danielle; Oftedal, Olav T; Power, Michael L

    2013-05-01

    Mother's milk provides building blocks necessary for infant development and growth postnatally. Minerals in milk are particularly important for infant skeletal development and may reflect maternal characteristics that are associated with the capacity to synthesize milk and sex-specific developmental priorities of the infant. Using a large sample of mother-infant dyads assigned to the outdoor breeding colony at the California National Primate Research Center (N=104), we investigated the relationship of milk calcium (Ca) and phosphorus (P) concentrations and the ratio of Ca/P to maternal and infant characteristics and to other milk variables. Ca and P are largely associated with casein micelles, and as expected, both Ca and P were positively correlated with protein concentrations in milk. Neither Ca nor P concentrations were associated with maternal parity. Mothers rearing daughters tended to produce higher mean Ca concentration in milk, and consequently a higher Ca/P ratio, than did mothers rearing sons, even though protein concentration was not elevated. These results suggest that the Ca/P ratio in rhesus milk may have been under separate selective pressure from protein content to facilitate the accelerated rate of skeletal calcification that has been observed in female Macaca mulatta infants.

  13. Use of assisted reproductive technologies in the propagation of rhesus macaque offspring.

    Science.gov (United States)

    Wolf, D P; Thormahlen, S; Ramsey, C; Yeoman, R R; Fanton, J; Mitalipov, S

    2004-08-01

    The assisted reproductive technologies (ARTs) as tailored to the production of rhesus monkeys at the Oregon National Primate Research Center (ONPRC) are described. Efficient fertilization of mature oocytes recovered by aspiration from females subjected to follicular stimulation was achieved with fresh or frozen sperm by intracytoplasmic sperm injection (ICSI). Embryo development to the early cleavage stage occurred at high frequency. Cryopreserved embryos showed high postthaw survival and were also transferred in efforts to establish pregnancies. Three methods of transfer were evaluated, two involving embryo placement into the oviduct, laparoscopy and minilaparotomy, and a nonsurgical, transcervical approach that resulted in uterine deposition. Early cleaving embryos (Days 1-4) were transferred into the oviducts of synchronized recipients with optimal results and pregnancy rates of up to 36%. Pregnancy rates were similar when two fresh or frozen embryos were transferred (28- 30%), although more than two embryos had to be thawed to compensate for embryo loss during freeze-thawing. Normal gestational lengths, birth weights, and growth curves were seen with ART-produced infants compared with infants produced by natural mating in the timed mated breeding (TMB) colony at the ONPRC. In 72 singleton pregnancies established following the transfer of ART-produced embryos, the live-birth rate, at 87.5%, was statistically identical to that for the TMB colony. Further development of the ARTs should result in increasing use of these techniques to augment conventional approaches to propagating monkeys, especially those of defined genotypes.

  14. Transfer of a serial representation between two distinct tasks by rhesus macaques.

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    Greg Jensen

    Full Text Available Do animals form task-specific representations, or do those representations take a general form that can be applied to qualitatively different tasks? Rhesus monkeys (Macaca mulatta learned the ordering of stimulus lists using two different serial tasks, in order to test whether prior experience in each task could be transfered to the other, enhancing performance. The simultaneous chaining paradigm delivered rewards only after subjects responded in the correct order to all stimuli displayed on a touch sensitive video monitor. The transitive inference paradigm presented pairs of items and delivered rewards when subjects selected the item with the lower ordinal rank. After learning a list in one paradigm, subjects' knowledge of that list was tested using the other paradigm. Performance was enhanced from the very start of transfer training. Transitive inference performance was characterized by 'symbolic distance effects,' whereby the ordinal distance between stimuli in the implied list ordering was strongly predictive of the probability of a correct response. The patterns of error displayed by subjects in both tasks were best explained by a spatially coded representation of list items, regardless of which task was used to learn the list. Our analysis permits properties of this representation to be investigated without the confound of verbal reasoning.

  15. Effects of Simian Betaretrovirus Serotype 1 (SRV1) Infection on the Differentiation of Hematopoietic Progenitor Cells (CD34+) Derived from Bone Marrow of Rhesus Macaques (Macaca mulatta)

    Science.gov (United States)

    Montiel, Nestor A; Todd, Patricia A; Yee, JoAnn; Lerche, Nicholas W

    2012-01-01

    Peripheral blood cytopenias, particularly persistent anemia and neutropenia, are commonly associated with simian betaretrovirus infection of Asian monkeys of the genus Macaca. The pathogenetic mechanisms underlying these hematologic abnormalities are not well understood. The current study investigated the in vitro tropism of simian betaretrovirus (SRV) for both hematopoietic progenitor (CD34+) and stromal cells obtained from rhesus macaque bone marrow and assessed the effects of infection on hematopoietic progenitor cell differentiation in vitro. After in vitro exposure, SRV proviral DNA could be demonstrated by real-time PCR in cells and the reverse transcriptase assay in supernatants from SRV-exposed progenitor-associated stroma, but not in differentiated colonies derived from SRV-exposed progenitors. Furthermore, in vitro exposure involving cell–cell contact of uninfected CD34+ progenitor cells with SRV-infected stromal cells resulted in a statistically significant reduction in granulocyte–macrophage colony formation in absence of detectable SRV-infection of progenitor cells. Reduction in colony formation occurred in a ‘dose-dependent’ fashion with increasing contact time. No effects on erythroid lineages and RBC differentiation were noted. Our results suggest that hematologic abnormalities observed during SRV disease (natural or experimental) of rhesus macaques may not result from direct effects of viral infection of progenitor cell populations, but rather be (at least in part) a consequence of SRV infection of supportive bone marrow stroma with secondary effects on differentiation of associated progenitor cells. PMID:22330653

  16. Correlation between genotypes of tRNA-linked short tandem repeats in Entamoeba nuttalli isolates and the geographical distribution of host rhesus macaques.

    Science.gov (United States)

    Feng, Meng; Komiyama, Tomoyoshi; Yanagi, Tetsuo; Cheng, Xunjia; Sherchand, Jeevan B; Tachibana, Hiroshi

    2014-01-01

    Several polymorphic markers, including serine-rich protein genes, have been used for the genotyping of isolates from the morphologically indistinguishable protozoan parasites Entamoeba histolytica, Entamoeba dispar, and Entamoeba nuttalli. Genotypes of tRNA-linked short tandem repeats (STRs) are highly polymorphic, but the correlation with geographical distribution is unknown. We have recently isolated 15 E. nuttalli strains from wild rhesus macaques in four locations in Kathmandu Valley, Nepal. The sequences of the serine-rich protein genes of the E. nuttalli strains differed among the four locations. In this study, we analyzed tRNA-linked STRs in six loci of the 15 strains. Two genotypes were found in loci N-K2, R-R, and S(TGA)-D, three in locus S-Q, and five in locus D-A. In locus A-L, one major genotype and ten minor genotypes were found, resulting in mixtures of two to six genotypes in eight strains. By combination of the main genotypes in the six loci, the 15 strains were divided into nine genotypes. The genotypes observed in E. nuttalli strains were quite different from those in E. histolytica and E. dispar. A phylogenetic tree constructed from tRNA-linked STRs in the six loci reflected the different places of isolation. These results suggest that sequence diversity of tRNA-linked STRs in E. nuttalli occurs with relatively high frequency and might be a marker of geographical distribution of host rhesus macaques, even in limited areas.

  17. CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques

    Science.gov (United States)

    Saito, Naoki; Chono, Hideto; Shibata, Hiroaki; Ageyama, Naohide; Yasutomi, Yasuhiro; Mineno, Junichi

    2014-01-01

    MazF, an endoribonuclease encoded by Escherichia coli, specifically cleaves the ACA (adenine–cytosine–adenine) sequence of single-stranded RNAs. Conditional expression of MazF under the control of the HIV-1 LTR promoter rendered CD4+ T cells resistant to HIV-1 replication without affecting cell growth. To investigate the safety, persistence and efficacy of MazF-modified CD4+ T cells in a nonhuman primate model in vivo, rhesus macaques were infected with a pathogenic simian/human immunodeficiency virus (SHIV) and transplanted with autologous MazF-modified CD4+ T cells. MazF-modified CD4+ T cells were clearly detected throughout the experimental period of more than 6 months. The CD4+ T cell count values increased in all four rhesus macaques. Moreover, the transplantation of the MazF-modified CD4+ T cells was not immunogenic, and did not elicit cellular or humoral immune responses. These data suggest that the autologous transplantation of MazF-modified CD4+ T cells in the presence of SHIV is effective, safe and not immunogenic, indicating that this is an attractive strategy for HIV-1 gene therapy. PMID:24914931

  18. CD4(+) T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques.

    Science.gov (United States)

    Saito, Naoki; Chono, Hideto; Shibata, Hiroaki; Ageyama, Naohide; Yasutomi, Yasuhiro; Mineno, Junichi

    2014-06-10

    MazF, an endoribonuclease encoded by Escherichia coli, specifically cleaves the ACA (adenine-cytosine-adenine) sequence of single-stranded RNAs. Conditional expression of MazF under the control of the HIV-1 LTR promoter rendered CD4(+) T cells resistant to HIV-1 replication without affecting cell growth. To investigate the safety, persistence and efficacy of MazF-modified CD4(+) T cells in a nonhuman primate model in vivo, rhesus macaques were infected with a pathogenic simian/human immunodeficiency virus (SHIV) and transplanted with autologous MazF-modified CD4(+) T cells. MazF-modified CD4(+) T cells were clearly detected throughout the experimental period of more than 6 months. The CD4(+) T cell count values increased in all four rhesus macaques. Moreover, the transplantation of the MazF-modified CD4(+) T cells was not immunogenic, and did not elicit cellular or humoral immune responses. These data suggest that the autologous transplantation of MazF-modified CD4(+) T cells in the presence of SHIV is effective, safe and not immunogenic, indicating that this is an attractive strategy for HIV-1 gene therapy.

  19. The HMW1 and HMW2 Adhesins Enhance the Ability of Nontypeable Haemophilus influenzae To Colonize the Upper Respiratory Tract of Rhesus Macaques.

    Science.gov (United States)

    Rempe, Katherine A; Porsch, Eric A; Wilson, Jolaine M; St Geme, Joseph W

    2016-10-01

    Nontypeable Haemophilus influenzae (NTHi) initiates infection by colonizing the upper respiratory tract and is a common cause of localized respiratory tract disease. Previous work has established that the NTHi HMW1 and HMW2 proteins are potent adhesins that mediate efficient in vitro adherence to cultured human respiratory epithelial cells. In this study, we used a rhesus macaque model to assess the contributions of HMW1 and HMW2 to in vivo colonization. In experiments involving inoculation of individual isogenic derivatives of NTHi strain 12, the parent strain expressing both HMW1 and HMW2 and the mutant strains expressing either HMW1 or HMW2 were able to colonize more frequently than the double mutant strain lacking HMW1 and HMW2. In competition experiments, the parent strain efficiently outcompeted the double mutant lacking HMW1 and HMW2. Colonization with strains expressing HMW2 resulted in development of antibody against HMW2 in a number of the animals, demonstrating that colonization can stimulate an antibody response. In conclusion, we have established that the HMW1 and HMW2 adhesins play a major role in facilitating colonization of the upper respiratory tract of rhesus macaques, in some cases associated with stimulation of an immune response.

  20. Development of a Rotavirus-Shedding Model in Rhesus Macaques, Using a Homologous Wild-Type Rotavirus of a New P Genotype

    Science.gov (United States)

    McNeal, Monica M.; Sestak, Karol; Choi, Anthony H.-C.; Basu, Mitali; Cole, Michael J.; Aye, Pyone P.; Bohm, Rudolf P.; Ward, Richard L.

    2005-01-01

    Although there are several reports on rotavirus inoculation of nonhuman primates, no reliable model exists. Therefore, this study was designed to develop a rhesus macaque model for rotavirus studies. The goals were to obtain a wild-type macaque rotavirus and evaluate it as a challenge virus for model studies. Once rotavirus was shown to be endemic within the macaque colony at the Tulane National Primate Research Center, stool specimens were collected from juvenile animals (2.6 to 5.9 months of age) without evidence of previous rotavirus infection and examined for rotavirus antigen. Six of 10 animals shed rotavirus during the 10-week collection period, and the electropherotypes of all isolates were identical to each other but distinct from those of prototype simian rotaviruses. These viruses were characterized as serotype G3 and subgroup 1, properties typical of many animal rotaviruses, including simian strains. Nucleotide sequence analysis of the VP4 gene was performed with a culture-grown isolate from the stool of one animal, designated the TUCH strain. Based on both genotypic and phylogenetic comparisons between TUCH VP4 and cognate proteins of representatives of the reported 22 P genotypes, the TUCH virus belongs to a new genotype, P[23]. A pool of wild-type TUCH was prepared and intragastrically administered to eight cesarean section-derived, specific-pathogen-free macaques 14 to 42 days of age. All animals were kept in a biocontainment level 2 facility. Although no diarrhea was observed and the animals remained clinically normal, all animals shed large quantities of rotavirus antigen in their feces after inoculation, which resolved by the end of the 14-day observation period. Therefore, TUCH infection of macaques provides a useful nonhuman primate model for studies on rotavirus protection. PMID:15613323

  1. Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities

    DEFF Research Database (Denmark)

    Southwood, Scott; Solomon, Christopher; Hoof, Ilka;

    2011-01-01

    -binding characteristics with the HLA-A2 and HLA-A3 supertypes, respectively, the next most frequent human supertypes after HLA-B7. These data suggest that Chinese rhesus macaques may indeed be a more representative model of HLA gene diversity and function as compared to the species of Indian origin and therefore a better...

  2. Ecological genetics of Chinese rhesus macaque in response to mountain building: all things are not equal.

    Directory of Open Access Journals (Sweden)

    Shan-Jin Wu

    Full Text Available BACKGROUND: Pliocene uplifting of the Qinghai-Tibetan Plateau (QTP and Quaternary glaciation may have impacted the Asian biota more than any other events. Little is documented with respect to how the geological and climatological events influenced speciation as well as spatial and genetic structuring, especially in vertebrate endotherms. Macaca mulatta is the most widely distributed non-human primate. It may be the most suitable model to test hypotheses regarding the genetic consequences of orogenesis on an endotherm. METHODOLOGY AND PRINCIPAL FINDINGS: Using a large dataset of maternally inherited mitochondrial DNA gene sequences and nuclear microsatellite DNA data, we discovered two maternal super-haplogroups exist, one in western China and the other in eastern China. M. mulatta formed around 2.31 Ma (1.51-3.15, 95%, and divergence of the two major matrilines was estimated at 1.15 Ma (0.78-1.55, 95%. The western super-haplogroup exhibits significant geographic structure. In contrast, the eastern super-haplogroup has far greater haplotypic variability with little structure based on analyses of six variable microsatellite loci using Structure and Geneland. Analysis using Migrate detected greater gene flow from WEST to EAST than vice versa. We did not detect signals of bottlenecking in most populations. CONCLUSIONS: Analyses of the nuclear and mitochondrial datasets obtained large differences in genetic patterns for M. mulatta. The difference likely reflects inheritance mechanisms of the maternally inherited mtDNA genome versus nuclear biparentally inherited STRs and male-mediated gene flow. Dramatic environmental changes may be responsible for shaping the matrilineal history of macaques. The timing of events, the formation of M. mulatta, and the divergence of the super-haplogroups, corresponds to both the uplifting of the QTP and Quaternary climatic oscillations. Orogenesis likely drove divergence of western populations in China, and Pleistocene

  3. Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity.

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    Ilhem Messaoudi

    Full Text Available Chikungunya virus (CHIKV is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes albopictus. CHIKV re-emergence is also associated with new clinical complications including severe morbidity and, for the first time, mortality. In this study, we characterized disease progression and host immune responses in adult and aged Rhesus macaques infected with either the recent CHIKV outbreak strain La Reunion (LR or the West African strain 37997. Our results indicate that following intravenous infection and regardless of the virus used, Rhesus macaques become viremic between days 1-5 post infection. While adult animals are able to control viral infection, aged animals show persistent virus in the spleen. Virus-specific T cell responses in the aged animals were reduced compared to adult animals and the B cell responses were also delayed and reduced in aged animals. Interestingly, regardless of age, T cell and antibody responses were more robust in animals infected with LR compared to 37997 CHIKV strain. Taken together these data suggest that the reduced immune responses in the aged animals promotes long-term virus persistence in CHIKV-LR infected Rhesus monkeys.

  4. Altered immune responses in rhesus macaques co-infected with SIV and Plasmodium cynomolgi: an animal model for coincident AIDS and relapsing malaria.

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    Jeffrey W Koehler

    Full Text Available BACKGROUND: Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens. METHODOLOGY/PRINCIPAL FINDINGS: Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response. CONCLUSIONS/SIGNIFICANCE: These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions.

  5. Myocarditis in CD8-depleted SIV-infected rhesus macaques after short-term dual therapy with nucleoside and nucleotide reverse transcriptase inhibitors.

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    Lakshmanan Annamalai

    Full Text Available BACKGROUND: Although highly active antiretroviral therapy (HAART has dramatically reduced the morbidity and mortality associated with HIV infection, a number of antiretroviral toxicities have been described, including myocardial toxicity resulting from the use of nucleotide and nucleoside reverse transcriptase inhibitors (NRTIs. Current treatment guidelines recommend the use of HAART regimens containing two NRTIs for initial therapy of HIV-1 positive individuals; however, potential cardiotoxicity resulting from treatment with multiple NRTIs has not been addressed. METHODOLOGY/PRINCIPAL FINDINGS: We examined myocardial tissue from twelve CD8 lymphocyte-depleted adult rhesus macaques, including eight animals infected with simian immunodeficiency virus, four of which received combined antiretroviral therapy (CART consisting of two NRTIs [(9-R-2-Phosphonomethoxypropyl Adenine (PMPA and (+/--beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine (RCV] for 28 days. Multifocal infiltrates of mononuclear inflammatory cells were present in the myocardium of all macaques that received CART, but not untreated SIV-positive animals or SIV-negative controls. Macrophages were the predominant inflammatory cells within lesions, as shown by immunoreactivity for the macrophage markers Iba1 and CD68. Heart specimens from monkeys that received CART had significantly lower virus burdens than untreated animals (p<0.05, but significantly greater quantities of TNF-α mRNA than either SIV-positive untreated animals or uninfected controls (p<0.05. Interferon-γ (IFN-γ, IL-1β and CXCL11 mRNA were upregulated in heart tissue from SIV-positive monkeys, independent of antiretroviral treatment, but CXCL9 mRNA was only upregulated in heart tissue from macaques that received CART. CONCLUSIONS/SIGNIFICANCE: These results suggest that short-term treatment with multiple NRTIs may be associated with myocarditis, and demonstrate that the CD8-depleted SIV-positive rhesus monkey is a useful

  6. Comparative analysis of immune activation markers of CD8+ T cells in lymph nodes of different origins in SIV-infected Chinese rhesus macaques

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    Jinbiao Liu

    2016-09-01

    Full Text Available Altered T-cell homeostasis, such as expansion of CD8+ T cells to the secondary lymphatic compartments has been suggested as a mechanism of HIV/SIV-pathogenesis. However, the role of immune activation of CD8+ T cells in the CD4/CD8 turnover and viral replication in these tissues is not completely understood. In the present study, we compared the expression of immune activation markers (CD69 and HLA-DR on CD8+ T cells in the peripheral blood and lymph nodes (LNs of SIV-infected/uninfected Chinese rhesus macaques. SIV-infected macaques had significantly higher percentages of CD8+CD69+ and CD8+HLA-DR+ T cells in all these anatomical compartments than uninfected macaques except for CD8+HLA-DR+ T cells in peripheral blood. LNs that located close to the gastrointestinal (GI tract (colon, mesenteric and iliac LNs of SIV-infected macaques had profoundly lower numbers of CD4+ T cells, but no significantly difference in expression of activation marker (CD8+CD69+ and CD8+HLA-DR+ as compared with the peripheral lymphatic tissues (axillary and inguinal LNs. The CD4/CD8 ratios were negatively correlated with the activation of CD8 T cells in the overall LNs, with further associations with CD8+HLA-DR+ in GI LNs while CD8+CD69+ in peripheral LNs. These observations demonstrate that the increase of CD8+ T cell activation is a contributing factor for the decline of CD4/CD8 ratios in GI system.

  7. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

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    Shengtao Fan

    2017-01-01

    Full Text Available As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1 causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post‐infection,and viral latency‐associated transcript (LAT mRNA was found in the trigeminal ganglia (TGon day 365 post‐infection. Neutralization testing and enzyme‐linked immunospot (ELISpot detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

  8. Memory B cells and CD8⁺ lymphocytes do not control seasonal influenza A virus replication after homologous re-challenge of rhesus macaques.

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    Timothy D Carroll

    Full Text Available This study sought to define the role of memory lymphocytes in the protection from homologous influenza A virus re-challenge in rhesus macaques. Depleting monoclonal antibodies (mAb were administered to the animals prior to their second experimental inoculation with a human seasonal influenza A virus strain. Treatment with either anti-CD8α or anti-CD20 mAbs prior to re-challenge had minimal effect on influenza A virus replication. Thus, in non-human primates with pre-existing anti-influenza A antibodies, memory B cells and CD8α⁺ T cells do not contribute to the control of virus replication after re-challenge with a homologous strain of influenza A virus.

  9. An adjuvanted, tetravalent dengue virus purified inactivated vaccine candidate induces long-lasting and protective antibody responses against dengue challenge in rhesus macaques.

    Science.gov (United States)

    Fernandez, Stefan; Thomas, Stephen J; De La Barrera, Rafael; Im-Erbsin, Rawiwan; Jarman, Richard G; Baras, Benoît; Toussaint, Jean-François; Mossman, Sally; Innis, Bruce L; Schmidt, Alexander; Malice, Marie-Pierre; Festraets, Pascale; Warter, Lucile; Putnak, J Robert; Eckels, Kenneth H

    2015-04-01

    The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques. One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes. Most of the formulations tested prevented viremia after challenge, with the dengue serotype 1 and 2 virus strains administered at 40 and 32 weeks post-dose 2, respectively. This study shows that inactivated dengue vaccines, when formulated with alum or an Adjuvant System, are candidates for further development.

  10. SIV antigen immunization induces transient antigen-specific T cell responses and selectively activates viral replication in draining lymph nodes in retroviral suppressed rhesus macaques

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    Barry Peter A

    2011-07-01

    Full Text Available Abstract Background HIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART restores CD4+ T cell responses to many pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected, ART treated subjects results in poor induction of HIV-specific CD4 responses. In this study, we used a macaque model of ART treatment during chronic infection to study the virologic consequences of SIV antigen stimulation in lymph nodes early after immunization. Rhesus CMV (RhCMV seropositive, Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and RhCMV pp65 antigen immunization in draining lymph nodes and peripheral blood were analyzed. Animals were immunized on contralateral sides with SIV gag and RhCMV pp65 encoding plasmids, which allowed lymph nodes draining each antigen to be obtained at the same time from the same animal for direct comparison. Results We observed that both SIV and RhCMV immunizations stimulated transient antigen-specific T cell responses in draining lymph nodes. The RhCMV-specific responses were potent and sustained (50 days post-immunization in the periphery, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation selectively induced transient SIV replication in draining lymph nodes. Conclusions The data are consistent with a model whereby viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses and suggests a potential mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals.

  11. Characterization of B and plasma cells in blood, bone marrow, and secondary lymphoid organs of rhesus macaques by multicolor flow cytometry.

    Science.gov (United States)

    Neumann, Berit; Klippert, Antonina; Raue, Katharina; Sopper, Sieghart; Stahl-Hennig, Christiane

    2015-01-01

    B cells, as an important part of the humoral immune response, are generated in the BM, migrate to secondary lymphoid organs, and upon activation, differentiate into antibody-producing memory B cells or plasma cells. Despite the pivotal roles that they play in different diseases, a comprehensive characterization in healthy rhesus macaques, which serve as valuable models for a variety of human diseases, is still missing. With the use of multiparameter flow cytometry, we analyzed B cells in BM collected from two locations, i.e., the iliac crest (BMca) and the femur (BMfem), PB, as well as secondary lymphoid organs of healthy rhesus macaques. We assessed the frequencies of immature and mature B cells, as well as CD19(+) CD20(-) CD38(+/++) CD138(+/++) plasmablasts/plasma cells. Furthermore, we found site-specific differences in the expression of markers for B cell activation and proliferation, chemokine receptors and Igs, as well as the distribution of memory B cell subpopulations. As secondary lymphoid organs harbor the highest frequencies of naive B cells, expression of CD80, CD95, and Ki67 was lower compared with B cells in the periphery and BM, whereas expression of IgD, CXCR4 (CD184), and CCR7 (CD197) was higher. Interestingly, BMca differed from BMfem regarding frequencies of B cells, their expression of CD80 and CXCR4, T cells, and plasma cells. In summary, these data identify baseline values for the above-mentioned parameters and provide the foundation for future studies on B and plasma cells in different diseases.

  12. Sporozoite neutralizing antibodies elicited in mice and rhesus macaques immunized with a Plasmodium falciparum repeat peptide conjugated to meningococcal outer membrane protein complex

    Directory of Open Access Journals (Sweden)

    Craig ePrzysiecki

    2012-11-01

    Full Text Available Antibodies that neutralize infectivity of malaria sporozoites target the central repeat region of the circumsporozoite (CS protein, which in Plasmodium falciparum is comprised primarily of 30-40 tandem NANP tetramer repeats. We evaluated immunogenicity of an alum-adsorbed (NANP6 peptide conjugated to an outer membrane protein complex (OMPC derived from Neisseria meningitidis, a carrier protein used in a licensed H. influenzae pediatric vaccine. Mice immunized with alum-adsorbed (NANP6-OMPC, with or without Iscomatrix© as co-adjuvant, developed high levels of anti-repeat peptide antibody that inhibited in vitro invasion of human hepatoma cells by transgenic P. berghei sporozoites that express P. falciparum CS repeats (PfPb. Inhibition of sporozoite invasion in vitro correlated with in vivo resistance to challenge by the bites of PfPb infected mosquitoes. Challenged mice had > 90% reduction of hepatic stage parasites as measured by real-time PCR, and either sterile immunity, i.e. no detectable blood stage parasites, or delayed prepatent periods which indicate neutralization of a majority, but not all, sporozoites. Rhesus macaques immunized with two doses of (NANP6-OMPC/MAA formulated with Iscomatrix© developed anti-repeat antibodies that persisted for ~2 years. A third dose of (NANP6-OMPC/MAA+ Iscomatrix© at that time elicited strong anamnestic antibody responses. Rhesus macaque immune sera obtained post second and third dose of vaccine displayed high levels of sporozoite neutralizing activity in vitro that correlated with presence of high anti-repeat antibody titers. These preclinical studies in mice of different MHC haplotypes and a non-human primate support use of CS peptide-OMPC conjugates as a highly immunogenic platform to evaluate CS protective epitopes. Potential pre-erythrocytic vaccines can be combined with sexual blood stage vaccines as a multi-antigen malaria vaccine to block invasion and transmission of Plasmodium parasites

  13. Allo-reactivity of mesenchymal stem cells in rhesus macaques is dose and haplotype dependent and limits durable cell engraftment in vivo.

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    Iryna A Isakova

    Full Text Available The emerging paradigm that MSCs are immune privileged has fostered the use of "off-the-shelf" allogeneic MSC-based therapies in human clinical trials. However, this approach ignores studies in experimental animals wherein transplantation of MSCs across MHC boundaries elicits measurable allo-immune responses. To determine if MSCs are hypo-immunogeneic, we characterized the immune response in rhesus macaques following intracranial administration of allogeneic vs. autologous MSCs. This analysis revealed unambiguous evidence of productive allo-recognition based on expansion of NK, B and T cell subsets in peripheral blood and detection of allo-specific antibodies in animals administered allogeneic but not autologous MSCs. Moreover, the degree of MHC class I and II mismatch between the MSC donor and recipient significantly influenced the magnitude and nature of the allo-immune response. Consistent with these findings, real-time PCR analysis of brain tissue from female recipients administered varying doses of male, allogeneic MSCs revealed a significant inverse correlation between MSC engraftment levels and cell dose. Changes in post-transplant neutrophil and lymphocyte counts also correlated with dose and were predictive of overall MSC engraftment levels. However, secondary antigen challenge failed to elicit a measurable immune response in allogeneic recipients. Finally, extensive behavior testing of animals revealed no main effect of cell dose on motor skills, social development, or temperament. Collectively, these data indicate that allogeneic MSCs are weakly immunogenic when transplanted across MHC boundaries in rhesus macaques and this negatively impacts durable engraftment levels. Therefore the use of unrelated donor MSCs should be carefully evaluated in human patients.

  14. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

    OpenAIRE

    2016-01-01

    The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., ...

  15. A Practical Approach for Designing Breeding Groups to Maximize Genetic Diversity in a Large Colony of Captive Rhesus Macaques (Macaca mulatta).

    Science.gov (United States)

    Vinson, Amanda; Raboin, Michael J

    2015-11-01

    Limited guidance is available on practical approaches for maintaining genetic diversity in large NHP colonies that support biomedical research, despite the fact that reduced diversity in these colonies is likely to compromise the application of findings in NHP to human disease. In particular, constraints related to simultaneously housing, breeding, and providing ongoing veterinary care for thousands of animals with a highly complex social structure creates unique challenges for genetic management in these colonies. Because the composition of new breeding groups is a critical component of genetic management, here we outline a 3-stage protocol for forming new breeding groups of NHP that is aimed at maximizing genetic diversity in the face of frequent restrictions on age, sex, and numbers of animals per breeding group. As an example application of this protocol, we describe optimal combinations of rhesus macaques from an analysis of candidate animals available for breeding in July 2013, selected from among the approximately 4000 macaques maintained at the Oregon National Primate Research Center. In addition, a simulation study to explore the genetic diversity in breeding groups formed by using this protocol, indicated an approximate 10-fold higher genome uniqueness, 50% lower mean kinship, and an 84-fold lower mean inbreeding coefficient among potential offspring within groups, when compared with a suboptimal group design. We conclude that this protocol provides a practical and effective approach to breeding group design for colony managers who want to prevent the loss of genetic diversity in large, semiisolated NHP colonies.

  16. Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

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    Deborah Heydenburg Fuller

    Full Text Available Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT, during antiretroviral therapy (ART induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans.

  17. Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Hong Qin

    2010-01-01

    Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

  18. Multiple antibody targets on herpes B glycoproteins B and D identified by screening sera of infected rhesus macaques with peptide microarrays.

    Directory of Open Access Journals (Sweden)

    Sven-Kevin Hotop

    Full Text Available Herpes B virus (or Herpesvirus simiae or Macacine herpesvirus 1 is endemic in many populations of macaques, both in the wild and in captivity. The virus elicits only mild clinical symptoms (if any in monkeys, but can be transmitted by various routes, most commonly via bites, to humans where it causes viral encephalitis with a high mortality rate. Hence, herpes B constitutes a considerable occupational hazard for animal caretakers, veterinarians and laboratory personnel. Efforts are therefore being made to reduce the risk of zoonotic infection and to improve prognosis after accidental exposure. Among the measures envisaged are serological surveillance of monkey colonies and specific diagnosis of herpes B zoonosis against a background of antibodies recognizing the closely related human herpes simplex virus (HSV. 422 pentadecapeptides covering, in an overlapping fashion, the entire amino acid sequences of herpes B proteins gB and gD were synthesized and immobilized on glass slides. Antibodies present in monkey sera that bind to subsets of the peptide collection were detected by microserological techniques. With 42 different rhesus macaque sera, 114 individual responses to 18 different antibody target regions (ATRs were recorded, 17 of which had not been described earlier. This finding may pave the way for a peptide-based, herpes B specific serological diagnostic test.

  19. Refining the pole-and-collar method of restraint: emphasizing the use of positive training techniques with rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    McMillan, Jennifer L; Perlman, Jaine E; Galvan, Adriana; Wichmann, Thomas; Bloomsmith, Mollie A

    2014-01-01

    The pole-and-collar method is one of several techniques that enable the safe transfer of a nonhuman primate from its home environment into a restraint chair without the need for sedation. It has been used within the scientific community for decades. Traditional methods to train animals for pole-and-collar use rely primarily on aspects of negative reinforcement, with very little incorporation of positive-reinforcement techniques. With increasing emphasis on animal training and welfare, research facilities are incorporating positive-reinforcement training into husbandry and experimental procedures. Here we demonstrate the feasibility of training rhesus macaques (Macaca mulatta; n = 8) to cooperate for pole-and-collar transfer to a primate restraint chair. By using predominantly positive-reinforcement techniques, with supplemental elements of negative reinforcement, macaques were trained in a mean of 85 training sessions (a mean of 1085 min of training time). We also provide tools for investigators using the pole-and-collar method to help them successfully incorporate positive-reinforcement training into their procedures. This refinement has the potential to improve animal welfare and enhance the value of nonhuman primate models in research.

  20. The effects of reduced gluten barley diet on humoral and cell-mediated systemic immune responses of gluten-sensitive rhesus macaques.

    Science.gov (United States)

    Sestak, Karol; Thwin, Hazel; Dufour, Jason; Aye, Pyone P; Liu, David X; Moehs, Charles P

    2015-03-06

    Celiac disease (CD) affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS). The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD) is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten) barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS) and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA) serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ), tumor necrosis factor (TNF) and interleukin-8 (IL-8) by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading-by co-administration of additional treatments.

  1. The Effects of Reduced Gluten Barley Diet on Humoral and Cell-Mediated Systemic Immune Responses of Gluten-Sensitive Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    2015-03-01

    Full Text Available Celiac disease (CD affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS. The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ, tumor necrosis factor (TNF and interleukin-8 (IL-8 by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading—by co-administration of additional treatments.

  2. Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge.

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    Iskra Tuero

    2015-08-01

    Full Text Available Many viral infections, including HIV, exhibit sex-based pathogenic differences. However, few studies have examined vaccine-related sex differences. We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored a subsequent sex bias in vaccine outcome. Each immunization group (16 females, 8 males was primed twice mucosally with replication-competent Ad-recombinants encoding SIVsmH4env/rev, SIV239gag and SIV239nefΔ1-13 and boosted twice intramuscularly with SIVmac239 monomeric gp120 or oligomeric gp140 in MF59 adjuvant. Controls (7 females, 5 males received empty Ad and MF59. Up to 9 weekly intrarectal challenges with low-dose SIVmac251 were administered until macaques became infected. We assessed vaccine-induced binding, neutralizing, and non-neutralizing antibodies, Env-specific memory B cells and plasmablasts/plasma cells (PB/PC in bone marrow and rectal tissue, mucosal Env-specific antibodies, and Env-specific T-cells. Post-challenge, only one macaque (gp140-immunized remained uninfected. However, SIV acquisition was significantly delayed in vaccinated females but not males, correlated with Env-specific IgA in rectal secretions, rectal Env-specific memory B cells, and PC in rectal tissue. These results extend previous correlations of mucosal antibodies and memory B cells with protective efficacy. The gp140 regimen was more immunogenic, stimulating elevated gp140 and cyclic V2 binding antibodies, ADCC and ADCP activities, bone marrow Env-specific PB/PC, and rectal gp140-specific IgG. However, immunization with gp120, the form of envelope immunogen used in RV144, the only vaccine trial to show some efficacy, provided more significant acquisition delay. Further over 40 weeks of follow-up, no gp120 immunized macaques met euthanasia criteria in contrast to 7 gp140-immunized and 2 control animals. Although males had higher binding antibodies than females, ADCC

  3. Vaxfectin adjuvant improves antibody responses of juvenile rhesus macaques to a DNA vaccine encoding the measles virus hemagglutinin and fusion proteins.

    Science.gov (United States)

    Lin, Wen-Hsuan W; Vilalta, Adrian; Adams, Robert J; Rolland, Alain; Sullivan, Sean M; Griffin, Diane E

    2013-06-01

    DNA vaccines formulated with the cationic lipid-based adjuvant Vaxfectin induce protective immunity in macaques after intradermal (i.d.) or intramuscular (i.m.) delivery of 0.5 to 1 mg of codon-optimized DNA encoding the hemagglutinin (H) and fusion (F) proteins of measles virus (MeV). To characterize the effect of Vaxfectin at lower doses of H+F DNA, rhesus macaques were vaccinated twice with 20 μg of DNA plus Vaxfectin i.d., 100 μg of DNA plus Vaxfectin i.d., 100 μg of DNA plus Vaxfectin i.m. or 100 μg of DNA plus phosphate-buffered saline (PBS) i.m. using a needleless Biojector device. The levels of neutralizing (P = 0.036) and binding (P = 0.0001) antibodies were higher after 20 or 100 μg of DNA plus Vaxfectin than after 100 μg of DNA plus PBS. Gamma interferon (IFN-γ)-producing T cells were induced more rapidly than antibody, but were not improved with Vaxfectin. At 18 months after vaccination, monkeys were challenged with wild-type MeV. None developed rash or viremia, but all showed evidence of infection. Antibody levels increased, and IFN-γ- and interleukin-17-producing T cells, including cells specific for the nucleoprotein absent from the vaccine, were induced. At 3 months after challenge, MeV RNA was detected in the leukocytes of two monkeys. The levels of antibody peaked 2 to 4 weeks after challenge and then declined in vaccinated animals reflecting low numbers of bone marrow-resident plasma cells. Therefore, Vaxfectin was dose sparing and substantially improved the antibody response to the H+F DNA vaccine. This immune response led to protection from disease (rash/viremia) but not from infection. Antibody responses after challenge were more transient in vaccinated animals than in an unvaccinated animal.

  4. A cage-based training, cognitive testing and enrichment system optimized for rhesus macaques in neuroscience research.

    Science.gov (United States)

    Calapai, A; Berger, M; Niessing, M; Heisig, K; Brockhausen, R; Treue, S; Gail, A

    2017-02-01

    In neurophysiological studies with awake non-human primates (NHP), it is typically necessary to train the animals over a prolonged period of time on a behavioral paradigm before the actual data collection takes place. Rhesus monkeys (Macaca mulatta) are the most widely used primate animal models in system neuroscience. Inspired by existing joystick- or touch-screen-based systems designed for a variety of monkey species, we built and successfully employed a stand-alone cage-based training and testing system for rhesus monkeys (eXperimental Behavioral Intrument, XBI). The XBI is mobile and easy to handle by both experts and non-experts; animals can work with only minimal physical restraints, yet the ergonomic design successfully encourages stereotypical postures with a consistent positioning of the head relative to the screen. The XBI allows computer-controlled training of the monkeys with a large variety of behavioral tasks and reward protocols typically used in systems and cognitive neuroscience research.

  5. 桂林七星公园猕猴的食物组成及季节性变化%Diet and seasonal changes in Rhesus macaques (Macaca mulata) at Seven-star Park, Guilin

    Institute of Scientific and Technical Information of China (English)

    周岐海; 唐华兴; 韦春强; 黄乘明

    2009-01-01

    @@ 觅食是动物最重、最常见的行为,动物通过觅食获取其生长发育、繁殖和运动所需要的营养与能量.%Data on diet were collected from one group of Rhesus macaques (Macaca mulatto,) between November 2005 and October 2006 at Seven-star Park, Cuilin, Guangxi Province, using the instantaneous scan sampling method. Our results indicated that 60 plant species were used as food by the macaques. The types of foods including 40 species of trees, 12 species of shrubs, 4 species of vines, and 4 species of herbs. They showed food preference, and 69. 4% of the diet came only from 10 species. Leaves constituted 41. 0% of the diet, comprising 16. 7% young leaves and 24. 3% mature leaves. Petiole and bark accounted for 27. 3% and 21. 8% respectively. Fruits, flowers and seeds contributed a small proportion of the diet, 6. 2% , 2. 2% , and 1.4%, respectively. The macaques' diet varied according to season. In spring, the macaques fed predominantly on young leaves, petiole and bark. In summer, they increased the consumption of mature leaves and bark. The consumption of young leaves and mature leaves peaked in autumn, and the consumption of petiole and bark decreased significantly. In winter, the macaques increased significantly the consumption of petiole and bark, and also consumed mature leaves in large quantity.

  6. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

    Science.gov (United States)

    Mohan, Mahesh; Chow, Cheryl-Emiliane T.; Ryan, Caitlin N.; Chan, Luisa S.; Dufour, Jason; Aye, Pyone P.; Blanchard, James; Moehs, Charles P.; Sestak, Karol

    2016-01-01

    The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05) following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae) were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity) of gut microbiome in GS macaques started to change (p = 0.011) towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b) were upregulated (p < 0.05) in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911), Prevotella stercorea (NR_041364) and Streptococcus luteciae (AJ297218) that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes in GS

  7. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

    Directory of Open Access Journals (Sweden)

    Mahesh Mohan

    2016-10-01

    Full Text Available The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD, gluten-free diet (GFD, barley gluten-derived diet (BOMI and reduced gluten barley-derived diet (RGB. It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05 following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity of gut microbiome in GS macaques started to change (p = 0.011 towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b were upregulated (p < 0.05 in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911, Prevotella stercorea (NR_041364 and Streptococcus luteciae (AJ297218 that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes

  8. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease.

    Science.gov (United States)

    Mohan, Mahesh; Chow, Cheryl-Emiliane T; Ryan, Caitlin N; Chan, Luisa S; Dufour, Jason; Aye, Pyone P; Blanchard, James; Moehs, Charles P; Sestak, Karol

    2016-10-28

    The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae) were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity) of gut microbiome in GS macaques started to change (p = 0.011) towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b) were upregulated (p < 0.05) in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911), Prevotella stercorea (NR_041364) and Streptococcus luteciae (AJ297218) that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes in GS macaques will approach those of healthy

  9. Cashing out: The decisional flexibility of uncertainty responses in rhesus macaques (Macaca mulatta) and humans (Homo sapiens).

    Science.gov (United States)

    Zakrzewski, Alexandria C; Perdue, Bonnie M; Beran, Michael J; Church, Barbara A; Smith, J David

    2014-10-01

    Researchers are exploring whether animals share with humans something like a metacognitive capacity. Though some results point to human-animal continuities in this domain, they face the dominant criticism that animals' performances might be associative. A persistent problem is that animal-metacognition paradigms present static environments of risk and reward that may foster inflexible and conditioned responding. Those environments do not challenge animals to show the flexibility in their decision strategies that could indicate an antecedent capacity to metacognition. Accordingly, we tested macaques and humans on an uncertainty-monitoring paradigm in which risk changed dynamically. Participants classified stimuli of different difficulties while also choosing when to use a cashout response to collect the accumulated rewards that would be forfeit on a discrimination error. Macaques (Macaca mulatta) and humans flexibly adjusted their decision criteria to achieve appropriate protection against the cost of error that could differ depending on trial difficulty and the number of rewards at risk. In particular, monkeys widened their cashout-response region as their accumulated rewards increased, providing more protection against a more costly error. These findings demonstrate a new continuity between humans' and animals' uncertainty systems. They reveal a calibration by macaques of present risk to trial difficulty tolerated. They show that animals' uncertainty-monitoring and risk-management systems have substantial trial-by-trial flexibility.

  10. Low dose rectal inoculation of rhesus macaques by SIV SME660 or SIV MAC251 recapitulates human mucosal infection by HIV-1

    Energy Technology Data Exchange (ETDEWEB)

    Koraber, Bette [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory; Hraber, Peter [Los Alamos National Laboratory; Giorgi, E [Los Alamos National Laboratory; Bhattacharya, T [Los Alamos National Laboratory

    2009-01-01

    Recently, we developed a novel approach to the identification of transmitted or early founder HIV -1 genomes in acutely infected humans based on single genome amplification and sequencing. Here we tested this approach in 18 acutely infected Indian rhesus macaques to determine the molecular features of SIV transmission. Animals were inoculated intrarectally (IR) or intravenously (IV) with stocks of SIVmac251 or SIVsmE660 that exhibited sequence diversity typical of early-chronic HIV -1 infection. 987 full-length SIV env sequences (median of 48 per animal) were determined from plasma virion RNA one to five weeks after infection. IR inoculation was followed by productive infection by one or few viruses (median 1; range 1-5) that diversified randomly with near star-like phylogeny and a Poisson distribution of mutations. Consensus viral sequences from ramp-up and peak viremia were identical to viruses found in the inocula or differed from them by only one or few nuc1eotides, providing direct evidence that early plasma viral sequences coalesce to transmitted/founder virus( es). IV infection was approximately 10,000-fold more efficient than IR infection, and viruses transmitted by either route represented the full genetic spectra of the inocula. These findings identify key similarities in mucosal transmission and early diversification between SIV and HIV -1.

  11. Safety and colonization of two novel VirG(IcsA)-based live Shigella sonnei vaccine strains in rhesus macaques (Macaca mulatta).

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    Collins, Todd A; Barnoy, Shoshana; Baqar, Shahida; Ranallo, Ryan T; Nemelka, Kevin W; Venkatesan, Malabi M

    2008-02-01

    Shigella are gram-negative bacterium that cause bacillary dysentery (shigellosis). Symptoms include diarrhea and discharge of bloody mucoid stools, accompanied by severe abdominal pain, nausea, vomiting, malaise, and fever. Persons traveling to regions with poor sanitation and crowded conditions become particularly susceptible to shigellosis. Currently a vaccine for Shigella has not been licensed in the United States, and the organism quickly becomes resistant to medications. During the past 10 y, several live attenuated oral Shigella vaccines, including the strain WRSS1, have been tested in humans with considerable success. These Phase I vaccines lack the gene for the protein VirG also known as IcsA, which enables the organism to disseminate in the host target tissue. However, 5% to 20% of the vaccinated volunteers developed mild fever and brief diarrhea, and the removal of additional virulence-associated genes from the vaccine strain may reduce or eliminate these side effects. We administered 2 Shigella sonnei vaccines, WRSs2 and WRSs3, along with WRSS1 to compare their rates of colonization and clinical safety in groups of 5 rhesus macaques. The primate model provides the most physiologically relevant animal system to test the validity and efficacy of vaccine candidates. In this pilot study using a gastrointestinal model of infection, the vaccine candidates WRSs2 and WRSs3, which have additional deletions in the enterotoxin and LPS modification genes, provided better safety and comparable immunogenicity to those of WRSS1.

  12. Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques

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    Shudo, Emi [Los Alamos National Laboratory; Ribeiro, Ruy M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2008-01-01

    While CD8+ T cell responses are clearly important in anti-viral immunity during HIV/SIV infection, the mechanisms by which CD8+ T cells induce this effect remain poorly understood, as emphasized by the failure of the Merck adenovirus-based, cytotoxic T lymphocyte (CTL)-inducing AIDS vaccine in a large phase IIb clinical trial. In this study, we measured the in vivo effect of CD8+ lymphocytes on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques by treating two groups of animals (i.e., CD8+ lymphocyte-depleted or controls) with antiretroviral therapy (PMPA and FTC). The lifespan of productively infected cells was calculated based on the slope of the decline of SIV plasma viremia using a well-accepted mathematical model. We found that, in both early (i.e., day 57 post-inoculation) and late (i.e., day 177 post-inoculation) chronic SIV infection, depletion of CD8+ lymphocytes did not result in an increased lifespan of productively infected cells in vivo. This result indicates that direct killing of cells producing virus is unlikely to be a major mechanism underlying the anti-viral effect of CD8+ T cells during SIV infection. These results have profound implications for the development of AIDS vaccines.

  13. Use of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography to aid in diagnosing intestinal adenocarcinoma in 2 rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Caporizzo, Debra J; Kwiatkowski, Anna E; Chen, Ming-Kai; Beck, Amanda P; Booth, Carmen J; Zeiss, Caroline; Smith, Peter C; Carlson Scholz, Jodi A; Wilson, Steven R

    2014-06-01

    Two aged female rhesus macaques (Macaca mulatta) presented with weight loss and intermittent inappetence. The signalment and constellation of clinical signs led clinicians to suspect the presence of intestinal adenocarcinoma. Because of each animal's advanced age and inconclusive radiographic findings, a noninvasive diagnostic tool was preferred over exploratory laparotomy to assist in determining a diagnosis. Consequently, 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-CT (FDG-PET-CT) was chosen to aid in confirming a suspicion of gastrointestinal adenocarcinoma in both animals. FDG is a glucose analogue labeled with fluorine-18 and is taken up by highly metabolically active cells, as observed in many cancers. Tomography revealed an annular constriction of the small intestine with focal FDG uptake in one animal, and an FDG avid transmural mass in the ascending colon of the second animal. Necropsy later confirmed both sites to be adenocarcinomas. This report supports the use of FDG-PET-CT as an adjunct to conventional radiography in the diagnosis of intestinal adenocarcinoma in nonhuman primates.

  14. Ordered recall in rhesus macaques (Macaca mulatta: Can monkeys recall the correct order of sequentially presented images?

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    Heather E O'Neil

    2006-01-01

    Full Text Available Previous research has demonstrated that rhesus monkeys (Macaca mulatta are capable of identifying sequentially shown images in any order among distractors (i.e. images not part of the list sequence. We investigated ordered recall in rhesus monkeys in which subjects were expected to recognize the correct order of images during a “test” phase (simultaneous presentation of images after they had seen the images presented sequentially in a “presentation” phase (sequential presentation of images. If subjects were successfully able to execute the ordered recall task, the first trial accuracy data would appear close to 100% accuracy and it would only take one day to learn the list since the lists used were short, 3-item lists. While this study did not conclusively demonstrate monkeys are capable of ordered recall of sequentially presented, trial unique images (i.e. a list sequence presented only once per session, the data suggests that when the stimuli are not trial unique the monkeys treat each sequence as a simultaneous chaining task. A simultaneous chaining paradigm entails simultaneous presentation of all items without any previous sequential presentation of the images. It is unclear whether results resembling simultaneous chaining are seen because these animals have previous experience with simultaneous chaining, if the training procedure needs to be modified for the monkeys to understand the task, or if the task is beyond their cognitive abilities. Further research with serial learning will clarify this finding and also seek to prove whether rhesus monkeys are in fact capable of such ordered recall tasks.

  15. Necrotizing Scleritis, Conjunctivitis, and Other Pathologic Findings in the Left Eye and Brain of an Ebola Virus-Infected Rhesus Macaque (Macaca mulatta) With Apparent Recovery and a Delayed Time of Death.

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    Alves, Derron A; Honko, Anna N; Kortepeter, Mark G; Sun, Mei; Johnson, Joshua C; Lugo-Roman, Luis A; Hensley, Lisa E

    2016-01-01

    A 3.5-year-old adult female rhesus macaque (Macaca mulatta) manifested swelling of the left upper eyelid and conjunctiva and a decline in clinical condition 18 days following intramuscular challenge with Ebola virus (EBOV; Kikwit-1995), after apparent clinical recovery. Histologic lesions with strong EBOV antigen staining were noted in the left eye (scleritis, conjunctivitis, and peri-optic neuritis), brain (choriomeningoencephalitis), stomach, proximal duodenum, and pancreas. Spleen, liver, and adrenal glands, common targets for acute infection, appeared histologically normal with no evidence of EBOV immunoreactivity. These findings may provide important insight for understanding sequelae seen in West African survivors of Ebola virus disease.

  16. Immunogenicity of seven new recombinant yellow fever viruses 17D expressing fragments of SIVmac239 Gag, Nef, and Vif in Indian rhesus macaques.

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    Mauricio A Martins

    Full Text Available An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV. Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (rYF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIVmac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5 vectors resulted in robust expansion of SIV-specific CD8(+ T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4(+ cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D - a clinically relevant vaccine vector - can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D

  17. Development of space perception in relation to the maturation of the motor system in infant rhesus macaques (Macaca mulatta).

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    Sclafani, Valentina; Simpson, Elizabeth A; Suomi, Stephen J; Ferrari, Pier Francesco

    2015-04-01

    To act on the environment, organisms must perceive object locations in relation to their body. Several neuroscientific studies provide evidence of neural circuits that selectively represent space within reach (i.e., peripersonal) and space outside of reach (i.e., extrapersonal). However, the developmental emergence of these space representations remains largely unexplored. We investigated the development of space coding in infant macaques and found that they exhibit different motor strategies and hand configurations depending on the objects' size and location. Reaching-grasping improved from 2 to 4 weeks of age, suggesting a broadly defined perceptual body schema at birth, modified by the acquisition and refinement of motor skills through early sensorimotor experience, enabling the development of a mature capacity for coding space.

  18. Immunogenicity of a vaccine regimen composed of simian immunodeficiency virus DNA, rMVA, and viral particles administered to female rhesus macaques via four different mucosal routes.

    Science.gov (United States)

    Manrique, Mariana; Kozlowski, Pamela A; Cobo-Molinos, Antonio; Wang, Shainn-Wei; Wilson, Robert L; Montefiori, David C; Carville, Angela; Aldovini, Anna

    2013-04-01

    A comparative evaluation of the immunity stimulated with a vaccine regimen that includes simian immunodeficiency virus (SIV), interleukin 2 (IL-2), and IL-15 DNAs, recombinant modified vaccinia virus Ankara (rMVA), and inactivated SIVmac239 particles administered into the oral and nasal cavities, small intestine, and vagina was carried out in female rhesus macaques to determine the best route to induce diverse anti-SIV immunity that may be critical to protection from SIV infection and disease. All four immunizations generated mucosal SIV-specific IgA. Oral immunization was as effective as vaginal immunization in inducing SIV-specific IgA in vaginal secretions and generated greater IgA responses in rectal secretions and saliva samples compared to the other immunization routes. All four immunizations stimulated systemic T-cell responses against Gag and Env, albeit to a different extent, with oral immunization providing greater magnitude and nasal immunization providing wider functional heterogeneity. SIV-specific T cells producing gamma interferon (IFN-γ) dominated these responses. Limited levels of SIV-specific IgG antibodies were detected in plasma samples, and no SIV-specific IgG antibodies were detected in secretions. Vaccination also induced CD4(+) and CD8(+) T-cell responses in the rectal and vaginal mucosa with greater functional heterogeneity than in blood samples. Rectal T-cell responses were significantly greater in the orally vaccinated animals than in the other animals. The most balanced, diverse, and higher-magnitude vaginal T-cell responses were observed after intestinal vaccination. Significantly higher CD8(+) granzyme B-positive T-cell responses were observed systemically after intestinal vaccination and in rectal cells after oral immunization. The majority of SIV-specific T cells that produced granzyme B did not produce cytokines. Of the immunization routes tested, oral vaccination provided the most diverse and significant response to the vaccine.

  19. Effect of plasma viremia on apoptosis and immunophenotype of dendritic cells subsets in acute SIVmac239 infection of Chinese rhesus macaques.

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    Hou-Jun Xia

    Full Text Available Non-human primates such as Chinese rhesus macaques (Ch Rhs provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs in the peripheral blood of Ch Rhs: myeloid DCs (mDCs and plasmacytoid DCs (pDCs. In this study, two-color fluorescence-activated cell sorting (FACS analyses were used to identify the main DC subsets, namely CD1c(+ mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c(+ mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c(+ mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

  20. Efficacy and pharmacokinetic/pharmacodynamic study of 1,1'-methylenebis{4-[(hydroxyimino)methyl] pyridinium} dimethanesulfonate in guinea pigs and rhesus macaques exposed to cyclosarin.

    Science.gov (United States)

    Harvilchuck, Jill A; Hong, S Peter; Richey, Jamie S; Osheroff, Merrill R; Johnson, Jerry D

    2013-01-01

    Male Hartley guinea pigs and male rhesus macaques were used to determine an efficacious dose of 1,1'-methylenebis{4-[(hydroxyimino)methyl] pyridinium} dimethanesulfonate (MMB4 DMS) that would result in 80% survival, 24 hours following a single exposure to cyclosarin (GF). The pharmacokinetic/pharmacodynamic relationship between acetylcholinesterase activity and MMB4 plasma concentrations relative to survival was evaluated. Guinea pigs and non-human primates (NHPs) were concurrently administered MMB4 DMS (guinea pigs: 0, 10, 30, or 40 mg/kg, intramuscular [IM] and NHPs: 0.1, 1, 5, 10, or 20 mg/kg, IM), atropine, and diazepam following a 3 × median lethal dose (LD50) GF challenge. Clinical observations were evaluated using a quality-of-life (QOL) scoring system. All GF-exposed animals exhibited typical signs of nerve agent poisoning immediately following challenge. In guinea pigs, 24-hour survival was 0%, 50%, 90%, and 90% for 0, 10, 30, and 40 mg/kg MMB4 DMS groups, respectively. In addition, nearly all animals surviving to 24 hours were clinically normal, with many in the 30 and 40 mg/kg MMB4 DMS dose group observed as normal by 4 hours post-challenge. In NHPs, survival was 100% for all treatment groups, with all animals noted as clinically normal by 48 hours. Following treatment with atropine/MMB4 DMS/diazepam, NHPs exhibited dose- and temporal-related decreases in incidence and duration of the clinical signs of toxicity. The QOL scores improved with increasing MMB4 DMS dose in both species. The estimated ED80s were 25.5 mg/kg MMB4 DMS (human equivalent dose [HED] of 5.5 mg/kg) and ≤ 0.1 mg/kg (HED of 0.03 mg/kg) in guinea pigs and NHPs, respectively.

  1. Long-term programming of antigen-specific immunity from gene expression signatures in the PBMC of rhesus macaques immunized with an SIV DNA vaccine.

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    Sarah E Belisle

    Full Text Available While HIV-1-specific cellular immunity is thought to be critical for the suppression of viral replication, the correlates of protection have not yet been determined. Rhesus macaques (RM are an important animal model for the study and development of vaccines against HIV/AIDS. Our laboratory has helped to develop and study DNA-based vaccines in which recent technological advances, including genetic optimization and in vivo electroporation (EP, have helped to dramatically boost their immunogenicity. In this study, RMs were immunized with a DNA vaccine including individual plasmids encoding SIV gag, env, and pol alone, or in combination with a molecular adjuvant, plasmid DNA expressing the chemokine ligand 5 (RANTES, followed by EP. Along with standard immunological assays, flow-based activation analysis without ex vivo restimulation and high-throughput gene expression analysis was performed. Strong cellular immunity was induced by vaccination which was supported by all assays including PBMC microarray analysis that identified the up-regulation of 563 gene sequences including those involved in interferon signaling. Furthermore, 699 gene sequences were differentially regulated in these groups at peak viremia following SIVmac251 challenge. We observed that the RANTES-adjuvanted animals were significantly better at suppressing viral replication during chronic infection and exhibited a distinct pattern of gene expression which included immune cell-trafficking and cell cycle genes. Furthermore, a greater percentage of vaccine-induced central memory CD8+ T-cells capable of an activated phenotype were detected in these animals as measured by activation analysis. Thus, co-immunization with the RANTES molecular adjuvant followed by EP led to the generation of cellular immunity that was transcriptionally distinct and had a greater protective efficacy than its DNA alone counterpart. Furthermore, activation analysis and high-throughput gene expression data may

  2. Infection with host-range mutant adenovirus 5 suppresses innate immunity and induces systemic CD4+ T cell activation in rhesus macaques.

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    Huma Qureshi

    Full Text Available Ad5 is a common cause of respiratory disease and an occasional cause of gastroenteritis and conjunctivitis, and seroconversion before adolescence is common in humans. To gain some insight into how Ad5 infection affects the immune system of rhesus macaques (RM 18 RM were infected with a host-range mutant Ad5 (Ad5hr by 3 mucosal inoculations. There was a delay of 2 to 6 weeks after the first inoculation before plasmacytoid dendritic cell (pDC frequency and function increased in peripheral blood. Primary Ad5hr infection suppressed IFN-γ mRNA expression, but the second Ad5hr exposure induced a rapid increase in IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC. Primary Ad5hr infection suppressed CCL20, TNF and IL-1 mRNA expression in PBMC, and subsequent virus exposures further dampened expression of these pro-inflammatory cytokines. Primary, but not secondary, Ad5hr inoculation increased the frequency of CXCR3+ CD4+ T cells in blood, while secondary, but not primary, Ad5hr infection transiently increased the frequencies of Ki67+, HLADR+ and CD95+/CCR5+ CD4+ T cells in blood. Ad5hr infection induced polyfunctional CD4 and CD8+ T cells specific for the Ad5 hexon protein in all of the animals. Thus, infection with Ad5hr induced a complex pattern of innate and adaptive immunity in RM that included transient systemic CD4+ T cell activation and suppressed innate immunity on re-exposure to the virus. The complex effects of adenovirus infection on the immune system may help to explain the unexpected results of testing Ad5 vector expressing HIV antigens in Ad5 seropositive people.

  3. R5-SHIV induces multiple defects in T cell function during early infection of rhesus macaques including accumulation of T reg cells in lymph nodes.

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    Michael Santosuosso

    Full Text Available BACKGROUND: HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues. METHODS: Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation. RESULTS/CONCLUSIONS: We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection.

  4. Decreased TFR/TFH ratio in SIV-infected rhesus macaques may contribute to accumulation of TFH cells in chronic infection

    Science.gov (United States)

    Chowdhury, Ankita; Estrada Del Rio, Perla Maria; Tharp, Greg K; Trible, Ronald P; Amara, Rama R; Chahroudi, Ann; Reyes-Teran, Gustavo; Bosinger, Steven E.; Silvestri, Guido

    2015-01-01

    T follicular helper cells (TFH) are critical for the development and maintenance of germinal centers (GC) and humoral immune responses. During chronic HIV/SIV infection TFH accumulate, possibly as a result of antigen persistence. The HIV/SIV-associated TFH expansion may also reflect lack of regulation by suppressive follicular regulatory CD4+ T-cells (TFR). TFR are natural regulatory T-cells (TREG) that migrate into the follicle and, similarly to TFH, up-regulate CXCR5, Bcl-6, and PD1. Here we identified TFR as CD4+CD25+FoxP3+CXCR5+PD1hiBcl-6+ within lymph nodes of rhesus macaques (RM) and confirmed their localization within the GC by immunohistochemistry. RNA sequencing showed that TFR exhibit a distinct transcriptional profile with shared features of both TFH and TREG, including intermediate expression of FoxP3, Bcl-6, PRDM1, IL-10, and IL-21. In healthy, SIV-uninfected RM, we observed a negative correlation between frequencies of TFR and both TFH and GC B-cells as well as levels of CD4+ T-cell proliferation. Following SIV infection, the TFR/TFH ratio was reduced with no change in the frequency of TREG or TFR within the total CD4+ T-cell pool. Finally, we examined whether higher levels of direct virus infection of TFR were responsible for their relative depletion post-SIV infection. We found that TFH, TFR and TREG sorted from SIV- infected RM harbor comparable levels of cell-associated viral DNA. Our data suggests that TFR may contribute to the regulation and proliferation of TFH and GC B-cells in vivo and that a decreased TFR/TFH ratio in chronic SIV infection may lead to unchecked expansion of both TFH and GC B-cells. PMID:26297764

  5. Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

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    Walraven Vanessa

    2011-07-01

    Full Text Available Abstract Background Increasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1 multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo vaccine candidates formulated as an equimolar mixture (DiCo mix in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP119 fusion protein formulated in Montanide ISA 51. Methods Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains. Results These data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons. Conclusions The study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

  6. Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion.

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    Ivona Pandrea

    2011-08-01

    Full Text Available Understanding the mechanism of infection control in elite controllers (EC may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4(+ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4(+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This "functional cure" of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status.

  7. Long-term effects of tetanus toxoid inoculation on the demography and life expectancy of the Cayo Santiago rhesus macaques.

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    Kessler, Matthew J; Hernández Pacheco, Raisa; Rawlins, Richard G; Ruiz-Lambrides, Angelina; Delgado, Diana L; Sabat, Alberto M

    2015-02-01

    Tetanus was a major cause of mortality in the free-ranging population of rhesus monkeys on Cayo Santiago prior to 1985 when the entire colony was given its first dose of tetanus toxoid. The immediate reduction in mortality that followed tetanus toxoid inoculation (TTI) has been documented, but the long-term demographic effects of eliminating tetanus infections have not. This study uses the Cayo Santiago demographic database to construct comparative life tables 12 years before, and 12 years after, TTI. Life tables and matrix projection models are used to test for differences in: (i) survival among all individuals as well as among social groups, (ii) long-term fitness of the population, (iii) age distribution, (iv) reproductive value, and (v) life expectancy. A retrospective life table response experiment (LTRE) was performed to determine which life cycle transition contributed most to observed changes in long-term fitness of the population post-TTI. Elimination of clinical tetanus infections through mass inoculation improved the health and well-being of the monkeys. It also profoundly affected the population by increasing survivorship and long-term fitness, decreasing the differences in survival rates among social groups, shifting the population's age distribution towards older individuals, and increasing reproductive value and life expectancy. These findings are significant because they demonstrate the long-term effects of eradicating a major cause of mortality at a single point in time on survival, reproduction, and overall demography of a naturalistic population of primates.

  8. Urine culture - catheterized specimen

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    Culture - urine - catheterized specimen; Urine culture - catheterization; Catheterized urine specimen culture ... urinary tract infections may be found in the culture. This is called a contaminant. You may not ...

  9. Maintenance or Emergence of Chronic Phase Secondary Cytotoxic T Lymphocyte Responses after Loss of Acute Phase Immunodominant Responses Does Not Protect SIV-Infected Rhesus Macaques from Disease Progression

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    M. Shannon Keckler

    2010-01-01

    Full Text Available The simian immunodeficiency virus- (SIV- infected rhesus macaque is the preferred animal model for vaccine development, but the correlates of protection in this model are not completely understood. In this paper, we document the cytotoxic T lymphocyte (CTL response to SIV and its effects on viral evolution in an effort to identify events associated with disease progression regardless of MHC allele expression. We observed the evolution of epitopes targeted by CTLs in a group of macaques that included long-term nonprogressing (LTNP, slowly progressing (SP, normally progressing (NP, and rapidly progressing (RP animals. Collectively, our data (1 identify novel CTL epitopes from an SP animal that are not restricted by known protective alleles, (2 illustrate that, in this small study, RP and NP animals accrue more mutations in CTL epitopes than in SP or LTNP macaques, and (3 demonstrate that the loss of CTL responses to immunodominant epitopes is associated with viral replication increases, which are not controlled by secondary CTL responses. These findings provide further evidence for the critical role of the primary cell-mediated immune responses in the control of retroviral infections.

  10. Variability of bio-clinical parameters in Chinese-origin Rhesus macaques infected with simian immunodeficiency virus: a nonhuman primate AIDS model.

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    Song Chen

    Full Text Available BACKGROUND: Although Chinese-origin Rhesus macaques (Ch RhMs infected with simian immunodeficiency virus (SIV have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established. METHODOLOGY/PRINCIPAL FINDINGS: By randomizing 150 (78 male and 72 female Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group challenged with intrarectal (i.r. SIVmac239, intravenous (i.v. SIVmac239, or i.v. SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1-2 weeks. Plasma viral load (VL peaked at weeks 1-2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68. The rates of progression to AIDS or death were more rapid in SIVmac239 (i.r. or i.v.-infected than in SIVmac251 (i.v.-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with i.r. or i.v. SIVmac239. The variability (standard deviation in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (i.r. or i.v. than in those infected with SIVmac251 (i.v., allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251. CONCLUSION/SIGNIFICANCE: These results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

  11. Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation.

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    Francis Fieni

    Full Text Available HIV is shed in semen but the anatomic site of virus entry into the genital secretions is unknown. We determined viral RNA (vRNA levels and the envelope gene sequence in the SIVmac 251 viral populations in the genital tract and semen of 5 adult male rhesus monkeys (Macaca mulatta that were infected after experimental penile SIV infection. Paired blood and semen samples were collected from 1-9 weeks after infection and the monkeys were necropsied eleven weeks after infection. The axillary lymph nodes, testes, epididymis, prostate, and seminal vesicles were collected and vRNA levels and single-genome analysis of the SIVmac251 env variants was performed. At the time of semen collection, blood vRNA levels were between 3.09 and 7.85 log10 vRNA copies/ml plasma. SIV RNA was found in the axillary lymph nodes of all five monkeys and in 3 of 5 monkeys, all tissues examined were vRNA positive. In these 3 monkeys, vRNA levels (log10 SIVgag copies/ug of total tissue RNA in the axillary lymph node (6.48 ± 0.50 were significantly higher than in the genital tract tissues: testis (3.67 ± 2.16; p<0.05, epididymis (3.08 ± 1.19; p<0.0001, prostate (3.36 ± 1.30; p<0.01, and seminal vesicle (2.67 ± 1.50; p<0.0001. Comparison of the SIVmac251 env viral populations in blood plasma, systemic lymph node, and genital tract tissues was performed in two of the macaques. Visual inspection of the Neighbor-Joining phylograms revealed that in both animals, all the sequences were generally distributed evenly among all tissue compartments. Importantly, viral populations in the genital tissues were not distinct from those in the systemic tissues. Our findings demonstrate striking similarity in the viral populations in the blood and male genital tract tissues within 3 months of penile SIV transmission.

  12. Protection against SHIV-KB9 Infection by Combining rDNA and rFPV Vaccines Based on HIV Multiepitope and p24 Protein in Chinese Rhesus Macaques

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    Chang Li

    2012-01-01

    Full Text Available Developing an effective vaccine against HIV infection remains an urgent goal. We used a DNA prime/fowlpox virus boost regimen to immunize Chinese rhesus macaques. The animals were challenged intramuscularly with pathogenic molecularly cloned SHIV-KB9. Immunogenicity and protective efficacy of vaccines were investigated by measuring IFN-γ levels, monitoring HIV-specific binding antibodies, examining viral load, and analyzing CD4/CD8 ratio. Results show that, upon challenge, the vaccine group can induce a strong immune response in the body, represented by increased expression of IFN-γ, slow and steady elevated antibody production, reduced peak value of acute viral load, and increase in the average CD4/CD8 ratio. The current research suggests that rapid reaction speed, appropriate response strength, and long-lasting immune response time may be key protection factors for AIDS vaccine. The present study contributes significantly to AIDS vaccine and preclinical research.

  13. Unique pattern of enzootic primate viruses in Gibraltar macaques.

    Science.gov (United States)

    Engel, Gregory A; Pizarro, Mark; Shaw, Eric; Cortes, John; Fuentes, Agustin; Barry, Peter; Lerche, Nicholas; Grant, Richard; Cohn, Douglas; Jones-Engel, Lisa

    2008-07-01

    Because Gibraltar's macaques (Macaca sylvanus) have frequent contact with humans, we assayed 79 macaques for antibodies to enzootic primate viruses. All macaques were seronegative for herpesvirus B, simian T-cell lymphotropic virus, simian retrovirus, simian immunodeficiency virus, and rhesus cytomegalovirus. Seroprevalence of simian foamy virus reached 88% among adult animals.

  14. Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

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    Pahar Bapi

    2012-08-01

    Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

  15. Generation of lineage-related, mucosally transmissible subtype C R5 simian-human immunodeficiency viruses capable of AIDS development, induction of neurological disease, and coreceptor switching in rhesus macaques.

    Science.gov (United States)

    Ren, Wuze; Mumbauer, Alexandra; Gettie, Agegnehu; Seaman, Michael S; Russell-Lodrigue, Kasi; Blanchard, James; Westmoreland, Susan; Cheng-Mayer, Cecilia

    2013-06-01

    Most human immunodeficiency virus (HIV) transmissions are initiated with CCR5 (R5)-using viruses across mucosal surfaces, with the majority in regions where HIV type 1 (HIV-1) clade C predominates. Mucosally transmissible, highly replication competent, pathogenic R5 simian-human immunodeficiency viruses (SHIVs) encoding biologically relevant clade C envelopes are therefore needed as challenge viruses in vaccine efficacy studies with nonhuman primates. Here we describe the generation of three lineage-related subtype C SHIVs through four successive rapid transfers in rhesus macaques of SHIVC109F.PB4, a molecular clone expressing the soluble-CD4 (sCD4)-sensitive CCR5-tropic clade C envelope of a recently infected subject in Zambia. The viruses differed in their monkey passage histories and neutralization sensitivities but remained R5 tropic. SHIVC109P3 and SHIVC109P3N were recovered from a passage-3 rapid-progressor animal during chronic infection (24 weeks postinfection [wpi]) and at end-stage disease (34 wpi), respectively, and are classified as tier 1B strains, whereas SHIVC109P4 was recovered from a passage-4 normal-progressor macaque at 22 wpi and is a tier 2 virus, more difficult to neutralize. All three viruses were transmitted efficiently via intrarectal inoculation, reaching peak viral loads of 10(7) to 10(9) RNA copies/ml plasma and establishing viremia at various set points. Notably, one of seven (GC98) and two of six (CL31, FI08) SHIVC109P3- and SHIVC109P3N-infected macaques, respectively, progressed to AIDS, with neuropathologies observed in GC98 and FI08, as well as coreceptor switching in the latter. These findings support the use of these new SHIVC109F.PB4-derived viruses to study the immunopathology of HIV-1 clade C infection and to evaluate envelope-based AIDS vaccines in nonhuman primates.

  16. The Macaque Social Responsiveness Scale (mSRS: A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta.

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    Eric J Feczko

    Full Text Available Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD, has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS. Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological

  17. Poster: the macaque genome.

    Science.gov (United States)

    2007-04-13

    The rhesus macaque (Macaca mulatta) facilitates an extraordinary range of biomedical and basic research, and the publication of the genome only makes it a more powerful model for studies of human disease; moreover, the macaque's position relative to humans and chimpanzees affords the opportunity to learn about the processes that have shaped the last 25 million years of primate evolution. To allow users to explore these themes of the macaque genome, Science has created a special interactive version of the poster published in the print edition of the 13 April 2007 issue. The interactive version includes additional text and exploration, as well as embedded video featuring seven scientists discussing the importance of the macaque and its genome sequence in studies of biomedicine and evolution. We have also created an accompanying teaching resource, including a lesson plan aimed at teachers of advanced high school life science students, for exploring what a comparison of the macaque and human genomes can tell us about human biology and evolution. These items are free to all site visitors.

  18. Hematopoietic response to lineage-non-specific (rrIL-3) and lineage-specific (rhG-CSF, rhEpo, rhTpo) cytokine administration in SIV-infected rhesus macaques is related to stage of infection.

    Science.gov (United States)

    Bucur, S Z; Gillespie, T W; Lee, M E; Adams, J W; Bray, R A; Villinger, F; Ansari, A A; Hillyer, C D

    2000-04-01

    The present study reports the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + < 500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected animals exhibited significantly impaired bone marrow (BM) and peripheral blood (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to historic controls. In addition, compared to early-stage SIV-infected animals, late-stage SIV-infected macaques demonstrated a more marked dysfunction, as assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early-stage or late-stage SIV infection increased the viral load, as assessed by bDNA assay. These data suggest that hematopoietic reserve and the response to various cytokines is decreased even in early-stage SIV infection, with the hematopoietic dysfunction progressing in parallel to SIV infection.

  19. A fruit in hand is worth many more in the bush: steep spatial discounting by free-ranging rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kralik, Jerald D; Sampson, William W L

    2012-03-01

    Decision making is one of the principal cognitive processes underlying goal-directed behaviour and thus there is justifiably strong interest in modeling it. However, many of these models have yet to be tested outside of the laboratory. At the same time, field work would benefit from the use of experimental methods developed in the laboratory to determine the causal relationships between environmental variables and behaviour. We therefore adapted a laboratory-derived experimental paradigm to test decision making in the wild. The experiment used an indifference-point procedure to determine the influence of both the amount and distance of food on choice behaviour. Free-ranging rhesus monkeys were given the choice between a smaller amount of food at a closer distance and a larger amount farther away. In four conditions, we held the closer amount constant across trials and varied the farther amount to determine the point at which the monkeys were indifferent to the choice alternatives. For example, in condition one, we used one piece of food at the closer location, and determined how many pieces would be equivalent in the farther location. Four different closer amounts were tested to obtain an indifference point curve, with the indifference amounts at the farther location plotted against the closer amounts. The slope of the obtained linear indifference curve was surprisingly high, suggesting that rhesus monkeys significantly discount food that is farther away. Possible reasons for this steep spatial discounting are discussed.

  20. An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques

    Science.gov (United States)

    Sharpe, S. A.; White, A. D.; Sibley, L.; Gleeson, F.; Hall, G. A.; Basaraba, R. J.; McIntyre, A.; Clark, S. O.; Gooch, K.; Marsh, P. D.; Williams, A.; Dennis, M. J.

    2017-01-01

    Background New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. Methods Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. Results All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques Conclusions The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis. PMID:28273087

  1. Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing.

    Science.gov (United States)

    Hennessy, Michael B; Chun, Katie; Capitanio, John P

    2017-02-01

    Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1β showed increased responsiveness to immune challenge, and IL-1β and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.

  2. Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome.

    Science.gov (United States)

    Zhang, Yan; Zheng, Wen; Liu, Yuli; Wang, Jue; Peng, Ying; Shang, Haibao; Hou, Ning; Hu, Xiaomin; Ding, Yi; Xiao, Yao; Wang, Can; Zeng, Fanxin; Mao, Jiaming; Zhang, Jun; Ma, Dongwei; Sun, Xueting; Li, Chuanyun; Xiao, Rui-Ping; Zhang, Xiuqin

    2016-04-01

    Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications. Blood pressure circadian rhythm in hypertensive patients has been suggested to contribute to cardiovascular consequences and organ damage of hypertension. But circadian changes of BP and their response to drugs have not been clearly investigated in non-human primates (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we investigate BP changes and its circadian rhythm, together with the effect of antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive monkeys displayed higher BP, obesity, glucose intolerance, and dyslipidemia. We also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys. Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP circadian rhythm restoration, and decreased plasma concentration of inflammation factors and advanced glycation end-products. In summary, we identified a naturally-developed hypertensive MetS NHP model, which is of great value in the studies on pathogenesis of MetS-associated hypertension and development of novel therapeutic strategies. We also provided multiple novel mechanistic insights of the beneficial effect of Eplerenone on MetS with hypertension.

  3. Coupling of small leucine-rich proteoglycans to hypoxic survival of a progenitor cell-like subpopulation in Rhesus Macaque intervertebral disc.

    Science.gov (United States)

    Huang, Shishu; Leung, Victor Y L; Long, Dan; Chan, Danny; Lu, William W; Cheung, Kenneth M C; Zhou, Guangqian

    2013-09-01

    Degeneration of the intervertebral disc (IVD) is a major spinal disorder that associates with neck and back pain. Recent studies of clinical samples and animal models for IVD degeneration have identified cells with multi-potency in the IVD. However, IVD tissue-specific progenitor cells and their niche components are not clear, although degenerated IVD-derived cells possess in vitro characteristics of mesenchymal stromal cell (MSCs). Here, we firstly identified the tissue-specific intervertebral disc progenitor cells (DPCs) from healthy Rhesus monkey and report the niche components modulated the survival of DPCs under hypoxia. DPCs possess clonogenicity, multipotency and retain differentiation potential after extended expansion in vitro and in vivo. In particular, the nucleus pulposus-derived DPCs are sensitive to low oxygen tension and undergo apoptosis under hypoxic conditions due to their inability to induce/stabilize hypoxia-inducible factors (HIF). The presence of small leucine-rich proteoglycans (SLRP), biglycan or decorin, can reduce the susceptibility of DPCs to hypoxia-induced apoptosis via promoting the activation/stabilization of HIF-1α and HIF-2α. As IVD is avascular, we propose SLRPs are niche components of DPCs in IVD homeostasis, providing new insights in progenitor cell biology and niche factors under a hypoxic microenvironment.

  4. Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

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    For Yue Tso

    Full Text Available A better understanding of how the biological functions of the HIV-1 envelope (Env changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

  5. Spectral and spatial tuning of onset and offset response functions in auditory cortical fields A1 and CL of rhesus macaques.

    Science.gov (United States)

    Ramamurthy, Deepa L; Recanzone, Gregg H

    2016-12-07

    The mammalian auditory cortex is necessary for spectral and spatial processing of acoustic stimuli. Most physiological studies of single neurons in the auditory cortex have focused on the onset and sustained portions of evoked responses, but there have been far fewer studies on the relationship between onset and offset responses. In the current study, we compared spectral and spatial tuning of onset and offset responses of neurons in primary auditory cortex (A1) and the caudolateral (CL) belt area of awake macaque monkeys. Several different metrics were used to determine the relationship between onset and offset response profiles in both frequency and space domains. In the frequency domain, a substantial proportion of neurons in A1 and CL displayed highly dissimilar best stimuli for onset- and offset-evoked responses, though even for these neurons, there was usually a large overlap in the range of frequencies that elicited onset and offset responses and distributions of tuning overlap metrics were mostly unimodal. In the spatial domain, the vast majority of neurons displayed very similar best locations for onset- and offset-evoked responses, along with unimodal distributions of all tuning overlap metrics considered. Finally, for both spectral and spatial tuning, a slightly larger fraction of neurons in A1 displayed non-overlapping onset and offset response profiles, relative to CL, which supports hierarchical differences in the processing of sounds in the two areas. However, these differences are small compared to differences in proportions of simple cells (low overlap) and complex cells (high overlap) in primary and secondary visual areas.

  6. Orienting of Attention to Gaze Direction Cues in Rhesus Macaques: Species-specificity, and Effects of Cue Motion and Reward Predictiveness

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    Dian eYu

    2012-06-01

    Full Text Available Primates live in complex social groups and rely on social cues to direct their attention. For example, primates react faster to an unpredictable stimulus after seeing a conspecific looking in the direction of that stimulus. In the current study we tested the specificity of facial cues (gaze direction for orienting attention and their interaction with other cues that are known to guide attention. In particular, we tested whether macaque monkeys only respond to gaze cues from conspecifics or if the effect generalizes across species. We found an attentional advantage of conspecific faces over that of other human and cartoon faces. Because gaze cues are often conveyed by gesture, we also explored the effect of image motion (a simulated glance on the orienting of attention in monkeys. We found that the simulated glance did not significantly enhance the speed of orienting for monkey face stimuli, but had a significant effect for images of human faces. Finally, because gaze cues presumably guide attention towards relevant or rewarding stimuli, we explored whether orienting of attention was modulated by reward predictiveness. When the cue predicted reward location, face and non-face cues were effective in speeding responses towards the cued location. This effect was strongest for conspecific faces. In sum, our results suggest that while conspecific gaze cues activate an intrinsic process that reflexively directs spatial attention, its effect is relatively small in comparison to other features including motion and reward predictiveness. It is possible that gaze cues are more important for decision-making and voluntary orienting than for reflexive orienting.

  7. Vaccination of rhesus macaques with the live-attenuated HSV-1 vaccine VC2 stimulates the proliferation of mucosal T cells and germinal center responses resulting in sustained production of highly neutralizing antibodies.

    Science.gov (United States)

    Stanfield, Brent A; Pahar, Bapi; Chouljenko, Vladimir N; Veazey, Ronald; Kousoulas, Konstantin G

    2017-01-23

    We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG1 after two booster vaccinations, while IgG subtypes IgG2 and IgG3 remained at low to undetectable levels. All vaccinated animals produced high levels of cross protective neutralizing antibodies. Flow cytometry analysis of cells isolated from draining lymph nodes showed that VC2 vaccination stimulated significant increases in plasmablast (CD27(high)CD38(high)) and mature memory (CD21(-)IgM(-)) B cells. T cell analysis on cells isolated from draining lymph node biopsies demonstrated a statistically significant increase in proliferating (Ki67(+)) follicular T helper cells and regulatory CXCR5(+) CD8(+) cytotoxic T cells. Analysis of plasma isolated two weeks post vaccination showed significant increases in circulating CXCL13 indicating increased germinal center activity. Cells isolated from vaginal biopsy samples collected over the course of the study exhibited vaccination-dependent increases in proliferating (Ki67(+)) CD4(+) and CD8(+) T cell populations. These results suggest that intramuscular vaccination with the live-attenuated HSV-1 VC2 vaccine strain can stimulate robust IgG1 antibody responses that persist for >250days post vaccination. In addition, vaccination lead to the maturation of B cells into plasmablast and mature memory B cells, the expansion of follicular T helper cells, and affects in the mucosal immune responses. These data suggest that the HSV VC2 vaccine induces potent immune responses that could help

  8. Left heart catheterization

    Science.gov (United States)

    Catheterization - left heart ... to help guide the catheters up into your heart and arteries. Dye will be injected into your ... in the blood vessels that lead to your heart. The catheter is then moved through the aortic ...

  9. Molecular ABO phenotyping in cynomolgus macaques using real-time quantitative PCR.

    Science.gov (United States)

    Premasuthan, A; Ng, J; Kanthaswamy, S; Trask, J S; Houghton, P; Farkas, T; Sestak, K; Smith, D G

    2012-10-01

    Macaques are commonly used in biomedical research as animal models of human disease. The ABO phenotype of donors and recipients plays an important role in the success of transplantation and stem cell research of both human and macaque tissue. Traditional serological methods for ABO phenotyping can be time consuming, provide ambiguous results and/or require tissue that is unavailable or unsuitable. We developed a novel method to detect the A, B, and AB phenotypes of macaques using real-time quantitative polymerase chain reaction. This method enables the simple and rapid screening of these phenotypes in macaques without the need for fresh blood or saliva. This study reports the distribution of the A, B, and AB phenotypes of captive cynomolgus macaques that, while regionally variable, closely resembles that of rhesus macaques. Blood group B, as in rhesus macaques, predominates in cynomolgus macaques and its frequency distribution leads to a probability of major incompatibility of 41%. No silencing mutations have been identified in exon 6 or 7 in macaques that could be responsible for the O phenotype, that, although rare, have been reported. The excess homozygosity of rhesus and cynomolgus macaque genotypes in this study, that assumes the absence of the O allele, suggests the possibility of some mechanism preventing the expression of the A and B transferases.

  10. 恒河猴感染H5N1禽流感病毒后肺组织病理变化及病毒分布%Distribution of influenza A (H5N1) virus and pathological lesions in major organ tissues of experimentally infected rhesus macaques

    Institute of Scientific and Technical Information of China (English)

    赖天文; 邓少嫦; 吴东; 黎东明; 陈敏; 吕莹莹; 张钰; 黄韧; 吴斌

    2014-01-01

    Objective To investigate the pathological changes and viral invasion in the main organs of rhesus macaques after experimental infection with H5N1 virus.Methods The rhesus macaques were infected with H5N1 virus (AF148678/ACGoose/Guangdong/11961H5N1) by nasal inoculation under anesthesia.One rhesus macaque was killed respectively at 1,3,6,14 days after infection.The pathologic changes of the main organs were observed using HE staining and the characteristics of the viral invasion in the body were analyzed using viral isolation,RT-PCR andimmunohistochemistry.Results The influenza virus replicated only in the lung tissues characterized by diffuse alveolar damage in the infected rhesus macaques,mainly involving alveolar epithelial cells and pulmonary macrophages.The pathological changes showed 3 phases including exudative inflammation,hyperplasia and fibrosis.Extra-pulmonary organs also showed different degree of pathological changes such as degeneration and necrosis,but virus was not isolated in the corresponding organs.Conclusions Acute diffuse lung injury was a central part of the pathogenesis in H5N1 avian influenza virus infection.The lung was the main target organ in H5N1 viral infection,and H5N1 virus cannot replicate in other organs,which may be one of the obstacles to H5N1 viral transmission from person to person.%目的 探讨恒河猴感染H5N1病毒后肺组织病理变化及病毒分布特点.方法 在麻醉状态下对4只雄性恒河猴经鼻部滴入H5N1禽流感病毒(AF148678/ACGoose/Guangdong/11961H5N1),在染毒后第1、3、6及14天分别剖杀1只恒河猴.HE染色观察主要组织器官的病理变化,应用实时荧光(RT)-PCR及免疫组织化学方法分析H5N1禽流感病毒侵袭机体后肺及其他主要器官的病理改变及病毒分布情况.结果 恒河猴感染H5N1禽流感病毒后,病毒仅在肺组织复制,主要侵犯肺泡上皮细胞和肺巨噬细胞,表现为弥漫性肺泡损伤,先后经历渗出期、增生期和纤

  11. 恒河猴基因组SINEs和Alu元件的数量和分布%The Numbers and Distribution of SINEs and Alu Elements in Rhesus Macaque Genome

    Institute of Scientific and Technical Information of China (English)

    夏珊; 范振鑫

    2014-01-01

    哺乳动物的基因组中富含各种类型的重复序列,其中的微卫星作为分子标记在相关研究中得到了广泛的应用.而重复序列中的SINEs元件,在各类群物种的分子系统发育、遗传多样性等方面的研究也得到了使用.其中,灵长类物种特有的SINEs元件、Alu元件,也在灵长类物种的进化研究中得到了成功的使用.本研究对于重要的医学模式动物恒河猴的基因组中SINEs和Alu元件进行了搜索,并进一步统计分析其分布规律、长度等信息.在恒河猴基因组的20条常染色体上共发现了Alu元件1 093 185个,在性染色体X上发现了45 215个.长度为200 bp至300 bp区间的Alu元件分布最多;Alu元件中75%的分化值至少都为10,而只有6.2%左右的元件分化值能达到至少20,这一结果表明绝大部分的Alu元件都比较年轻.本研究的统计结果为后续应用SINEs和Alu元件作为分子标记的研究提供了重要的信息.%There are many different types of repeat elements in mammal genomes,and microsatellite has been widely used as molecular marker in researches.Additionally,another type of repeat element,SINEs,has also been used as molecular markers in molecular phylogeny and genetic diversity.Alu element,which was the primate-specific SINEs element,has been widely used in the evolutionary study of primate species.In this study,SINEs and Alu elements were screened in the genome of rhesus macaque Macaca mulatta,which was an important model animal in biomedical study.In total,there were 1 093 185 Alu elements in the 20 autosomes,and 45 215 Alu elements in the chromosome X.Most of the Alu elements were ranged in length from 200 bp to 300 bp,and 75% of which had a minimal divergence value of 10,whereas only 6.2% could reach 20,indicating that most of the Alu elements were relatively young.These results may provide important information for the future studies on the application of SINEs and Alu elements as molecular

  12. Testosterone Correlates with Venezuelan Equine Encephalitis Virus in Macaques

    Science.gov (United States)

    2006-03-29

    19], and azoosper- mia has been associated with SIV infection in young male rhesus macaques [20]. Depressed androgen levels during physiological...Cytokine Networks in Tissue Immunity Edited by: Meltzer MS, Mantovani A. New York:Wiley-Liss; 1991:77-82. 11. Muehlenbein MP, Bribiescas RG

  13. Endotracheal Intubation Inoculation of H5N1 Virus and Detection of Virus in Organ Tissues in the Rhesus Macaques%气管插管法接种H5N1病毒感染恒河猴及系统组织病毒检测

    Institute of Scientific and Technical Information of China (English)

    吕琦; 邓巍; 鲍琳琳; 许黎黎; 李枫棣; 陈霆; 占玲俊; 秦川

    2011-01-01

    目的 测试气管插管法接种高致病性禽流感病毒H5N1感染恒河猴的优势效果及疾病分析,为有效感染恒河猴、制备H5N1疾病模型提供实验依据.方法 使用人源H5N1病毒液经气管插管滴入恒河猴上呼吸道进行感染,观察感染恒河猴的临床表现,每天采集咽拭子、鼻灌洗液,在感染前2d感染后第3、5、7天采血,感染后第3和7天分别解剖1只恒河猴,取支气管淋巴结、肠淋巴结、鼻甲、心、肝、脾、肺、肾、肠、气管、脑及血液进行病毒分离、核酸载量检测和血常规测定.结果 感染后第2天恒河猴出现食欲下降,活动减少,并伴有一过性体温升高,白细胞数和淋巴细胞数下降.咽拭子、鼻灌洗液、肺、心、气管、脑、肝、肾、肠和血液中都能分离到H5N1病毒.结论 气管插管法接种H5N1病毒能有效感染恒河猴,并在猴体内多组织中分离、检测到病毒,为制备完善的H5N1模型和检测指标确定、进一步研究H5N1病毒的致病机制等奠定了基础.%Objective To evaluate the feasibility of endotracheal intubation route in preparation of H5N1 virus infection in rhesus macaques and to obtain a more sensitive animal model. Methods The rhesus macaques were infected with H5N1 avian influenza virus by endotracheal intubation. Clinical signs were assessed daily, and throat swab, nasal wash , major organs and blood were collected for detection of virus load, isolation and blood routine analysis. Results After infection the animals exhibited anorexia, lethargy and transient fever, and the total number of circulating leukocytes and lymphocytes was decreased. Virus isolation, RT-PCR assay of the throat swabs, nasal washs materials showed that the intestine, lung, brain, spleen, kidney, heart and liver were the target of the virus replication and the virus could replicate in organs outside the lung. In addition, virus was also detected in the blood 3 days after infection

  14. MaqFACS (Macaque Facial Action Coding System) can be used to document facial movements in Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Julle-Danière, Églantine; Micheletta, Jérôme; Whitehouse, Jamie; Joly, Marine; Gass, Carolin; Burrows, Anne M; Waller, Bridget M

    2015-01-01

    Human and non-human primates exhibit facial movements or displays to communicate with one another. The evolution of form and function of those displays could be better understood through multispecies comparisons. Anatomically based coding systems (Facial Action Coding Systems: FACS) are developed to enable such comparisons because they are standardized and systematic and aid identification of homologous expressions underpinned by similar muscle contractions. To date, FACS has been developed for humans, and subsequently modified for chimpanzees, rhesus macaques, orangutans, hylobatids, dogs, and cats. Here, we wanted to test whether the MaqFACS system developed in rhesus macaques (Macaca mulatta) could be used to code facial movements in Barbary macaques (M. sylvanus), a species phylogenetically close to the rhesus macaques. The findings show that the facial movement capacity of Barbary macaques can be reliably coded using the MaqFACS. We found differences in use and form of some movements, most likely due to specializations in the communicative repertoire of each species, rather than morphological differences.

  15. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV.

    Science.gov (United States)

    Van Rompay, Koen K A; Abel, Kristina; Earl, Patricia; Kozlowski, Pamela A; Easlick, Juliet; Moore, Joseph; Buonocore-Buzzelli, Linda; Schmidt, Kimberli A; Wilson, Robert L; Simon, Ian; Moss, Bernard; Rose, Nina; Rose, John; Marthas, Marta L

    2010-02-10

    In a previously developed infant macaque model mimicking HIV infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins provided partial protection against infection following oral inoculation with virulent SIV. In an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally administered, replicating vaccines. One group of newborn macaques received an oral prime immunization with a recombinant vesicular stomatitis virus expressing SIVmac239 gag, pol and env (VSV-SIVgpe), followed 2 weeks later by an intramuscular boost immunization with MVA-SIV. Another group received two immunizations with live-attenuated SIVmac1A11, administered each time both orally and intravenously. Control animals received mock immunizations or non-SIV VSV and MVA control vectors. Analysis of SIV-specific immune responses in blood and lymphoid tissues at 4 weeks of age demonstrated that both vaccine regimens induced systemic antibody responses and both systemic and local cell-mediated immune responses. The safety and immunogenicity of the VSV-SIVgpe+MVA-SIV immunization regimen described in this report provide the scientific incentive to explore the efficacy of this vaccine regimen against virulent SIV exposure in the infant macaque model.

  16. 恒河猴 H5 N1禽流感病毒性肺炎模型建立及其发病机制%Pathogenesis of influenza A (H5N1) virus-induced viral pneumonia in the rhesus macaque

    Institute of Scientific and Technical Information of China (English)

    黎东明; 赖天文; 邓少嫦; 吴东; 张钰; 陈敏; 吕莹莹; 吴斌

    2014-01-01

    目的:探讨H5N1病毒(AF148678/ACGoose/Guangdong/11961H5N1)感染恒河猴诱发自初期至恢复期过程肺炎的机制。方法以 H5N1病毒液经鼻滴入恒河猴,染毒后第0h、12h、1d、2d、3d、4d、6d、10d、12d和14d采血作血液学和流感特异抗体检测。染毒后第1、3、6、14 d分别剖杀1只恒河猴,取气管支气管淋巴结、肺、心、肝、肾、大脑及小脑进行病毒分离、滴定、病理及免疫组化检测并观察感染后临床表现。结果猴感染后出现发热、呼吸困难,食欲下降等。病毒仅在肺组织复制,主要侵犯下呼吸道的肺泡上皮细胞和肺巨噬细胞。感染后第1~3d引起暂时性的严重肺炎,主要为中性粒细胞浸润;第6 d后逐渐恢复,以巨噬细胞浸润为主;第14 d后以 T 淋巴细胞浸润为主,肺组织呈恢复期状态。结论下呼吸道是H5N1病毒感染主要攻击的对象,这可能是H5N1病毒在人与人之间传递的障碍之一,其发病可能经过病毒侵入、复制阶段及免疫损伤阶段。%At present ,the mechanism of highly pathogenic avian influenza H5N1 virus causing human infection or death is still not fully clear .In order to better understand the pathogenesis of the disease ,the rhesus macaques were infected with H5N1 virus (AF148678/ACGoose/Guangdong/11961H5N1) .We analyzed the clinical symptoms ,characteristics of the virus invades body ,pathological changes ,and immune response to discuss the pathogenesis of viral pneumonia induced by H 5N1 virus infection from the early time to the recovery time .The rhesus macaques were infected with H5N1 virus through nasal .Clinical signs were assessed daily ,and major organs and blood were collected for detection of blood routine analysis ,viruses were isola-ted and titrated from organs ,and pathologic and immunohistochemical were also conducted .As a result ,the rhesus macaques in-fected with H5N1 virus experienced fever ,dyspnea ,and anorexia

  17. Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study

    Directory of Open Access Journals (Sweden)

    Washington Parks Robyn

    2001-07-01

    Full Text Available Abstract Background HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. Methods For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIVmac251 viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. Results Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route. Conclusions These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development.

  18. Infections following epidural catheterization

    DEFF Research Database (Denmark)

    Holt, MS; Andersen, SS; Andersen, Ove;

    1995-01-01

    of central nervous system infection of at least 0.7% at Odense University Hospital. This degree of infection is of the same magnitude as that reported for intravascular devices. We found that the patients with generalized symptoms of infection had been catheterized for a longer time, and were older than......Seventy-eight patients with culture-positive epidural catheters, were studied. Fifty-nine had symptoms of exit site infection and 11 patients had clinical meningitis, two of whom also had an epidural abscess. This corresponds to a local infection incidence of at least 4.3% and an incidence...... patients with only local symptoms of infection. The microorganisms isolated from the tips of the epidural catheters were coagulase-negative staphylococci (41%), Staphylococcus aureus (35%), Gram-negative bacilli (14%) and others (10%). The Gram-negative bacilli and S. aureus caused serious infections more...

  19. Biomarkers of oral exposure to 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4-dinitroanisole (DNAN) in blood and urine of rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Hoyt, Nathan; Brunell, Marla; Kroeck, Karl; Hable, Mike; Crouse, Lee; O'Neill, Art; Bannon, Desmond I

    2013-11-01

    The U.S. Department of Defense is using the chemicals 2,4-dinitroanisole (DNAN) and 3-nitro-1, 2,4-triazol-5-one (NTO) in new munitions development. In a screen for biomarkers of exposure, these compounds were measured in urine and blood of male rhesus monkeys after oral doses. NTO peaked at 4 h, with urinary concentrations at least 100-fold higher than that of blood or serum while 4-dinitrophenol (DNP), a metabolite of DNAN, appeared in blood at concentrations 10- to 20-fold higher than the parent compound. For human exposure monitoring, urine is optimal for NTO while the metabolite DNP in blood is best for DNAN.

  20. Characterization of the SIVmac251 in a Chinese-origin rhesus macaque showing severe neurological symptoms and sequence variation of Gp120%表现神经症状的SIVmac251感染猴大脑基底节病毒gp120序列变异分析

    Institute of Scientific and Technical Information of China (English)

    刘克剑; 丛喆; 金光; 王卫; 陈霆; 蒋虹; 魏强

    2012-01-01

    Objective To investigate the possible neurotropism, neuroinvasion and their mechanism in a Chinese-origin rhesus macaque infected with SIVmac251 showing neurological symptoms. Methods Eight healthy laboratory rhesus macaques were infected with SIVmac251-155p6N by intravenous injection. Among them 3 monkeys showed neurological symptoms to a different degree, and one of these 3 animals (R21755) developed severe neurological symptoms. This monkey was sacrificed and the virus was isolated from the basal ganglia of the brain, the plasma viral load was quantified by real-time RT-PCR, and T cell subsets were determined by flow cytometry. The brain lesions were examined by histopathology using HE staining. The RNAs were extracted from SIVmac251-155p6N, plasma and basal ganglia, the gpl20 genes were amplified with single genome amplification, and the changes of JV-glycosylation site in gp20 regions were analyzed. Results The monkey K21755 presented AIDS encephalopathy-like symptoms after half a year post the viral infection. Pathological examination showed infiltration of macrophages and multinucleated giant cells in perivascular space, and degeneration and necrosis of neurons were observed in the brain tissue. The gp120 sequence analysis showed that the virus isolated from the brain was partly different from that of the other sequences of SIVmac251-155p6N and plasma virus of the monkey R21755. The variations were mainly in the V1/V4 regions and the loss of a N-glycosylation site in era Cl. Conclusions It seems that the neuroinvasion and neurovinilence of SIVmac2Sl are significantly enhanced during the long-term adaption in vivo. The finding of this study provide a firm molecular basis for establishing a strain of SIVmac251 with neurotropism and neurovinilence. This would be very meaningful for investigating the role of SIV in neurologic disease and studies of AIDS neuropathy.%目的 研究猴免疫缺陷病毒SIVmac251在中国恒河猴感染传代过程中产生的可能

  1. 高+Gx环境对猴舌黏膜上皮热休克蛋白质70表达的影响%Effect of high + Gx load on heat-shock protein 70 expression of tongue mucous membrane epithelium in rhesus macaques

    Institute of Scientific and Technical Information of China (English)

    汤楚华; 张建中; 牛忠英; 施生根; 张铭

    2007-01-01

    目的 研究模拟高+Gx环境中猴舌黏膜上皮热休克蛋白质70(HSP-70)的表达. 方法 以9只雄性猕猴为对象,随机分为4组,对照组+1 Gx/300 s;实验1、2、3组,分别为+15 Gx/200 s、+18 Gx/165 s、+21 Gx/140 s.采用免疫组织化学方法 ,研究模拟高+Gx环境作用下猴舌黏膜上皮细胞组织病理学改变及HSP-70基因的表达情况,探讨其表达水平的改变与高+Gx环境的关系. 结果 组织病理学观察:实验组和对照组猴舌黏膜上皮细胞无明显变化;免疫组织化学观察:对照组舌黏膜上皮细胞核HSP-70呈阴性表达或弱阳性表达.实验组舌黏膜上皮细胞核HSP-70着色明显,呈强阳性表达,不同高+Gx组之间无明显差别. 结论 本研究表明模拟高+Gx环境可引起猴舌黏膜上皮细胞HSP-70基因表达增强.%Objective To observe the expression of heat-shock protein 70 (HSP-70) in tongue mucous membrane epithelium in the stress reaction of rhesus macaque under+Gx loads. Methods Nine male rhesus macaques were randomly divided into 4 groups: control group was exposed to +1 Gx/300 s load, and experimental groups 1, 2 and 3 were exposed to + 15 Gx/200 s,+21 Gx/165 s and + 21 Gx/140 s respectively. Tongue tissue was fixed with 10% buffered formaldehyde and embedded with paraffin, and histopathological changes were observed under microscope. The expression of HSP-70 was detected by immunohistochemical PicTureTM method in the mucous membrane epithelium of tongue. Results Gross and histological analyses showed that no significant pathological changes were observed in the membrane of tongue mucous epithelium in different experimental groups of the animals. Immunohistochemical staining demonstrated that overexpression of HSP-70 was detected in the nuclei of the epithelium in the experimental groups, but no or slight positive staining was also observed in the nuclei of the epithelium in control animals. There was no significant difference in HSP-70 expression in

  2. Expression of the memory marker CD45RO on helper T cells in macaques.

    Directory of Open Access Journals (Sweden)

    Michael Valentine

    Full Text Available BACKGROUND: In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for studying HIV pathogenesis and testing new therapies. There is now a major effort to eradicate HIV reservoirs and cure the infection. One approach is to eliminate subsets of cells housing the latent reservoir, using UCHL1 to target these cells. So that such studies may be performed in macaques, it is essential to determine expression of CD45RO. METHODS: We have used immunofluorescence and flow cytometry to study cell surface expression of CD45RO on lymphocytes from PBMC, lymphoid, and GI organs of rhesus, pigtailed, and cynomolgus macaques. Both direct and indirect immunofluorescence experiments were performed. FINDINGS: CD45RO is expressed on a subset of CD4+ lymphocytes of all pigtailed, a fraction of rhesus, and neither of the cynomolgus macaques studied. The binding of UCHL1 to macaque cells was of lower avidity than to human cells. This could be overcome by forming UCHL1 multimers. Directly conjugating fluors to UCHL1 can inhibit UCHL1 binding to macaque cells. Patterns of UCHL1 expression differ somewhat in macaques and humans, and from that of other memory markers often used in macaques. CONCLUSIONS: CD45RO, defined with mAb UCHL1, is well expressed on CD4+ cells in pigtailed macaques. Using tissues recovered from latently infected pigtailed macaques we are determining whether UCHL1, or other memory markers, can define the cellular locus of the reservoir. The low avidity of this interaction could limit the utility of UCHL1, in its conventional form, to eliminate cells in vivo and test this approach in macaque models of HIV infection.

  3. Rhesus monkeys (Macaca mulatta) map number onto space

    OpenAIRE

    Drucker, Caroline B.; Brannon, Elizabeth M.

    2014-01-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance...

  4. Social Facilitation of Cognition in Rhesus Monkeys: Audience Vs. Coaction.

    Science.gov (United States)

    Reynaud, Amélie J; Guedj, Carole; Hadj-Bouziane, Fadila; Meunier, Martine; Monfardini, Elisabetta

    2015-01-01

    Social psychology has long established that the mere presence of a conspecific, be it an active co-performer (coaction effect), or a passive spectator (audience effect) changes behavior in humans. Yet, the process mediating this fundamental social influence has so far eluded us. Brain research and its nonhuman primate animal model, the rhesus macaque, could shed new light on this long debated issue. For this approach to be fruitful, however, we need to improve our patchy knowledge about social presence influence in rhesus macaques. Here, seven adults (two dyads and one triad) performed a simple cognitive task consisting in touching images to obtain food treats, alone vs. in presence of a co-performer or a spectator. As in humans, audience sufficed to enhance performance to the same magnitude as coaction. Effect sizes were however four times larger than those typically reported in humans in similar tasks. Both findings are an encouragement to pursue brain and behavior research in the rhesus macaque to help solve the riddle of social facilitation mechanisms.

  5. A Vaccine against CCR5 Protects a Subset of Macaques upon Intravaginal Challenge with Simian Immunodeficiency Virus SIVmac251

    OpenAIRE

    2014-01-01

    As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque ...

  6. Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection

    Directory of Open Access Journals (Sweden)

    Pedersen Niels C

    2007-04-01

    Full Text Available Abstract Background We reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251 mutants with a K65R mutation in reverse transcriptase (RT, and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later. Results The early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia. Conclusion This is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be

  7. Social interactions through the eyes of macaques and humans.

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    Richard McFarland

    Full Text Available Group-living primates frequently interact with each other to maintain social bonds as well as to compete for valuable resources. Observing such social interactions between group members provides individuals with essential information (e.g. on the fighting ability or altruistic attitude of group companions to guide their social tactics and choice of social partners. This process requires individuals to selectively attend to the most informative content within a social scene. It is unclear how non-human primates allocate attention to social interactions in different contexts, and whether they share similar patterns of social attention to humans. Here we compared the gaze behaviour of rhesus macaques and humans when free-viewing the same set of naturalistic images. The images contained positive or negative social interactions between two conspecifics of different phylogenetic distance from the observer; i.e. affiliation or aggression exchanged by two humans, rhesus macaques, Barbary macaques, baboons or lions. Monkeys directed a variable amount of gaze at the two conspecific individuals in the images according to their roles in the interaction (i.e. giver or receiver of affiliation/aggression. Their gaze distribution to non-conspecific individuals was systematically varied according to the viewed species and the nature of interactions, suggesting a contribution of both prior experience and innate bias in guiding social attention. Furthermore, the monkeys' gaze behavior was qualitatively similar to that of humans, especially when viewing negative interactions. Detailed analysis revealed that both species directed more gaze at the face than the body region when inspecting individuals, and attended more to the body region in negative than in positive social interactions. Our study suggests that monkeys and humans share a similar pattern of role-sensitive, species- and context-dependent social attention, implying a homologous cognitive mechanism of

  8. Macaque monkeys experience visual crowding.

    Science.gov (United States)

    Crowder, Erin A; Olson, Carl R

    2015-01-01

    In peripheral vision, objects that are easily discriminated on their own become less discriminable in the presence of surrounding clutter. This phenomenon is known as crowding.The neural mechanisms underlying crowding are not well understood. Better insight might come from single-neuron recording in nonhuman primates, provided they exhibit crowding; however, previous demonstrations of crowding have been confined to humans. In the present study, we set out to determine whether crowding occurs in rhesus macaque monkeys. We found that animals trained to identify a target letter among flankers displayed three hallmarks of crowding as established in humans. First, at a given eccentricity, increasing the spacing between the target and the flankers improved recognition accuracy. Second, the critical spacing, defined as the minimal spacing at which target discrimination was reliable, was proportional to eccentricity. Third, the critical spacing was largely unaffected by object size. We conclude that monkeys, like humans, experience crowding. These findings open the door to studies of crowding at the neuronal level in the monkey visual system.

  9. Methemoglobin and sulfhemoglobin formation due to benzocaine and lidocaine in macaques

    Energy Technology Data Exchange (ETDEWEB)

    Martin, D.G.; Woodard, C.L.; Gold, M.B.; Watson, C.E.; Baskin, S.I.

    1993-05-13

    Benzocaine (BNZ) and lidocaine (LC) are commonly used topical (spray) anesthetics approved for use in humans. BNZ has structural similarities to methemoglobin (MHb) forming drugs that are current candidates for cyanide prophylaxis, while LC has been reported to increase MHb in man. We therefore, compared MHb and sulfhemoglobin (SHb) production in three groups of Macaques (Macaca mulata, Chinese rhesus and Indian rhesus, and Macaca nemistrina, Pig-tailed Macaques) after exposure to BNZ and LC. Formation of SHb, unlike MHb, is not thought to be reversible and is considered to be toxic. MHb and SHb levels were measured periodically on a CO-Oximeter. All rhesus (n=8) were dosed intratrachealy/intranasaly with 56 mg and 280 mg BNZ and with 40 mg of LC in a randomized cross-over design. Pig-tailed macaques (n=6) were dosed with BNZ intranasaly 56 mg and with 40 mg of LC. Since no differences in the peak MHb or time to peak (mean +/- SD) were observed among the three macaque subspecies, the data were pooled. LC did not cause MHb or SHb formation above baseline in any monkey.

  10. Nursing ultrasound examination in catheterization

    Directory of Open Access Journals (Sweden)

    Luca Romei

    2007-12-01

    Full Text Available Ultrasound (US examination of the bladder can precisely determine the bladder volume and is a useful tool in estimating the residual urine volume. Its application is consequently recommended as an alternative to catheterization for the determination of residual urine. Moreover it represents a simple, noninvasive method to predict the outcome of a voiding trial following acute urine retention based on intravesical prostatic protrusion and on the US pattern of the bladder content. In this article, the Authors review the implementation and results of a bladder US program developed for non-medical caregivers at one Emergency Department.

  11. Venous catheterization with ultrasound navigation

    Science.gov (United States)

    Kasatkin, A. A.; Urakov, A. L.; Nigmatullina, A. R.

    2015-11-01

    By ultrasound scanning it was determined that respiratory movements made by chest of healthy and sick person are accompanied by respiratory chest rise of internal jugular veins. During the exhalation of an individual diameter of his veins increases and during the breath it decreases down to the complete disappearing if their lumen. Change of the diameter of internal jugular veins in different phases can influence significantly the results of vein puncture and cauterization in patients. The purpose of this research is development of the method increasing the efficiency and safety of cannulation of internal jugular veins by the ultrasound visualization. We suggested the method of catheterization of internal jugular veins by the ultrasound navigation during the execution of which the puncture of venous wall by puncture needle and the following conduction of J-guide is carried out at the moment of patient's exhalation. This method decreases the risk of complications development during catheterization of internal jugular vein due to exclusion of perforating wound of vein and subjacent tissues and anatomical structures.

  12. Venous catheterization with ultrasound navigation

    Energy Technology Data Exchange (ETDEWEB)

    Kasatkin, A. A., E-mail: ant-kasatkin@yandex.ru; Nigmatullina, A. R. [Izhevsk State Medical Academy, Kommunarov street, 281, Izhevsk, Russia, 426034 (Russian Federation); Urakov, A. L., E-mail: ant-kasatkin@yandex.ru [Institute of Mechanics Ural Branch of Russian Academy of Sciences, T.Baramzinoy street 34, Izhevsk, Russia, 426067, Izhevsk (Russian Federation); Izhevsk State Medical Academy, Kommunarov street, 281, Izhevsk, Russia, 426034 (Russian Federation)

    2015-11-17

    By ultrasound scanning it was determined that respiratory movements made by chest of healthy and sick person are accompanied by respiratory chest rise of internal jugular veins. During the exhalation of an individual diameter of his veins increases and during the breath it decreases down to the complete disappearing if their lumen. Change of the diameter of internal jugular veins in different phases can influence significantly the results of vein puncture and cauterization in patients. The purpose of this research is development of the method increasing the efficiency and safety of cannulation of internal jugular veins by the ultrasound visualization. We suggested the method of catheterization of internal jugular veins by the ultrasound navigation during the execution of which the puncture of venous wall by puncture needle and the following conduction of J-guide is carried out at the moment of patient’s exhalation. This method decreases the risk of complications development during catheterization of internal jugular vein due to exclusion of perforating wound of vein and subjacent tissues and anatomical structures.

  13. Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys.

    Science.gov (United States)

    Maestripieri, Dario

    2005-07-01

    Maternal abuse of offspring in macaque monkeys shares some similarities with child maltreatment in humans, including its transmission across generations. This study used a longitudinal design and a cross-fostering experiment to investigate whether abusive parenting in rhesus macaques is transmitted from mothers to daughters and whether transmission occurs through genetic or experiential factors. Nine of 16 females who were abused by their mothers in their first month of life, regardless of whether they were reared by their biological mothers or by foster mothers, exhibited abusive parenting with their firstborn offspring, whereas none of the females reared by nonabusive mothers did. These results suggest that the intergenerational transmission of infant abuse in rhesus monkeys is the result of early experience and not genetic inheritance. The extent to which the effects of early experience on the intergenerational transmission of abusive parenting are mediated by social learning or experience-induced physiological alterations remains to be established.

  14. Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

    Science.gov (United States)

    Burrows, Anne M; Waller, Bridget M; Micheletta, Jérôme

    2016-10-01

    Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc.

  15. Morphological and hormonal parameters in two species of macaques: impact of seasonal breeding.

    Science.gov (United States)

    Muehlenbein, Michael P; Campbell, Benjamin C; Murchison, Mark A; Phillippi, Kathrine M

    2002-03-01

    To compare physiological and developmental differences between two cogeneric species that differ by seasonal vs. aseasonal breeding, values for morphological measurements, testicular volume, serum testosterone, estradiol, and dehydroepiandrosterone-sulfate levels were obtained from 53 rhesus during the early breeding season, as well as 41 pig-tailed macaque males maintained at the Tulane Primate Center. The two species exhibited similar body size, testosterone, and estradiol levels, but differed substantially in testicular volume (3.00 +/- 1.7 vs. 1.72 +/- 1.3 cc), abdominal skinfold measures (15.7 +/- 9.2 vs. 9.0 +/- 7.7 mm), and DHEA-S levels (18.0 +/- 11.7 vs. 7.6 +/- 5.4 microg/dl). Significant interaction effects for species by age group were found for weight, tricep circumference, length, and estradiol level. In addition, length was more closely related to testicular volume among rhesus compared to pig-tailed macaques, suggesting different developmental patterns between the species. Predictors of hormonal levels differed between the two species. In the rhesus, estradiol levels were related to testicular volume and testosterone levels while there were no anthropometric predictors of testosterone or DHEA-S. For the pig-tailed macaques, testicular volume was related to tricep circumference, testosterone to triceps skinfold and testicular volume, and estradiol to weight. It is argued that rhesus have larger testes for body size and more abdominal fat deposits during the early breeding season relative to pig-tailed macaques reflecting the increased demands of sperm competition in a seasonally breeding species. Hormonal differences associated with the difference in breeding system appear to be primarily related to adrenal rather than testicular activity.

  16. Rhesus monkeys (Macaca mulatta) map number onto space.

    Science.gov (United States)

    Drucker, Caroline B; Brannon, Elizabeth M

    2014-07-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance, location, and spacing of the vertical array. We next asked whether monkeys show a spatially-oriented number mapping by testing their responses to the same five-element stimulus array rotated ninety degrees into a horizontal line. In these horizontal probe trials, monkeys preferentially selected the fourth position from the left, but not the fourth position from the right. Our results indicate that rhesus macaques map number onto space, suggesting that the association between number and space in human cognition is not purely a result of cultural experience and instead has deep evolutionary roots.

  17. Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.

    Science.gov (United States)

    Daniel, M D; Letvin, N L; Sehgal, P K; Schmidt, D K; Silva, D P; Solomon, K R; Hodi, F S; Ringler, D J; Hunt, R D; King, N W

    1988-04-15

    The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme-linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero-positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease.

  18. Massive hydrothorax following subclavian vein catheterization

    OpenAIRE

    Omar, Hesham R.; fathy, Ahmad; Elghonemy, Mohamed; Rashad, Rania; Helal, Engy; Mangar, Devanand; Camporesi, Enrico

    2010-01-01

    Since the introduction of central venous catheterization for monitoring of the venous pressure, fluid infusion and hyperalimentation, the literature has been full of serious life-threatening complications. Of these complications is the false positioning of the central venous catheter and subsequent development of pleural effusion. In this report we are describing a case of iatrogenic massive pleural effusion following subclavian vein catheterization necessitating intercostal tube drainage and...

  19. Tonal frequency affects amplitude but not topography of rhesus monkey cranial EEG components.

    Science.gov (United States)

    Teichert, Tobias

    2016-06-01

    The rhesus monkey is an important model of human auditory function in general and auditory deficits in neuro-psychiatric diseases such as schizophrenia in particular. Several rhesus monkey studies have described homologs of clinically relevant auditory evoked potentials such as pitch-based mismatch negativity, a fronto-central negativity that can be observed when a series of regularly repeating sounds is disrupted by a sound of different tonal frequency. As a result it is well known how differences of tonal frequency are represented in rhesus monkey EEG. However, to date there is no study that systematically quantified how absolute tonal frequency itself is represented. In particular, it is not known if frequency affects rhesus monkey EEG component amplitude and topography in the same way as previously shown for humans. A better understanding of the effect of frequency may strengthen inter-species homology and will provide a more solid foundation on which to build the interpretation of frequency MMN in the rhesus monkey. Using arrays of up to 32 cranial EEG electrodes in 4 rhesus macaques we identified 8 distinct auditory evoked components including the N85, a fronto-central negativity that is the presumed homolog of the human N1. In line with human data, the amplitudes of most components including the N85 peaked around 1000 Hz and were strongly attenuated above ∼1750 Hz. Component topography, however, remained largely unaffected by frequency. This latter finding may be consistent with the known absence of certain anatomical structures in the rhesus monkey that are believed to cause the changes in topography in the human by inducing a rotation of generator orientation as a function of tonal frequency. Overall, the findings are consistent with the assumption of a homolog representation of tonal frequency in human and rhesus monkey EEG.

  20. Development of a Charge Adjustment Model for Cardiac Catheterization

    OpenAIRE

    Brennan, Andrew; Gauvreau, Kimberlee; Connor, Jean; O’Connell, Cheryl; David, Sthuthi; Almodovar, Melvin; DiNardo, James; Banka, Puja; Mayer, John E.; Marshall, Audrey C.; Bergersen, Lisa

    2014-01-01

    A methodology that would allow for comparison of charges across institutions has not been developed for catheterization in congenital heart disease. A single institution catheterization database with prospectively collected case characteristics was linked to hospital charges related and limited to an episode of care in the catheterization laboratory for fiscal years 2008–2010. Catheterization charge categories (CCC) were developed to group types of catheterization procedures using a combinati...

  1. Visualization of transepithelial passage of the immunogenic 33-residue peptide from alpha-2 gliadin in gluten-sensitive macaques.

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    Kaushiki Mazumdar

    Full Text Available BACKGROUND: Based on clinical, histopathological and serological similarities to human celiac disease (CD, we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2 antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from alpha(2-gliadin in the distal duodenum of gluten-sensitive macaques. METHODOLOGY/PRINCIPAL FINDINGS: Six rhesus macaques were selected for study from a pool of 500, including two healthy controls and four gluten-sensitive animals with elevated anti-gliadin or anti-TG2 antibodies as well as history of non-infectious chronic diarrhea. Pediatric endoscope-guided pinch biopsies were collected from each animal's distal duodenum following administration of a gluten-containing diet (GD and again after remission by gluten-free diet (GFD. Control biopsies always showed normal villous architecture, whereas gluten-sensitive animals on GD exhibited histopathology ranging from mild lymphocytic infiltration to villous atrophy, typical of human CD. Immunofluorescent microscopic analysis of biopsies revealed IgG+ and IgA+ plasma-like cells producing antibodies that colocalized with TG2 in gluten-sensitive macaques only. Following instillation in vivo, the Cy-3-labeled 33-residue gluten peptide colocalized with the brush border protein villin in all animals. In a substantially enteropathic macaque with "leaky" duodenum, the peptide penetrated beneath the epithelium into the lamina propria. CONCLUSIONS/SIGNIFICANCE: The rhesus macaque model of gluten sensitivity not only resembles the histopathology of CD but it also may provide a model for studying intestinal permeability in states of epithelial integrity and disrepair.

  2. Genomic plasticity of the immune-related Mhc class I B region in macaque species

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    Bontrop Ronald E

    2008-10-01

    Full Text Available Abstract Background In sharp contrast to humans and great apes, the expanded Mhc-B region of rhesus and cynomolgus macaques is characterized by the presence of differential numbers and unique combinations of polymorphic class I B genes per haplotype. The MIB microsatellite is closely linked to the single class I B gene in human and in some great apes studied. The physical map of the Mhc of a heterozygous rhesus monkey provides unique material to analyze MIB and Mamu-B copy number variation and then allows one to decipher the compound evolutionary history of this region in primate species. Results In silico research pinpointed 12 MIB copies (duplicons, most of which are associated with expressed B-genes that cluster in a separate clade in the phylogenetic tree. Generic primers tested on homozygous rhesus and pedigreed cynomolgus macaques allowed the identification of eight to eleven MIB copies per individual. The number of MIB copies present per haplotype varies from a minimum of three to six in cynomolgus macaques and from five to eight copies in rhesus macaques. Phylogenetic analyses highlight a strong transpecific sharing of MIB duplicons. Using the physical map, we observed that, similar to MIB duplicons, highly divergent Mamu-B genes can be present on the same haplotype. Haplotype variation as reflected by the copy number variation of class I B loci is best explained by recombination events, which are found to occur between MIBs and Mamu-B. Conclusion The data suggest the existence of highly divergent MIB and Mamu-B lineages on a given haplotype, as well as variable MIB and B copy numbers and configurations, at least in rhesus macaque. Recombination seems to occur between MIB and Mamu-B loci, and the resulting haplotypic plasticity at the individual level may be a strategy to better cope with pathogens. Therefore, evolutionary inferences based on the multiplicated MIB loci but also other markers close to B-genes appear to be promising for

  3. Internal jugular versus subclavian vein catheterization for central venous catheterization in orthotopic liver transplantation.

    Science.gov (United States)

    Torgay, A; Pirat, A; Candan, S; Zeyneloglu, P; Arslan, G; Haberal, M

    2005-09-01

    The aim of this study was to compare incidence rates of mechanical and infectious complications associated with central venous catheterization via the internal jugular vein (IJV) versus the subclavian vein (SV) among 45 consecutive patients undergoing orthotopic liver transplantation (OLT) between January 2000 and June 2004. The subjects were divided into two groups according to the site of central venous catheterization (IJV or SV). We recorded each patient's physical characteristics, international normalized ratio (INR), partial thromboplastin time, platelet levels, number of puncture attempts, success/failure of central venous catheterization, duration of catheter placement, occurrence of catheter tip misplacement, arterial puncture, incidence of hematoma or pneumothorax, catheter-related infection, or bacterial colonization of the catheter. Senior staff anesthesiologists performed 22 SV and 23 IJV catheterizations for the 45 OLT procedures. The SV and IVJ groups both had minor coagulation abnormalities with slightly increased INR values at the time of catheterization. There were no significant differences between the groups with respect to success of central venous catheterization (100% for both), numbers of attempted punctures, duration of catheter placement, and incidence rates of mechanical and infectious complications. Both groups showed high frequencies of catheter tip misplacement, with right atrium as the site of misplacement in all cases. Two patients in the IJV group (8.7%) developed hematomas after accidental carotid artery puncture. The results suggest that, when performed by experienced anesthesiologists, central venous catheterization via the SV is an acceptable alternative to IJV catheterization for patients undergoing OLT.

  4. Auditory artificial grammar learning in macaque and marmoset monkeys.

    Science.gov (United States)

    Wilson, Benjamin; Slater, Heather; Kikuchi, Yukiko; Milne, Alice E; Marslen-Wilson, William D; Smith, Kenny; Petkov, Christopher I

    2013-11-27

    Artificial grammars (AG) are designed to emulate aspects of the structure of language, and AG learning (AGL) paradigms can be used to study the extent of nonhuman animals' structure-learning capabilities. However, different AG structures have been used with nonhuman animals and are difficult to compare across studies and species. We developed a simple quantitative parameter space, which we used to summarize previous nonhuman animal AGL results. This was used to highlight an under-studied AG with a forward-branching structure, designed to model certain aspects of the nondeterministic nature of word transitions in natural language and animal song. We tested whether two monkey species could learn aspects of this auditory AG. After habituating the monkeys to the AG, analysis of video recordings showed that common marmosets (New World monkeys) differentiated between well formed, correct testing sequences and those violating the AG structure based primarily on simple learning strategies. By comparison, Rhesus macaques (Old World monkeys) showed evidence for deeper levels of AGL. A novel eye-tracking approach confirmed this result in the macaques and demonstrated evidence for more complex AGL. This study provides evidence for a previously unknown level of AGL complexity in Old World monkeys that seems less evident in New World monkeys, which are more distant evolutionary relatives to humans. The findings allow for the development of both marmosets and macaques as neurobiological model systems to study different aspects of AGL at the neuronal level.

  5. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

    Directory of Open Access Journals (Sweden)

    J Gerardo García-Lerma

    2008-02-01

    Full Text Available BACKGROUND: In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. METHODS AND FINDINGS: We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. CONCLUSIONS: This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising Pr

  6. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

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    Laura M J Ylinen

    Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

  7. Iatrogenic intravascular pneumocephalus secondary to intravenous catheterization

    Energy Technology Data Exchange (ETDEWEB)

    Yildiz, Altan; Oezer, Caner; Egilmez, Hulusi; Duce, Meltem Nass; Apaydin, Demir F.; Yalcinoglu, Orhan [Department of Radiology, Faculty of Medicine, Mersin University (Turkey)

    2002-03-01

    The presence of pneumocephalus without a history of intracranial or intrathecal procedures is a significant radiographic finding. Although pneumocephalus means a violation of the dural barrier or the presence of infection, intravascular pneumocephalus is different from intraparenchymal pneumocephalus and its benign nature must be known in the presence of intravenous catheterization. Herein, we present a case of iatrogenic intravascular pneumocephalus with CT findings. To our knowledge, there are only a few reported cases of iatrogenic intravascular pneumocephalus in the literature. Careful intravenous catheterization and diagnosis of the condition on imaging helps to prevent unnecessary treatment procedures. (orig.)

  8. Pandemic Swine-Origin H1N1 Influenza Virus Replicates to Higher Levels and Induces More Fever and Acute Inflammatory Cytokines in Cynomolgus versus Rhesus Monkeys and Can Replicate in Common Marmosets.

    Science.gov (United States)

    Mooij, Petra; Koopman, Gerrit; Mortier, Daniëlla; van Heteren, Melanie; Oostermeijer, Herman; Fagrouch, Zahra; de Laat, Rudy; Kobinger, Gary; Li, Yan; Remarque, Edmond J; Kondova, Ivanela; Verschoor, Ernst J; Bogers, Willy M J M

    2015-01-01

    The close immunological and physiological resemblance with humans makes non-human primates a valuable model for studying influenza virus pathogenesis and immunity and vaccine efficacy against infection. Although both cynomolgus and rhesus macaques are frequently used in influenza virus research, a direct comparison of susceptibility to infection and disease has not yet been performed. In the current study a head-to-head comparison was made between these species, by using a recently described swine-origin pandemic H1N1 strain, A/Mexico/InDRE4487/2009. In comparison to rhesus macaques, cynomolgus macaques developed significantly higher levels of virus replication in the upper airways and in the lungs, involving both peak level and duration of virus production, as well as higher increases in body temperature. In contrast, clinical symptoms, including respiratory distress, were more easily observed in rhesus macaques. Expression of sialyl-α-2,6-Gal saccharides, the main receptor for human influenza A viruses, was 50 to 73 times more abundant in trachea and bronchus of cynomolgus macaques relative to rhesus macaques. The study also shows that common marmosets, a New World non-human primate species, are susceptible to infection with pandemic H1N1. The study results favor the cynomolgus macaque as model for pandemic H1N1 influenza virus research because of the more uniform and high levels of virus replication, as well as temperature increases, which may be due to a more abundant expression of the main human influenza virus receptor in the trachea and bronchi.

  9. Anaesthesia in the cardiac catheterization laboratory

    NARCIS (Netherlands)

    Braithwaite, Sue; Kluin, Jolanda; Buhre, Wolfgang F.; de Waal, Eric E. C.

    2010-01-01

    Purpose of review Interventions in the cardiac catheterization laboratory (CCL) requiring anaesthetic expertise are becoming routine. These interventions involve a heterogeneous patient population and take place in an offsite location. This review aims to give an insight into anaesthetic issues surr

  10. FACIAL ASYMMETRY IS NEGATIVELY RELATED TO CONDITION IN FEMALE MACAQUE MONKEYS.

    Science.gov (United States)

    Little, Anthony C; Paukner, Annika; Woodward, Ruth A; Suomi, Stephen J

    2012-09-01

    The face is an important visual trait in social communication across many species. In evolutionary terms there are large and obvious selective advantages in detecting healthy partners, both in terms of avoiding individuals with poor health to minimise contagion and in mating with individuals with high health to help ensure healthy offspring. Many models of sexual selection suggest that an individual's phenotype provides cues to their quality. Fluctuating asymmetry is a trait that is proposed to be an honest indicator of quality and previous studies have demonstrated that rhesus monkeys gaze longer at symmetric faces, suggesting preferences for such faces. The current study examined the relationship between measured facial symmetry and measures of health in a captive population of female rhesus macaque monkeys. We measured asymmetry from landmarks marked on front-on facial photographs and computed measures of health based on veterinary health and condition ratings, number of minor and major wounds sustained, and gain in weight over the first four years of life. Analysis revealed that facial asymmetry was negatively related to condition related health measures, with symmetric individuals being healthier than more asymmetric individuals. Facial asymmetry appears to be an honest indicator of health in rhesus macaques and asymmetry may then be used by conspecifics in mate-choice situations. More broadly, our data support the notion that faces are valuable sources of information in non-human primates and that sexual selection based on facial information is potentially important across the primate lineage.

  11. Activation of innate immunity in healthy Macaca mulatta macaques by a single subcutaneous dose of GMP CpG 7909: safety data and interferon-inducible protein-10 kinetics for humans and macaques.

    Science.gov (United States)

    Stewart, V Ann; McGrath, Shannon; Krieg, Arthur M; Larson, Noelle S; Angov, Evelina; Smith, Christopher L; Brewer, Thomas G; Heppner, D Gray

    2008-02-01

    Following a demonstration that mouse-optimized cytosine-guanosine dinucleotide (CpG) oligodeoxynucleotides stimulated innate immune protection against intracellular pathogens, we tested the ability of CpG 7909, a primate-optimized Toll-like receptor 9 (TLR9) agonist, to stimulate rhesus macaques to produce interferon-inducible protein-10 (IP-10), a biomarker of immune activation. This study was performed prior to a similar trial with humans in order to facilitate the development of CpG 7909 as an immunomodulator for biodefense. A single subcutaneous dose of clinical-grade CpG 7909 was given to four groups of healthy adult rhesus macaques (0-mg dose [n = 5], 0.75-mg dose [n = 9], 1.5-mg dose [n = 9], and 3.0-mg dose [n = 9]). Directed physical examination findings, clinical laboratory values, and serum IP-10 concentrations were collected at scheduled intervals for 28 days. All three dose levels of CpG 7909 were safe and not associated with significant clinical or laboratory abnormality. The time to peak serum IP-10 concentration was 1.0 days at the 0.75-mg dose and 0.5 days at the 1.5- and 3.0-mg doses. A dose-dependent response was observed for the magnitude and duration of IP-10 concentrations, which remained significantly above baseline for 3 days for the 3.0-mg and 1.5-mg dose groups but above baseline for only 2 days for the 0.75-mg dose group. There were no nonresponders to CpG 7909. These rhesus macaque safety and IP-10 response data closely parallel a subsequent phase 1 human study of subcutaneously administered CpG 7909. A single dose of clinical-grade CpG 7909 induced a rapid, sustained IP-10 response, a biomarker for activation of the innate immune system. Given the similar susceptibilities of humans and rhesus macaques to infectious diseases, the rhesus macaque appears to be a suitable model to evaluate the potential of CpG 7909-mediated innate immune activation to protect humans against pathogens.

  12. Bladder calculi complicating intermittent clean catheterization.

    Science.gov (United States)

    Amendola, M A; Sonda, L P; Diokno, A C; Vidyasagar, M

    1983-10-01

    Eight male patients on clean intermittent catheterization programs for neurogenic bladder dysfunction developed vesical calculi around pubic hairs inadvertently introduced into the bladder, acting as a nidus for incrustation. In three patients, the radiographic appearance of serpentine calcifications in the pelvis was highly consistent with calcareous deposits on strands of hair. Familiarity with this radiologic appearance should suggest the diagnosis in the appropriate clinical setting and help avoid misinterpretation of these calcifications, atypical of usual bladder stones.

  13. Entrapment of guidewire during central venous catheterization

    Directory of Open Access Journals (Sweden)

    Tarun S.

    2016-07-01

    Full Text Available Central venous catheterization (CVC is common in the setting of ICU for various reasons like monitoring of CVP, fluid administration and vasopressor or drug infusions. Guidewires are routinely used in the Seldinger technique during central venous catheter placement CVC placement is not innocuous as numerous complications may occur, with varying frequency and severity. [Int J Res Med Sci 2016; 4(7.000: 3080-3081

  14. A Review of Plasmodium coatneyi-Macaque Models of Severe Malaria.

    Science.gov (United States)

    Lombardini, E D; Gettayacamin, M; Turner, G D H; Brown, A E

    2015-11-01

    Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.

  15. Macaque cardiac physiology is sensitive to the valence of passively viewed sensory stimuli.

    Directory of Open Access Journals (Sweden)

    Eliza Bliss-Moreau

    Full Text Available Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period increased and parasympathetic activity (as measured by respiratory sinus arrhythmia decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals.

  16. Mixed-complexity artificial grammar learning in humans and macaque monkeys: evaluating learning strategies.

    Science.gov (United States)

    Wilson, Benjamin; Smith, Kenny; Petkov, Christopher I

    2015-03-01

    Artificial grammars (AG) can be used to generate rule-based sequences of stimuli. Some of these can be used to investigate sequence-processing computations in non-human animals that might be related to, but not unique to, human language. Previous AG learning studies in non-human animals have used different AGs to separately test for specific sequence-processing abilities. However, given that natural language and certain animal communication systems (in particular, song) have multiple levels of complexity, mixed-complexity AGs are needed to simultaneously evaluate sensitivity to the different features of the AG. Here, we tested humans and Rhesus macaques using a mixed-complexity auditory AG, containing both adjacent (local) and non-adjacent (longer-distance) relationships. Following exposure to exemplary sequences generated by the AG, humans and macaques were individually tested with sequences that were either consistent with the AG or violated specific adjacent or non-adjacent relationships. We observed a considerable level of cross-species correspondence in the sensitivity of both humans and macaques to the adjacent AG relationships and to the statistical properties of the sequences. We found no significant sensitivity to the non-adjacent AG relationships in the macaques. A subset of humans was sensitive to this non-adjacent relationship, revealing interesting between- and within-species differences in AG learning strategies. The results suggest that humans and macaques are largely comparably sensitive to the adjacent AG relationships and their statistical properties. However, in the presence of multiple cues to grammaticality, the non-adjacent relationships are less salient to the macaques and many of the humans.

  17. Clinical monitoring and correlates of nephropathy in SIV-infected macaques during high-dose antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Hebblewaite Diane

    2011-01-01

    Full Text Available Abstract Background In many preclinical AIDS research studies, antiretroviral therapy (ART is administered to experimentally simian immunodeficiency (SIV-infected rhesus macaques for reduction of viral load to undetectable levels. Prolonged treatment of macaques with a high dose of PMPA (9-[2-(r-(phosphonomethoxy propyl] adenine or tenofovir; 30 mg/kg of body weight subcutaneously once daily can result in proximal renal tubular dysfunction, a Fanconi-like syndrome characterized by glucosuria, aminoaciduria, hypophosphatemia, and bone pathology. In contrast, chronic administration of a low dose of PMPA (10 mg/kg subcutaneously once daily starting at birth does not seem to be associated with any adverse health effects within 3 years of treatment. In contrast to PMPA, limited information on systemic toxicity in rhesus monkeys is available for FTC (5-fluoro-1-(2R,5S-[2-(hydroxymethyl-1,3-oxathiolan-5-yl]cytosine; emtricitabine and stavudine (d4T. Results In this study, the clinical and biochemical correlates of tubular nephrosis in SIV-infected rhesus macaques associated with systemic administration of high-dose ART consisting of the three nucleoside analog inhibitors PMPA, FTC, and d4T were investigated. It was found that acute renal failure was uncommon (7.1% of treated animals and that morphologic evidence of nephropathy, which persisted for more than 300 days following discontinuation of the drug cocktail, was more frequent (52.4% of treated animals. While parameters from single time points lacked predictive value, biochemical alterations in Blood Urea Nitrogen (BUN and phosphorus were frequently identified longitudinally in the blood of ART-treated animals that developed evidence of nephropathy, and these longitudinal changes correlated with disease severity. Conclusions Recommendations are proposed to limit the impact of drug-induced renal disease in future SIV macaque studies.

  18. [Heart catheterization in Mexico. Results of the 1996 census of heart catheterization services by the Mexican Society of Cardiology].

    Science.gov (United States)

    Gaspar H, J; Guadalajara Boo, J F; de la Llata Romero, M

    1996-01-01

    The findings of the 1996 Cardiac Catheterization Laboratory Survey of the Sociedad Mexicana de Cardiología are presented. There are 52 cardiac catheterization laboratory departments distributed in 16 cities of which Mexico City has 20, Guadalajara 6 and Monterrey 5. Ninety-six percent are in hospitals where heart surgery can be performed and 8 (17%) have a training program in cardiac catheterization. Only two (3.8%) are exclusively dedicated to pediatric cardiac catheterization. In 1995, 19,214 diagnostic procedures and 2,429 PTCAs were done. A total of 270 physicians were reported to have privileges to perform cardiac catheterization. The geographical distribution of the cath labs, procedure volumes and number of physicians performing catheterization are discussed.

  19. A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251.

    Science.gov (United States)

    Van Rompay, Koen K A; Hunter, Zoe; Jayashankar, Kartika; Peabody, Julianne; Montefiori, David; LaBranche, Celia C; Keele, Brandon F; Jensen, Kara; Abel, Kristina; Chackerian, Bryce

    2014-02-01

    As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque CCR5 could prevent or suppress vaginal infection with highly virulent SIVmac251. Twelve macaques were vaccinated with a bacteriophage Qß-based vaccine targeting macaque CCR5 (Qß.CCR5). Six control animals were immunized with the Qß platform alone. All animals immunized with Qß.CCR5 developed high-titer anti-CCR5 antibody responses. Macaques were vaginally challenged with a high dose of SIVmac251. The mean peak viral RNA levels in the vaccinated groups were 30-fold lower than in the control group (10(6.8) versus 10(8.3) copies/ml plasma). Three of the 12 vaccinated macaques dramatically suppressed simian immunodeficiency virus (SIV) replication: peak viral loads were low (10(3) to 10(4) RNA copies/ml), and SIV RNA became undetectable from 6 weeks onward. No viral RNA or DNA could be detected in colon and lymph node biopsy specimens collected 13 months after challenge. In vivo depletion of CD8(+) cells failed to induce a viral rebound. However, once anti-CCR5 antibody responses had waned, the 3 animals became infected after intravaginal and/or intravenous rechallenge. In conclusion, vaccination against CCR5 was associated with dramatic suppression of virus replication in a subset (25%) of macaques. These data support further research of vaccination against CCR5 to combat HIV infection.

  20. Improved xenobiotic metabolism and reduced susceptibility to cancer in gluten-sensitive macaques upon introduction of a gluten-free diet.

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    Full Text Available BACKGROUND: A non-human primate (NHP model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta. METHODOLOGY: Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD and gluten-containing (GD diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies,targeting expression of over 20,000 genes. PRINCIPAL FINDINGS: When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories--cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function--this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function and actin-collagen-matrix metalloproteinases (MMP genes. CONCLUSIONS/SIGNIFICANCE: A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research.

  1. Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Brian T [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory

    2008-01-01

    Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

  2. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Science.gov (United States)

    Hill, F. S.; Cox, A. B.; Salmon, Y. L.; Cantu, A. O.; Lucas, J. N.

    1994-01-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

  3. Illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, Daan

    2014-01-01

    While Morocco is well known as the main port between Africa and the EU for the illegal drugs trade and migration, the illegal trade in wildlife is flourishing as well. Next to the illegal large-scale trafficking of tortoises and birds, it is estimated that as few as 5,000 Barbary macaques remain in

  4. Current Trends in the Management of Difficult Urinary Catheterizations

    Directory of Open Access Journals (Sweden)

    Paul A Willette

    2012-12-01

    Full Text Available Routine urinary catheter placement may cause trauma and poses a risk of infection. Male catheterization, in particular, can be difficult, especially in patients with enlarged prostate glands or other potentially obstructive conditions in the lower urinary tract. Solutions to problematic urinary catheterization are not well known and when difficult catheterization occurs, the risk of failed catheterization and concomitant complications increase. Repeated and unsuccessful attempts at urinary catheterization induce stress and pain for the patient, injury to the urethra, potential urethral stricture requiring surgical reconstruction, and problematic subsequent catheterization. Improper insertion of catheters also can significantly increase healthcare costs due to added days of hospitalization, increased interventions, and increased complexity of follow-up evaluations. Improved techniques for catheter placement are essential for all healthcare personnel involved in the management of the patient with acute urinary retention, including attending emergency physicians who often are the first physicians to encounter such patients. Best practice methods for blind catheter placement are summarized in this review. In addition, for progressive clinical practice, an algorithm for the management of difficult urinary catheterizations that incorporates technology enabling direct visualization of the urethra during catheter insertion is presented. This algorithm will aid healthcare personnel in decision making and has the potential to improve quality of care of patients.

  5. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever

    Science.gov (United States)

    Zapata, Juan C.; Pauza, C. David; Djavani, Mahmoud M.; Rodas, Juan D.; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S.; Salvato, Maria S.

    2011-01-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets. PMID:21820469

  6. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever.

    Science.gov (United States)

    Zapata, Juan C; Pauza, C David; Djavani, Mahmoud M; Rodas, Juan D; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S; Salvato, Maria S

    2011-11-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets.

  7. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

    Science.gov (United States)

    Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

    2015-01-01

    The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research.

  8. Development of a Zika Virus Infection Model in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Fusataka Koide

    2016-12-01

    Full Text Available Limited availability of Indian rhesus macaques (IRM is a bottleneck to study Zika virus (ZIKV pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM model for ZIKV infection. In brief, six MCMs (seronegative for dengue and ZIKV were subdivided into 3 cohorts with a male and female each and challenged with different doses of Asian PRVABC59 (Puerto Rico or FSS13025 (Cambodia or African (IBH30656 lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva and urine and tissues (testes and brain were assessed for viral load by quantitative RT-PCR and neutralizing antibodies (Nab by 50% Plaque Reduction Neutralization Test (PRNT50 at various times post infection (p.i. PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2 to 3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 ×103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.

  9. Suprapubic compared with transurethral bladder catheterization for gynecologic surgery: a systematic review and meta-analysis.

    LENUS (Irish Health Repository)

    Healy, Eibhlín F

    2012-09-01

    Suprapubic catheterization is commonly used for postoperative bladder drainage after gynecologic procedures. However, recent studies have suggested an increased rate of complications compared with urethral catheterization. We undertook a systematic review and meta-analysis of randomized controlled trials comparing suprapubic catheterization and urethral catheterization in gynecologic populations.

  10. A novel cannulation technique for difficult urethral catheterization

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    Mehmet Kaynar

    2016-03-01

    Full Text Available Introduction: To propose a novel cannulation technique for difficult urethral catheterization procedures. Technique: The sheath tip of an intravenous catheter is cut off, replaced to the needle tip and pushed through the distal drainage side hole to Foley catheter tip, and finally withdrawn for cannulation. In situations making urethral catheterization difficult, a guide wire is placed under direct vision. The modified Foley catheter is slid successfully over the guide wire from its distal end throughout the urethral passage into the bladder. Results: The modified Foley catheter was used successfully in our clinic in cases requiring difficult urethral catheterization. Conclusions: This easy and rapid modification of a Foley catheter may minimize the potential complications of blind catheter placement in standard catheterization.

  11. Acute urinary retention and the difficult catheterization: current emergency management.

    Science.gov (United States)

    Sliwinski, Ania; D'Arcy, Frank T; Sultana, Ron; Lawrentschuk, Nathan

    2016-04-01

    Acute urinary retention (AUR) is a common presentation to emergency departments. This article updates the reader on the appropriate management, investigations and guidelines for AUR. It looks at the mechanism of normal micturition and describes the theories of AUR. It outlines urethral catheterization techniques for difficult cases, reviews suprapubic catheterization procedures and describes the management of AUR in polytrauma. Although emergency management is by bladder drainage, key points in the history and examination may expose significant, latent pathologies.

  12. Clean intermittent self-catheterization in neuro-urology.

    Science.gov (United States)

    Di Benedetto, P

    2011-12-01

    Neurogenic lower urinary tract dysfunction (NLUTD) is commonly encountered in rehabilitation settings, and is caused by a variety of pathologies. The management of spinal cord injury (SCI) has been the model of reference for the management of other pathologies with NLUTD. The introduction of intermittent catheterization (IC) led to decline in renal related mortality in SCI patients and allowed an improvement of quality of life (QoL) in all neurogenic patients with NLUTD. IC could be sterile, aseptic or clean. Sterile intermittent catheterization (SIC) is the preferred method of bladder drainage in emergency medicine units and during spinal shock in SCI patients, but it is costly and time-consuming. Catheterizations performed in institutions, such as rehabilitation hospitals and nursing homes, are done aseptically. Clean intermittent catheterization (CIC), i.e. self-catheterization (CISC) or third party catheterization, represents the "gold standard" method for bladder emptying in all neuropathic patients with NLUTD: the technique is safe and effective and results in improved kidney and upper urinary tract status, lessening of vesico-ureteral reflux and amelioration of urinary continence. CISC is mandatory in patients with NLUTD secondary to detrusor areflexia/hypocontractility and in patients suffering from neurogenic detrusor overactivity with detrusor external sphincter dyssynergia and high post void residual of urine, often in combination with antimuscarinics/bladder relaxants. The review summarizes the most important aspects of IC and CISC. Attention was focused on the history of urethral catheterization, aims, materials, advantages, indications, and present-day techniques of CISC, emphasizing the importance of teaching in order to perform correctly the catheterization technique.

  13. 基于团抱行为的太行山猕猴社会联属%Social affiliation of Taihangshan macaque based on huddling behavior

    Institute of Scientific and Technical Information of China (English)

    鹿鹤; 王振龙; 王白石; 刘金栋; 路纪琪

    2013-01-01

    From September 2011 to June 2012,using instantaneous and scan sampling methods,we collected data,with 10 min interval,on huddling behaviors between individuals of troop Wangwu 1 (WW-1) of Taihangshan macaque (Macaca mulatta tcheliensis) inhabiting the Taihangshan Macaque National Nature Reserve (TMNNR),and then analyzed the individual social affiliation within troop WW-1.The results showed that:(1) huddling among individuals of troop WW-1was categorized into 5 huddling groups,and huddling behavior was more frequently observed in adult females inside a given unit (84.21%) ; (2) individual ages and sexes significantly influenced frequency of huddling behaviors.The sexual dimorphism of huddling behavior arose during the subadult period ; and (3) proportions of social affiliations that happened between mother and offspring was significantly larger than that of the other huddling types.Our results indicated that,within Taihangshan macaque society,social affiliation exhibited a web-like structure based on matrilineal units,and that the mother-offspring link was the strongest affiliation inside a unit.We established the affiliation sociogram of Taihangshan macaques based on method of behavioral ecology,and we hope this will be helpful for better understanding socioecology of rhesus macaques.

  14. Paediatric cardiac catheterization: an information sheet.

    Science.gov (United States)

    Bonnet, Caroline; Greffier, Angelique

    2013-04-01

    The need to inform patients using validated scientific data is acknowledged internationally. The obligation to inform patients is based on a fundamental principle of French law: the principle of the unavailability of the human body. Before engaging in diagnostic or therapeutic strategies such as paediatric cardiac catheterization, the healthcare professional must explain the disease, the advantages and drawbacks of each treatment strategy and their foreseeable benefit/risk ratio in order to help older children and their parents come to a decision. To obtain this required consent and before the care is provided, the infant and their legal representative must have received clear, accurate and understandable information. An information sheet cannot substitute for verbal information. Guidelines for good practices on the delivery of information have been established by the Health Authorities and officially recognized in a decree from the Ministry of Health. These documents allow professionals to draft a written information document for patients and healthcare users. This document must help the patient to take part in decisions that concern them. The law of 4th March 2002 regarding the rights of patients and the quality of the healthcare system states that 'in cases of litigation, it is the responsibility of the professional or the healthcare establishment to provide proof that the information was given to the person concerned in the conditions set out in the present article. This proof can be brought by any means'.

  15. Using central venous catheter for suprapubic catheterization in cardiac surgery

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    Bilehjani E

    2017-01-01

    Full Text Available Eissa Bilehjani,1 Solmaz Fakhari2 1Department of Cardiovascular Anesthesia, Tabriz University of Medical Sciences, Madani Heart Hospital, 2Department of Anesthesiology, Tabriz University of Medical Sciences, Madani Heart Hospital, Tabriz, Iran Abstract: Suprapubic catheterization is an alternative method for urinary drainage that is used when transurethral catheterization fails. Traditionally, inserted large-bore suprapubic catheters may cause fatal complications. During the past decade, we used a small central venous catheter (CVC suprapubicly in 16 male patients for the purpose of urinary drainage, when transurethral catheterization failed. The procedure is performed in no more than 10 minutes. Success rate was 100% and this approach did not lead to any complications. In conclusion, placing a CVC for suprapubic drainage is a safe method with a high success rate and we recommend it in patients with failed transurethral catheterization after a few attempts (2–3 attempts. Keywords: suprapubic catheterization complication, urethral catheterization, central venous catheter, Seldinger’s technique, cardiac surgery

  16. Parthenogenetic activation of rhesus monkey oocytes and reconstructed embryos.

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    Mitalipov, S M; Nusser, K D; Wolf, D P

    2001-07-01

    This study determines the efficiency of sequential calcium treatments (electroporation or ionomycin) combined with protein synthesis (cycloheximide) or phosphorylation inhibitors (6-dimethylaminopurine) or the specific maturation promoting factor (MPF) inhibitor, roscovitine, in inducing artificial activation and development of rhesus macaque parthenotes or nuclear transfer embryos. Exposure of oocytes arrested at metaphase II (MII) to ionomycin followed by 6-dimethylaminopurine or to electroporation followed by cycloheximide and cytochalasin B induced pronuclear formation and development to the blastocyst stage at a rate similar to control embryos produced by intracytoplasmic sperm injection. Parthenotes did not complete meiosis or extrude a second polar body, consistent with their presumed diploid status. In contrast, oocytes treated sequentially with ionomycin and roscovitine extruded the second polar body and formed a pronucleus at a rate higher than that observed in controls. Following reconstruction by nuclear transfer, activation with ionomycin/6-dimethylaminopurine resulted in embryos that contained a single pronucleus and no polar bodies. All nuclear transfer embryos activated with ionomycin/roscovitine contained one large pronucleus. However, a third of these embryos emitted one or two polar bodies, clearly containing chromatin material. In summary, we have identified simple yet effective methods of oocyte or cytoplast activation in the monkey, ionomycin/6-dimethylaminopurine, electroporation/cycloheximide/cytochalasin B, and ionomycin/roscovitine, which are applicable to parthenote or nuclear transfer embryo production.

  17. Aberrant genomic imprinting in rhesus monkey embryonic stem cells.

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    Fujimoto, Akihisa; Mitalipov, Shoukhrat M; Kuo, Hung-Chih; Wolf, Don P

    2006-03-01

    Genomic imprinting involves modification of a gene or a chromosomal region that results in the differential expression of parental alleles. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. Additionally, abnormal imprinting occurs in mouse embryonic stem cells (ESCs) and in clonally derived animals. Imprinted gene expression patterns in primate ESCs are largely unknown, despite the clinical potential of the latter in the cell-based treatment of human disease. Because of the possible implications of abnormal gene expression to cell or tissue replacement therapies involving ESCs, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ESC lines containing useful single nucleotide polymorphisms were subjected to polymerase chain reaction-based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting whereas IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ESCs, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ESC progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ESC differentiation in vitro and on ESC-derived cell function in vivo after transplantation are unknown.

  18. Estrogen enhances cystatin C expression in the macaque vagina.

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    Slayden, Ov D; Hettrich, Kevin; Carroll, Rebecca S; Otto, Lesley N; Clark, Amanda L; Brenner, Robert M

    2004-02-01

    Cystatin C is a secreted inhibitor of cysteine proteinases that participates in extracellular matrix remodeling. Whether hormones affect its expression in the vagina was unknown. Consequently, we examined the effects of estradiol (E(2)), progesterone (P), and raloxifene on vaginal cystatin C in rhesus macaques. In experiment 1, ovariectomized animals were treated sequentially with E(2) (14 d) and E(2) + P (14 d) to induce 28-d menstrual cycles. Vaginal samples were collected on d 6, 8, 14, and 28 of the induced cycle. Some cycled animals were deprived of both E(2) + P for 28 d. In experiment 2, ovariectomized animals were treated for 5 months with E(2) alone, E(2) + P, raloxifene, or left untreated. Total RNA from the vaginal wall was analyzed for the cystatin C transcript with a commercially prepared cDNA array and semiquantitative RT-PCR. Vaginal cryosections were analyzed by in situ hybridization for cystatin C transcript and by immunocytochemistry for the protein. E(2) treatment significantly (5-fold; P pelvic floor prolapse.

  19. Cardiac catheterization in children with pulmonary hypertensive vascular disease.

    Science.gov (United States)

    Bobhate, Prashant; Guo, Long; Jain, Shreepal; Haugen, Richard; Coe, James Y; Cave, Dominic; Rutledge, Jennifer; Adatia, Ian

    2015-04-01

    The risks associated with cardiac catheterization in children with pulmonary hypertension (PH) are increased compared with adults. We reviewed retrospectively all clinical data in children with PH [mean pulmonary artery pressure (mean PAp) ≥25 mmHg and pulmonary vascular resistance index (PVRI) ≥3 Wood units m(2)] undergoing cardiac catheterization between 2009 and 2014. Our strategy included a team approach, minimal catheter manipulation and sildenafil administration prior to extubation. Adverse events occurring within 48 h were noted. Seventy-five patients (36 males), median age 4 years (0.3-17) and median weight 14.6 kg (2.6-77 kg), underwent 97 cardiac catheterizations. Diagnoses included idiopathic or heritable pulmonary arterial hypertension (PAH) (29 %), PAH associated with congenital heart disease (52 %), left heart disease (5 %) and lung disease (14 %). Mean PAp was 43 ± 19 mmHg; mean PVRI was 9.7 ± 6 Wood units m(2). There were no deaths or serious arrhythmias. No patient required cardiac massage. Three patients who suffered adverse events had suprasystemic PAp (3/3), heritable PAH (2/3), decreased right ventricular function (3/3), and pulmonary artery capacitance index <1 ml/mmHg/m(2) (3/3) and were treatment naïve (3/3). No patient undergoing follow-up cardiac catheterization suffered a complication. In 45 % of cases, the data acquired from the follow-up cardiac catheterization resulted in an alteration of therapy. Three percent of children with PH undergoing cardiac catheterization suffered adverse events. However, there were no intra or post procedural deaths and no one required cardiac massage or cardioversion. Follow-up cardiac catheterization in patients receiving pulmonary hypertensive targeted therapy is safe and provides useful information.

  20. Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal Treatment, and Genetic Influences.

    Science.gov (United States)

    Schneider, Mary L; Moore, Colleen F; Adkins, Miriam; Barr, Christina S; Larson, Julie A; Resch, Leslie M; Roberts, Andrew

    2017-01-01

    Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood.

  1. Functional MRI of the vocalization-processing network in the macaque brain

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    Michael eOrtiz-Rios

    2015-04-01

    Full Text Available Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC, medial geniculate nucleus (MGN, auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG and sulcus (STS. Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls (scrambled calls also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt.

  2. A Forgotten Guidewire: Complication of Central Venous Catheterization

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    Funda Gümüş

    2011-08-01

    Full Text Available Central venous catheterization is an invasive procedure commonly preferred for hemodynamic monitorization, total parenteral nutrition, cardiac pacemaker implantation, long-term use of vasoactive or irritating agents and hemodialysis. We present a 19-year-old woman with acute renal failure scheduled for hemodialysis catheterization. A catheter guidewire extending from the right internal jugular vein to the right external iliac vein was detected in the chest X-ray, taken two hours following catheterization after occurrence of arrhythmia and hypotension. Catheteter guidewire was extracted noninvasively without any complications. Most common reasons for this complication are stated to be attention deficits, lack of experience, overtired staff, and inadequate supervision of trainees. In this paper, we discussed this complication’s causes and preventive methods. (Journal of the Turkish Society Intensive Care 2011; 9:64-7

  3. Ultra-rapid categorization of fourier-spectrum equalized natural images: macaques and humans perform similarly.

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    Pascal Girard

    Full Text Available BACKGROUND: Comparative studies of cognitive processes find similarities between humans and apes but also monkeys. Even high-level processes, like the ability to categorize classes of object from any natural scene under ultra-rapid time constraints, seem to be present in rhesus macaque monkeys (despite a smaller brain and the lack of language and a cultural background. An interesting and still open question concerns the degree to which the same images are treated with the same efficacy by humans and monkeys when a low level cue, the spatial frequency content, is controlled. METHODOLOGY/PRINCIPAL FINDINGS: We used a set of natural images equalized in Fourier spectrum and asked whether it is still possible to categorize them as containing an animal and at what speed. One rhesus macaque monkey performed a forced-choice saccadic task with a good accuracy (67.5% and 76% for new and familiar images respectively although performance was lower than with non-equalized images. Importantly, the minimum reaction time was still very fast (100 ms. We compared the performances of human subjects with the same setup and the same set of (new images. Overall mean performance of humans was also lower than with original images (64% correct but the minimum reaction time was still short (140 ms. CONCLUSION: Performances on individual images (% correct but not reaction times for both humans and the monkey were significantly correlated suggesting that both species use similar features to perform the task. A similar advantage for full-face images was seen for both species. The results also suggest that local low spatial frequency information could be important, a finding that fits the theory that fast categorization relies on a rapid feedforward magnocellular signal.

  4. Pharmacokinetics and immunogenicity of broadly neutralizing HIV monoclonal antibodies in macaques.

    Science.gov (United States)

    Rosenberg, Yvonne; Sack, Markus; Montefiori, David; Labranche, Celia; Lewis, Mark; Urban, Lori; Mao, Lingjun; Fischer, Rainer; Jiang, Xiaoming

    2015-01-01

    The identification of highly potent broadly neutralizing antibodies (bnAbs) against HIV-1, and success in preventing SHIV infection following their passive administration, have increased the likelihood that immunotherapeutic strategies can be adopted to prevent and treat HIV-1 infection. However, while broad and potent neutralizing activity is an essential prerequisite, in vivo properties such as good circulatory stability and non-immunogenicity are equally critical for developing a human treatment. In the present study, glycoforms of the bnAbs 10-1074, NIH45-46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, PG9, PG16, VRC01 and b12 were produced by Agrobacterium-mediated transient transfection of Nicotiana benthamiana and assessed following administration in rhesus macaques. The results indicate that (i) N-glycans within the VL domain impair plasma stability of plant-derived bnAbs and (ii) while PGT121 and b12 exhibit no immunogenicity in rhesus macaques after multiple injections, VRC01, 10-1074 and NIH45-46G54W elicit high titer anti-idiotypic antibodies following a second injection. These anti-idiotypic antibodies specifically bind the administered bnAb or a close family member, and inhibit the bnAb in neutralization assays. These findings suggest that specific mutations in certain bnAbs contribute to their immunogenicity and call attention to the prospect that these mutated bnAbs will be immunogenic in humans, potentially compromising their value for prophylaxis and therapy of HIV-1.

  5. Placental lactogen levels in rhesus isoimmunization.

    Science.gov (United States)

    Ward, R H; Letchworth, A T; Niven, P A; Chard, T

    1974-03-02

    A prospective study of the plasma levels of human placental lactogen (HPL) in pregnancies complicated by rhesus isoimmunization showed that in mild and moderately affected cases the levels were normal, while in severely affected cases they were raised. Serial levels of HPL before the 26th week provide a valuable indication of fetal outcome, and we suggest that this estimation should be used routinely as an adjunct to other tests in the management of rhesus isoimmunization.

  6. Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex.

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    Morozov, Yury M; Datta, Dibyadeep; Paspalas, Constantinos D; Arnsten, Amy F T

    2017-03-01

    Dorsolateral prefrontal cortex mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dorsolateral prefrontal cortex neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the 'mitochondria-on-a-string' phenotype, similar to those recently reported in patients with Alzheimer's disease. The thin mitochondrial segments were associated with endoplasmic reticulum cisterns, and the mitochondrial proteins Fis1 and Drp1, all of which initiate mitochondrial fission. These data suggest that the 'mitochondria-on-a-string' phenotype may reflect malfunction in mitochondrial dynamics, whereby fission is initiated, but the process is incomplete due to malfunction of subsequent step(s). Thus, aged rhesus monkeys may be particularly helpful in exploring the age-related changes that render higher cortical circuits so vulnerable to degeneration.

  7. Effect of prolonged ketamine exposure on cardiovascular physiology in pregnant and infant rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Hotchkiss, Charlotte E; Wang, Cheng; Slikker, William

    2007-11-01

    Physiologic measurements in nonhuman primates usually are collected from animals that are chemically or physically restrained. Both types of restraint may affect the parameters measured, and those effects can vary with age. Heart rate, respiratory rate, oxygen saturation, expired CO2, blood pressure, temperature, blood glucose, hematocrit, and venous blood gasses were measured in rhesus monkeys that were either infused intravenously with ketamine for 24 h or were cage-housed and physically restrained for sample collection. The subjects were pregnant monkeys at gestational day 120 to 123, infants 5 to 6 d old, and infants 35 to 37 d old. Heart rate and blood pressure were lower in ketamine-treated monkeys than physically restrained monkeys. Heart rate was higher in infants than adults, whereas blood pressure was lower in infants. Respiratory rate was higher in infants than adults and higher in physically restrained infants than ketamine-sedated infants but was not affected by ketamine in pregnant adults. Hematocrit was decreased in older infants. In summary, both physical restraint and ketamine sedation altered several physiologic parameters in pregnant and infant rhesus macaques. Investigators should consider these effects when designing experiments and evaluating experimental outcomes in monkeys.

  8. Rhesus monkey embryos produced by nuclear transfer from embryonic blastomeres or somatic cells.

    Science.gov (United States)

    Mitalipov, Shoukhrat M; Yeoman, Richard R; Nusser, Kevin D; Wolf, Don P

    2002-05-01

    Production of genetically identical nonhuman primates would reduce the number of animals required for biomedical research and dramatically impact studies pertaining to immune system function, such as development of the human-immunodeficiency-virus vaccine. Our long-term goal is to develop robust somatic cell cloning and/or twinning protocols in the rhesus macaque. The objective of this study was to determine the developmental competence of nuclear transfer (NT) embryos derived from embryonic blastomeres (embryonic cell NT) or fetal fibroblasts (somatic cell NT) as a first step in the production of rhesus monkeys by somatic cell cloning. Development of cleaved embryos up to the 8-cell stage was similar among embryonic and somatic cell NT embryos and comparable to controls created by intracytoplasmic sperm injection (ICSI; mean +/- SEM, 81 +/- 5%, 88 +/- 7%, and 87 +/- 4%, respectively). However, significantly lower rates of development to the blastocyst stage were observed with somatic cell NT embryos (1%) in contrast to embryonic cell NT (34 +/- 15%) or ICSI control embryos (46 +/- 6%). Development of somatic cell NT embryos was not markedly affected by donor cell treatment, timing of activation, or chemical activation protocol. Transfer of embryonic, but not of somatic cell NT embryos, into recipients resulted in term pregnancy. Future efforts will focus on optimizing the production of somatic cell NT embryos that develop in high efficiency to the blastocyst stage in vitro.

  9. Rhesus monkeys show human-like changes in gaze following across the lifespan.

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    Rosati, Alexandra G; Arre, Alyssa M; Platt, Michael L; Santos, Laurie R

    2016-05-11

    Gaze following, or co-orienting with others, is a foundational skill for human social behaviour. The emergence of this capacity scaffolds critical human-specific abilities such as theory of mind and language. Non-human primates also follow others' gaze, but less is known about how the cognitive mechanisms supporting this behaviour develop over the lifespan. Here we experimentally tested gaze following in 481 semi-free-ranging rhesus macaques (Macaca mulatta) ranging from infancy to old age. We found that monkeys began to follow gaze in infancy and this response peaked in the juvenile period-suggesting that younger monkeys were especially attuned to gaze information, like humans. After sexual maturity, monkeys exhibited human-like sex differences in gaze following, with adult females showing more gaze following than males. Finally, older monkeys showed reduced propensity to follow gaze, just as older humans do. In a second study (n = 80), we confirmed that macaques exhibit similar baseline rates of looking upwards in a control condition, regardless of age. Our findings indicate that-despite important differences in human and non-human primate life-history characteristics and typical social experiences-monkeys undergo robust ontogenetic shifts in gaze following across early development, adulthood and ageing that are strikingly similar to those of humans.

  10. Vitreal syneresis in rhesus monkeys.

    Science.gov (United States)

    Stuck, B E; Talsma, D M; Beatrice, E S

    1977-11-01

    The eyes of 15 rhesus monkeys were evaluated. Various degrees of vitreal syneresis were observed in 28 of the 30 eyes. The observed vitreal structures varied from fine strands randomly spaced throughout the vitreous to thick, intertwining, fibrous networks with some clumping of the collagenous condensate at the fiber junctions. Qualitatively, the degree of syneresis was slightly more extensive in the eight older mature males than in the seven younger animals. In all animals a clear view of the fundus could be obtained with the ophthalmoscope. The vitreous structures may be one cause of variability in ocular dose-response relationships for exposure to laser radiation. The effect on retinal exposure experiments of the finer vitreal structure is considered minimal.

  11. Generation of chimeric rhesus monkeys.

    Science.gov (United States)

    Tachibana, Masahito; Sparman, Michelle; Ramsey, Cathy; Ma, Hong; Lee, Hyo-Sang; Penedo, Maria Cecilia T; Mitalipov, Shoukhrat

    2012-01-20

    Totipotent cells in early embryos are progenitors of all stem cells and are capable of developing into a whole organism, including extraembryonic tissues such as placenta. Pluripotent cells in the inner cell mass (ICM) are the descendants of totipotent cells and can differentiate into any cell type of a body except extraembryonic tissues. The ability to contribute to chimeric animals upon reintroduction into host embryos is the key feature of murine totipotent and pluripotent cells. Here, we demonstrate that rhesus monkey embryonic stem cells (ESCs) and isolated ICMs fail to incorporate into host embryos and develop into chimeras. However, chimeric offspring were produced following aggregation of totipotent cells of the four-cell embryos. These results provide insights into the species-specific nature of primate embryos and suggest that a chimera assay using pluripotent cells may not be feasible.

  12. The utility of rhesus monkey (Macaca mulatta and other non-human primate models for preclinical testing of Leishmania candidate vaccines

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    Gabriel Grimaldi Jr

    2008-11-01

    Full Text Available Leishmaniasis causes significant morbidity and mortality, constituting an important global health problem for which there are few effective drugs. Given the urgent need to identify a safe and effective Leishmania vaccine to help prevent the two million new cases of human leishmaniasis worldwide each year, all reasonable efforts to achieve this goal should be made. This includes the use of animal models that are as close to leishmanial infection in humans as is practical and feasible. Old world monkey species (macaques, baboons, mandrills etc. have the closest evolutionary relatedness to humans among the approachable animal models. The Asian rhesus macaques (Macaca mulatta are quite susceptible to leishmanial infection, develop a human-like disease, exhibit antibodies to Leishmania and parasite-specific T-cell mediated immune responses both in vivo and in vitro, and can be protected effectively by vaccination. Results from macaque vaccine studies could also prove useful in guiding the design of human vaccine trials. This review summarizes our current knowledge on this topic and proposes potential approaches that may result in the more effective use of the macaque model to maximize its potential to help the development of an effective vaccine for human leishmaniasis.

  13. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

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    John K. Maxi

    2016-11-01

    Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

  14. [Visually-guided discrimination and preference of sexuality in female macaque monkeys].

    Science.gov (United States)

    Mizuno, M

    1997-04-01

    Visual information about face and body including facial expression and bodily behavioral patterns has been known to play an important role in social and emotional communication in monkeys. Its involvement in sexual activity has also been demonstrated in male monkeys but it is poorly understood in female monkeys. In the present study, visually-guided discrimination and preference of sexuality were investigated in female macaque monkeys performing operant bar-press tasks in an experimental cage which had a transparent panel facing a display. In the sex discrimination task, two rhesus monkeys (Macaca mulatta) were trained to discriminate sex of a monkey shown in a picture which was randomly selected from six photographs (three males and three females) and was presented on the display. The monkey pressed a right or left bar for male or female monkey, respectively, to get water as a reward. Under this discrimination task, the monkeys could discriminate the sexes of monkeys shown in newly presented pictures. When choice bars were reversed, correct responses significantly decreased below chance level. In the sex preference task, three rhesus monkeys and three Japanese monkeys (M. juscata) were used. The monkeys voluntarily pressed the bar to watch the video movie showing either male or female rhesus monkeys. The movies were presented as long as the subject kept pressing the bar. The same movie was continued when the monkey pressed the bar again within 10s after the previous release of the bar, while it was changed to the other when 10s passed after the subject released the bar. The total duration of the responses in daily sessions was measured. In this visual preference task, four out of six monkeys showed sex preference. Three adult Japanese monkeys (6-8 y) pressed the bar to watch the video movie of male monkeys which was taken in breeding season with longer duration than that of female monkeys taken in the same season. The other two adult rhesus monkeys (7 8 y) did not

  15. Broad distribution of ataxin 1 silencing in rhesus cerebella for spinocerebellar ataxia type 1 therapy.

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    Keiser, Megan S; Kordower, Jeffrey H; Gonzalez-Alegre, Pedro; Davidson, Beverly L

    2015-12-01

    Spinocerebellar ataxia type 1 is one of nine polyglutamine expansion diseases and is characterized by cerebellar ataxia and neuronal degeneration in the cerebellum and brainstem. Currently, there are no effective therapies for this disease. Previously, we have shown that RNA interference mediated silencing of ATXN1 mRNA provides therapeutic benefit in mouse models of the disease. Adeno-associated viral delivery of an engineered microRNA targeting ATXN1 to the cerebella of well-established mouse models improved motor phenotypes, neuropathy, and transcriptional changes. Here, we test the translatability of this approach in adult rhesus cerebella. Nine adult male and three adult female rhesus macaque were unilaterally injected with our therapeutic vector, a recombinant adeno-associated virus type 1 (rAAV1) expressing our RNAi trigger (miS1) and co-expressing enhanced green fluorescent protein (rAAV1.miS1eGFP) into the deep cerebellar nuclei using magnetic resonance imaging guided techniques combined with a Stealth Navigation system (Medtronics Inc.). Transduction was evident in the deep cerebellar nuclei, cerebellar Purkinje cells, the brainstem and the ventral lateral thalamus. Reduction of endogenous ATXN1 messenger RNA levels were ≥30% in the deep cerebellar nuclei, the cerebellar cortex, inferior olive, and thalamus relative to the uninjected hemisphere. There were no clinical complications, and quantitative and qualitative analyses suggest that this therapeutic intervention strategy and subsequent reduction of ATXN1 is well tolerated. Collectively the data illustrate the biodistribution and tolerability of rAAV1.miS1eGFP administration to the adult rhesus cerebellum and are supportive of clinical application for spinocerebellar ataxia type 1.

  16. Indwelling versus Intermittent Urinary Catheterization following Total Joint Arthroplasty: A Systematic Review and Meta-Analysis.

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    Wei Zhang

    Full Text Available The purpose of this study is to compare the rates of urinary tract infection (UTI and postoperative urinary retention (POUR in patients undergoing lower limb arthroplasty after either indwelling urinary catheterization or intermittent urinary catheterization.We conducted a meta-analysis of relevant randomized controlled trials (RCT to compare the rates of UTI and POUR in patients undergoing total joint arthroplasty after either indwelling urinary catheterization or intermittent urinary catheterization. A comprehensive search was carried out to identify RCTs. Study-specific risk ratios (RR with 95% confidence intervals (CI were pooled. Additionally, a meta-regression analysis, as well as a sensitivity analysis, was performed to evaluate the heterogeneity.Nine RCTs with 1771 patients were included in this meta-analysis. The results showed that there was no significant difference in the rate of UTIs between indwelling catheterization and intermittent catheterization groups (P>0.05. Moreover, indwelling catheterization reduced the risk of POUR, versus intermittent catheterization, in total joint surgery (P<0.01.Based on the results of the meta-analysis, indwelling urinary catheterization, removed 24-48 h postoperatively, was superior to intermittent catheterization in preventing POUR. Furthermore, indwelling urinary catheterization with removal 24 to 48 hours postoperatively did not increase the risk of UTI. In patients with multiple risk factors for POUR undergoing total joint arthroplasty of lower limb, the preferred option should be indwelling urinary catheterization removed 24-48 h postoperatively.Level I.

  17. Decreased dengue replication and an increased anti-viral humoral response with the use of combined Toll-like receptor 3 and 7/8 agonists in macaques.

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    Carlos A Sariol

    Full Text Available BACKGROUND: Pathogenic versus protective outcomes to Dengue virus (DENV infection are associated with innate immune function. This study aimed to determine the role of increased TLR3- and TLR7/8-mediated innate signaling after Dengue infection of rhesus macaques in vivo to evaluate its impact on disease and anti-DENV immune responses. METHODOLOGY/PRINCIPAL FINDINGS: TLR3 and TLR7/8 agonists (emulsified in Montanide were administered subcutaneously to rhesus macaques at 48 hours and 7 days after DENV infection. The Frequency and activation of myeloid dendritic cells, plasmacytoid dendritic cells, and B cells were measured by flow cytometry while the serum levels of 14 different cytokines and chemokines were quantified. Adaptive immune responses were measured by DENV-specific antibody subtype measurements. Results showed that the combined TLR agonists reduced viral replication and induced the development of a proinflammatory reaction, otherwise absent in Dengue infection alone, without any clear signs of exacerbated disease. Specifically, the TLR-induced response was characterized by activation changes in mDC subsets concurrent with higher serum levels of CXCL-10 and IL-1Ra. TLR stimulation also induced higher titers of anti-DENV antibodies and acted to increase the IgG2/IgG1 ratio of anti-DENV to favor the subtype associated with DENV control. We also observed an effect of DENV-mediated suppression of mDC activation consistent with prior in vitro studies. CONCLUSIONS/SIGNIFICANCE: These data show that concurrent TLR3/7/8 activation of the innate immune response after DENV infection in vivo acts to increase antiviral mechanisms via increased inflammatory and humoral responses in rhesus macaques, resulting in decreased viremia and melioration of the infection. These findings underscore an in vivo protective rather than a pathogenic role for combined TLR3/7/8-mediated activation in Dengue infection of rhesus macaques. Our study provides definitive

  18. A macaque model for hantavirus infection.

    NARCIS (Netherlands)

    J. Groen (Jan); M.N. Gerding; J.P. Koeman; P.J.M. Roholl (Paul); G. van Amerongen (Geert); H.G.M. Jordans; A.D.M.E. Osterhaus (Albert); H.G.M. Niesters (Bert)

    1995-01-01

    textabstractCynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hallnas), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild pro

  19. Cardiac Catheterization in Thoraco-Omphalocardiopagus Twins: A Case Report

    Directory of Open Access Journals (Sweden)

    Minati Choudhury

    2008-01-01

    literature on the anaesthetic management of these cases is sparse. The following case report details the expert and vigilant anaesthetic management leading to successful diagnostic cardiac catheterization. The report emphasizes the importance of synchronous ventilation, teamwork and communication required in cases such as this. This case report also details the difficulties encountered and how to overcome them during the prolonged procedure.

  20. Urethral catheterization:The need for adequate undergraduate exposure

    Directory of Open Access Journals (Sweden)

    E.V. Ezenwa

    2017-03-01

    Conclusion: Newly recruited interns have poor practical exposure to urethral catheterization. Efforts should be made to improve the quality of supervised training given to medical undergraduates so as to avoid complications that could arise if this procedure is not properly done when they qualify.

  1. Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin

    Science.gov (United States)

    Pincus, Seth H.; Bhaskaran, Manoj; Brey, Robert N.; Didier, Peter J.; Doyle-Meyers, Lara A.; Roy, Chad J.

    2015-01-01

    Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands) developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN). Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome. PMID:26067369

  2. Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin

    Directory of Open Access Journals (Sweden)

    Seth H. Pincus

    2015-06-01

    Full Text Available Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN. Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome.

  3. Endothelial Progenitor Cells in Peripheral Blood of Cardiac Catheterization Personnel

    Directory of Open Access Journals (Sweden)

    Soheir Korraa1, Tawfik M.S.1, Mohamed Maher 2 and Amr Zaher

    2014-07-01

    Full Text Available Background: The aim of the present study was to evaluate the rejuvenation capacity among cardiac catheterization technicians occupationally exposed to ionizing radiation. Subjects and methods: The individual annual collective dose information was measured by thermoluminscent personal dosimeters (TLD for those technicians and found to be ranging between 2.16 and 8.44 mSv/y. Venous blood samples were obtained from 30 cardiac catheterization technicians exposed to X-ray during fluoroscopy procedures at the National Heart Institute in Embaba. The control group involved 25 persons not exposed to ionizing radiation and not working in hospitals in addition to 20 persons not exposed to ionizing radiation and working in hospitals. Blood samples were assayed for total and differential blood counts, micronucleus formation (FMN plasma stromal derived growth factor-1α (SDF-1 α and cell phenotype of circulating endothelial progenitor cells (EPCs, whose surface markers were identified as the CD34, CD133 and kinase domain receptors (KDR. Results: SDF-1α (2650± 270 vs. 2170 ± 430 pg/ml and FMN (19.9 ± 5.5 vs. 2.8 ± 1.4/1000 cells were significantly higher among cardiac catheterization staff compared to those of the controls respectively. Similarly, EPCs: CD34 (53 ± 3.9 vs. 48 ± 8.5/105 mononuclear cells, CD133 (62.4 ± 4.8 vs. 54.2 ± 10.6 /105 mononuclear cells KDR (52.7 ± 10.6 vs.43.5± 8.2 /105 mononuclear cells were also significantly higher among cardiac catheterization staff compared to the values of controls respectively. Smoking seemed to have a positive effect on the FMN and SDF-1 but had a negative effect on EPCs. It was found that among cardiac catheterization staff, the numbers of circulating progenitor cells had increased and accordingly there was an increased capacity for tissue repair. Conclusion: In conclusion, the present work shows that occupational exposure to radiation, well within permissible levels, leaves a genetic mark on the

  4. Oct-4 expression in pluripotent cells of the rhesus monkey.

    Science.gov (United States)

    Mitalipov, Shoukhrat M; Kuo, Hung-Chih; Hennebold, Jon D; Wolf, Don P

    2003-12-01

    The POU (Pit-Oct-Unc)-domain transcription factor, Oct-4, has become a useful marker of pluripotency in the mouse. It is found exclusively in mouse preimplantation-stage embryos after embryonic genome activation and is a characteristic of mouse embryonic stem (ES) cells, and its absence in knockout mice precludes inner cell mass (ICM) formation in blastocysts. Expression of Oct-4 has also been associated with pluripotency in primate cells. Here, we undertook a systematic study of Oct-4 expression in rhesus macaque preimplantation embryos produced by intracytoplasmic sperm injection and in ES cells before and after exposure to differentiating conditions in vitro. We also evaluated Oct-4 expression as a means of monitoring the extent of reprogramming following somatic cell nuclear transfer. Oct-4 was detected by reverse transcription-polymerase chain reaction and immunocytochemistry with a monoclonal antibody. Monkey pronuclear-stage zygotes and cleaving embryos up to the 8-cell stage showed no detectable Oct-4. Nuclear staining for Oct-4 first became obvious at the 16-cell stage, and a strong signal was observed in morula and compact morula stages. Both ICM and trophectodermal cell nuclei of monkey early blastocysts were positive for Oct-4. However, the signal was diminished in trophectodermal cells of expanded blastocysts, whereas expression remained high in ICM nuclei. Similar to the mouse, hatched monkey blastocysts showed strong Oct-4 expression in the ICM, with no detectable signal in the trophectoderm. Undifferentiated monkey ES cells derived from the ICM of in vitro-produced blastocysts expressed Oct-4, consistent with their pluripotent nature, whereas ES cell differentiation was associated with signal loss. Therefore, Oct-4 expression in the monkey, as in the mouse, provides a useful marker for pluripotency after activation of the embryonic genome. Finally, the observed lack or abnormal expression of Oct-4 in monkey nuclear transfer embryos suggests

  5. Safety and Immunogenicity of a Live-Attenuated Junin (Argentine Hemorrhagic Fever) Vaccine in Rhesus Macaques

    Science.gov (United States)

    1993-01-01

    immunization of the MATERIALS AND METHODS at-risk population offers the only practical so- Iltron for control of the disease. Attempts to develop a...saphenous or femoral veins using a 23- or 21 -gauge butterfly Materials for direct quantitative viral titration needle. Venipuncture sites were cleansed...21702-5011. 14. Contigiani MS. Sabattini MS. 1977. Virulencia diferencial de cepas de virus Junin per marca- dores biologicos en ratones % coba’.os

  6. The Peculiar Evolution of Apolipoprotein(a) in Human and Rhesus Macaque

    OpenAIRE

    Pesole, G.; A. Gerardi; di-Jeso, F.; Saccone, C.

    1994-01-01

    Apo(a) is a low density lipoprotein homologous to plasminogen and has been shown to be involved in coronary atheroschlerosis. In the present paper we will try to analyze the interesting evolutionary pattern of Apo(a). The plasminogen gene contains 5 cysteine-rich sequences, called kringles, followed by a protease domain. Apo(a), probably arisen by duplication of an ancestral plasminogen gene, contains many tandemly repeated copies of a sequence domain similar to the fourth kringle of plasmino...

  7. Measuring infant attachment security in rhesus macaques (Macaca mulatta): adaptation of the attachment Q-set.

    Science.gov (United States)

    Warfield, James J; Kondo-Ikemura, Kiyomi; Waters, Everett

    2011-02-01

    John Bowlby defined offspring-parent attachment as a relationship in which an infant or child uses one or a few preferred adults as a secure base from which to explore and as a haven of safety. He defined attachment security in terms of confidence in the adult's availability and responsiveness and the smooth organization of exploration and proximity seeking. Developmental psychologists have found this perspective productive in both observational and laboratory research. At the same time, they emphasize that such a construct cannot be operationalized in terms of one or a few behaviors. Instead, naturalistic observations of human infant attachment typically employ the Q-sort method to develop the Attachment q-set (AQS), 90 behaviorally descriptive items sorted in terms of how characteristic each item is of the infant's typical behavior. Meta-analyses of research using the AQS attest to its reliability and validity. This article reports an adaptation of the AQS to the task of assessing infant attachment security in nonhuman primates and illustrates its use. The availability of comparable measures of attachment security will contribute to an expanded understanding of patterns of attachment behavior in nonhuman primate societies and will facilitate interaction between comparative and developmental psychologists.

  8. Alcohol Consumption Modulates Host Defense in Rhesus Macaques by Altering Gene Expression in Circulating Leukocytes.

    Science.gov (United States)

    Barr, Tasha; Girke, Thomas; Sureshchandra, Suhas; Nguyen, Christina; Grant, Kathleen; Messaoudi, Ilhem

    2016-01-01

    Several lines of evidence indicate that chronic alcohol use disorder leads to increased susceptibility to several viral and bacterial infections, whereas moderate alcohol consumption decreases the incidence of colds and improves immune responses to some pathogens. In line with these observations, we recently showed that heavy ethanol intake (average blood ethanol concentrations > 80 mg/dl) suppressed, whereas moderate alcohol consumption (blood ethanol concentrations consumption. To uncover the molecular basis for impaired immunity with heavy alcohol consumption and enhanced immune response with moderate alcohol consumption, we performed a transcriptome analysis using PBMCs isolated on day 7 post-modified vaccinia Ankara vaccination, the earliest time point at which we detected differences in T cell and Ab responses. Overall, chronic heavy alcohol consumption reduced the expression of immune genes involved in response to infection and wound healing and increased the expression of genes associated with the development of lung inflammatory disease and cancer. In contrast, chronic moderate alcohol consumption upregulated the expression of genes involved in immune response and reduced the expression of genes involved in cancer. To uncover mechanisms underlying the alterations in PBMC transcriptomes, we profiled the expression of microRNAs within the same samples. Chronic heavy ethanol consumption altered the levels of several microRNAs involved in cancer and immunity and known to regulate the expression of mRNAs differentially expressed in our data set.

  9. Simian varicella virus infection of Chinese rhesus macaques produces ganglionic infection in the absence of rash

    NARCIS (Netherlands)

    W.J.D. Ouwendijk (Werner ); R. Mahalingam (Ravi); V. Traina-Dorge (Vicki); G. van Amerongen (Geert); M. Wellish (Mary); A.D.M.E. Osterhaus (Albert); D. Gilden (Don); G.M.G.M. Verjans (George)

    2012-01-01

    textabstractVaricella-zoster virus (VZV) causes varicella (chickenpox), becomes latent in ganglia along the entire neuraxis, and may reactivate to cause herpes zoster (shingles). VZV may infect ganglia via retrograde axonal transport from infected skin or through hematogenous spread. Simian varicell

  10. Type 2 diabetes mellitus non-genetic Rhesus monkey model induced by high fat and high sucrose diet.

    Science.gov (United States)

    Lu, Shuai-yao; Qi, Su-dong; Zhao, Yuan; Li, Yan-yan; Yang, Feng-mei; Yu, Wen-hai; Jin, Ma; Chen, Li-Xiong; Wang, Jun-bin; He, Zhan-long; Li, Hong-jun

    2015-01-01

    To build an ideal animal model for studying the mechanism of occurrence, developing and treating of diabetes become a more important issue, facing with the fact that the big threat of diabetes to human health has been worsen. First, we used the normal control diets or the high-fat/high-sucrose diets to feed the adult rhesus monkeys and the macaques induced by the high-fat/high-sucrose diets in the high-fat/high-sucrose group and the type 2 diabetes mellitus (T2DM) group developed the hyperglycemia, hyperinsulinemia at 6 months in accordance with the precious researches that reported that minipigs, rats and mice could develop hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity after being induced with high-fat/high-carbohydrate diets. Second, the rhesus monkeys in T2DM group were injected STZ at a low dosage of 35 mg/kg BW to induce glucose persistent elevation which maintained pretty well after 12 months. Third, we took the assay of glucose tolerance test and insulin resistance index, assessed the changing tendency of serum resistin and analysed the pathological characteristics of the tissues like pancreas and liver by staining in different ways. The results indicate the rhesus monkeys in T2DM group have lots of clinical features of T2DM. The experimental non-genetic T2DM rhesus monkeys model not only contribute to simulating of clinical manifestations and pathological features of human T2DM, but also may be a good kind of model for research on the treatment of T2DM and for new drugs evaluation.

  11. Development of Broadly Neutralizing Antibodies and Their Mapping by Monomeric gp120 in Human Immunodeficiency Virus Type 1-Infected Humans and Simian-Human Immunodeficiency Virus SHIVSF162P3N-Infected Macaques

    Science.gov (United States)

    Jia, Manxue; Lu, Hong; Markowitz, Martin; Cheng-Mayer, Cecilia

    2016-01-01

    ABSTRACT To improve our understanding of the similarities and differences between neutralizing antibodies elicited by simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and human immunodeficiency virus type 1 (HIV-1)-infected humans, we examined the plasma of 13 viremic macaques infected with SHIVSF162P3N and 85 HIV-1-infected humans with known times of infection. We identified 5 macaques (38%) from 1 to 2 years postinfection (p.i.) with broadly neutralizing antibodies (bnAbs) against tier 2 HIV-1. In comparison, only 2 out of 42 (5%) human plasma samples collected in a similar time frame of 1 to 3 years p.i. exhibited comparable neutralizing breadths and potencies, with the number increasing to 7 out of 21 (30%) after 3 years p.i. Plasma mapping with monomeric gp120 identified only 2 out of 9 humans and 2 out of 4 macaques that contained gp120-reactive neutralizing antibodies, indicating distinct specificities in these plasma samples, with most of them recognizing the envelope trimer (including gp41) rather than the gp120 monomer. Indeed, a total of 20 gp120-directed monoclonal antibodies (MAbs) isolated from a human subject (AD358) and a Chinese rhesus macaque (GB40) displayed no or limited neutralizing activity against tier 2 strains. These isolated MAbs, mapped to the CD4-binding site, the V3 loop, the inner domain, and the C5 region of gp120, revealed genetic similarity between the human and macaque immunoglobulin genes used to encode some V3-directed MAbs. These results also support the use of envelope trimer probes for efficient isolation of HIV-1 bnAbs. IMPORTANCE HIV-1 vaccine research can benefit from understanding the development of broadly neutralizing antibodies (bnAbs) in rhesus macaques, commonly used to assess vaccine immunogenicity and efficacy. Here, we examined 85 HIV-1-infected humans and 13 SHIVSF162P3N-infected macaques for bnAbs and found that, similar to HIV-1-infected humans, bnAbs in SHIV-infected macaques are also rare

  12. [Treatment of severe Rhesus erythroblastosis].

    Science.gov (United States)

    Bichler, A; Frisch, H

    1977-01-01

    Report about the management of cases of severe Rhesus erythroblastosis. One case is specially discussed because of it's actuality. This was a patient with severe Rh-sensitization (OOD at 450 mm from the beginning of the 30th week of gestation in zone III according to Liley). Because of the haemolytic disease and the chronic fetal distress the Caesarean section was already performed in the 32nd week of gestation after Betamethason treatment of the mother. The Lecithin-Sphingomyelin (L/S) ratio in the amniotic fluid as a criterium of fetal lung maturity raised almost twicefold (from 0.9 to 1.6) after Cortison treatment. The intensive care (assisted ventilation with PEEP, correction of the acidosis and transfusion of packed red cells) of the severely anaemic (Hb 3.5 g%, Hk 15 vol.%) and hydropic newborn was already started in the delivery room. The newborn developed no RDS and was discharged healthy. With reference to this and other cases the management of severe Rh-sensitization before the 34th week of gestation is discussed. Premature infants are mainly susceptable to the development of a Respiratory Distress syndrome (RDS). After antepartum Cortison treatment for prevention of an RDS the date of confinement should be arranged earlier. The value of an early Caesarian section after antepartum Glucocorticoid treatment as compared to the application of intrauterine transfusions in cases of severe erythroblastosis is discussed. It is also reported about recent methods of treatment of severe conditions of hydrops fetalis.

  13. Spontaneous Metacognition in Rhesus Monkeys.

    Science.gov (United States)

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience.

  14. Urinary catheterization in gynecological surgery: When should it be removed?

    Directory of Open Access Journals (Sweden)

    Adly N.A. Fattah

    2013-08-01

    Full Text Available Background: The aim of this study was to determine the most appropriate time for urinary catheter removal following a gynecological surgery.Methods: Critical appraisal of clinical trial articles were conducted. It was aimed to answer our clinical question whether 24-hour postoperative urinary catheter removal is superior compared to other durations in avoiding postoperative urinary retention (PUR and urinary tract infection (UTI. The search was conducted on the Cochrane Library® and PubMed® using keywords “postoperative urinary retention”, “postoperative catheterization” and “urinary retention AND catheterization”. Reference lists of relevant articles were searched for other possibly relevant trials.Results: Seven articles were available as full text, then appraisals of six prospective RCTs involving 846 women underwent hysterectomy and vaginal prolapse surgery were performed finding at the re-catheterization and UTI rate. Subjects in earlier-removal groups were 3 to 4 times more likely to have re-catheterization (OR = 3.10-4.0 compared to later-removal groups, while they who have it removed on 5th day were 14 times more likely to develop UTI compared with immediate group (OR = 14.786, 95% CI 3.187- 68.595.Conclusion: The 24-hour catheterization policy in hysterectomy and vaginal prolapse surgery remains most appropriate although associated with an increased risk of re-catheterization. The removal of catheter before 24 hour (6 or 12 hour could be considered to be used as one of interventions in further RCT(s to find out the best duration which would result in lowest incidence in both of UTI and  PUR. (Med J Indones. 2013;22:183-8. doi: 10.13181/mji.v22i3.589Keywords: Catheter, hysterectomy, prolapse, urinary tract infection

  15. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys.

    Science.gov (United States)

    Dong, Qiao-Xiang; Rodenburg, Sarah E; Hill, Dana; Vandevoort, Catherine A

    2011-05-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  16. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Qiao-Xiang Dong; Sarah E Rodenburg; Dana Hill; Catherine A VandeVoort

    2011-01-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  17. Candiduria in catheterized intensive care unit patients : Emerging microbiological trends

    Directory of Open Access Journals (Sweden)

    Manisha Jain

    2011-01-01

    Full Text Available Objectives: Urinary tract infection (UTI as a result of Candida spp. is becoming increasingly common in hospitalized setting. Clinicians face dilemma in differentiating colonization from true infection and whether to treat candiduria or not. The objective of the present study was to look into the significance of candiduria in catheterized patients admitted in the ICUs and perform microbiological characterization of yeasts to guide treatment protocols. Materials and Methods: One hundred consecutive isolates of Candida spp. from the urine sample of 70 catheterized patients admitted in the ICU were collected and stocked for further characterization. A proforma was maintained containing demographic and clinical details. Blood cultures were obtained from all these 70 patients and processed. Species identification of yeasts was done on VITEK. Results: Candiduria was more common at extremes of age. The mean duration of catheter days was 11.1 ± 6 days. Other associated risk factors such as diabetes mellitus and antibiotic usage were seen in 38% and 100% of our study group. Concomitant candidemia was seen in 4.3% of cases. Non-albicans Candida spp. (71.4% emerged as the predominant pathogen causing nosocomial UTI. Conclusion: The present study reiterates the presence of candiduria in catheterized patients, especially in the presence of diabetes and antibiotic usage. Non-albicans Candida spp. are replacing Candida albicans as the predominant pathogen for nosocomial UTI. Hence, we believe that surveillance for nosocomial candiduria should be carried out in hospitalized patients.

  18. Comparative Pathobiology of Macaque Lymphocryptoviruses

    Science.gov (United States)

    Carville, Angela; Mansfield, Keith G

    2008-01-01

    Lymphocryptoviruses (LCVs) have been identified as naturally occurring infections of both Old and New World nonhuman primates. These viruses are closely related to Epstein–Barr virus (EBV, Human herpesvirus 4) and share similar genomic organization and biological properties. Nonhuman primate LCVs have the ability to immortalize host cells and express a similar complement of viral lytic and latent genes as those found in EBV. Recent evidence indicates that nonhuman primate LCVs can immortalize B cells from genetically related species, suggesting a close evolutionary relationship between these viruses and their respective hosts. Early work with EBV in tamarins and owl monkeys revealed that cross species transmission of lymphocryptoviruses from the natural to inadvertent host may be associated with oncogenesis and the development of malignant lymphoma. Moreover, simian LCVs have the ability to induce malignant lymphomas in immunodeficient hosts and have been associated with posttransplantation lymphoproliferative disease in cynomolgus macaques undergoing solid organ transplantation. This review will focus on the comparative pathobiology of lymphocryptoviral infection and discuss the derivation of specific pathogen-free animals. PMID:19793458

  19. Physiology responses of Rhesus monkeys to vibration

    Science.gov (United States)

    Hajebrahimi, Zahra; Ebrahimi, Mohammad; Alidoust, Leila; Arabian Hosseinabadi, Maedeh

    Vibration is one of the important environmental factors in space vehicles that it can induce severe physiological responses in most of the body systems such as cardiovascular, respiratory, skeletal, endocrine, and etc. This investigation was to assess the effect of different vibration frequencies on heart rate variability (HRV), electrocardiograms (ECG) and respiratory rate in Rhesus monkeys. Methods: two groups of rhesus monkey (n=16 in each group) was selected as control and intervention groups. Monkeys were held in a sitting position within a specific fixture. The animals of this experiment were vibrated on a table which oscillated right and left with sinusoidal motion. Frequency and acceleration for intervention group were between the range of 1 to 2000 Hz and +0.5 to +3 G during 36 weeks (one per week for 15 min), respectively. All of the animals passed the clinical evaluation (echocardiography, sonography, radiography and blood analysis test) before vibration test and were considered healthy and these tests repeated during and at the end of experiments. Results and discussions: Our results showed that heart and respiratory rates increased significantly in response to increased frequency from 1 to 60 Hz (p monkeys passed vibration experiment successfully without any arrhythmic symptoms due to electrocardiography analysis. Conclusion: Our results indicate that vibration in low frequency can effect respiratory and cardiovascular function in rhesus monkey. Keywords: Vibration, rhesus monkey, heart rate, respiratory rate

  20. Canine distemper outbreak in rhesus monkeys, China.

    Science.gov (United States)

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-08-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People's Republic of China. Approximately 10,000 animals were infected (25%-60% disease incidence); 5%-30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  1. Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues.

    Science.gov (United States)

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Sherwood, Chet C; Hof, Patrick R; Ely, John J; Li, Yan; Steinhauser, Dirk; Willmitzer, Lothar; Giavalisco, Patrick; Khaitovich, Philipp

    2015-02-18

    Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution.

  2. New puncture needle (Seldinger technique) for easy antegrade catheterization of the superficial femoral artery

    Energy Technology Data Exchange (ETDEWEB)

    Saltzmann, J.; Probst, P.

    1987-02-01

    Mainly for anatomical reasons a guide-wire or a catheter has a tendency to turn into the deep femoral artery during antegrade catheterization of the lower limb. To overcome this problem a curved puncture needle has been designed which allows positioning of the guide-wire in an anterior direction. Antegrade catheterization of the superficial femoral artery was achieved in 25 patients without lengthy manipulations or complications. With this technique the rate of complications at antegrade catheterization will probably be reduced.

  3. A macaque model for hantavirus infection

    NARCIS (Netherlands)

    Groen, J; Gerding, M; Koeman, J P; Roholl, P J; van Amerongen, G; Jordans, H G; Niesters, H G; Osterhaus, A D

    1995-01-01

    Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hällnäs), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and

  4. Complication of Right Subclavian Vein Catheterization: Superior Vena Cava Perforation

    OpenAIRE

    ÇELİK, B.; KOCAMANOĞLU, S.; BÜYÜKKARABACAK, Y. B.; SARIHASAN, E.

    2013-01-01

    Central venous catheterization is an invasive approach which is routinely used in thoracic surgery operations. Pneumothorax and hemothorax are among the most frequent complications. Vena cava superior (VCS) perforation (0.5 %) is very rarely observed. A 65-year-old male patient was admitted to the hospital with the complaint of cough. With the examinations performed, he was diagnosed with epidermoid lung cancer located in the right lower lobe of the lung (Stage IB, T2N0M0). To prepare the pat...

  5. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Hill, F.S.; Cantu, A.O.; Lucas, J.N. (Lawrence Livermore National Lab., CA (United States)); Cox, A.B.; Salmon, Y.L. (Air Force Armstrong Lab., Brookes AFB, TX (United States))

    1994-10-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 [mu]g/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) that that produced by PHA (M1<0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture. (author).

  6. Differential requirements for hematopoietic commitment between human and rhesus embryonic stem cells.

    Science.gov (United States)

    Rajesh, Deepika; Chinnasamy, Nachimuthu; Mitalipov, Shoukhrat M; Wolf, Don P; Slukvin, Igor; Thomson, James A; Shaaban, Aimen F

    2007-02-01

    Progress toward clinical application of ESC-derived hematopoietic cellular transplantation will require rigorous evaluation in a large animal allogeneic model. However, in contrast to human ESCs (hESCs), efforts to induce conclusive hematopoietic differentiation from rhesus macaque ESCs (rESCs) have been unsuccessful. Characterizing these poorly understood functional differences will facilitate progress in this area and likely clarify the critical steps involved in the hematopoietic differentiation of ESCs. To accomplish this goal, we compared the hematopoietic differentiation of hESCs with that of rESCs in both EB culture and stroma coculture. Initially, undifferentiated rESCs and hESCs were adapted to growth on Matrigel without a change in their phenotype or karyotype. Subsequent differentiation of rESCs in OP9 stroma led to the development of CD34(+)CD45(-) cells that gave rise to endothelial cell networks in methylcellulose culture. In the same conditions, hESCs exhibited convincing hematopoietic differentiation. In cytokine-supplemented EB culture, rESCs demonstrated improved hematopoietic differentiation with higher levels of CD34(+) and detectable levels of CD45(+) cells. However, these levels remained dramatically lower than those for hESCs in identical culture conditions. Subsequent plating of cytokine-supplemented rhesus EBs in methylcellulose culture led to the formation of mixed colonies of erythroid, myeloid, and endothelial cells, confirming the existence of bipotential hematoendothelial progenitors in the cytokine-supplemented EB cultures. Evaluation of four different rESC lines confirmed the validity of these disparities. Although rESCs have the potential for hematopoietic differentiation, they exhibit a pause at the hemangioblast stage of hematopoietic development in culture conditions developed for hESCs.

  7. Effect of mother's dominance rank on offspring temperament in infant rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Suarez-Jimenez, Benjamin; Hathaway, Amanda; Waters, Carlos; Vaughan, Kelli; Suomi, Stephen J; Noble, Pamela L; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2013-01-01

    In humans, temperament plays an important role in socialization and personality. Some temperaments, such as behavioral inhibition are associated with an increased risk for psychopathology. Nonhuman primates can serve as a model for neurobiological and developmental contributions to emotional development and several recent studies have begun to investigate temperament in nonhuman primates. In rhesus monkeys, dominance rank is inherited from the mother and is associated with social and emotional tendencies that resemble differences in temperament. The current study assessed differences in temperament in infant rhesus monkeys as a function of maternal dominance rank. Temperament was assessed in 26 infants (13 males) from birth until 6 months of age with a battery that included Brazelton test, human intruder test, human intruder-startle, cortisol stress reactivity, and home cage observations of interactions with peers and the mother. Throughout testing, infants lived with their mothers and a small group of other monkeys in indoor/outdoor runs. Dominance rank of the mothers within each run was rated as either low/middle (N = 18, 9 male) or high/alpha (N = 8, 4 female). Infants of high-ranking mothers displayed more intruder-directed aggression and reduced startle potentiation in the human intruder tests. Dominant offspring also had reduced levels cortisol and startle across development and spent more time away from mothers in the interaction tests. These results suggest that dominance of the mother may be reflected in behavioral reactivity of infants early in life. These findings set up future studies, which may focus on contributing factors to both dominance and temperament such as genetics, rearing, and socialization. Such factors are likely to interact across development in meaningful ways. These results also suggest future human-based studies of a similar relationship may be warranted, although social dominance is clearly more complex in human than macaque societies.

  8. Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta).

    Science.gov (United States)

    Novak, Melinda A; Menard, Mark T; El-Mallah, Saif N; Rosenberg, Kendra; Lutz, Corrine K; Worlein, Julie; Coleman, Kris; Meyer, Jerrold S

    2017-01-01

    Hair loss is common in macaque colonies. Very little is known about the relationship between psychological stress and hair loss. We initially examined alopecia and hair cortisol concentrations in 198 (89 male) rhesus macaques from three primate centers and demonstrated replicability of our previous finding that extensive alopecia (>30% hair loss) is associated with increased chronic cortisol concentrations and significantly affected by facility. A subset of these monkeys (142 of which 67 were males) were sampled twice approximately 8 months apart allowing us to examine the hypotheses that gaining hair should be associated with decreases in cortisol concentrations and vice versa. Hair loss was digitally scored using ImageJ software for the first sample. Then visual assessment was used to examine the second sample, resulting in three categories of coat condition: (i) monkeys that remained fully haired; (ii) monkeys that remained alopecic (with more than 30% hair loss); or (iii) monkeys that showed more than a 15% increase in hair. The sample size for the group that lost hair was too small to be analyzed. Consistent with our hypothesis, monkeys that gained hair showed a significant reduction in hair cortisol concentrations but this effect only held for females. Coat condition changed little across sampling periods with only 25 (11 male) monkeys showing a greater than 15% gain of hair. Twenty (7 male) monkeys remained alopecic, whereas 97 (49 males) remained fully haired. Hair cortisol was highly correlated across samples for the monkeys that retained their status (remained alopecic or retained their hair). Am. J. Primatol. 79:e22547, 2017. © 2016 Wiley Periodicals, Inc.

  9. Expression of gelatinases and tissue inhibitors of metallo- proteinases in the rhesus monkey (Macaca mulatta) corpus luteum

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are believed to play important roles in the formation and regression of corpus luteum (CL). This study is to investigate the expression of gelatinases (MMP-2, -9) and TIMPs in the rhesus monkey CL in both early and late luteal phases and during the early stages of pregnancy. Ovaries were collected from regularly cycling rhesus monkey at D5 and D15 following ovulation and at D12, D18 and D26 of pregnancy. In situ hybridization revealed that in the CL MMP-2 mRNA was expressed during both formation and regression, while MMP-9 mRNA was mainly localized in the late luteal phase. Reduction of MMP-2, -9 transcripts in the CL was observed during pregnancy. MMP-2 mRNA in the CL reduced to an undetectable level at D26 of pregnancy. TIMP-1 mRNA was highly expressed in the CL in both early and late luteal phases and persisted throughout the early stages of pregnancy. Strong signal for TIMP-2 mRNA was also detected in both luteal phases, and the level of TIMP-2 mRNA gradually increased with the progresses of pregnancy. No TIMP-3 mRNA was detected in the macaque CL in this study. In conclusion, these results suggest that MMP-2, -9 and TIMP-1, -2 may have functional roles in rhesus monkey CL. Coordinated expression of MMP-2, -9 and TIMP-2 may play a role in the maintaining of luteal function during early pregnancy. The unchanged expression pattern of TIMP-1 indicates that it may have other functions in the primate CL than inhibition of MMPs.

  10. Activation of Innate Immunity in Healthy Macaca mulatta Macaques by a Single Subcutaneous Dose of GMP CpG 7909: Safety Data and Interferon-Inducible Protein-10 Kinetics for Humans and Macaques▿

    OpenAIRE

    Stewart, V. Ann; McGrath, Shannon; Krieg, Arthur M.; Larson, Noelle S.; Angov, Evelina; Smith, Christopher L.; Brewer, Thomas G; Heppner, D. Gray

    2007-01-01

    Following a demonstration that mouse-optimized cytosine-guanosine dinucleotide (CpG) oligodeoxynucleotides stimulated innate immune protection against intracellular pathogens, we tested the ability of CpG 7909, a primate-optimized Toll-like receptor 9 (TLR9) agonist, to stimulate rhesus macaques to produce interferon-inducible protein-10 (IP-10), a biomarker of immune activation. This study was performed prior to a similar trial with humans in order to facilitate the development of CpG 7909 a...

  11. Two cases of chronic radiodermatitis caused by cardiac catheterization

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Makiko; Soh, Inketsu; Sueki, Hirohiko; Iijima, Masafumi [Showa Univ., Tokyo (Japan). School of Medicine; Hayashi, Ken; Wakugawa, Motoshi

    1999-12-01

    Coronary angiography (CAG) and percutaneous transluminal coronary angioplasty (PTCA) associated with fluoroscopy and cineradiography deliver higher radiation doses than any other conventional methods and, as a result, expose patients to ionizing radiation. We herein report two cases of radiodermatitis caused by cardiac catheterization whose irradiation dose could be retrospectively calculated. One sixty-year-old female and one sixty eight-year-old female who had suffered from myocardial infarction and angina pectoris, respectively, developed erythematous plaques on the right submammary area and the lesions were initially diagnosed to be fixed drug eruptions. The lesions of submammary area gradually showed the findings of poikiloderma and finally demonstrated ulceration, however, we could not make an accurate diagnosis at that time, due to our lack of knowledge about these radiologic examinations. The cumulative irradiation dose of these cases was calculated to be 58.5 Gy and 45.5 Gy, respectively, and both cases were finally diagnosed to have chronic radiodermatitis as a result of cardiac catheterization. (author)

  12. Prevalence of renal artery stenosis in patients undergoing cardiac catheterization.

    Science.gov (United States)

    Marcantoni, Carmelita; Carmelita, Marcantoni; Rastelli, Stefania; Stefania, Rastelli; Zanoli, Luca; Luca, Zanoli; Tripepi, Giovanni; Giovanni, Tripepi; Di Salvo, Marilena; Marilena, Di Salvo; Monaco, Sergio; Sergio, Monaco; Sgroi, Carmelo; Carmelo, Sgroi; Capodanno, Davide; Davide, Capodanno; Tamburino, Corrado; Corrado, Tamburino; Castellino, Pietro; Pietro, Castellino

    2013-08-01

    To investigate the prevalence of significant renal artery stenosis (RAS ≥50%), and to identify clinical predictors for significant RAS in patients with an elevated cardiovascular risk, such as those affected by ischemic heart disease. In patients with an elevated cardio-vascular risk, both atherosclerotic renovascular disease and coronary artery disease (CAD) are likely to occur. Prospectively from April 2007 to March 2008, all consecutive patients with ischemic heart disease undergoing non-emergent cardiac catheterization were also evaluated for atherosclerotic RAS by renal arteriography. A RAS ≥50% was considered as significant. A total of 1,298 patients underwent cardiac and renal angiography. Significant RAS was found in 70 out of 1,298 patients (5.4%). The presence of peripheral vascular disease, eGFR 66 years, dyslipidemia, CAD severity and pulse pressure >52 mmHg were independent clinical predictors of significant RAS, and jointly produced a ROC AUC of 0.79 (95% CI 0.73-0.85, P < 0.001). Based on these data, a prediction rule for significant RAS was developed, and it showed an adequate predictive performance with 64% sensitivity and 82% specificity. In a large cohort of patients undergoing coronary angiography, significant RAS is a relatively rare comorbidity (5.4%). A model based on simple clinical variables may be useful for the clinical identification of high CV risk patients who may be suitable for renal arteriography at the time of cardiac catheterization.

  13. MicroRNA expression and regulation in human, chimpanzee, and macaque brains.

    Directory of Open Access Journals (Sweden)

    Hai Yang Hu

    2011-10-01

    Full Text Available Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA in the regulation of gene expression divergence among adult humans, chimpanzees, and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using a combination of high-throughput sequencing, miRNA microarrays, and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2%-4% of mRNA and 4%-6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA-driven regulation on the human evolutionary lineage, was further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions.

  14. 基因修饰中国猕猴技术的研究进展%Advances in Genetically Modified Chinese Macaques

    Institute of Scientific and Technical Information of China (English)

    马云瀚; 杨世华

    2014-01-01

    developing genetically modified monkeys.Now in China,ARTs in Chinese rhesus macaques included semen collection and cryopreservation,superovulation,in vitro fertilization and embryo culture,embryo transfer and pregnancy management,thus "test-tube monkey",and all have been efficiently completed.The establishment and development of the current gene editing technology,ZFN (zinc-finger nucleases),TALEN (transcription activator-like effector nucleases) and CRJSPR/Cas9 (Clustered regularly interspaced short palindromic repeats/Cas9),create great chances for production of genetically modified macaques.Scientists in China have successfully developed transgenic macaques with overexpression of green fluorescence protein gene and gene mutagenesis in macaques.With the breakthrough and development of various technologies,combined with abundant experimental macaque resources,avoiding various reproductive physiological obstructions of macaques,China is expected to become an appropriate international base in application of genetic engineering macaques.

  15. MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

    Science.gov (United States)

    Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

    2017-03-01

    The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

  16. Surgical technique for allogeneic uterus transplantation in macaques

    OpenAIRE

    Hideaki Obara; Iori Kisu; Yojiro Kato; Yohei Yamada; Kentaro Matsubara; Katsura Emoto; Masataka Adachi; Yusuke Matoba; Kiyoko Umene; Yuya Nogami; Kouji Banno; Hideaki Tsuchiya; Iori Itagaki; Ikuo Kawamoto; Takahiro Nakagawa

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac art...

  17. One-day versus 3-day suprapubic catheterization after vaginal prolapse surgery : a prospective randomized trial

    NARCIS (Netherlands)

    Van der Steen, Annemarie; Detollenaere, Renee; Den Boon, Jan; Van Eijndhoven, Hugo

    2011-01-01

    For prolonged catheterization after vaginal prolapse surgery with anterior colporrhaphy, the optimal duration to prevent overdistention of the bladder remains unknown. We designed this study to determine the optimal length of catheterization. We conducted a prospective randomized trial in which 179

  18. Ultrasound-guided subclavian catheterization in pediatric patients with a linear probe: a case series

    OpenAIRE

    Park, Sang Il; Kim, Yoon Hee; So, Sang Young; Kim, Myoung Joong; Kim, Hyun Joong; Kim, Jae Kook

    2013-01-01

    Central venous catheterization (CVC) can be difficult, especially with pediatric patients in critical care. Accessing the subclavian vein (SCV) can cause serious complications, including pneumothorax, arterial puncture, and hemothorax. Recently, the ultrasonographic (USG) technique has gained popularity, but its efficiency is not yet confirmed. Subclavian venous catheterization (SCVC) through the supraclavicular approach (SCA) with USG or accessing the brachiocephalic vein through the infracl...

  19. Urinary retention and the role of indwelling catheterization following total knee arthroplasty

    Directory of Open Access Journals (Sweden)

    P. Kumar

    2006-02-01

    Full Text Available INTRODUCTION: We aimed to investigate the rate of urinary retention after knee arthroplasty, the various factors involved in predicting those at risk for retention and to assess the impact of retention and catheterization on joint sepsis. MATERIALS AND METHODS: A retrospective review was conducted of all available case notes of patients undergoing total knee arthroplasty in a consecutive 2-year period (2000-2002. Adequate data was available for 142 patients. RESULTS: 142 patients underwent total knee arthroplasty. 19 patients were catheterized preoperatively for monitoring urine output. 123 patients were not catheterized. Urinary retention occurred in 19.7% (28/142. The mean day of catheterization for retention was 0.66. The mean duration of catheterization in patients developing retention was 3.58 days and was 3 days in the patients catheterized pre - or perioperatively. Deep joint sepsis occurred in 2.1% (3/142 - only one had been catheterized and that was preoperatively. No case of infection had urinary retention or had a symptomatic urinary tract infection. The only factors predicting those at significant risk of retention following knee arthroplasty was a past medical history of urinary retention (p = 0.049 and postoperative morphine requirement (p = 0.035. No patients required urological surgical intervention at mean follow up of 1.97 years. CONCLUSIONS: This study supports the use of indwelling urinary catheterization for patients developing urinary retention after total knee arthroplasty.

  20. The present and future of interventional catheterization for congenital heart disease

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Over the past decade, the focus of the pediatric catheterization laboratory has changed dramatically from its primary function of providing diagnosis to offering treatment.Since Rashkind first described the technique for atrial septostomy in the setting of complete transposition of the great arteries in 1966, therapeutic catheterization techniques have replaced conventional surgery, including both corrective and palliative surgeries, for many lesions. Interventional catheterization has become an important modality in the treatment of congenital heart disease. In addition, in the staged management of complex congenital heart disease, better outcomes have been acquired by combined surgical and interventional catheterization strategies. Although great advances have been made in the therapeutic catheterization for congenital heart disease in some Chinese medical centers, there is considerable difference in both clinical applications and basic researches between China and other developed countries. Thus, it is very important to expand this advanced technique aggressively but carefully.

  1. The Effect of Heterogeneity on Numerical Ordering in Rhesus Monkeys

    Science.gov (United States)

    Cantlon, Jessica F.; Brannon, Elizabeth M.

    2006-01-01

    We investigated how within-stimulus heterogeneity affects the ability of rhesus monkeys to order pairs of the numerosities 1 through 9. Two rhesus monkeys were tested in a touch screen task where the variability of elements within each visual array was systematically varied by allowing elements to vary in color, size, shape, or any combination of…

  2. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques.

    Science.gov (United States)

    Schwartz, Jennifer A; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K; Gallo, Robert C; DeVico, Anthony L; Fouts, Timothy R

    2016-07-01

    A promising concept for human immunodeficiency virus (HIV) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the HIV glycoprotein gp120 binds to its receptor, CD4. We are developing chimeric antigens (full-length single chain, or FLSC) in which gp120 and CD4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (A. DeVico et al., Proc Natl Acad Sci U S A 104:17477-17482, 2007, doi:10.1073/pnas.0707399104; T. R. Fouts et al., J Virol 74:11427-11436, 2000, doi:10.1128/JVI.74.24.11427-11436.2000). Proof of concept studies with nonhuman primates show that FLSC elicited heterologous protection against simian-human immunodeficiency virus (SHIV)/simian immunodeficiency virus (SIV) (T. R. Fouts et al., Proc Natl Acad Sci U S A 112:E992-E999, 2016, doi:10.1073/pnas.1423669112), which correlated with antibodies against transition state gp120 epitopes. Nevertheless, advancement of any vaccine that comprises gp120-CD4 complexes must consider whether the CD4 component breaks tolerance and becomes immunogenic in the autologous host. To address this, we performed an immunotoxicology study with cynomolgus macaques vaccinated with either FLSC or a rhesus variant of FLSC containing macaque CD4 sequences (rhFLSC). Enzyme-linked immunosorbent assay (ELISA) binding titers, primary CD3(+) T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4(+) T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures

  3. Postoperative Urinary Catheterization Thresholds of 500 versus 800 ml after Fast-track Total Hip and Knee Arthroplasty

    DEFF Research Database (Denmark)

    Bjerregaard, Lars S; Hornum, Ulla; Troldborg, Charlotte;

    2016-01-01

    BACKGROUND: No evidence-based threshold exists for postoperative urinary bladder catheterization. The authors hypothesized that a catheterization threshold of 800 ml was superior to 500 ml in reducing postoperative urinary catheterization and urological complications after fast-track total hip ar...

  4. Monozygotic twinning in rhesus monkeys by manipulation of in vitro-derived embryos.

    Science.gov (United States)

    Mitalipov, Shoukhrat M; Yeoman, Richard R; Kuo, Hung-Chih; Wolf, Don P

    2002-05-01

    The nonhuman primate is a relevant model for human disease that can be used for diverse biomedical investigations. The ability to propagate a founder animal by application of assisted reproductive technologies is pressing, but an even greater need in many studies is access to genetically identical animals. In an effort to create genetically identical monkeys, we evaluated two approaches to monozygotic twinning; blastomere separation, and blastocyst bisection. Embryos were produced by intracytoplasmic sperm injection of oocytes recovered following controlled ovarian stimulation. The quality of demiembryos produced in these efforts was evaluated by quantitating the efficiency of creating identical pairs for embryo transfer, by morphological assessment, by the allocation of cells to the inner cell mass (ICM) and trophectoderm (TE) in the blastocyst, and by the outcome of embryo transfer to synchronized host animals. Pairs were produced in high yield (85%-95%) by both twinning methods. Demiembryos resulting from blastomere separations at the 2- or 4-cell stage grew to blastocysts at the control frequency. Demiblastocysts contained, on average, half the number of cells of the intact controls while maintaining the same ICM:TE or ICM:total cell ratio. The equivalency of demiblastocysts within a set was also evaluated by differential cell counting. Embryo transfers of identical sets led to a 33% clinical pregnancy rate, with two twin pregnancies initiated. Neither pregnancy resulted in term birth of monozygotic twins, but our results are sufficiently encouraging to justify a large-scale twinning trial in the rhesus macaque.

  5. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm.

    Science.gov (United States)

    Hermann, Brian P; Sukhwani, Meena; Winkler, Felicity; Pascarella, Julia N; Peters, Karen A; Sheng, Yi; Valli, Hanna; Rodriguez, Mario; Ezzelarab, Mohamed; Dargo, Gina; Peterson, Kim; Masterson, Keith; Ramsey, Cathy; Ward, Thea; Lienesch, Maura; Volk, Angie; Cooper, David K; Thomson, Angus W; Kiss, Joseph E; Penedo, Maria Cecilia T; Schatten, Gerald P; Mitalipov, Shoukhrat; Orwig, Kyle E

    2012-11-02

    Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man's life and may have application for treating some cases of male infertility, including those caused by chemotherapy before puberty. We performed autologous and allogeneic SSC transplantations into the testes of 18 adult and 5 prepubertal recipient macaques that were rendered infertile with alkylating chemotherapy. After autologous transplant, the donor genotype from lentivirus-marked SSCs was evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients after they reached maturity. Allogeneic transplant led to donor-recipient chimerism in sperm from 2/6 adult recipients. Ejaculated sperm from one recipient transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via intracytoplasmic sperm injection. Eighty-one oocytes were fertilized, producing embryos ranging from four-cell to blastocyst with donor paternal origin confirmed in 7/81 embryos. This demonstration of functional donor spermatogenesis following SSC transplantation in primates is an important milestone for informed clinical translation.

  6. Reengineering the Cardiac Catheterization Lab Processes: A Lean Approach

    Directory of Open Access Journals (Sweden)

    Venkatesh Raghavan

    2010-01-01

    Full Text Available This paper presents a cross-functional effort in a US community hospital for an overall process improvement in its Cardiac Catheterization Lab (CCL. One of the key system performance metrics identified was the patient turnaround time. The objective of this study was to identify the sources of delays in the system that lead to prolonged patient turnaround time using a structured lean approach. A set of qualitative recommendations were proposed and implemented. Quantification of some of these recommendations and certain additional ‘what-if’ scenarios were evaluated using Discrete Event Simulation (DES. The simulation results showed that significant reduction in patient turnaround time could be achieved if the proposed recommendations were implemented. This study demonstrated the benefits of adopting the lean philosophy in the continuous process improvement journey in the healthcare delivery arena.

  7. Radiation Dose Estimation for Pediatric Patients Undergoing Cardiac Catheterization

    Science.gov (United States)

    Wang, Chu

    Patients undergoing cardiac catheterization are potentially at risk of radiation-induced health effects from the interventional fluoroscopic X-ray imaging used throughout the clinical procedure. The amount of radiation exposure is highly dependent on the complexity of the procedure and the level of optimization in imaging parameters applied by the clinician. For cardiac catheterization, patient radiation dosimetry, for key organs as well as whole-body effective, is challenging due to the lack of fixed imaging protocols, unlike other common X-ray based imaging modalities. Pediatric patients are at a greater risk compared to adults due to their greater cellular radio-sensitivities as well as longer remaining life-expectancy following the radiation exposure. In terms of radiation dosimetry, they are often more challenging due to greater variation in body size, which often triggers a wider range of imaging parameters in modern imaging systems with automatic dose rate modulation. The overall objective of this dissertation was to develop a comprehensive method of radiation dose estimation for pediatric patients undergoing cardiac catheterization. In this dissertation, the research is divided into two main parts: the Physics Component and the Clinical Component. A proof-of-principle study focused on two patient age groups (Newborn and Five-year-old), one popular biplane imaging system, and the clinical practice of two pediatric cardiologists at one large academic medical center. The Physics Component includes experiments relevant to the physical measurement of patient organ dose using high-sensitivity MOSFET dosimeters placed in anthropomorphic pediatric phantoms. First, the three-dimensional angular dependence of MOSFET detectors in scatter medium under fluoroscopic irradiation was characterized. A custom-made spherical scatter phantom was used to measure response variations in three-dimensional angular orientations. The results were to be used as angular dependence

  8. Characterization of the 10q26-orthologue in rhesus monkeys corroborates a functional connection between ARMS2 and HTRA1.

    Science.gov (United States)

    Pahl, Lisa; Spangenberg, Astrid; Schubert, Stephanie; Schönmann, Uwe; Schmidtke, Jörg; Stuhrmann, Manfred

    2012-05-01

    these blocks spanned the whole ARMS2 locus and the 5' part of HTRA1 - almost perfectly resembling the situation found in humans. Tests for association revealed a variant in the promoter region of HTRA1 and two variants in the 5'-UTR of ARMS2 to be associated with drusen. The strong linkage disequilibrium inhibits - as in humans - a determination of the risk gene using statistical methods only. However, the conserved linkage disequilibrium structure in humans and macaques goes in line with the recently emerged dual causality model proposing that ARMS2 and HTRA1 are functionally connected and that both genes contribute to the disease pathology. Moreover, the characterization of the 10q26-orthologue genomic region of the rhesus monkey provides a basis for now needed functional investigations in a well-characterized model organism.

  9. Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq.

    Directory of Open Access Journals (Sweden)

    Augix Guohua Xu

    Full Text Available Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts located outside of the known genes' boundaries is limited. Here, we use high-throughput transcriptome sequencing (RNA-Seq to characterize the total non-ribosomal transcriptome of human, chimpanzee, and rhesus macaque brain. In all species, only 20-28% of non-ribosomal transcripts correspond to annotated exons and 20-23% to introns. By contrast, transcripts originating within intronic and intergenic repetitive sequences constitute 40-48% of the total brain transcriptome. Notably, some repeat families show elevated transcription. In non-repetitive intergenic regions, we identify and characterize 1,093 distinct regions highly expressed in the human brain. These regions are conserved at the RNA expression level across primates studied and at the DNA sequence level across mammals. A large proportion of these transcripts (20% represents 3'UTR extensions of known genes and may play roles in alternative microRNA-directed regulation. Finally, we show that while transcriptome divergence between species increases with evolutionary time, intergenic transcripts show more expression differences among species and exons show less. Our results show that many yet uncharacterized evolutionary conserved transcripts exist in the human brain. Some of these transcripts may play roles in transcriptional regulation and contribute to evolution of human-specific phenotypic traits.

  10. Characteristics of Spontaneous Square-Wave Jerks in the Healthy Macaque Monkey during Visual Fixation.

    Directory of Open Access Journals (Sweden)

    Francisco M Costela

    Full Text Available Saccadic intrusions (SIs, predominantly horizontal saccades that interrupt accurate fixation, include square-wave jerks (SWJs; the most common type of SI, which consist of an initial saccade away from the fixation target followed, after a short delay, by a return saccade that brings the eye back onto target. SWJs are present in most human subjects, but are prominent by their increased frequency and size in certain parkinsonian disorders and in recessive, hereditary spinocerebellar ataxias. SWJs have been also documented in monkeys with tectal and cerebellar etiologies, but no studies to date have investigated the occurrence of SWJs in healthy nonhuman primates. Here we set out to determine the characteristics of SWJs in healthy rhesus macaques (Macaca mulatta during attempted fixation of a small visual target. Our results indicate that SWJs are common in healthy nonhuman primates. We moreover found primate SWJs to share many characteristics with human SWJs, including the relationship between the size of a saccade and its likelihood to be part of a SWJ. One main discrepancy between monkey and human SWJs was that monkey SWJs tended to be more vertical than horizontal, whereas human SWJs have a strong horizontal preference. Yet, our combined data indicate that primate and human SWJs play a similar role in fixation correction, suggesting that they share a comparable coupling mechanism at the oculomotor generation level. These findings constrain the potential brain areas and mechanisms underlying the generation of fixational saccades in human and nonhuman primates.

  11. No effects of dioxin singly on limb malformations in macaque monkeys through epidemiological and treated studies

    Energy Technology Data Exchange (ETDEWEB)

    Asaoka, Kazuo; Iida, Hiroko [Kyoto Univ. (Japan). Primate Research Insitute, Dept. of Molecular and Cellular Biochemistry; Watanabe, Kunio [Kyoto Univ. (Japan). Primate Research Institute, Field Research Center; Goda, Hiroshi [Towa Kagaku Co., Ltd. (Japan); Ihara, Toshio; Nagata, Ryoichi [Shin Nippon Biomedical Laboratories, Ltd. (Japan). Safety Research Facility; Yasuda, Mineo [Hiroshima International Univ. (Japan). Fac. of Health Sciences, Dept. of Clinical Engineering; Kubata, Shunichiro [Tokyo Univ. (Japan). Dept. of Life Science, Graduate School of Arts and Sciences

    2004-09-15

    Human populations exposed with highly dioxin were suspected to be caused immunological dysfunctions, carcinogenesis, and developmental and reproductive dysfunctions. Because of species resemblances, the dioxin effects have been investigating using monkeys as a model for assessment of dioxin exposure on human health. Since 1957 the limb malformations of monkeys in Japan have been reported. The higher frequency of them was found in provisional groups of monkeys who were given the same kind of food for human. The chromosomal abnormalities are excluded from the factor for the congenital limb malformations that are still producing in Japan. In this study, the relations between dioxin and the limb malformations of macaque monkeys were estimated by the epidemiological and administered researches. The dioxin levels in monkeys were measured at two districts that one has the provisional groups including monkeys with limb malformations and the other has breeding groups never seeing the malformations for a long time. TEQ was calculated by the levels of dioxin isomers in the monkeys and the values show no difference between the two places and between the individuals with and without the limb malformations. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered via subcutaneous to pregnant rhesus monkeys from the day 20 of gestation to the day 90 after birth. The exposed babies, including the offspring and died in neonatal, had observed normal limbs in the range of 30-300 ng TCDD /kg of body weight.

  12. UNC-Emory Infant Atlases for Macaque Brain Image Analysis: Postnatal Brain Development through 12 Months

    Science.gov (United States)

    Shi, Yundi; Budin, Francois; Yapuncich, Eva; Rumple, Ashley; Young, Jeffrey T.; Payne, Christa; Zhang, Xiaodong; Hu, Xiaoping; Godfrey, Jodi; Howell, Brittany; Sanchez, Mar M.; Styner, Martin A.

    2017-01-01

    Computational anatomical atlases have shown to be of immense value in neuroimaging as they provide age appropriate reference spaces alongside ancillary anatomical information for automated analysis such as subcortical structural definitions, cortical parcellations or white fiber tract regions. Standard workflows in neuroimaging necessitate such atlases to be appropriately selected for the subject population of interest. This is especially of importance in early postnatal brain development, where rapid changes in brain shape and appearance render neuroimaging workflows sensitive to the appropriate atlas choice. We present here a set of novel computation atlases for structural MRI and Diffusion Tensor Imaging as crucial resource for the analysis of MRI data from non-human primate rhesus monkey (Macaca mulatta) data in early postnatal brain development. Forty socially-housed infant macaques were scanned longitudinally at ages 2 weeks, 3, 6, and 12 months in order to create cross-sectional structural and DTI atlases via unbiased atlas building at each of these ages. Probabilistic spatial prior definitions for the major tissue classes were trained on each atlas with expert manual segmentations. In this article we present the development and use of these atlases with publicly available tools, as well as the atlases themselves, which are publicly disseminated to the scientific community. PMID:28119564

  13. Teaching practices of thoracic epidural catheterizations in different grade of anesthesia residents

    Directory of Open Access Journals (Sweden)

    Ali Alagoz

    2016-02-01

    Full Text Available BACKGROUND AND OBJECTIVES: In this study, we aimed to clarify the importance of residency grade and other factors which influence the success of thoracic epidural catheterization in thoracotomy patients. METHODS: After the ethical committee approval, data were recorded retrospectively from the charts of 415 patients. All patients had given written informed consent. The thoracic epidural catheterization attempts were divided into two groups as second-third year (Group I and fourth year (Group II according to residency grade. We retrospectively collected demographic data, characteristics of thoracic epidural catheterization attempts, and all difficulties and complications during thoracic epidural catheterization. RESULTS: Overall success rate of thoracic epidural catheterization was similar between the groups. Levels of catheter placement, number and duration of thoracic epidural catheterization attempts were not different between the groups (p > 0.05. Change of needle insertion level was statistically higher in Group II (p = 0.008, whereas paresthesia was significantly higher in Group I (p = 0.007. Dural puncture and postdural puncture headache rates were higher in Group I. Higher body mass index and level of the insertion site were significant factors for thoracic epidural catheterization failure and postoperative complication rate and those were independence from residents' experience (p < 0.001, 0.005. CONCLUSION: Body mass index and level of insertion site were significant on thoracic epidural catheterization failure and postoperative complication rate. We think that residents' grade is not a significant factor in terms overall success rate of thoracic epidural catheterization, but it is important for outcome of these procedures.

  14. Effects of tourists on Barbary macaques at Gibraltar.

    Science.gov (United States)

    O'Leary, H; Fa, J E

    1993-01-01

    Interactions between tourists and Barbary macaques (Macaca sylvanus) at Queen's Gate, Gibraltar, are described. Interaction rates are high, with 99.6 interactions/h at peak times. Macaques spend 13.2% of their day interacting with tourists and 41.9% inactive. An overall ratio of 3.2:1 between human-initiated and macaque-initiated interactions was found. Of interactions involving humans, 85% concerned tourists. Diurnal activity patterns of the macaques were adapted to tourist visitation patterns. Old animals initiated more food-related interactions than younger ones. Infants/juveniles were the commonest class in contacts with humans and vehicles. Interactions involving more than one macaque were rare. High interaction rates were recorded for mothers and babies.

  15. Analysis of the N-terminal positively charged residues of the simian immunodeficiency virus Vif reveals a critical amino acid required for the antagonism of rhesus APOBEC3D, G, and H.

    Science.gov (United States)

    Schmitt, Kimberly; Katuwal, Miki; Wang, Yaqiong; Li, Cicy; Stephens, Edward B

    2014-01-20

    Previous studies have shown that apolipoprotein B mRNA editing, enzyme catalytic, polypeptide G (APOBEC3G; hA3G) and F (APOBEC3F; hA3F) proteins interact with a nonlinear binding site located at the N-terminal region of the HIV-1 Vif protein. We have analyzed the role of 12 positively charged amino acids of the N-terminal region of the SIV Vif. Simian-human immunodeficiency viruses (SHIV) were constructed that expressed each of these amino acid substitutions. These viruses were examined for replication in the presence of rhesus macaque APOBEC3 proteins (rhA3A-rhA3H), incorporation of the different A3 proteins into virions, and replication in rhesus macaque PBMC. Similar to other studies, we found that K27 was essential for rhA3G activity and rhA3F but was not important for restriction of SHIVΔvif by rhA3A, rhA3D or rhA3H. Our results identified the arginine at position 14 of the SIV Vif as a critical residue for virus restriction by rhA3D, rhA3G and rhA3H.

  16. White-cheeked macaque (Macaca leucogenys): A new macaque species from Medog, southeastern Tibet.

    Science.gov (United States)

    Li, Cheng; Zhao, Chao; Fan, Peng-Fei

    2015-07-01

    We describe a newly discovered Macaca species from the Medog, in southeastern Tibet, China, Macaca leucogenys sp. nov or the "white-cheeked macaque". Based on 738 photos taken during direct observations and captured by camera traps this new species appears to be distinct from the Macaca sinica species group. Moreover, the species is distinguished from all potential sympatric macaque species (M. mulatta, M. thibetana, M. assamensis, and M. munzala) in exhibiting a suite of pelage characteristics including relatively uniform dorsal hair pattern, hairy ventral pelage, relative hairless short tail, prominent pale to white side- and chin-whiskers creating a white cheek and round facial appearance, dark facial skin on the muzzle, long and thick hairs on its neck, and a round rather than arrow-shaped male genitalia. This new macaque species was found to exploit a diverse set of habitat types from tropical forest at 1395 m, to primary and secondary evergreen broad-leaved forest at 2000 m, as well as mixed broadleaf-conifer forest at 2700 m. Its range may extend to neighboring counties in Tibet and the part of southeastern Tibet controlled by India. The white-cheeked macaque is threatened by illegal hunting and the construction of hydropower stations. Discovery of this new primate species further highlights the high value for biodiversity conservation of southeastern Tibet and calls for more intensive surveys, studies, and environmental protection in this area.

  17. Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant.

    Science.gov (United States)

    Barnett, Susan W; Burke, Brian; Sun, Yide; Kan, Elaine; Legg, Harold; Lian, Ying; Bost, Kristen; Zhou, Fengmin; Goodsell, Amanda; Zur Megede, Jan; Polo, John; Donnelly, John; Ulmer, Jeffrey; Otten, Gillis R; Miller, Christopher J; Vajdy, Michael; Srivastava, Indresh K

    2010-06-01

    We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV(SF162P4) following sequential immunization with alphavirus replicon particles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1(SF162) gp140DeltaV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV(SF162P4) (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against

  18. Artificial Nursing Procedure Establishment for Infant Rhesus Monkeys

    Institute of Scientific and Technical Information of China (English)

    Wang Hong; Si Wei; Zhou Yin; Chen Lixian

    2015-01-01

    Rhesus monkey can not achieve natural delivery due to various reasons,and cesarean section becomes an important midwifery to get infant monkeys. After caesarean section,the pregnant monkey is weak and postoperative wound pain,so it can not personally feed infant monkeys which must be artificially fed. Thus,establishing suitable feeding management program is very important for improving survival rate of infant rhesus monkey and maintaining good health. We summarized food preparation method for infant rhesus monkeys as well as temperature setting and light control,and established the nursing program for newborn infant monkey and daily management process for infant monkeys.

  19. Spaceflight and Immune Responses of Rhesus Monkeys

    Science.gov (United States)

    Sonnenfeld, Gerald

    1997-01-01

    In the grant period, we perfected techniques for determination of interleukin production and leukocyte subset analysis of rhesus monkeys. These results are outlined in detail in publication number 2, appended to this report. Additionally, we participated in the ARRT restraint test to determine if restraint conditions for flight in the Space Shuttle could contribute to any effects of space flight on immune responses. All immunological parameters listed in the methods section were tested. Evaluation of the data suggests that the restraint conditions had minimal effects on the results observed, but handling of the monkeys could have had some effect. These results are outlined in detail in manuscript number 3, appended to this report. Additionally, to help us develop our rhesus monkey immunology studies, we carried out preliminary studies in mice to determine the effects of stressors on immunological parameters. We were able to show that there were gender-based differences in the response of immunological parameters to a stressor. These results are outlined in detail in manuscript number 4, appended to this report.

  20. Association Between Endovascular Performance in a Simulated Setting and in the Catheterization Laboratory

    DEFF Research Database (Denmark)

    Räder, Sune B E W; Abildgaard, Ulrik; Jørgensen, Erik;

    2014-01-01

    INTRODUCTION: Simulation-based assessment studies have related simulator performance to clinical experience instead of actual clinical performance. This study validates a novel rating scale for coronary angiography (CA) performance and at the same time explores the association between CA...... in the catheterization laboratory. The correlation between operators' previous clinical experience in CA and CARS scores was R = 0.65 (P = 0.005) in the catheterization laboratory and R = 0.11 (P = 0.353) in the simulated setting. CONCLUSIONS: The association between CA performance in a simulated setting and actual...... performance in a simulated setting and in the catheterization laboratory. METHODS: Ten cardiologists and cardiology residents with varying degrees of CA experience performed 2 CAs in the catheterization laboratory and 2 CAs in a simulated setting. The residents had prior simulator experience opposite...

  1. Predicting patient volume in cardiac catheterization laboratory to improve resource management.

    Science.gov (United States)

    Liu, Jianhua; Santangelo, Jennifer; James, Randy; Watters, Coyt D; Orsini, Anthony; Mekhjian, Hagop; Kamal, Jyoti

    2008-11-06

    Using historical data within the Information Warehouse of the Ohio State University Medical Center, prediction on daily patient volume to catheterization laboratory was attempted to facilitate resource management and planning.

  2. Antibiotic Prophylaxis for Urinary Tract Infections in Children With Spina Bifida on Intermittent Catheterization

    NARCIS (Netherlands)

    Zegers, Bas; Uiterwaal, Cuno; Kimpen, Jan; van Gool, Jan; de Jong, Tom; Winkler-Seinstra, Pauline; Houterman, Saskia; Verpoorten, Carla; van Steenwijk, Catharine de Jong-de Vos

    2011-01-01

    Purpose: Antibiotic prophylaxis (low dose chemoprophylaxis) has been prescribed since the introduction of clean intermittent catheterization in children with spina bifida. We hypothesized that stopping low dose chemoprophylaxis does not increase the number of urinary tract infections in these patien

  3. Gluten-sensitive enteropathy coincides with decreased capability of intestinal T cells to secrete IL-17 and IL-22 in a macaque model for celiac disease.

    Science.gov (United States)

    Xu, Huanbin; Feely, Stephanie L; Wang, Xiaolei; Liu, David X; Borda, Juan T; Dufour, Jason; Li, Weiwei; Aye, Pyone P; Doxiadis, Gaby G; Khosla, Chaitan; Veazey, Ronald S; Sestak, Karol

    2013-04-01

    Celiac disease (CD) is an autoimmune disorder caused by intolerance to dietary gluten. The interleukin (IL)-17 and IL-22 function as innate regulators of mucosal integrity. Impaired but not well-understood kinetics of the IL-17/22 secretion was described in celiac patients. Here, the IL-17 and IL-22-producing intestinal cells were studied upon their in vitro stimulation with mitogens in class II major histocompatibility complex-defined, gluten-sensitive rhesus macaques. Pediatric biopsies were collected from distal duodenum during the stages of disease remission and relapse. Regardless of dietary gluten content, IL-17 and IL-22-producing cells consisted of CD4+ and CD8+ T lymphocytes as well as of lineage-negative (Lin-) cells. Upon introduction of dietary gluten, capability of intestinal T cells to secrete IL-17/22 started to decline (pgluten-sensitive primates.

  4. Right Cardiac Catheterization Using the Antecubital Fossa Vein in Korean Patients

    Science.gov (United States)

    Lee, Sang Hyun; Lee, Dae Sung; Lee, Soo Yong; Hwang, Jongmin; Chon, Min Ku; Hwang, Ki Won; Kim, Jeong Su; Park, Yong Huyn; Kim, June Hong

    2016-01-01

    Background and Objectives Right heart catheterization is traditionally performed using a femoral vein approach that involves admission, bed rest, and risks of bleeding and hematoma. Recent studies have confirmed safety of the use of forearm vein for right cardiac catheterization. In the present study, we evaluated the feasibility of right cardiac catheterization via the antecubital fossa vein in Korean patients. Subjects and Methods The medical records of all patients who underwent right heart catheterization at our hospital between January 2003 and December 2014 were reviewed retrospectively. Right cardiac catheterizations via the antecubital fossa vein and the femoral vein were compared in terms of demographic data (age, sex, weight, height, and body mass index), indications for right cardiac catheterization, and procedural and outcome data (initial success rate, procedure time, compression to ambulation time, and complications). Results We reviewed 132 cases (antecubital fossa vein approach, n=37; femoral vein approach, n=95). The demographic data, initial success rate (100% vs. 100%) and procedure time (21.6±16.8 min vs. 25.6±12.6 min, p=0.14) were similar in both groups. The antecubital fossa vein group had a shorter mean compression to ambulation time than the femoral vein group (0.0 min vs. 201.2±48.1 min, p<0.01). No complications were observed in either group. Conclusion Our study indicated the ease of performance of right cardiac catheterization via the antecubital fossa vein. Thus, the antecubital fossa vein can be an alternative access site for right cardiac catheterization in Korean patients. PMID:27014351

  5. Bilateral hydrothorax and cardiac tamponade after right subclavian vein catheterization -A case report-

    OpenAIRE

    Kim, Myoung Hwa; Lee, Dong-Jun; Kim, Mun Chul

    2010-01-01

    Central venous catheterization is typically used for the anesthetic management of patients undergoing a major surgery or care of patients in Intensive Care Unit (ICU). The occurrence of complications associated with central venous catheterization such as pneumothorax or vascular injury have decreased, while delayed complications such as hydrothorax, hydromediastinum, or cardiac tamponade have risen recently. We report a case of complications of bilateral hydrothorax with cardiac tamponade by ...

  6. Radiation Dose Reduction during Radial Cardiac Catheterization: Evaluation of a Dedicated Radial Angiography Absorption Shielding Drape

    OpenAIRE

    Andrew Ertel; Jeffrey Nadelson; Adhir R. Shroff; Ranya Sweis; Dean Ferrera; Vidovich, Mladen I.

    2012-01-01

    Objectives. Radiation scatter protection shield drapes have been designed with the goal of decreasing radiation dose to the operators during transfemoral catheterization. We sought to investigate the impact on operator radiation exposure of various shielding drapes specifically designed for the radial approach. Background. Radial access for cardiac catheterization has increased due to improved patient comfort and decreased bleeding complications. There are concerns for increased radiation exp...

  7. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Martin Cranage

    2008-08-01

    Full Text Available BACKGROUND: The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model. METHODS AND FINDINGS: A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were

  8. Development of Needle Insertion Manipulator for Central Venous Catheterization

    Science.gov (United States)

    Kobayashi, Yo; Hong, Jaesung; Hamano, Ryutaro; Hashizume, Makoto; Okada, Kaoru; Fujie, Masakatsu G.

    Central venous