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Sample records for dna vaccine-primed macaques

  1. Mucosal prior to systemic application of recombinant adenovirus boosting is more immunogenic than systemic application twice but confers similar protection against SIV-challenge in DNA vaccine-primed macaques

    SciTech Connect

    Schulte, Reiner; Suh, You-Suk; Sauermann, Ulrike; Ochieng, Washingtone; Sopper, Sieghart; Kim, Kwang S.; Ahn, So-Shin; Park, Ki S.; Stolte-Leeb, Nicole; Hunsmann, Gerhard; Sung, Young C. Stahl-Hennig, Christiane

    2009-01-20

    We investigated the immunogenicity and efficacy of a bimodal prime/boost vaccine regimen given by various routes in the Simian immunodeficiency virus (SIV) rhesus monkey model for AIDS. Twelve animals were immunized with SIV DNA-vectors followed by the application of a recombinant adenovirus (rAd5) expressing the same genes either intramuscularly (i.m.) or by oropharyngeal spray. The second rAd5-application was given i.m. All vaccinees plus six controls were challenged orally with SIVmac239 12 weeks post-final immunization. Both immunization strategies induced strong SIV Gag-specific IFN-{gamma} and T-cell proliferation responses and mediated a conservation of CD4{sup +} memory T-cells and a reduction of viral load during peak viremia following infection. Interestingly, the mucosal group was superior to the systemic group regarding breadth and strength of SIV-specific T-cell responses and exhibited lower vector specific immune responses. Therefore, our data warrant the inclusion of mucosal vector application in a vaccination regimen which makes it less invasive and easier to apply.

  2. DNA vaccine prime and recombinant FPV vaccine boost: an important candidate immunization strategy to control bluetongue virus type 1.

    PubMed

    Li, Junping; Yang, Tao; Xu, Qingyuan; Sun, Encheng; Feng, Yufei; Lv, Shuang; Zhang, Qin; Wang, Haixiu; Wu, Donglai

    2015-10-01

    Bluetongue virus (BTV) is the causative agent of bluetongue (BT), an important sheep disease that caused great economic loss to the sheep industry. There are 26 BTV serotypes based on the outer protein VP2. However, the serotypes BTV-1 and BTV-16 are the two most prevalent serotypes in China. Vaccination is the most effective method of preventing viral infections. Therefore, the need for an effective vaccine against BTV is urgent. In this study, DNA vaccines and recombinant fowlpox virus (rFPV) vaccines expressing VP2 alone or VP2 in combination with VP5 or co-expressing the VP2 and VP5 proteins of BTV-1 were evaluated in both mice and sheep. Several strategies were tested in mice, including DNA vaccine prime and boost, rFPV vaccine prime and boost, and DNA vaccine prime and rFPV vaccine boost. We then determined the best vaccine strategy in sheep. Our results indicated that a strategy combining a DNA vaccine prime (co-expressing VP2 and VP5) followed by an rFPV vaccine boost (co-expressing VP2 and VP5) induced a high titer of neutralizing antibodies in sheep. Therefore, our data suggest that a DNA vaccine consisting of a pCAG-(VP2+VP5) prime and an rFPV-(VP2+VP5) boost is an important candidate for the design of a novel vaccine against BTV-1. PMID:26048472

  3. Prime-Boost Interval Matters: A Randomized Phase 1 Study to Identify the Minimum Interval Necessary to Observe the H5 DNA Influenza Vaccine Priming Effect

    PubMed Central

    Ledgerwood, Julie E.; Zephir, Kathryn; Hu, Zonghui; Wei, Chih-Jen; Chang, LeeJah; Enama, Mary E.; Hendel, Cynthia S.; Sitar, Sandra; Bailer, Robert T.; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.

    2013-01-01

    Background. H5 DNA priming was previously shown to improve the antibody response to influenza A(H5N1) monovalent inactivated vaccine (MIV) among individuals for whom there was a 24-week interval between prime and boost receipt. This study defines the shortest prime-boost interval associated with an improved response to MIV. Methods. We administered H5 DNA followed by MIV at intervals of 4, 8, 12, 16, or 24 weeks and compared responses to that of 2 doses of MIV (prime-boost interval, 24 weeks). Results. H5 DNA priming with an MIV boost ≥12 weeks later showed an improved response, with a positive hemagglutination inhibition (HAI) titer in 91% of recipients (geometric mean titer [GMT], 141–206), compared with 55%–70% of recipients with an H5 DNA and MIV prime-boost interval of ≤8 weeks (GMT, 51–70) and 44% with an MIV-MIV prime-boost interval of 24 weeks (GMT, 27). Conclusion. H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12–24 weeks. Clinical Trials Registration. NCT01086657. PMID:23633407

  4. Mitochondrial DNA variation within and among regional populations of longtail macaques (Macaca fascicularis) in relation to other species of the fascicularis group of macaques.

    PubMed

    Smith, David Glenn; McDonough, John W; George, Debra A

    2007-02-01

    An 835 base pair (bp) fragment of mitochondrial DNA (mtDNA) was sequenced to characterize genetic variation within and among 1,053 samples comprising five regional populations each of longtail macaques (Macaca fascicularis) and rhesus macaques (Macaca mulatta), and one sample each of Japanese (M. fuscata) and Taiwanese (M. cyclopis) macaques. The mtDNA haplotypes of longtail macaques clustered in two large highly structured clades (Fas1 and Fas2) of a neighbor-joining tree that were reciprocally monophyletic with respect to those representing rhesus macaques, Japanese macaques, and Taiwanese macaques. Both clades exhibited haplotypes of Indonesian and Malaysian longtail macaques widely dispersed throughout them; however, longtail macaques from Indochina, Philippines, and Mauritius each clustered in a separate well-defined clade together with one or a few Malaysian and/or Indonesian longtail macaques, suggesting origins on the Sunda shelf. Longtail macaques from Malaysia and Indonesia were far more genetically diverse, and those from Mauritius were far less diverse than any other population studied. Nucleotide diversity between mtDNA sequences of longtail macaques from different geographic regions is, in some cases, greater than that between Indian and Chinese rhesus macaques. Approximately equal amounts of genetic diversity are due to differences among animals in the same regional population, different regional populations, and different species. A greater proportion of genetic variance was explained by interspecies differences when Japanese and Taiwanese macaques were regarded as regional populations of rhesus macaques than when they were treated as separate species. Rhesus macaques from China were more closely related to both Taiwanese and Japanese macaques than to their own conspecifics from India. PMID:17177314

  5. SIV DNA vaccine trial in macaques: post-challenge necropsy in vaccine and control groups.

    PubMed

    Lu, S; Manson, K; Wyand, M; Robinson, H L

    1997-06-01

    In this study we describe the histopathologic findings from nine macaques in a simian immunodeficiency virus (SIV) DNA vaccine trial evaluating the ability of a 5-plasmid DNA vaccine to protect against an uncloned SIVmac251 challenge (Lu et al., J. Virol. 1996, 70, 3978-3991). Three vaccinated and one control macaque developed disease and were euthanized in the first year following challenge. The other four vaccinated and one control macaque remained clinically normal and were euthanized at the end of the trial (60 weeks post-challenge). The necropsy data revealed that both diseased and clinically normal macaques had developed typical SIV-related lymphoid changes, inflammatory disorders and opportunistic infections. All animals had variable degrees of follicular and/or paracortical lymphoid hyperplasia suggesting immune activation. All but one vaccinated macaque and both control macaques had SIV-associated opportunistic infections. Within the small groups of animals, the ability to contain opportunistic infections was superior, and the overall lymphoid changes less severe, in the macaques that had received vaccine DNAs by three routes of inoculation (intravenous, intramuscular and gene gun) than in those that had received control DNAs or vaccine DNAs by gene gun only. In the future it will be important to further test how the route and method of DNA inoculation impact the efficacy of immunodeficiency virus vaccines. PMID:9234548

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

    PubMed

    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. PMID:24810278

  7. Protection from immunodeficiency virus challenges in rhesus macaques by multicomponent DNA immunization.

    PubMed

    Kim, J J; Yang, J S; Nottingham, L K; Lee, D J; Lee, M; Manson, K H; Wyand, M S; Boyer, J D; Ugen, K E; Weiner, D B

    2001-07-01

    Multicomponent DNA vaccines were used to elicit immune responses, which can impact viral challenge in three separate rhesus macaque models. Eight rhesus macaques were immunized with DNA vaccines for HIV env/rev and SIV gag/pol and were challenged intravenously with 10 animal infective doses (AID(50)) of cell-free SHIV IIIB. Three of eight immunized rhesus macaques were protected, exhibiting no detectable virus. Animals protected from nonpathogenic SHIVIIIB challenge were rested for extended periods of time and were rechallenged first with pathogenic SIV(mac239) and subsequently with pathogenic SHIV89.6P viruses. Following the pathogenic challenges, all three vaccinated animals were negative for viral coculture and antigenemia and were negative by PCR. In contrast, the control animals exhibited antigenemia by 2 weeks postchallenge and exhibited greater than 10 logs of virus/10(6) cells in limiting dilution coculture. The control animals exhibited CD4 cell loss and developed SIV-related wasting with high viral burden and subsequently failed to thrive. Vaccinated animals remained virus-negative and were protected from the viral load, CD4 loss, disease, and death. We observed strong Th1-type cellular immune responses in the protected macaques throughout the study, suggesting their important roles in protection. These studies support the finding that multicomponent DNA vaccines can directly impact viral replication and disease in a highly pathogenic challenge system, thus potentially broadening our strategies against HIV. PMID:11437655

  8. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    SciTech Connect

    Sparger, Ellen E. Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-05-10

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-{gamma} enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus.

  9. Altered Response Hierarchy and Increased T-Cell Breadth upon HIV-1 Conserved Element DNA Vaccination in Macaques

    PubMed Central

    Kulkarni, Viraj; Valentin, Antonio; Rosati, Margherita; Alicea, Candido; Singh, Ashish K.; Jalah, Rashmi; Broderick, Kate E.; Sardesai, Niranjan Y.; Le Gall, Sylvie; Mothe, Beatriz; Brander, Christian; Rolland, Morgane; Mullins, James I.; Pavlakis, George N.; Felber, Barbara K.

    2014-01-01

    HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24gag elements (CE) induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55gag increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist. PMID:24465991

  10. Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques.

    PubMed

    Kulkarni, Viraj; Valentin, Antonio; Rosati, Margherita; Alicea, Candido; Singh, Ashish K; Jalah, Rashmi; Broderick, Kate E; Sardesai, Niranjan Y; Le Gall, Sylvie; Mothe, Beatriz; Brander, Christian; Rolland, Morgane; Mullins, James I; Pavlakis, George N; Felber, Barbara K

    2014-01-01

    HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24(gag) elements (CE) induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55(gag) increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist. PMID:24465991

  11. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomolgus macaques from lethal Ebola and Marburg virus challenges

    PubMed Central

    Grant-Klein, Rebecca J; Altamura, Louis A; Badger, Catherine V; Bounds, Callie E; Van Deusen, Nicole M; Kwilas, Steven A; Vu, Hong A; Warfield, Kelly L; Hooper, Jay W; Hannaman, Drew; Dupuy, Lesley C; Schmaljohn, Connie S

    2015-01-01

    Cynomolgus macaques were vaccinated by intramuscular electroporation with DNA plasmids expressing codon-optimized glycoprotein (GP) genes of Ebola virus (EBOV) or Marburg virus (MARV) or a combination of codon-optimized GP DNA vaccines for EBOV, MARV, Sudan virus and Ravn virus. When measured by ELISA, the individual vaccines elicited slightly higher IgG responses to EBOV or MARV than did the combination vaccines. No significant differences in immune responses of macaques given the individual or combination vaccines were measured by pseudovirion neutralization or IFN-γ ELISpot assays. Both the MARV and mixed vaccines were able to protect macaques from lethal MARV challenge (5/6 vs. 6/6). In contrast, a greater proportion of macaques vaccinated with the EBOV vaccine survived lethal EBOV challenge in comparison to those that received the mixed vaccine (5/6 vs. 1/6). EBOV challenge survivors had significantly higher pre-challenge neutralizing antibody titers than those that succumbed. PMID:25996997

  12. Recombinant rubella vectors elicit SIV Gag-specific T cell responses with cytotoxic potential in rhesus macaques.

    PubMed

    Rosati, Margherita; Alicea, Candido; Kulkarni, Viraj; Virnik, Konstantin; Hockenbury, Max; Sardesai, Niranjan Y; Pavlakis, George N; Valentin, Antonio; Berkower, Ira; Felber, Barbara K

    2015-04-27

    Live-attenuated rubella vaccine strain RA27/3 has been demonstrated to be safe and immunogenic in millions of children. The vaccine strain was used to insert SIV gag sequences and the resulting rubella vectors were tested in rhesus macaques alone and together with SIV gag DNA in different vaccine prime-boost combinations. We previously reported that such rubella vectors induce robust and durable SIV-specific humoral immune responses in macaques. Here, we report that recombinant rubella vectors elicit robust de novo SIV-specific cellular immune responses detectable for >10 months even after a single vaccination. The antigen-specific responses induced by the rubella vector include central and effector memory CD4(+) and CD8(+) T cells with cytotoxic potential. Rubella vectors can be administered repeatedly even after vaccination with the rubella vaccine strain RA27/3. Vaccine regimens including rubella vector and SIV gag DNA in different prime-boost combinations resulted in robust long-lasting cellular responses with significant increase of cellular responses upon boost. Rubella vectors provide a potent platform for inducing HIV-specific immunity that can be combined with DNA in a prime-boost regimen to elicit durable cellular immunity. PMID:25802183

  13. DNA and Protein Co-Immunization Improves the Magnitude and Longevity of Humoral Immune Responses in Macaques

    PubMed Central

    Jalah, Rashmi; Kulkarni, Viraj; Patel, Vainav; Rosati, Margherita; Alicea, Candido; Bear, Jenifer; Yu, Lei; Guan, Yongjun; Shen, Xiaoying; Tomaras, Georgia D.; LaBranche, Celia; Montefiori, David C.; Prattipati, Rajasekhar; Pinter, Abraham; Bess, Julian; Lifson, Jeffrey D.; Reed, Steven G.; Sardesai, Niranjan Y.; Venzon, David J.; Valentin, Antonio; Pavlakis, George N.; Felber, Barbara K.

    2014-01-01

    We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques. PMID:24626482

  14. DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques.

    PubMed

    Jalah, Rashmi; Kulkarni, Viraj; Patel, Vainav; Rosati, Margherita; Alicea, Candido; Bear, Jenifer; Yu, Lei; Guan, Yongjun; Shen, Xiaoying; Tomaras, Georgia D; LaBranche, Celia; Montefiori, David C; Prattipati, Rajasekhar; Pinter, Abraham; Bess, Julian; Lifson, Jeffrey D; Reed, Steven G; Sardesai, Niranjan Y; Venzon, David J; Valentin, Antonio; Pavlakis, George N; Felber, Barbara K

    2014-01-01

    We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques. PMID:24626482

  15. Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques

    PubMed Central

    Kulkarni, Viraj; Rosati, Margherita; Bear, Jenifer; Pilkington, Guy R; Jalah, Rashmi; Bergamaschi, Cristina; Singh, Ashish K; Alicea, Candido; Chowdhury, Bhabadeb; Zhang, Gen-Mu; Kim, Eun-Young; Wolinsky, Steven M; Huang, Wensheng; Guan, Yongjun; LaBranche, Celia; Montefiori, David C; Broderick, Kate E; Sardesai, Niranjan Y; Valentin, Antonio; Felber, Barbara K; Pavlakis, George N

    2013-01-01

    A panel of SIVmac251 transmitted Env sequences were tested for expression, function and immunogenicity in mice and macaques. The immunogenicity of a DNA vaccine cocktail expressing SIVmac239 and three transmitted SIVmac251 Env sequences was evaluated upon intradermal or intramuscular injection followed by in vivo electroporation in macaques using sequential vaccination of gp160, gp120 and gp140 expressing DNAs. Both intradermal and intramuscular vaccination regimens using the gp160 expression plasmids induced robust humoral immune responses, which further improved using the gp120 expressing DNAs. The responses showed durability of binding and neutralizing antibody titers and high avidity for > 1 y. The intradermal DNA delivery regimen induced higher cross-reactive responses able to neutralize the heterologous tier 1B-like SIVsmE660_CG7V. Analysis of cellular immune responses showed induction of Env-specific memory responses and cytotoxic granzyme B+ T cells in both vaccine groups, although the magnitude of the responses were ~10x higher in the intramuscular/electroporation group. The cellular responses induced by both regimens were long lasting and could be detected ~1 y after the last vaccination. These data show that both DNA delivery methods are able to induce robust and durable immune responses in macaques. PMID:23811579

  16. Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques.

    PubMed

    Kulkarni, Viraj; Rosati, Margherita; Bear, Jenifer; Pilkington, Guy R; Jalah, Rashmi; Bergamaschi, Cristina; Singh, Ashish K; Alicea, Candido; Chowdhury, Bhabadeb; Zhang, Gen-Mu; Kim, Eun-Young; Wolinsky, Steven M; Huang, Wensheng; Guan, Yongjun; LaBranche, Celia; Montefiori, David C; Broderick, Kate E; Sardesai, Niranjan Y; Valentin, Antonio; Felber, Barbara K; Pavlakis, George N

    2013-10-01

    A panel of SIVmac251 transmitted Env sequences were tested for expression, function and immunogenicity in mice and macaques. The immunogenicity of a DNA vaccine cocktail expressing SIVmac239 and three transmitted SIVmac251 Env sequences was evaluated upon intradermal or intramuscular injection followed by in vivo electroporation in macaques using sequential vaccination of gp160, gp120 and gp140 expressing DNAs. Both intradermal and intramuscular vaccination regimens using the gp160 expression plasmids induced robust humoral immune responses, which further improved using the gp120 expressing DNAs. The responses showed durability of binding and neutralizing antibody titers and high avidity for>1 y. The intradermal DNA delivery regimen induced higher cross-reactive responses able to neutralize the heterologous tier 1B-like SIVsmE660_CG7V. Analysis of cellular immune responses showed induction of Env-specific memory responses and cytotoxic granzyme B(+) T cells in both vaccine groups, although the magnitude of the responses were ~10x higher in the intramuscular/electroporation group. The cellular responses induced by both regimens were long lasting and could be detected ~1 y after the last vaccination. These data show that both DNA delivery methods are able to induce robust and durable immune responses in macaques. PMID:23811579

  17. Detection of Neospora from tissues of experimentally infected rhesus macaques by PCR and specific DNA probe hybridization.

    PubMed

    Ho, M S; Barr, B C; Tarantal, A F; Lai, L T; Hendrickx, A G; Marsh, A E; Sverlow, K W; Packham, A E; Conrad, P A

    1997-07-01

    Neospora is a newly recognized Toxoplasma-like cyst-forming coccidian parasite that causes abortion or congenital infections in naturally or experimentally infected animals. In this study, pregnant rhesus macaques were inoculated with culture-derived tachyzoites of a bovine Neospora isolate, and tissue samples from various major organs were collected from dams and fetuses for the detection of parasite DNA by using oligonucleotide primers COC-1 and COC-2 for PCR amplification of a conserved coccidial nuclear small-subunit rRNA gene sequence, and amplification products were confirmed by hybridization with a Neospora-specific DNA probe. PCR products were amplified from DNAs of different fetal monkey tissues, including brain, heart, lung, liver, spleen, skeletal muscle, skin, and placenta. In addition, Neospora DNA was amplified from the brain, heart, and lung tissues of infected rhesus macaque dams. The PCR and probe hybridization system may provide an effective method for the detection of Neospora infection in fetuses and dams from nonhuman primates and may be useful in determining the zoonotic potential of Neospora. PMID:9196184

  18. A Nonhuman Primate Scrub Typhus Model: Protective Immune Responses Induced by pKarp47 DNA Vaccination in Cynomolgus Macaques

    PubMed Central

    Chattopadhyay, Suchismita; Jiang, Ju; Nawtaisong, Pruksa; Lee, John S.; Tan, Esterlina; Dela Cruz, Eduardo; Burgos, Jasmin; Abalos, Rodolfo; Blacksell, Stuart D.; Lombardini, Eric; Turner, Gareth D.; Day, Nicholas P. J.; Richards, Allen L.

    2015-01-01

    We developed an intradermal (ID) challenge cynomolgus macaque (Macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical Asia, caused by the obligate intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. We investigated scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa, Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus-vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle) for safety, immunogenicity, and efficacy against homologous ID challenge with O. tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars, lymphadenopathy, bacteremia, altered liver function, increased WBC counts, pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses. Vaccinated macaques receiving the DNA plasmid pKarp47 vaccine had significantly increased O. tsutsugamushi–specific, IFN-γ–producing PBMCs (p = 0.04), reduced eschar frequency and bacteremia duration (p ≤ 0.01), delayed bacteremia onset (p < 0.05), reduced circulating bacterial biomass (p = 0.01), and greater reduction of liver transaminase levels (p < 0.03) than controls. This study demonstrates a vaccine-induced immune response capable of conferring sterile immunity against high-dose homologous ID challenge of O. tsutsugamushi in a nonhuman primate model, and it provides insight into cell-mediated immune control of O. tsutsugamushi and dissemination dynamics, highlights the importance of bacteremia indices for evaluation of both natural and vaccine-induced immune responses, and importantly, to our knowledge, has determined the first phenotypic correlates of immune protection in scrub typhus. We conclude that this model is suitable for detailed investigations into vaccine

  19. A nonhuman primate scrub typhus model: protective immune responses induced by pKarp47 DNA vaccination in cynomolgus macaques.

    PubMed

    Paris, Daniel H; Chattopadhyay, Suchismita; Jiang, Ju; Nawtaisong, Pruksa; Lee, John S; Tan, Esterlina; Dela Cruz, Eduardo; Burgos, Jasmin; Abalos, Rodolfo; Blacksell, Stuart D; Lombardini, Eric; Turner, Gareth D; Day, Nicholas P J; Richards, Allen L

    2015-02-15

    We developed an intradermal (ID) challenge cynomolgus macaque (Macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical Asia, caused by the obligate intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. We investigated scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa, Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus-vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle) for safety, immunogenicity, and efficacy against homologous ID challenge with O. tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars, lymphadenopathy, bacteremia, altered liver function, increased WBC counts, pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses. Vaccinated macaques receiving the DNA plasmid pKarp47 vaccine had significantly increased O. tsutsugamushi-specific, IFN-γ-producing PBMCs (p = 0.04), reduced eschar frequency and bacteremia duration (p ≤ 0.01), delayed bacteremia onset (p < 0.05), reduced circulating bacterial biomass (p = 0.01), and greater reduction of liver transaminase levels (p < 0.03) than controls. This study demonstrates a vaccine-induced immune response capable of conferring sterile immunity against high-dose homologous ID challenge of O. tsutsugamushi in a nonhuman primate model, and it provides insight into cell-mediated immune control of O. tsutsugamushi and dissemination dynamics, highlights the importance of bacteremia indices for evaluation of both natural and vaccine-induced immune responses, and importantly, to our knowledge, has determined the first phenotypic correlates of immune protection in scrub typhus. We conclude that this model is suitable for detailed investigations into vaccine-induced immune

  20. Preliminary study of the genetic diversity of eastern Assamese macaques (Macaca assamensis assamensis) in Thailand based on mitochondrial DNA and microsatellite markers.

    PubMed

    Sukmak, Manakorn; Malaivijitnond, Suchinda; Schülke, Oliver; Ostner, Julia; Hamada, Yuzuru; Wajjwalku, Worawidh

    2014-04-01

    Human overpopulation, deforestation, invasion of agricultural areas, and livestock are the primary causes for population fragmentation of wildlife. The distribution range of species of the genus Macaca is constantly decreasing and becoming increasingly fragmented due to forest deterioration. Assamese macaques (M. assamensis) are classified as near threatened in the International Union for Conservation of Nature (IUCN) Red List of Threatened Animals (2008) and have been declared a protected wildlife animal according to Wildlife Preservation and Protection Act, B.E.2535 (1992) of Thailand. As studies of the population history and genetic diversity of Assamese macaques in Thailand are currently lacking, we aimed at a first investigation of their genetic diversity based on mitochondrial DNA [hypervariable regions 1 and 2 (HV1, HV2) and cytochrome B (CYTB) regions], as well as 15 microsatellite markers of five sampling sites distributed across Thailand. Our results indicate that Assamese macaques in Thailand are diverse, with eight maternal haplotypes and a low inbreeding coefficient in the Phu Khieo Wildlife Sanctuary (PKWS) population. Moreover, our phylogenetic and median-joining network analysis based on mitochondrial (mt)DNA suggests a population distribution in accordance with the evolutionary scenario proposed for M. sinica. Today, the population of Assamese macaques is fragmented, and conservation strategies are needed to ensure the maintenance of genetic diversity of this primate species. PMID:24142419

  1. Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

    PubMed Central

    2011-01-01

    Background There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-γ ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl β-galactosidase assay with primary isolates of HIV-1. Results This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody

  2. Ovarian steroids regulate gene expression related to DNA repair and neurodegenerative diseases in serotonin neurons of macaques

    PubMed Central

    Bethea, Cynthia L.; Reddy, Arubala P.

    2015-01-01

    Depression often accompanies the peri-menopausal transition and it often precedes overt symptomology in common neurodegenerative diseases (NDD; Alzheimer's, Parkinson's, Huntington, ALS). Serotonin dysfunction is frequently found in the different etiologies of depression. We have shown that ovariectomized (Ovx) monkeys treated with estradiol (E) for 28 days supplement with placebo or progesterone (P) on days 14-28 had reduced DNA fragmentation in serotonin neurons of the dorsal raphe nucleus; and long-term Ovx monkeys had fewer serotonin neurons than intact controls. We questioned the effect of E alone or E+P on gene expression related to DNA repair, protein folding (chaperones), the ubiquitin proteosome, axon transport, and NDD specific genes in serotonin neurons. Ovx macaques were treated with placebo, E or E+P (n=3/group) for 1 month. Serotonin neurons were laser captured and subjected to microarray analysis and qRT-PCR. Increases were confirmed with qRT-PCR in 5 genes that code for proteins involved in repair of strand breaks and nucleotide excision. NBN1, PCNA, GADD45A, RAD23A and GTF2H5 significantly increased with E or E+P treatment (all ANOVA p< 0.01). Chaperone genes HSP70, HSP60 and HSP27 significantly increased with E or E+P treatment (all ANOVA p<0.05). HSP90 showed a similar trend. Ubiquinase coding genes UBEA5, UBE2D3 and UBE3A (Parkin) increased with E or E+P (all ANOVA p<0.003). Transport related genes coding kinesin, dynein, and dynactin increased with E or E+P (all ANOVA p<0.03). SCNA (α synuclein) and ADAM10 (α secretase) increased (both ANOVA p<0.02), but PSEN1 (presenilin1) decreased (ANOVA p<0.02) with treatment. APP decreased 10-fold with E or E+P administration. Newman-Keuls posthoc comparisons indicated variation in the response to E alone versus E+P across the different genes. In summary, E or E+P increased gene expression for DNA repair mechanisms in serotonin neurons, thereby rendering them less vulnerable to stress-induced DNA

  3. Ovarian steroids regulate gene expression related to DNA repair and neurodegenerative diseases in serotonin neurons of macaques.

    PubMed

    Bethea, C L; Reddy, A P

    2015-12-01

    Depression often accompanies the perimenopausal transition and it often precedes overt symptomology in common neurodegenerative diseases (NDDs, such as Alzheimer's, Parkinson's, Huntington, amyotrophic lateral sclerosis). Serotonin dysfunction is frequently found in the different etiologies of depression. We have shown that ovariectomized (Ovx) monkeys treated with estradiol (E) for 28 days supplemented with placebo or progesterone (P) on days 14-28 had reduced DNA fragmentation in serotonin neurons of the dorsal raphe nucleus, and long-term Ovx monkeys had fewer serotonin neurons than intact controls. We questioned the effect of E alone or E+P (estradiol supplemented with progesterone) on gene expression related to DNA repair, protein folding (chaperones), the ubiquitin-proteosome, axon transport and NDD-specific genes in serotonin neurons. Ovx macaques were treated with placebo, E or E+P (n=3 per group) for 1 month. Serotonin neurons were laser captured and subjected to microarray analysis and quantitative real-time PCR (qRT-PCR). Increases were confirmed with qRT-PCR in five genes that code for proteins involved in repair of strand breaks and nucleotide excision. NBN1, PCNA (proliferating nuclear antigen), GADD45A (DNA damage-inducible), RAD23A (DNA damage recognition) and GTF2H5 (gene transcription factor 2H5) significantly increased with E or E+P treatment (all analysis of variance (ANOVA), P<0.01). Chaperone genes HSP70 (heat-shock protein 70), HSP60 and HSP27 significantly increased with E or E+P treatment (all ANOVA, P<0.05). HSP90 showed a similar trend. Ubiquinase coding genes UBEA5, UBE2D3 and UBE3A (Parkin) increased with E or E+P (all ANOVA, P<0.003). Transport-related genes coding kinesin, dynein and dynactin increased with E or E+P treatment (all ANOVA, P<0.03). SCNA (α-synuclein) and ADAM10 (α-secretase) increased (both ANOVA, P<0.02) but PSEN1 (presenilin1) decreased (ANOVA, P<0.02) with treatment. APP decreased 10-fold with E or E

  4. Intramuscular delivery of heterodimeric IL-15 DNA in macaques produces systemic levels of bioactive cytokine inducing proliferation of NK and T cells.

    PubMed

    Bergamaschi, C; Kulkarni, V; Rosati, M; Alicea, C; Jalah, R; Chen, S; Bear, J; Sardesai, N Y; Valentin, A; Felber, B K; Pavlakis, G N

    2015-01-01

    Interleukin-15 (IL-15) is a common γ-chain cytokine that has a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting infection and cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha (IL-15Rα) chain, which together form the IL-15 heterodimer. We have generated DNA vectors expressing the heterodimeric IL-15 by optimizing mRNA expression and protein trafficking. Repeated administration of these DNA plasmids by intramuscular injection followed by in vivo electroporation in rhesus macaques resulted in sustained high levels of IL-15 in plasma, with no significant toxicity. Administration of DNAs expressing heterodimeric IL-15 also resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8(+)NK cells, all memory CD8(+) T-cell subsets and effector memory CD4(+) T cells. Expression of heterodimeric IL-15 by DNA delivery to the muscle is an efficient procedure to obtain high systemic levels of bioactive cytokine, without the toxicity linked to the high transient cytokine peak associated with protein injection. PMID:25273353

  5. Intramuscular delivery of heterodimeric IL-15 DNA in macaques produces systemic levels of bioactive cytokine inducing proliferation of NK and T cells

    PubMed Central

    Bergamaschi, C; Kulkarni, V; Rosati, M; Alicea, C; Jalah, R; Chen, S; Bear, J; Sardesai, N Y; Valentin, A; Felber, B K; Pavlakis, G N

    2015-01-01

    Interleukin-15 (IL-15) is a common γ-chain cytokine that has a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting infection and cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha (IL-15Rα) chain, which together form the IL-15 heterodimer. We have generated DNA vectors expressing the heterodimeric IL-15 by optimizing mRNA expression and protein trafficking. Repeated administration of these DNA plasmids by intramuscular injection followed by in vivo electroporation in rhesus macaques resulted in sustained high levels of IL-15 in plasma, with no significant toxicity. Administration of DNAs expressing heterodimeric IL-15 also resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8+NK cells, all memory CD8+ T-cell subsets and effector memory CD4+ T cells. Expression of heterodimeric IL-15 by DNA delivery to the muscle is an efficient procedure to obtain high systemic levels of bioactive cytokine, without the toxicity linked to the high transient cytokine peak associated with protein injection. PMID:25273353

  6. Dose-dependent protection against or exacerbation of disease by a polylactide glycolide microparticle-adsorbed, alphavirus-based measles virus DNA vaccine in rhesus macaques.

    PubMed

    Pan, Chien-Hsiung; Nair, Nitya; Adams, Robert J; Zink, M Christine; Lee, Eun-Young; Polack, Fernando P; Singh, Manmohan; O'Hagan, Derek T; Griffin, Diane E

    2008-04-01

    Measles remains an important cause of vaccine-preventable child mortality. Development of a low-cost, heat-stable vaccine for infants under the age of 6 months could improve measles control by facilitating delivery at the time of other vaccines and by closing a window of susceptibility prior to immunization at 9 months of age. DNA vaccines hold promise for development, but achieving protective levels of antibody has been difficult and there is an incomplete understanding of protective immunity. In the current study, we evaluated the use of a layered alphavirus DNA/RNA vector encoding measles virus H (SINCP-H) adsorbed onto polylactide glycolide (PLG) microparticles. In mice, antibody and T-cell responses to PLG-formulated DNA were substantially improved compared to those to naked DNA. Rhesus macaques received two doses of PLG/SINCP-H delivered either intramuscularly (0.5 mg) or intradermally (0.5 or 0.1 mg). Antibody and T-cell responses were induced but not sustained. On challenge, the intramuscularly vaccinated monkeys did not develop rashes and had lower viremias than vector-treated control monkeys. Monkeys vaccinated with the same dose intradermally developed rashes and viremia. Monkeys vaccinated intradermally with the low dose developed more severe rashes, with histopathologic evidence of syncytia and intense dermal and epidermal inflammation, eosinophilia, and higher viremia compared to vector-treated control monkeys. Protection after challenge correlated with gamma interferon-producing T cells and with early production of high-avidity antibody that bound wild-type H protein. We conclude that PLG/SINCP-H is most efficacious when delivered intramuscularly but does not provide an advantage over standard DNA vaccines for protection against measles. PMID:18287579

  7. The Ovarian Cancer Chemokine Landscape is Conducive to Homing of Vaccine-primed and CD3/CD28 Costimulated T cells Prepared for Adoptive Therapy

    PubMed Central

    Zsiros, Emese; Duttagupta, Priyanka; Dangaj, Denarda; Li, Hongzhe; Frank, Renee; Garrabrant, Thomas; Hagemann, Ian S.; Levine, Bruce L.; June, Carl H.; Zhang, Lin; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide; Powell, Daniel J.; Tanyi, Janos; Feldman, Michael D.; Kandalaft, Lana E.; Coukos, George

    2016-01-01

    Purpose Chemokines are implicated in T cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous DC-vaccine primed T cells in the context of cell-based immunotherapy. Experimental design The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray. Peripheral blood T cells from five HLA-A2 patients with recurrent ovarian cancer, who previously received autologous tumor DC vaccine, underwent CD3/CD28 costimulation and expansion ex vivo. Tumor-specific T cells were identified by HER2/neu pentamer staining and were evaluated for the expression and functionality of chemokine receptors important for homing to ovarian cancer. Results The chemokine landscape of ovarian cancer is heterogeneous with high expression of known lymphocyte-recruiting chemokines (CCL2, CCL4 and CCL5) in tumors with intraepithelial T cells, whereas CXCL10, CXCL12 and CXCL16 are expressed quasi-universally, including in tumors lacking tumor infiltrating T cells. DC-vaccine primed T cells were found to express the cognate receptors for the above chemokines. Ex vivo CD3/CD28 costimulation and expansion of vaccine-primed T cells upregulated CXCR3 and CXCR4, and enhanced their migration toward universally expressed chemokines in ovarian cancer. Conclusions DC-primed tumor specific T cells are armed with the appropriate receptors to migrate towards universal ovarian cancer chemokines, and these receptors are further upregulated by ex vivo CD3/CD28 costimulation, which render T cells more fit for migrating towards these chemokines. PMID:25712684

  8. Dose-dependent inhibition of Gag cellular immunity by Env in SIV/HIV DNA vaccinated macaques

    PubMed Central

    Valentin, Antonio; Li, Jinyao; Rosati, Margherita; Kulkarni, Viraj; Patel, Vainav; Jalah, Rashmi; Alicea, Candido; Reed, Steven; Sardesai, Niranjan; Berkower, Ira; Pavlakis, George N; Felber, Barbara K

    2015-01-01

    The induction of a balanced immune response targeting the major structural proteins, Gag and Env of HIV, is important for the development of an efficacious vaccine. The use of DNA plasmids expressing different antigens offers the opportunity to test in a controlled manner the influence of different vaccine components on the magnitude and distribution of the vaccine-induced cellular and humoral immune responses. Here, we show that increasing amounts of env DNA results in greatly enhanced Env antibody titers without significantly affecting the levels of anti-Env cellular immune responses. Co-immunization with Env protein further increased antibody levels, indicating that vaccination with DNA only is not sufficient for eliciting maximal humoral responses against Env. In contrast, under high env:gag DNA plasmid ratio, the development of Gag cellular responses was significantly reduced by either SIV or HIV Env, whereas Gag humoral responses were not affected. Our data indicate that a balanced ratio of the 2 key HIV/SIV vaccine components, Gag and Env, is important to avoid immunological interference and to achieve both maximal humoral responses against Env to prevent virus acquisition and maximal cytotoxic T cell responses against Gag to prevent virus spread. PMID:26125521

  9. Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine

    PubMed Central

    Latimer, Brian; Toporovski, Roberta; Yan, Jian; Pankhong, Panyupa; Morrow, Matthew P; Khan, Amir S; Sardesai, Niranjan Y; Welles, Seth L; Jacobson, Jeffrey M; Weiner, David B; Kutzler, Michele A

    2014-01-01

    Chronic HCV is a surreptitious disease currently affecting approximately 3% of the world's population that can lead to liver failure and cancer decades following initial infection. However, there are currently no vaccines available for the prevention of chronic HCV. From patients who acutely resolve HCV infection, it is apparent that a strong and broad cytotoxic T lymphocyte (CTL) response is important in HCV clearance. DNA vaccines are naked plasmid DNA molecules that encode pathogen antigens to induce a pathogen-specific immune response. They are inexpensive to produce and have an excellent safety profile in animals and humans. Additionally, DNA vaccines are able to induce strong CTL responses, making them well-suited for an HCV vaccine. We aimed to maximize vaccine recipients' opportunity to induce a broad T cell response with a novel antigenic sequence, multi-antigen vaccine strategy. We have generated DNA plasmids encoding consensus sequences of HCV genotypes 1a and 1b non-structural proteins NS3/4a, NS4b, NS5a, and NS5b. Rhesus macaques were used to study the immunogenicity of these constructs. Four animals were immunized 3 times, 6 weeks apart, at a dose of 1.0mg per antigen construct, as an intramuscular injection followed by in vivo electroporation, which greatly increases DNA uptake by local cells. Immune responses were measured 2 weeks post-immunization regimen (PIR) in immunized rhesus macaques and showed a broad response to multiple HCV nonstructural antigens, with up to 4680 spot-forming units per million peripheral blood mononuclear cells (PBMCs) as measured by Interferon-γ ELISpot. In addition, multiparametric flow cytometry detected HCV-specific CD4+ and CD8+ T cell responses by intracellular cytokine staining and detected HCV-specific CD107a+/GrzB+ CD8+ T cells indicating an antigen specific cytolytic response 2 weeks PIR compared with baseline measurements. At the final study time point, 6 weeks PIR, HCV-specific CD45RA- memory-like T cells

  10. Population dynamics of rhesus macaques and associated foamy virus in Bangladesh

    PubMed Central

    Feeroz, Mostafa M; Soliven, Khanh; Small, Christopher T; Engel, Gregory A; Andreina Pacheco, M; Yee, JoAnn L; Wang, Xiaoxing; Kamrul Hasan, M; Oh, Gunwha; Levine, Kathryn L; Rabiul Alam, SM; Craig, Karen L; Jackson, Dana L; Lee, Eun-Gyung; Barry, Peter A; Lerche, Nicholas W; Escalante, Ananias A; Matsen IV, Frederick A; Linial, Maxine L; Jones-Engel, Lisa

    2013-01-01

    Foamy viruses are complex retroviruses that have been shown to be transmitted from nonhuman primates to humans. In Bangladesh, infection with simian foamy virus (SFV) is ubiquitous among rhesus macaques, which come into contact with humans in diverse locations and contexts throughout the country. We analyzed microsatellite DNA from 126 macaques at six sites in Bangladesh in order to characterize geographic patterns of macaque population structure. We also included in this study 38 macaques owned by nomadic people who train them to perform for audiences. PCR was used to analyze a portion of the proviral gag gene from all SFV-positive macaques, and multiple clones were sequenced. Phylogenetic analysis was used to infer long-term patterns of viral transmission. Analyses of SFV gag gene sequences indicated that macaque populations from different areas harbor genetically distinct strains of SFV, suggesting that geographic features such as forest cover play a role in determining the dispersal of macaques and SFV. We also found evidence suggesting that humans traveling the region with performing macaques likely play a role in the translocation of macaques and SFV. Our studies found that individual animals can harbor more than one strain of SFV and that presence of more than one SFV strain is more common among older animals. Some macaques are infected with SFV that appears to be recombinant. These findings paint a more detailed picture of how geographic and sociocultural factors influence the spectrum of simian-borne retroviruses. PMID:26038465

  11. Poster: the macaque genome.

    PubMed

    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. PMID:17431172

  12. Color categories in macaques.

    PubMed

    Sandell, J H; Gross, C G; Bornstein, M H

    1979-08-01

    This experiment investigated whether macaque monkeys partition the photic spectrum into the same four basic hue categories that humans do, i.e., blue, green, yellow, and red. Monkeys were trained to respond in the presence of one chromatic stimulus and were tested, in extinction, for generalization to others. In extinction, the monkeys responded at similar and high levels to stimuli that fell in the same basic human hue category as the training stimulus and at similar and much lower levels to stimuli that fell in a different human hue category from the training stimulus. It was concluded that macaques and humans categorize the spectrum in a similar fashion. PMID:113431

  13. Infinium Monkeys: Infinium 450K Array for the Cynomolgus macaque (Macaca fascicularis)

    PubMed Central

    Ong, Mei-Lyn; Tan, Peck Yean; MacIsaac, Julia L; Mah, Sarah M; Buschdorf, Jan Paul; Cheong, Clara Y; Stunkel, Walter; Chan, Louiza; Gluckman, Peter D.; Chng, Keefe; Kobor, Michael S.; Meaney, Michael J; Holbrook, Joanna D

    2014-01-01

    The Infinium Human Methylation450 BeadChip Array (Infinium 450K) is a robust and cost-efficient survey of genome-wide DNA methylation patterns. Macaca fascicularis (Cynomolgus macaque) is an important disease model; however, its genome sequence is only recently published, and few tools exist to interrogate the molecular state of Cynomolgus macaque tissues. Although the Infinium 450K is a hybridization array designed to the human genome, the relative conservation between the macaque and human genomes makes its use in macaques feasible. Here, we used the Infinium 450K array to assay DNA methylation in 11 macaque muscle biopsies. We showed that probe hybridization efficiency was related to the degree of sequence identity between the human probes and the macaque genome sequence. Approximately 61% of the Human Infinium 450K probes could be reliably mapped to the Cynomolgus macaque genome and contain a CpG site of interest. We also compared the Infinium 450K data to reduced representation bisulfite sequencing data generated on the same samples and found a high level of concordance between the two independent methodologies, which can be further improved by filtering for probe sequence identity and mismatch location. We conclude that the Infinium 450K array can be used to measure the DNA methylome of Cynomolgus macaque tissues using the provided filters. We also provide a pipeline for validation of the array in other species using a simple BLAST-based sequence identify filter. PMID:24815017

  14. Macacine Herpesvirus 1 in Long-Tailed Macaques, Malaysia, 2009–2011

    PubMed Central

    Lee, Mei-Ho; Rostal, Melinda K.; Hughes, Tom; Sitam, Frankie; Lee, Chee-Yen; Japning, Jeffrine; Harden, Mallory E.; Griffiths, Anthony; Basir, Misliah; Wolfe, Nathan D.; Daszak, Peter

    2015-01-01

    Macacine herpesvirus 1 (MaHV1; B virus) naturally infects macaques (Macaca spp.) and can cause fatal encephalitis in humans. In Peninsular Malaysia, wild macaques are abundant, and translocation is used to mitigate human–macaque conflict. Most adult macaques are infected with MaHV1, although the risk for transmission to persons who handle them during capture and translocation is unknown. We investigated MaHV1 shedding among 392 long-tailed macaques (M. fascicularis) after capture and translocation by the Department of Wildlife and National Parks in Peninsular Malaysia, during 2009–2011. For detection of MaHV1 DNA, PCR was performed on urogenital and oropharyngeal swab samples. Overall, 39% of macaques were shedding MaHV1 DNA; rates of DNA detection did not differ between sample types. This study demonstrates that MaHV1 was shed by a substantial proportion of macaques after capture and transport and suggests that persons handling macaques under these circumstances might be at risk for exposure to MaHV1. PMID:26080081

  15. Macacine Herpesvirus 1 in Long-Tailed Macaques, Malaysia, 2009-2011.

    PubMed

    Lee, Mei-Ho; Rostal, Melinda K; Hughes, Tom; Sitam, Frankie; Lee, Chee-Yen; Japning, Jeffrine; Harden, Mallory E; Griffiths, Anthony; Basir, Misliah; Wolfe, Nathan D; Epstein, Jonathan H; Daszak, Peter

    2015-07-01

    Macacine herpesvirus 1 (MaHV1; B virus) naturally infects macaques (Macaca spp.) and can cause fatal encephalitis in humans. In Peninsular Malaysia, wild macaques are abundant, and translocation is used to mitigate human-macaque conflict. Most adult macaques are infected with MaHV1, although the risk for transmission to persons who handle them during capture and translocation is unknown. We investigated MaHV1 shedding among 392 long-tailed macaques (M. fascicularis) after capture and translocation by the Department of Wildlife and National Parks in Peninsular Malaysia, during 2009-2011. For detection of MaHV1 DNA, PCR was performed on urogenital and oropharyngeal swab samples. Overall, 39% of macaques were shedding MaHV1 DNA; rates of DNA detection did not differ between sample types. This study demonstrates that MaHV1 was shed by a substantial proportion of macaques after capture and transport and suggests that persons handling macaques under these circumstances might be at risk for exposure to MaHV1. PMID:26080081

  16. DNA Priming for Seasonal Influenza Vaccine: A Phase 1b Double-Blind Randomized Clinical Trial

    PubMed Central

    Ledgerwood, Julie E.; Bellamy, Abbie R.; Belshe, Robert; Bernstein, David I.; Edupuganti, Srilatha; Patel, Shital M.; Renehan, Phyllis; Zajdowicz, Thad; Schwartz, Richard; Koup, Richard; Bailer, Robert T.; Yamshchikov, Galina V.; Enama, Mary E.; Sarwar, Uzma; Larkin, Brenda; Graham, Barney S.

    2015-01-01

    Background The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost. Methods Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective. Results The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study. Conclusion While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative. Trial Registration ClinicalTrials.gov NCT01498718 PMID:25950433

  17. Molecular Identification of Oesophagostomum and Trichuris Eggs Isolated from Wild Japanese Macaques

    PubMed Central

    Yamada, Minoru; Tegoshi, Tatsuya; Onishi, Kotaro

    2012-01-01

    Natural habitat fragmentation and reducing habitat quality have resulted in an increased appearance of Japanese macaques, Macaca fuscata (Gray, 1870), in suburban areas in Japan. To investigate the risk of zoonotic infections, a coprological survey of helminth eggs passed by wild Japanese macaques was carried out in 2009 and 2010 in Shiga Prefecture, Japan. Microscopic examination found helminth eggs in high prevalence, and nucleotide sequencing of DNA extracted from the eggs identified Oesophagostomum cf. aculeatum and Trichuris trichiura. A fecal culture also detected infective larvae of Strongyloides fuelleborni. These zoonotic nematodes pose a potential health issue to local people in areas frequented by Japanese macaques. PMID:22949756

  18. Molecular identification of Oesophagostomum and Trichuris eggs isolated from wild Japanese macaques.

    PubMed

    Arizono, Naoki; Yamada, Minoru; Tegoshi, Tatsuya; Onishi, Kotaro

    2012-09-01

    Natural habitat fragmentation and reducing habitat quality have resulted in an increased appearance of Japanese macaques, Macaca fuscata (Gray, 1870), in suburban areas in Japan. To investigate the risk of zoonotic infections, a coprological survey of helminth eggs passed by wild Japanese macaques was carried out in 2009 and 2010 in Shiga Prefecture, Japan. Microscopic examination found helminth eggs in high prevalence, and nucleotide sequencing of DNA extracted from the eggs identified Oesophagostomum cf. aculeatum and Trichuris trichiura. A fecal culture also detected infective larvae of Strongyloides fuelleborni. These zoonotic nematodes pose a potential health issue to local people in areas frequented by Japanese macaques. PMID:22949756

  19. PCR detection and DNA sequence analysis of the regulatory region of lymphotropic papovavirus in peripheral blood mononuclear cells of an immunocompromised rhesus macaque

    NASA Technical Reports Server (NTRS)

    Lednicky, John A.; Halvorson, Steven J.; Butel, Janet S.

    2002-01-01

    A lymphotropic papovavirus (LPV) archetypal regulatory region was amplified from DNA from the blood of an immunocompromised rhesus monkey. We believe this is the first nonserological evidence of LPV infection in rhesus monkeys.

  20. Rapid high resolution MHC class I genotyping of Chinese rhesus macaques by capillary reference strand mediated conformational analysis

    PubMed Central

    Blasky, Alex J.; Karl, Julie A.; Wiseman, Roger W.; Read, Daniel S.; O’Connor, David H.

    2008-01-01

    Rhesus macaques (Macaca mulatta) provide well-established models for studying human disease pathogenesis and vaccine development. When challenged with infectious agents macaques exhibit individual differences in susceptibility. An important determinant of these differences is the complement of major histocompatability complex (MHC) class I sequences expressed by each animal. Although previous studies have reported strong associations between MHC expression and disease outcome, a rapid, cost effective method for high resolution MHC genotyping in macaques is lacking. Here, we adapted a modified heteroduplex assay, reference strand mediated conformational analysis (RSCA), to an ABI 3130xl capillary electrophoresis genetic analyzer for macaque MHC class I genotyping. For validation, we investigated the concordance of RSCA genotyping for fourteen MHC class I sequences in twelve Chinese rhesus macaques whose genotypes were established through cDNA cloning and sequencing of MHC class I sequences. We observed a concordance greater than 98% between RSCA and the cloning and sequencing data. Further, RSCA confirmed the presence of MHC haplotype sharing between three macaques as predicted previously by microsatellite analysis. RSCA genotyping of an additional 25 Chinese rhesus macaques demonstrated that the frequency of these fourteen MHC class I sequences ranged from 5 to 32%, with the Mamu-A1*2601 sequence being most common in this cohort. Capillary RSCA genotyping has the potential to enable researchers to rapidly evaluate MHC class I genotypes in rhesus macaques and associate specific MHC sequences with disease susceptibility. PMID:18629489

  1. DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques.

    PubMed

    Obeng-Adjei, N; Hutnick, N A; Yan, J; Chu, J S; Myles, D J F; Morrow, M P; Sardesai, N Y; Weiner, D B

    2013-12-01

    There are well over a quarter of a billion chronic hepatitis B virus (HBV) carriers across the globe. Most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is therefore imperative to develop new approaches for immunotherapy against this infection. Antibodies and cytotoxic T cells to different HBV antigens are believed to be important for reducing viral load and clearing HBV-infected cells from the liver. Some of the major challenges facing current vaccine candidates have been their inability to induce both humoral and cellular immunity to multiple antigenic targets and the induction of potent immune responses against the major genotypes of HBV. In this study, highly optimized synthetic DNA plasmids against the HBV consensus core (HBc) and surface (HBs) antigens genotypes A and C were developed and evaluated for their immune potential. These plasmids, which encode the most prevalent genotypes of the virus, were observed to individually induce binding antibodies to HBs antigens and drove robust cell-mediated immunity in animal models. Similar responses to both HBc and HBs antigens were observed when mice and non-human primates were inoculated with the HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited by the immunized mice, the vaccine-induced responses were broadly distributed across multiple antigenic epitopes. These elements are believed to be important to develop an effective therapeutic vaccine. These data support further evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines. PMID:24310062

  2. Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost

    PubMed Central

    Hulot, Sandrine L.; Korber, Bette; Giorgi, Elena E.; Vandergrift, Nathan; Saunders, Kevin O.; Balachandran, Harikrishnan; Mach, Linh V.; Lifton, Michelle A.; Pantaleo, Giuseppe; Tartaglia, Jim; Phogat, Sanjay; Jacobs, Bertram; Kibler, Karen; Perdiguero, Beatriz; Gomez, Carmen E.; Esteban, Mariano; Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.; Parks, Robert; Lloyd, Krissey; Sutherland, Laura; Scearce, Richard; Letvin, Norman L.; Seaman, Michael S.; Alam, S. Munir; Montefiori, David; Liao, Hua-Xin; Haynes, Barton F.

    2015-01-01

    ABSTRACT An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4+ and CD8+ T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using in silico-designed centralized immunogens for global HIV-1 vaccine development strategies. IMPORTANCE There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1

  3. Chagas disease in 2 geriatric rhesus macaques (Macaca mulatta) housed in the Pacific Northwest.

    PubMed

    Dickerson, Mary F; Astorga, Nestor Gerardo; Astorga, Nestor Rodrigo; Lewis, Anne D

    2014-08-01

    Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission. PMID:25296019

  4. Chagas Disease in 2 Geriatric Rhesus Macaques (Macaca mulatta) Housed in the Pacific Northwest

    PubMed Central

    Dickerson, Mary F; Astorga, Nestor Gerardo; Astorga, Nestor Rodrigo; Lewis, Anne D

    2014-01-01

    Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission. PMID:25296019

  5. An update of the macaque testis proteome

    PubMed Central

    Zhou, Tao; Guo, Yueshuai; Zhou, Zuomin; Guo, Xuejiang; Sha, Jiahao

    2015-01-01

    The genome sequence of rhesus macaque is a draft version with many errors and is lack of Y chromosome annotation. In the present dataset, we reanalyzed the previously published macaque testis proteome. We searched for refined protein sequences, potential Y chromosome proteins and transcripts predicted proteins in addition to the latest Ensembl protein sequences of macaque. A total of 74,433 peptides corresponding to 9247 protein groups were identified, and the data are supplied in this paper. The updated version of macaque testis proteome provided evidences for predicted genes or transcripts at the peptide level. It can be used for further in-depth proteogenomic annotation of macaque genome and is useful for studying the mechanisms of macaque spermatogenesis. PMID:26484360

  6. DC-expressed MHC class I single-chain trimer-based vaccines prime cytotoxic T lymphocytes against exogenous but not endogenous antigens.

    PubMed

    Ordaz, Maria L; Larmonier, Nicolas; Lybarger, Lonnie

    2010-01-01

    The poor immunogenicity of many tumors can be partly explained by the inefficiency of the MHC class I peptide presentation pathway. MHC-I-based single-chain trimers (SCT) represent a new class of molecules with the potential to overcome this limitation. We here evaluated the ability of SCT presenting a melanoma antigen peptide (TRP-2) to prime cytotoxic T lymphocyte (CTL) responses in mice when given as DNA vaccines via Gene Gun or when expressed by dendritic cells. The SCT was unable to induce detectable priming or significant anti-tumor activity of CTL using either vaccination strategy, whereas control SCT (with an exogenous peptide) primed strong responses. This study thus provides the first data related to the use of SCT in combination with DC and their application toward self antigens and suggest this potent technology, alone, is insufficient to overcome self tolerance. PMID:20199770

  7. Beyond specific pathogen-free: biology and effect of common viruses in macaques.

    PubMed

    Lerche, Nicholas W; Simmons, Joe H

    2008-02-01

    Macaque models have contributed to key advances in our basic knowledge of behavior, anatomy, and physiology as well as to our understanding of a wide variety of human diseases. This issue of Comparative Medicine focuses on several of the viral agents (members of Retroviridae, Herpesviridae and 2 small DNA viruses) that can infect both nonhuman primates and humans as well as confound research studies. Featured articles also address the challenges of developing colonies of macaques and other nonhuman primates that are truly specific pathogen-free for these and other adventitious infectious agents. PMID:19793451

  8. Macaque-human interactions and the societal perceptions of macaques in Singapore.

    PubMed

    Sha, John Chih Mun; Gumert, Michael D; Lee, Benjamin P Y-H; Jones-Engel, Lisa; Chan, Sharon; Fuentes, Agustín

    2009-10-01

    Humans and long-tailed macaques (Macaca fascicularis) interface in several locations in Singapore. We investigated six of these interface zones to assess the level of conflict between the two species. We observed macaque-to-human interactions and distributed questionnaires to residents and visitors of nature reserves. We observed an average of two macaque-to-human interactions per hour at the sites, which included affiliative or submissive behaviors (46.9%), aggression (19.1%), taking food and other items (18.5%) searching bins, cars, and houses (13.4%), and nonaggressive contact (2.1%). Two-thirds of interactions occurred when a human was carrying food or food cues, and one-quarter occurred when a human provoked macaques. Only 8% of interactions occurred without a clear human-triggered context. Our interview showed one-third of respondents experienced nuisance problems from macaques. They had items taken from them (50.5%) and received threats (31.9%). Residents reported more nuisance problems than visitors, and their perceptions toward macaques differed. Residents were more aware of the consequences of food provisioning and that there were regulations against feeding. Residents fed macaques less and held more negative sentiments toward macaques. Nearly half of the interviewed people held neutral attitudes toward macaques and only 26.2% of respondents thought conflict with macaques warranted urgent action. Nearly two-thirds of the respondents supported education programs to ameliorate human-macaque conflict, and less than 15% supported removing or eradicating macaques. 87.6% felt that it is importance to conserve and protect macaques. Our results show that human-macaque conflict exists in Singapore, but that it may not be severe. Human behavior is largely responsible for macaque-to-human interactions, and thus could be lessened with management of human behavior in interface zones (i.e. restrict food carrying and provocation). Moreover, our interviews shows people

  9. The Mammary Glands of Macaques

    PubMed Central

    Cline, J. Mark; Wood, Charles E.

    2009-01-01

    This review describes the normal biology and physiology of the mammary gland in macaques, including the typical histologic appearance across the life span (development, reproductive maturity, lactation, and senescence). The molecular events regulating breast morphogenesis are described, as well as systemic and local hormonal regulators of mammary gland proliferation, differentiation, and function. Similarities and differences to the human breast are described. Regulatory events are illuminated by discussion of genetically modified mouse models. Tissue response markers, including immunohistochemical markers of proliferation and other hormonally induced changes and studies to date, regarding the effects of exogenous hormones, are briefly summarized. In general, estrogens stimulate progesterone receptor expression and proliferation in the mammary gland, and combinations of estrogens and progestogens cause greater proliferation than estrogens alone. Evaluation of novel chemical agents in macaques requires careful evaluation of age and hormonal context to avoid the confounding effects of mammary gland development, past reproductive history, and other influences on mammary gland morphology. The expression of proliferation markers and progesterone receptors may be used as biomarkers to measure chemically induced hormonal effects. PMID:21475638

  10. Construction of Soluble Mamu-B*1703, a Class I Major Histocompatibility Complex of Chinese Rhesus Macaques, Monomer and Tetramer Loaded with a Simian Immunodeficiency Virus Peptide

    PubMed Central

    Ouyang, Dongyun; Wang, Xiaoying; He, Xianhui; Xu, Lihui; Shi, Huanjing; Gao, Qi; Guo, He

    2009-01-01

    Chinese-descent rhesus macaques have become more prevalent for HIV infection and vaccine investigation than Indian-origin macaques. Most of the currently available data and reagents such as major histocompatibility complex (MHC) class I tetramers, however, were derived from Indian-origin macaques due to the dominant use of these animals in history. Although there are significant differences in the immunogenetic background between the two macaque populations, they share a few of common MHC class I alleles. We reported in this study the procedure for preparation of a soluble Mamu-B*1703 (a MHC class I molecule of Chinese macaques) monomer and tetramer loaded with a dominant simian immunodeficiency virus (SIV) epitope IW9 (IRYPKTFGW) that was identified to be Mamu-B*1701-restricted in Indian macaques. The DNA fragment encoding the Mamu-B*1703 extracellular domain fused with a BirA substrate peptide (BSP) was amplified from a previously cloned cDNA and inserted into a prokaratic expression vector. In the presence of the antigenic peptide IW9 and light chain β2-microglobulin, the expressed heavy chain was refolded into a soluble monomer. After biotinylation, four monomers were polymerized as a tetramer by phycoerythrin-conjugated streptavidin. The tetramer, having been confirmed to have the right conformation, was a potential tool for investigation of antigen-specific CD8+ T-lymphocytes in SIV vaccine models of Chinese macaques. And our results also suggested that some antigenic peptides reported in Indian-origin macaques could be directly recruited as ligands for construction of Chinese macaque MHC tetramers. PMID:19403061

  11. Tonkean macaques communicate with their right hand.

    PubMed

    Meunier, Hélène; Fizet, Jonas; Vauclair, Jacques

    2013-08-01

    There are two conflicting hypotheses to explain the origins of language. Vocal origin theory states that language results from the gradual evolution of animals' vocal communication, but gestural origin theory considers that language evolved from gestures, with the initial left-hemispheric control of manual gestures gradually encompassing vocalizations. To contribute to this debate, we investigated functional hemispheric specialization related to hand biases when grasping or showing an object through manual gesture in Tonkean macaques. The results of this study, the first quantitative study on Tonkean macaques' handedness, showed a remarkable convergence of the Tonkean macaques' handedness patterns with those of baboons and human infants, with hand preferences for manual communicative gestures significantly favoring the use of the right hand. Our findings support the hypothesis that left hemispheric lateralization for language is derived from a gestural communication system that was present in the common ancestor of macaques, baboons and humans. PMID:23748098

  12. Japanese Macaques (Macaca fuscata) as Natural Reservoir of Bartonella quintana.

    PubMed

    Sato, Shingo; Kabeya, Hidenori; Yoshino, Aika; Sekine, Wataru; Suzuki, Kazuo; Tamate, Hidetoshi B; Yamazaki, Shouki; Chomel, Bruno B; Maruyama, Soichi

    2015-12-01

    Bartonella quintana bacteremia was detected in 6 (13.3%) of 45 wild-caught Japanese macaques (Macaca fuscata). Multilocus sequence typing of the isolates revealed that Japanese macaques were infected with a new and specific B. quintana sequence type. Free-ranging Japanese macaques thus represent another natural reservoir of B. quintana. PMID:26584238

  13. Septic Arthritis Due to Moraxella osloensis in a Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Wren, Melissa A; Caskey, John R; Liu, David X; Embers, Monica E

    2013-01-01

    A 5.5-y-old Chinese-origin female rhesus macaque (Macaca mulatta) presented for bilateral hindlimb lameness. The primate had been group-reared in an SPF breeding colony and was seronegative for Macacine herpesvirus 1, SIV, simian retrovirus type D, and simian T-lymphotropic virus. The macaque's previous medical history included multiple occasions of swelling in the left tarsus, and trauma to the right arm and bilateral hands. In addition, the macaque had experienced osteomyelitis of the left distal tibia and rupture of the right cranial cruciate ligament that had been surgically repaired. Abnormal physical examination findings on presentation included a thin body condition, mild dehydration, and bilaterally swollen stifles that were warm to the touch, with the right stifle more severely affected. Mild instability in the left stifle was noted, and decreased range of motion and muscle atrophy were present bilaterally. Hematologic findings included marked neutrophilia and lymphopenia and moderate anemia. Arthrocentesis and culture of joint fluid revealed Moraxella-like organisms. Treatment with enrofloxacin was initiated empirically and subsequently switched to cephalexin, which over time alleviated the joint swelling and inflammation. Definitive diagnosis of Moraxella osloensis septic arthritis was made through isolation of the organism and sequencing of the 16S rDNA region. To our knowledge, this report is the first description of Moraxella osloensis septic arthritis in a rhesus macaque. PMID:24326229

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

    PubMed Central

    Hunter, Zoe; Jayashankar, Kartika; Peabody, Julianne; Montefiori, David; LaBranche, Celia C.; Keele, Brandon F.; Jensen, Kara; Abel, Kristina

    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 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 (106.8 versus 108.3 copies/ml plasma). Three of the 12 vaccinated macaques dramatically suppressed simian immunodeficiency virus (SIV) replication: peak viral loads were low (103 to 104 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. PMID:24307581

  15. Macaque monkeys experience visual crowding

    PubMed Central

    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. PMID:26067532

  16. Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells

    PubMed Central

    Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

    2015-01-01

    Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs. PMID:25996084

  17. Natural Norovirus Infections in Rhesus Macaques

    PubMed Central

    2016-01-01

    Using a recently developed real-time reverse transcription PCR, I retested 500 fecal samples from rhesus macaques collected in 2008. Previous conventional reverse transcription PCR testing identified 1 isolate of GII norovirus; retesting found GI, GII, and possible GIV noroviruses in the samples, indicating the natural circulation of noroviruses in nonhuman primate colonies. PMID:27314565

  18. Extraintestinal Campylobacteriosis in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Clemmons, Elizabeth A; Jean, Sherrie M; Machiah, Deepa K; Breding, Eileen; Sharma, Prachi

    2014-01-01

    Two cases of clinical disease associated with extraintestinal Campylobacter infection were recently encountered in rhesus macaques (Macaca mulatta). The first case was that of a 3-y-old, male, rhesus macaque experimentally infected with SIV, who presented with abdominal pain and a midabdominal mass and was euthanized. Pathology findings included an abscess within the median liver lobe, fibrinopurulent peritonitis, and intestinal serositis with isolation of Campylobacter fetus from the blood, liver, and the hepatic abscess. The second case was that of a 1-mo-old, female, rhesus macaque who died with no apparent history of illness. Gross pathology findings included thin body condition and diarrheic staining of the perineum; histologically, acute multifocal hepatitis with intralesional bacteria was noted. Campylobacter coli was isolated from the liver and colon. Extraintestinal Campylobacter infection is uncommon in humans, usually occurring in immunocompromised subjects and most commonly manifesting as bacteremia. Extraintestinal Campylobacter infections in animals are rare but have been associated with bacteremia and cholecystitis. The macaques presented here were either immunocompromised due to SIV infection (case 1) or more vulnerable due to young age (case 2). These factors likely contributed to the extraintestinal spread of Campylobacter. PMID:25527031

  19. Natural Norovirus Infections in Rhesus Macaques.

    PubMed

    Farkas, Tibor

    2016-07-01

    Using a recently developed real-time reverse transcription PCR, I retested 500 fecal samples from rhesus macaques collected in 2008. Previous conventional reverse transcription PCR testing identified 1 isolate of GII norovirus; retesting found GI, GII, and possible GIV noroviruses in the samples, indicating the natural circulation of noroviruses in nonhuman primate colonies. PMID:27314565

  20. Parentage analysis within a semi-free-ranging group of Barbary macaques Macaca sylvanus.

    PubMed

    von Segesser, F; Scheffrahn, W; Martin, R D

    1995-02-01

    This study of a group of semi-free-ranging Barbary macaques Macaca sylvanus aimed to determine paternity, to establish whether any individual male achieved prominent mating success and to assess genetic variability. Analyses involved electrophoresis of 15 blood protein systems and multilocus DNA fingerprinting (isotopic and nonisotopic). Genetic variability was low; only two blood protein systems were polymorphic. Although all DNA-fingerprints were individual-specific, they showed a high average band-sharing index value (0.67). Nevertheless, a combination of all methods permitted inference of paternity in 11 out of 15 (73%) cases tested. Several males from different age classes fathered infants. PMID:7711950

  1. DNA.

    ERIC Educational Resources Information Center

    Felsenfeld, Gary

    1985-01-01

    Structural form, bonding scheme, and chromatin structure of and gene-modification experiments with deoxyribonucleic acid (DNA) are described. Indicates that DNA's double helix is variable and also flexible as it interacts with regulatory and other molecules to transfer hereditary messages. (DH)

  2. Identifying rhesus macaque gene orthologs using heterospecific human CNV probes

    PubMed Central

    Ng, Jillian; Fass, Joseph N.; Durbin-Johnson, Blythe; Smith, David Glenn; Kanthaswamy, Sree

    2015-01-01

    We used the Affymetrix® Genome-Wide Human SNP Array 6.0 to identify heterospecific markers and compare copy number and structural genomic variation between humans and rhesus macaques. Over 200,000 human copy number variation (CNV) probes were mapped to a Chinese and an Indian rhesus macaque sample. Observed genomic rearrangements and synteny were in agreement with the results of a previously published genomic comparison between humans and rhesus macaques. Comparisons between each of the two rhesus macaques and humans yielded 206 regions with copy numbers that differed by at least two fold in the Indian rhesus macaque and human, 32 in the Chinese rhesus macaque and human, and 147 in both rhesus macaques. The detailed genomic map and preliminary CNV data are useful for better understanding genetic variation in rhesus macaques, identifying derived changes in human CNVs that may have evolved by selection, and determining the suitability of rhesus macaques as human models for particular biomedical studies. PMID:26697375

  3. Identifying rhesus macaque gene orthologs using heterospecific human CNV probes.

    PubMed

    Ng, Jillian; Fass, Joseph N; Durbin-Johnson, Blythe; Smith, David Glenn; Kanthaswamy, Sree

    2015-12-01

    We used the Affymetrix(®) Genome-Wide Human SNP Array 6.0 to identify heterospecific markers and compare copy number and structural genomic variation between humans and rhesus macaques. Over 200,000 human copy number variation (CNV) probes were mapped to a Chinese and an Indian rhesus macaque sample. Observed genomic rearrangements and synteny were in agreement with the results of a previously published genomic comparison between humans and rhesus macaques. Comparisons between each of the two rhesus macaques and humans yielded 206 regions with copy numbers that differed by at least two fold in the Indian rhesus macaque and human, 32 in the Chinese rhesus macaque and human, and 147 in both rhesus macaques. The detailed genomic map and preliminary CNV data are useful for better understanding genetic variation in rhesus macaques, identifying derived changes in human CNVs that may have evolved by selection, and determining the suitability of rhesus macaques as human models for particular biomedical studies. PMID:26697375

  4. Serial Cognition and Personality in Macaques

    PubMed Central

    Altschul, Drew M.; Terrace, Herbert S.; Weiss, Alexander

    2016-01-01

    We examined the associations between serial cognition and personality in rhesus macaques (Macaca mulatta). Nine macaques were tested on a simultaneous chaining task to assess their cognitive abilities. They were also rated for personality traits and scored according to a previously extracted six component structure derived from free-ranging rhesus macaques. Friendliness and Openness were positively associated with good performance on three measures of accuracy on the serial learning task: Progress, Error, and Rewarded (i.e., correctly completed) Trials. Faster Reaction Times were associated with lower Friendliness and higher Confidence, as well as higher Openness when only correct responses were analyzed. We also used regularized exploratory factor analysis to extract two, three, four, five, and six factor structures, and found consistent associations between accuracy and single factors within each of these structures. Prior results on intelligence in other nonhuman primate species have focused on basic intelligence tests; this study demonstrates that more complex, abstract cognitive tasks can be used to assess intelligence and personality in nonhuman primates. PMID:27158661

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

    PubMed Central

    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

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

    PubMed

    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

  7. Alopecia in three macaque species housed in a laboratory environment

    PubMed Central

    Kroeker, R.; Bellanca, R. U.; Lee, G. H.; Thom, J. P.; Worlein, J. M.

    2014-01-01

    Alopecia is a persistent problem in captive macaque populations and despite recent interest, no factors have been identified that can unequivocally explain the presence of alopecia in a majority of cases. Seasonal, demographic and environmental factors have been identified as affecting alopecia presentation in rhesus macaques, the most widely studied macaque species. However, few studies have investigated alopecia rates in other macaque species. We report alopecia scores over a period of 12 months for three macaque species (Macaca nemestrina, M. mulatta, and M. fascicularis) housed at three indoor facilities within the Washington National Primate Research Center (WaNPRC) in Seattle. Clear species differences emerged with cynomolgus (M. fascicularis) showing the lowest alopecia rates and pigtails (M. nemestrina) the highest rates. Further analysis of pigtail and rhesus (M. mulatta) macaques revealed that sex effects were apparent for rhesus but not pigtails. Age and seasonal effects were evident for both species. In contrast to previous reports, we found that older animals (over 10 years of age) had improved alopecia scores in comparison to younger adults. This is the first report on alopecia rates in pigtail macaques and the first comparison of alopecia scores in pigtail, cynomolgus, and rhesus macaques housed under similar conditions. PMID:24243351

  8. Variation in CCL3L1 Copy Number in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Taormina, Patrick L; Trask, Jessica A Satkoski; Smith, David G; Kanthaswamy, Sreetharan

    2012-01-01

    We used real-time quantitative PCR (qPCR) methodology to examine copy number variation (CNV) of the CCL3L1 gene among pure Indian-origin, pure Chinese-origin, and hybrid Indian–Chinese rhesus macaques (Macaca mulatta). CNV among purebred macaques fell within expected ranges, with Indian macaques having lower copy numbers than those of Chinese macaques. Compared with the purebred macaques, Indian–Chinese hybrid rhesus macaques showed much greater variance in copy number and an intermediate average copy number. Copy numbers of CCL3L1 in rhesus macaque trios (sire, dam, and offspring) were consistent with Mendelian inheritance. PMID:22776055

  9. Variation in CCL3L1 copy number in rhesus macaques (Macaca mulatta).

    PubMed

    Taormina, Patrick L; Satkoski Trask, Jessica A; Smith, David G; Kanthaswamy, Sreetharan

    2012-06-01

    We used real-time quantitative PCR (qPCR) methodology to examine copy number variation (CNV) of the CCL3L1 gene among pure Indian-origin, pure Chinese-origin, and hybrid Indian-Chinese rhesus macaques (Macaca mulatta). CNV among purebred macaques fell within expected ranges, with Indian macaques having lower copy numbers than those of Chinese macaques. Compared with the purebred macaques, Indian-Chinese hybrid rhesus macaques showed much greater variance in copy number and an intermediate average copy number. Copy numbers of CCL3L1 in rhesus macaque trios (sire, dam, and offspring) were consistent with Mendelian inheritance. PMID:22776055

  10. Comparing face patch systems in macaques and humans

    PubMed Central

    Tsao, Doris Y.; Moeller, Sebastian; Freiwald, Winrich A.

    2008-01-01

    Face recognition is of central importance for primate social behavior. In both humans and macaques, the visual analysis of faces is supported by a set of specialized face areas. The precise organization of these areas and the correspondence between individual macaque and human face-selective areas are debated. Here, we examined the organization of face-selective regions across the temporal lobe in a large number of macaque and human subjects. Macaques showed 6 regions of face-selective cortex arranged in a stereotypical pattern along the temporal lobe. Human subjects showed, in addition to 3 reported face areas (the occipital, fusiform, and superior temporal sulcus face areas), a face-selective area located anterior to the fusiform face area, in the anterior collateral sulcus. These results suggest a closer anatomical correspondence between macaque and human face-processing systems than previously realized. PMID:19033466

  11. Stone handling behavior in rhesus macaques (Macaca mulatta), a behavioral propensity for solitary object play shared with Japanese macaques.

    PubMed

    Nahallage, Charmalie A D; Huffman, Michael A

    2012-01-01

    Stone handling (SH) behavior was systematically studied in a captive troop of rhesus macaques housed at the Primate Research Institute of Kyoto University, and compared with the results of long-term studies of this behavior in Japanese macaques, to evaluate the similarities of SH behavior in these two closely related species. Similar to Japanese macaques, rhesus macaques showed age-related differences in SH. Young animals were more active and displayed more SH patterns and bouts than did adults. Furthermore, the young displayed SH at a higher frequency and their bouts were of a shorter duration, compared to adults. Young adults were more active and displayed more patterns than did older adults. On the other hand, older adults were more conservative and displayed fewer patterns, and engaged in them for longer durations. All individuals displayed SH more frequently in relaxed environmental and social conditions. While lacking an apparent immediate adaptive value, practice of the behavior has been proposed to have long-term functional value for neural and cognitive development in the young and for the maintenance or repair of neuro-pathways in aging macaques that habitually perform the behavior. The results presented here are consistent with what we know about Japanese macaque SH. Given the uniformity of SH behavioral parameters and these two macaque species' close phylogenetic relatedness, we propose that a similar functional and adaptive value for SH can be inferred for rhesus macaques. PMID:22037669

  12. 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.

    PubMed

    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. PMID:25185576

  13. 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

    PubMed Central

    Beernink, Peter T.; Shaughnessy, Jutamas; Stefek, Heather; Ram, Sanjay

    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. 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. PMID:25185576

  14. DNA

    ERIC Educational Resources Information Center

    Stent, Gunther S.

    1970-01-01

    This history for molecular genetics and its explanation of DNA begins with an analysis of the Golden Jubilee essay papers, 1955. The paper ends stating that the higher nervous system is the one major frontier of biological inquiry which still offers some romance of research. (Author/VW)

  15. White-cheeked macaque (Macaca leucogenys): A new macaque species from Medog, southeastern Tibet.

    PubMed

    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. PMID:25809642

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

    SciTech Connect

    Na, Lei; Tang, Yan-Dong; Liu, Jian-Dong; Yu, Chang-Qing; Sun, Liu-Ke; Lin, Yue-Zhi; Wang, Xue-Feng; Wang, Xiaojun; Zhou, Jian-Hua

    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.

  17. Efficient Cooperative Restraint Training With Rhesus Macaques

    PubMed Central

    Bliss-Moreau, Eliza; Theil, Jacob H.; Moadab, Gilda

    2013-01-01

    It is sometimes necessary for nonhuman primates to be restrained during biomedical and psychosocial research. Such restraint is often accomplished using a “primate chair.” The present paper details a method for training adult rhesus macaques to cooperate with a chair restraint procedure using positive and negative reinforcement. Successful training was accomplished rapidly in approximately 14 training days. The success of this training technique suggests that this method represents a refinement to traditional techniques despite the behavioral heterogeneity in the animal sample (which includes animals previously deemed unfit for traditional pole-and-collar training). PMID:23544752

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

    PubMed

    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. PMID:27538863

  19. Osteochondromatosis in a Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Matthews, Kristin A; Strait, Karen; Connor-Stroud, Fawn; Courtney, Cynthia L

    2012-01-01

    A 5-y-old, male, rhesus macaque (Macaca mulatta) presented with a prominent mass slightly anteriomedial to the right stifle. On exam, multiple radiopaque masses were identified protruding from the mid- and distal femur. Lateral and anteroposterior radiographs of the right stifle region revealed multiple exophytic masses arising from the femur, with mild bony reaction of the proximal tibia. Histologic examination of biopsy tissue revealed woven and lamellar bone with granulation tissue and skeletal muscle. Because the macaque was exhibiting no lameness or signs of pain, we decided to monitor the progression of the masses. Minimal change was noted during the time prior to study termination at 6.5 y of age. Necropsy revealed that the bony masses were cartilage-capped lesions arising near the growth plate of the distal femur and midshaft of the femur and tibia. Histologic examination revealed chondro-osseous exophytic growths that blended imperceptibly with the cortex and spongiosa of the femur, consistent with a final diagnosis of multiple osteochondromas. PMID:22546923

  20. The function of Barbary macaque copulation calls.

    PubMed Central

    Semple, S

    1998-01-01

    In a wide variety of animal species, females produce vocalizations specific to mating contexts. It has been proposed that these copulation calls function to incite males to compete for access to the calling female. Two separate advantages of inciting male-male competition in this way have been put forward. The first suggests that as a result of calling, females are only mated by the highest ranking male in the vicinity (indirect mate choice hypothesis). The second proposes that copulation calling results in a female being mated by many males, thus promoting competition at the level of sperm (sperm competition hypothesis). In this paper, I give results from the first experimental study to test these hypotheses. Playback was used to examine the function of copulation calls of female Barbary macaques (Macaca sylvanus) in Gibraltar. Although rank did not affect lone males' likelihood of approaching copulation calls, when playbacks were given to pairs of males only the higher ranking individual approached. Moreover, females were mated significantly sooner after playback of their copulation call than after playback of a control stimulus. These results suggest that the copulation calls of female Barbary macaques play a key role in affecting patterns of male reproductive behaviour, not only providing an indirect mechanism of female choice, but also promoting sperm competition by reducing the interval between copulations. Potential fitness benefits of inciting male-male competition at these two levels are discussed. PMID:9523431

  1. High prevalence of infection with Entamoeba dispar, but not E. histolytica, in captive macaques.

    PubMed

    Tachibana, H; Cheng, X J; Kobayashi, S; Matsubayashi, N; Gotoh, S; Matsubayashi, K

    2001-01-01

    A total of 268 nonhuman primates (20 species) kept in the Primate Research Institute, Kyoto University, Japan, were surveyed for intestinal amebas. Total positive rates as based on the presence of cysts in the stool following formalin-ether sedimentation were as follows: Entamoeba histolytica/E. dispar, 53%; E. coli, 34%; E. hartmanni, 34%; Iodamoeba buetschlii, 25%; Endolimax nana, 8%; and E. chattoni, 3%. Positive rates were higher in Old World monkeys and lower in New World monkeys. All the 141 E. histolytica/E. dispar-positive animals were Macaca monkeys. The E. histolytica/E. dispar-positive samples were analyzed by polymerase chain reaction (PCR) for identification of E. histolytica and E. dispar. E. dispar DNA was detected in 137 samples, whereas no E. histolytica DNA was seen. Zymodeme analysis and reactivity to monoclonal antibodies of cultured trophozoites also supported the presence of E. dispar and the absence of E. histolytica. When the sera of 93 macaques were examined by an indirect fluorescent antibody test, only 3 animals proved to be positive for E. histolytica, showing the lowest titer. These results demonstrate that infection with E. dispar, but not E. histolytica, is predominant in macaques. PMID:11199843

  2. Working with rather than against macaques during blood collection.

    PubMed

    Reinhardt, Viktor

    2003-01-01

    Training macaques to cooperate during blood collection is a practicable and safe alternative to the traditional procedure implying forced restraint. It takes a cumulative total of about 1 hr to train an adult female or adult male rhesus macaque successfully to present a leg voluntarily and accept venipuncture in the homecage. Cooperative animals do not show the significant cortisol response and defensive reactions that typically occur in animals who are forcibly restrained during this common procedure. PMID:14612267

  3. Manual lateralization in macaques: handedness, target laterality and task complexity.

    PubMed

    Regaiolli, Barbara; Spiezio, Caterina; Vallortigara, Giorgio

    2016-01-01

    Non-human primates represent models to understand the evolution of handedness in humans. Despite several researches have been investigating non-human primates handedness, few studies examined the relationship between target position, hand preference and task complexity. This study aimed at investigating macaque handedness in relation to target laterality and tastiness, as well as task complexity. Seven pig-tailed macaques (Macaca nemestrina) were involved in three different "two alternative choice" tests: one low-level task and two high-level tasks (HLTs). During the first and the third tests macaques could select a preferred food and a non-preferred food, whereas by modifying the design of the second test, macaques were presented with no-difference alternative per trial. Furthermore, a simple-reaching test was administered to assess hand preference in a social context. Macaques showed hand preference at individual level both in simple and complex tasks, but not in the simple-reaching test. Moreover, target position seemed to affect hand preference in retrieving an object in the low-level task, but not in the HLT. Additionally, individual hand preference seemed to be affected from the tastiness of the item to be retrieved. The results suggest that both target laterality and individual motivation might influence hand preference of macaques, especially in simple tasks. PMID:26292019

  4. Keep children away from macaque monkeys!

    PubMed

    Bréhin, Camille; Debuisson, Cécile; Mansuy, Jean-Michel; Niphuis, Henk; Buitendijk, Hester; Mengelle, Catherine; Grouteau, Erick; Claudet, Isabelle

    2016-03-01

    To warn physicians and parents about the risk of macaque bites, we present two pediatric cases (a 4-year-old boy and a 10-year-old girl) of bites sustained while on holiday. The young boy developed febrile dermohypodermitis and was hospitalized for IV antibiotic treatment. He received an initial antirabies vaccine while still in the holiday destination. Except for local wound disinfection and antibiotic ointment, the girl did not receive any specific treatment while abroad. Both were negative for simian herpes PCR. When travelling in countries or cities with endemic simian herpes virus, parents should keep children away from monkeys. Travel agencies, pediatricians and family physicians should better inform families about the zoonotic risk. PMID:26984356

  5. Chronic, multisite, multielectrode recordings in macaque monkeys

    NASA Astrophysics Data System (ADS)

    Nicolelis, Miguel A. L.; Dimitrov, Dragan; Carmena, Jose M.; Crist, Roy; Lehew, Gary; Kralik, Jerald D.; Wise, Steven P.

    2003-09-01

    A paradigm is described for recording the activity of single cortical neurons from awake, behaving macaque monkeys. Its unique features include high-density microwire arrays and multichannel instrumentation. Three adult rhesus monkeys received microwire array implants, totaling 96-704 microwires per subject, in up to five cortical areas, sometimes bilaterally. Recordings 3-4 weeks after implantation yielded 421 single neurons with a mean peak-to-peak voltage of 115 ± 3 μV and a signal-to-noise ratio of better than 5:1. As many as 247 cortical neurons were recorded in one session, and at least 58 neurons were isolated from one subject 18 months after implantation. This method should benefit neurophysiological investigation of learning, perception, and sensorimotor integration in primates and the development of neuroprosthetic devices.

  6. A Putative Multiple-Demand System in the Macaque Brain

    PubMed Central

    Bell, Andrew H.; Buckley, Mark J.; Mitchell, Anna S.; Sallet, Jerome; Duncan, John

    2016-01-01

    In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this “multiple-demand” (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. SIGNIFICANCE STATEMENT In humans, a frontoparietal “multiple-demand” (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar

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

    PubMed

    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. PMID:24838181

  8. Genetic diversity and differentiation of the rhesus macaque (Macaca mulatta) population in western Sichuan, China, based on the second exon of the major histocompatibility complex class II DQB (MhcMamu-DQB1) alleles

    PubMed Central

    2014-01-01

    Abstracts Background Rhesus macaques living in western Sichuan, China, have been separated into several isolated populations due to habitat fragmentation. Previous studies based on the neutral or nearly neutral markers (mitochondrial DNA or microsatellites) showed high levels of genetic diversity and moderate genetic differentiation in the Sichuan rhesus macaques. Variation at the major histocompatibility complex (MHC) loci is widely accepted as being maintained by balancing selection, even with a low level of neutral variability in some species. However, in small and isolated or bottlenecked populations, balancing selection may be overwhelmed by genetic drift. To estimate microevolutionary forces acting on the isolated rhesus macaque populations, we examined genetic variation at Mhc-DQB1 loci in 119 wild rhesus macaques from five geographically isolated populations in western Sichuan, China, and compared the levels of MHC variation and differentiation among populations with that previously observed at neutral microsatellite markers. Results 23 Mamu-DQB1 alleles were identified in 119 rhesus macaques in western Sichuan, China. These macaques exhibited relatively high levels of genetic diversity at Mamu-DQB1. The Hanyuan population presented the highest genetic variation, whereas the Heishui population was the lowest. Analysis of molecular variance (AMOVA) and pairwise FST values showed moderate genetic differentiation occurring among the five populations at the Mhc-DQB1 locus. Non-synonymous substitutions occurred at a higher frequency than synonymous substitutions in the peptide binding region. Levels of MHC variation within rhesus macaque populations are concordant with microsatellite variation. On the phylogenetic tree for the rhesus and crab-eating macaques, extensive allele or allelic lineage sharing is observed betweenthe two species. Conclusions Phylogenetic analyses confirm the apparent trans-species model of evolution of the Mhc-DQB1 genes in these

  9. Therapy of calcium oxalate urolithiasis in a rhesus macaque (Macaca mulatta).

    PubMed

    Conze, Theresa; Wehrend, Axel; Exner, Cornelia; Kaminiarz, André

    2016-08-01

    A rhesus macaque (Macaca mulatta) was presented for anuria. Examination revealed calcium oxalate concrements in the bladder. A cystotomy was performed, and a therapy with alfuzosin was conducted. Over 1 year after the treatment, the rhesus macaque had not shown any more signs of stranguria. This is the first case reporting the successful treatment of urolithiasis in a rhesus macaque. PMID:27283130

  10. Risk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes

    ERIC Educational Resources Information Center

    Stevens, Hanna E.; Leckman, James F.; Coplan, Jeremy D.; Suomi, Stephen J.

    2009-01-01

    A literature review on macaque monkeys finds that peer rearing of young macaques and rearing of young macaques by mothers that are undergoing variable foraging conditions result in emotional and neurophysiological disturbance. Certain genotypes contribute to resilience to this disturbance. The findings have implications to child mental health and…

  11. Cercopithecine Herpesvirus 9 (Simian Varicella Virus) Infection after Total-Body Irradiation in a Rhesus Macaque (Macaca mulatta).

    PubMed

    Gulani, Jatinder; Koch, Amory; Chappell, Mark G; Christensen, Christine L; Facemire, Paul; Singh, Vijay K; Ossetrova, Natalia I; Srinivasan, Venkataraman; Holt, Rebecca K

    2016-01-01

    This case report describes a rhesus macaque (Macaca mulatta; male; age, 5 y; weight, 6.7 kg) with anorexia, dehydration, lethargy, ataxia, and generalized skin rashes that occurred 30 d after total-body irradiation at 6.5 Gy ((60)Co γ-rays). Physical examination revealed pale mucus membranes, a capillary refill time of 4 s, heart rate of 180 bpm. and respirations at 50 breaths per minute. Diffuse multifocal maculopapulovesicular rashes were present on the body, including mucocutaneous junctions. The CBC analysis revealed a Hct of 48%, RBC count of 6.2 × 10(6)/μL, platelet count of 44 × 10(3)/μL, and WBC count of 25 × 10(3)/μL of WBC. The macaque was euthanized in light of a grave prognosis. Gross examination revealed white foci on the liver, multifocal generalized petechiation on serosal and mucosal surfaces of the gastrointestinal tract, hemorrhagic lymph nodes, and hemorrhagic fluid in the thoracic cavity. Microscopic examination revealed cutaneous vesicular lesions with intranuclear eosinophilic viral inclusions within the epithelial cells, consistent with herpesvirus. Immunohistochemistry was positive for herpesvirus. The serum sample was negative for antibodies against Macacine herpesvirus 1 and Cercopithecine herpesvirus 9 (simian varicella virus, SVV). Samples submitted for PCR-based identification of the etiologic agent confirmed the presence of SVV DNA. PCR analysis, immunohistochemistry, and histology confirmed that lesions were attributed to an active SVV infection in this macaque. This case illustrates the importance of screening for SVV in rhesus macaques, especially those used in studies that involve immunosuppressive procedures. PMID:27053570

  12. Socioendocrine and morphological correlates of paternity in rhesus macaques (Macaca mulatta).

    PubMed

    Bercovitch, F B; Nürnberg, P

    1996-05-01

    When females mate with several males, problems arise in identifying sire and in determining factors contributing to differential male reproductive success. Three potential primary correlates of differential reproduction in males include fighting ability, sperm competition, and body condition. We collected a variety of socioendocrine and morphological measurements from sexually mature rhesus macaques to determine corollaries of paternity. We studied a troop of about 150 rhesus macaques living in a 0.3 ha corral and identified the sires of 70% of infants using multilocus DNA fingerprints. Eight of 21 males sired offspring, and dominant males were more successful than subordinate males. Neither canine size nor age influenced the probability of siring offspring. Male reproductive success was primarily an outcome of the number of females mated with, which was associated with an ensemble of traits including high dominance rank, large body size, relatively voluminous testicles and good body condition. Testes size was significantly larger in sires than in non-sires, but among sires the number of progeny produced was not correlated with testicle size. Sires began the mating season with more body fat than non-sires, but the energetic costs of mating resulted in a 50% reduction in abdominal skinfold thickness during the mating season. We conclude that social status exerts a major impact on paternity by affecting the number of females mated with, that male quality is a critical factor modulating paternity, and that male feeding strategies have a direct influence on variation in male reproductive success. PMID:8699435

  13. Oxidative stress as an indicator of the costs of reproduction among free-ranging rhesus macaques

    PubMed Central

    Georgiev, Alexander V.; Thompson, Melissa Emery; Mandalaywala, Tara M.; Maestripieri, Dario

    2015-01-01

    ABSTRACT Sex differences in longevity may reflect sex-specific costs of intra-sexual competition and reproductive effort. As male rhesus macaques experience greater intrasexual competition and die younger, we predicted that males would experience greater oxidative stress than females and that oxidative stress would reflect sex-specific measures of reproductive effort. Males, relative to females, had higher concentrations of 8-OHdG and malondialdehyde, which are markers of DNA oxidative damage and lipid peroxidation, respectively. Older macaques had lower 8-OHdG levels than younger ones, suggesting that oxidative stress decreases in parallel with known age-related declines in reproductive investment. Among males, a recent period of social instability affected oxidative status: males who attacked others at higher rates had higher 8-OHdG levels. Multiparous lactating females with daughters had higher 8-OHdG levels than those with sons. No differences in antioxidant capacity were found. These results lend initial support for the use of oxidative stress markers to assess trade-offs between reproductive effort and somatic maintenance in primates. PMID:25908058

  14. Examining the Species-Specificity of Rhesus Macaque Cytomegalovirus (RhCMV) in Cynomolgus Macaques

    PubMed Central

    Perciani, Catia T.; Russell, Justen N. Hoffman; Chan, Jacqueline K.; Janes, Michelle; Antony, Joseph M.; Pilon, Richard; Sandstrom, Paul; Willer, David O.; MacDonald, Kelly S.

    2015-01-01

    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. PMID:25822981

  15. A Combination DNA and Attenuated Simian Immunodeficiency Virus Vaccine Strategy Provides Enhanced Protection from Simian/Human Immunodeficiency Virus-Induced Disease†

    PubMed Central

    Amara, Rama Rao; Patel, Kalpana; Niedziela, Genevieve; Nigam, Pragati; Sharma, Sunita; Staprans, Silvija I.; Montefiori, David C.; Chenareddi, Lakshmi; Herndon, James G.; Robinson, Harriet L.; McClure, Harold M.; Novembre, Francis J.

    2005-01-01

    Among the most effective vaccine candidates tested in the simian immunodeficiency virus (SIV)/macaque system, live attenuated viruses have been shown to provide the best protection from challenge. To investigate if preimmunization would increase the level of protection afforded by live attenuated SIVmac239Δnef (Δnef), macaques were given two priming immunizations of DNA encoding SIV Gag and Pol proteins, with control macaques receiving vector DNA immunizations. In macaques receiving the SIV DNA inoculation, SIV-specific cellular but not humoral responses were readily detectable 2 weeks after the second DNA inoculation. Following boosting with live attenuated virus, control of Δnef replication was superior in SIV-DNA-primed macaques versus vector-DNA-primed macaques and was correlated with higher levels of CD8+/gamma-interferon-positive and/or interleukin-2-positive cells. Challenge with an intravenous inoculation of simian/human immunodeficiency virus (SHIV) strain SHIV89.6p resulted in infection of all animals. However, macaques receiving SIV DNA as the priming immunizations had statistically lower viral loads than control animals and did not develop signs of disease, whereas three of seven macaques receiving vector DNA showed severe CD4+ T-cell decline, with development of AIDS in one of these animals. No correlation of immune responses to protection from disease could be derived from our analyses. These results demonstrate that addition of a DNA prime to a live attenuated virus provided better protection from disease following challenge than live attenuated virus alone. PMID:16306607

  16. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

    PubMed

    Yu, Guo-Yun; Mate, Suzanne; Garcia, Karla; Ward, Michael D; Brueggemann, Ernst; Hall, Matthew; Kenny, Tara; Sanchez-Lockhart, Mariano; Lefranc, Marie-Paule; Palacios, Gustavo

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development. PMID:27233955

  17. Whole-genome sequencing of tibetan macaque (Macaca Thibetana) provides new insight into the macaque evolutionary history.

    PubMed

    Fan, Zhenxin; Zhao, Guang; Li, Peng; Osada, Naoki; Xing, Jinchuan; Yi, Yong; Du, Lianming; Silva, Pedro; Wang, Hongxing; Sakate, Ryuichi; Zhang, Xiuyue; Xu, Huailiang; Yue, Bisong; Li, Jing

    2014-06-01

    Macaques are the most widely distributed nonhuman primates and used as animal models in biomedical research. The availability of full-genome sequences from them would be essential to both biomedical and primate evolutionary studies. Previous studies have reported whole-genome sequences from rhesus macaque (Macaca mulatta) and cynomolgus macaque (M. fascicularis, CE), both of which belong to the fascicularis group. Here, we present a 37-fold coverage genome sequence of the Tibetan macaque (M. thibetana; TM). TM is an endemic species to China belonging to the sinica group. On the basis of mapping to the rhesus macaque genome, we identified approximately 11.9 million single-nucleotide variants), of which 3.9 million were TM specific, as assessed by comparison two Chinese rhesus macaques (CR) and two CE genomes. Some genes carried TM-specific homozygous nonsynonymous variants (TSHNVs), which were scored as deleterious in human by both PolyPhen-2 and SIFT (Sorting Tolerant From Intolerant) and were enriched in the eye disease genes. In total, 273 immune response and disease-related genes carried at least one TSHNV. The heterozygosity rates of two CRs (0.002617 and 0.002612) and two CEs (0.003004 and 0.003179) were approximately three times higher than that of TM (0.000898). Polymerase chain reaction resequencing of 18 TM individuals showed that 29 TSHNVs exhibited high allele frequencies, thus confirming their low heterozygosity. Genome-wide genetic divergence analysis demonstrated that TM was more closely related to CR than to CE. We further detected unusual low divergence regions between TM and CR. In addition, after applying statistical criteria to detect putative introgression regions (PIRs) in the TM genome, up to 239,620 kb PIRs (8.84% of the genome) were identified. Given that TM and CR have overlapping geographical distributions, had the same refuge during the Middle Pleistocene, and show similar mating behaviors, it is highly likely that there was an ancient

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

    PubMed Central

    Julle-Danière, Églantine; 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. PMID:26401458

  19. A ventral salience network in the macaque brain.

    PubMed

    Touroutoglou, Alexandra; Bliss-Moreau, Eliza; Zhang, Jiahe; Mantini, Dante; Vanduffel, Wim; Dickerson, Bradford C; Barrett, Lisa Feldman

    2016-05-15

    Successful navigation of the environment requires attending and responding efficiently to objects and conspecifics with the potential to benefit or harm (i.e., that have value). In humans, this function is subserved by a distributed large-scale neural network called the "salience network". We have recently demonstrated that there are two anatomically and functionally dissociable salience networks anchored in the dorsal and ventral portions of the human anterior insula (Touroutoglou et al., 2012). In this paper, we test the hypothesis that these two subnetworks exist in rhesus macaques (Macaca mulatta). We provide evidence that a homologous ventral salience network exists in macaques, but that the connectivity of the dorsal anterior insula in macaques is not sufficiently developed as a dorsal salience network. The evolutionary implications of these finding are considered. PMID:26899785

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

    PubMed

    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. PMID:25348896

  1. DNAVaxDB: the first web-based DNA vaccine database and its data analysis

    PubMed Central

    2014-01-01

    Since the first DNA vaccine studies were done in the 1990s, thousands more studies have followed. Here we report the development and analysis of DNAVaxDB (http://www.violinet.org/dnavaxdb), the first publically available web-based DNA vaccine database that curates, stores, and analyzes experimentally verified DNA vaccines, DNA vaccine plasmid vectors, and protective antigens used in DNA vaccines. All data in DNAVaxDB are annotated from reliable resources, particularly peer-reviewed articles. Among over 140 DNA vaccine plasmids, some plasmids were more frequently used in one type of pathogen than others; for example, pCMVi-UB for G- bacterial DNA vaccines, and pCAGGS for viral DNA vaccines. Presently, over 400 DNA vaccines containing over 370 protective antigens from over 90 infectious and non-infectious diseases have been curated in DNAVaxDB. While extracellular and bacterial cell surface proteins and adhesin proteins were frequently used for DNA vaccine development, the majority of protective antigens used in Chlamydophila DNA vaccines are localized to the inner portion of the cell. The DNA vaccine priming, other vaccine boosting vaccination regimen has been widely used to induce protection against infection of different pathogens such as HIV. Parasitic and cancer DNA vaccines were also systematically analyzed. User-friendly web query and visualization interfaces are available in DNAVaxDB for interactive data search. To support data exchange, the information of DNA vaccines, plasmids, and protective antigens is stored in the Vaccine Ontology (VO). DNAVaxDB is targeted to become a timely and vital source of DNA vaccines and related data and facilitate advanced DNA vaccine research and development. PMID:25104313

  2. DNAVaxDB: the first web-based DNA vaccine database and its data analysis.

    PubMed

    Racz, Rebecca; Li, Xinna; Patel, Mukti; Xiang, Zuoshuang; He, Yongqun

    2014-01-01

    Since the first DNA vaccine studies were done in the 1990s, thousands more studies have followed. Here we report the development and analysis of DNAVaxDB (http://www.violinet.org/dnavaxdb), the first publically available web-based DNA vaccine database that curates, stores, and analyzes experimentally verified DNA vaccines, DNA vaccine plasmid vectors, and protective antigens used in DNA vaccines. All data in DNAVaxDB are annotated from reliable resources, particularly peer-reviewed articles. Among over 140 DNA vaccine plasmids, some plasmids were more frequently used in one type of pathogen than others; for example, pCMVi-UB for G- bacterial DNA vaccines, and pCAGGS for viral DNA vaccines. Presently, over 400 DNA vaccines containing over 370 protective antigens from over 90 infectious and non-infectious diseases have been curated in DNAVaxDB. While extracellular and bacterial cell surface proteins and adhesin proteins were frequently used for DNA vaccine development, the majority of protective antigens used in Chlamydophila DNA vaccines are localized to the inner portion of the cell. The DNA vaccine priming, other vaccine boosting vaccination regimen has been widely used to induce protection against infection of different pathogens such as HIV. Parasitic and cancer DNA vaccines were also systematically analyzed. User-friendly web query and visualization interfaces are available in DNAVaxDB for interactive data search. To support data exchange, the information of DNA vaccines, plasmids, and protective antigens is stored in the Vaccine Ontology (VO). DNAVaxDB is targeted to become a timely and vital source of DNA vaccines and related data and facilitate advanced DNA vaccine research and development. PMID:25104313

  3. Effect of habitat quality on diet flexibility in Barbary macaques.

    PubMed

    Ménard, Nelly; Motsch, Peggy; Delahaye, Alexia; Saintvanne, Alice; Le Flohic, Guillaume; Dupé, Sandrine; Vallet, Dominique; Qarro, Mohamed; Tattou, Mohamed Ibn; Pierre, Jean-Sébastien

    2014-07-01

    Barbary macaques live in extreme temperate environments characterized by strongly seasonal resource availability. They are mainly terrestrial while foraging, harvesting food from the herbaceous layer. These monkeys are threatened mainly because of anthropogenic habitat degradation. We studied the adaptive capacities of wild groups of Barbary macaques that lived in different cedar forests undergoing varying extents of grazing pressure from domestic livestock. In all three sites, diet varied seasonally. Heavy grazing led to a significant decrease in herbaceous production and species richness. As a consequence, the monkeys' diet in this poor habitat showed a decreased plant species richness. Moreover, it incorporated fewer above-ground herbaceous resources, and a greater proportion of subterranean resources (especially hypogeous fungi and subterranean invertebrates such as earthworms, eggs and adults of earwigs, and ant's larvae) than the diet of monkeys inhabiting ungrazed forest. Cedar bark, cedar strobiles, earthworms, and earwigs were part of the monkeys' diet only in grazed forest. Monkeys in heavily grazed forest compensated for a lack of herbaceous foods by eating subterranean foods preferentially to tree and shrub products. The foods they consumed take longer to harvest and process than the seeds or leaves consumed by Barbary macaques in less heavily grazed forest habitats. Our results suggest that monkeys do differ in their diets according to the degree of habitat change induced by human activities. They also highlight the dietary flexibility of Barbary macaques as a key element that allows them to cope with degraded habitats. We later compare the dietary adjustments of Barbary macaques facing environmental change to dietary strategies of other macaques and temperate-zone primates. PMID:24573596

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

    PubMed

    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. PMID:26723919

  5. A suitable method for the detection of a potential fraud of bringing macaque monkey meat into the food chain.

    PubMed

    Rashid, Nur Raifana Abdul; Ali, Md Eaqub; Hamid, Sharifah Bee Abd; Rahman, Md Mahfujur; Razzak, Md Abdur; Asing; Amin, Md Al

    2015-01-01

    Being the third-largest primate population has not made macaque (Macaca fascicularis sp.) monkeys less exposed to threats and dangers. Despite wildlife protection, they have been widely hunted and consumed in several countries because of their purported nutritional values. In addition to trading as pure bush meats in several places, monkey meat has been sold in meatball and soup products in Indonesia. Thus the possibility of macaque meat trafficking under the label of common meats is quite high. This paper reports the development of a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with the shortest amplicon length for the confirmed detection of monkey meat under compromised states which are known to degrade DNA. We amplified a 120-bp region of d-loop gene using a pair of macaque-specific primers and confirmed their specificity for the target species through cross-challenging against 17 different species using a 141-bp site of an 18 S rRNA gene as an endogenous control for eukaryotes. This eliminated the possibilities of any false-negative detection with complex matrices or degraded specimens. The detection limit was 0.00001 ng DNA in a pure state and 0.1% of meat in mixed matrices and commercial meatball products. RFLP analysis further authenticated the originality of the PCR product and distinctive restriction patterns were found upon AluI and CViKI-1 digestion. A micro-fluidic lab-on-a-chip automated electrophoretic system separated the fragments with high resolution. The assay was validated for screening commercial meatball products with sufficient internal control. PMID:25906074

  6. Cholinergic Control of Visual Categorization in Macaques

    PubMed Central

    Aggelopoulos, Nikolaos C.; Liebe, Stefanie; Logothetis, Nikos K.; Rainer, Gregor

    2011-01-01

    Acetylcholine (ACh) is a neurotransmitter acting via muscarinic and nicotinic receptors that is implicated in several cognitive functions and impairments, such as Alzheimer’s disease. It is believed to especially affect the acquisition of new information, which is particularly important when behavior needs to be adapted to new situations and to novel sensory events. Categorization, the process of assigning stimuli to a category, is a cognitive function that also involves information acquisition. The role of ACh on categorization has not been previously studied. We have examined the effects of scopolamine, an antagonist of muscarinic ACh receptors, on visual categorization in macaque monkeys using familiar and novel stimuli. When the peripheral effects of scopolamine on the parasympathetic nervous system were controlled for, categorization performance was disrupted following systemic injections of scopolamine. This impairment was observed only when the stimuli that needed to be categorized had not been seen before. In other words, the monkeys were not impaired by the central action of scopolamine in categorizing a set of familiar stimuli (stimuli which they had categorized successfully in previous sessions). Categorization performance also deteriorated as the stimulus became less salient by an increase in the level of visual noise. However, scopolamine did not cause additional performance disruptions for difficult categorization judgments at lower coherence levels. Scopolamine, therefore, specifically affects the assignment of new exemplars to established cognitive categories, presumably by impairing the processing of novel information. Since we did not find an effect of scopolamine in the categorization of familiar stimuli, scopolamine had no significant central action on other cognitive functions such as perception, attention, memory, or executive control within the context of our categorization task. PMID:22110428

  7. Cholinergic control of visual categorization in macaques.

    PubMed

    Aggelopoulos, Nikolaos C; Liebe, Stefanie; Logothetis, Nikos K; Rainer, Gregor

    2011-01-01

    Acetylcholine (ACh) is a neurotransmitter acting via muscarinic and nicotinic receptors that is implicated in several cognitive functions and impairments, such as Alzheimer's disease. It is believed to especially affect the acquisition of new information, which is particularly important when behavior needs to be adapted to new situations and to novel sensory events. Categorization, the process of assigning stimuli to a category, is a cognitive function that also involves information acquisition. The role of ACh on categorization has not been previously studied. We have examined the effects of scopolamine, an antagonist of muscarinic ACh receptors, on visual categorization in macaque monkeys using familiar and novel stimuli. When the peripheral effects of scopolamine on the parasympathetic nervous system were controlled for, categorization performance was disrupted following systemic injections of scopolamine. This impairment was observed only when the stimuli that needed to be categorized had not been seen before. In other words, the monkeys were not impaired by the central action of scopolamine in categorizing a set of familiar stimuli (stimuli which they had categorized successfully in previous sessions). Categorization performance also deteriorated as the stimulus became less salient by an increase in the level of visual noise. However, scopolamine did not cause additional performance disruptions for difficult categorization judgments at lower coherence levels. Scopolamine, therefore, specifically affects the assignment of new exemplars to established cognitive categories, presumably by impairing the processing of novel information. Since we did not find an effect of scopolamine in the categorization of familiar stimuli, scopolamine had no significant central action on other cognitive functions such as perception, attention, memory, or executive control within the context of our categorization task. PMID:22110428

  8. Pre-Historic and Recent Vicariance Events Shape Genetic Structure and Diversity in Endangered Lion-Tailed Macaque in the Western Ghats: Implications for Conservation

    PubMed Central

    Ram, Muthuvarmadam S.; Marne, Minal; Gaur, Ajay; Kumara, Honnavalli N.; Singh, Mewa; Kumar, Ajith; Umapathy, Govindhaswamy

    2015-01-01

    Genetic isolation of populations is a potent force that helps shape the course of evolution. However, small populations in isolation, especially in fragmented landscapes, are known to lose genetic variability, suffer from inbreeding depression and become genetically differentiated among themselves. In this study, we assessed the genetic diversity of lion-tailed macaques (Macaca silenus) inhabiting the fragmented landscape of Anamalai hills and examined the genetic structure of the species across its distributional range in the Western Ghats. We sequenced around 900 bases of DNA covering two mitochondrial regions–hypervariable region-I and partial mitochondrial cytochrome b–from individuals sampled both from wild and captivity, constructed and dated phylogenetic trees. We found that the lion-tailed macaque troops in the isolated forest patches in Anamalai hills have depleted mitochondrial DNA diversity compared to troops in larger and continuous forests. Our results also revealed an ancient divergence in the lion-tailed macaque into two distinct populations across the Palghat gap, dating to 2.11 million years ago. In light of our findings, we make a few suggestions on the management of wild and captive populations. PMID:26561307

  9. Pre-Historic and Recent Vicariance Events Shape Genetic Structure and Diversity in Endangered Lion-Tailed Macaque in the Western Ghats: Implications for Conservation.

    PubMed

    Ram, Muthuvarmadam S; Marne, Minal; Gaur, Ajay; Kumara, Honnavalli N; Singh, Mewa; Kumar, Ajith; Umapathy, Govindhaswamy

    2015-01-01

    Genetic isolation of populations is a potent force that helps shape the course of evolution. However, small populations in isolation, especially in fragmented landscapes, are known to lose genetic variability, suffer from inbreeding depression and become genetically differentiated among themselves. In this study, we assessed the genetic diversity of lion-tailed macaques (Macaca silenus) inhabiting the fragmented landscape of Anamalai hills and examined the genetic structure of the species across its distributional range in the Western Ghats. We sequenced around 900 bases of DNA covering two mitochondrial regions-hypervariable region-I and partial mitochondrial cytochrome b-from individuals sampled both from wild and captivity, constructed and dated phylogenetic trees. We found that the lion-tailed macaque troops in the isolated forest patches in Anamalai hills have depleted mitochondrial DNA diversity compared to troops in larger and continuous forests. Our results also revealed an ancient divergence in the lion-tailed macaque into two distinct populations across the Palghat gap, dating to 2.11 million years ago. In light of our findings, we make a few suggestions on the management of wild and captive populations. PMID:26561307

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

    PubMed

    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. PMID:21255839

  11. Evaluation of endoscopic salpingectomy for sterilization of female Formosan macaques (Macaca cyclopis).

    PubMed

    Yu, Pin-Huan; Weng, Chia-Chun; Kuo, Hung-Chih; Chi, Chau-Hwa

    2015-04-01

    We evaluated the safety and postsurgical outcomes of endoscopic salpingectomy for sterilization of female Formosan macaques (Macaca cyclopis) as a method of population control. Nineteen adult female Formosan macaques were included in our study. The fallopian tubes of each anesthetized macaque were cauterized and excised endoscopically using a 2.7-mm rigid endoscope system. We recorded the complications encountered, and objectively scored the amount of hemorrhage throughout the procedure. Postoperative ovarian function was evaluated by monitoring the serum levels of sex hormones in ten of the macaques for two ovarian cycles following the salpingectomy. Two to 13 months later, eight of the 19 macaques underwent laparoscopy for the objective evaluation of inflammation at the surgical sites on the fallopian tubes. No major anesthetic- or surgical-associated complications were observed in any of the macaques. The hormonal evaluation showed cyclic ovarian function after salpingectomy in all of the ten macaques examined, and the parameters were comparable to those of other macaque species. The long-term postoperative level of inflammation at the surgical site was minimal to low, and was lower than that reported for other tubal occlusion techniques used in macaques. The use of a 2.7-mm rigid endoscope for salpingectomy in macaques is safe and efficient, with fewer postoperative complications than comparable sterilization techniques. PMID:25407314

  12. Dermatologic investigation of alopecia in rhesus macaques (Macaca mulatta).

    PubMed

    Steinmetz, Hanspeter W; Kaumanns, Werner; Neimeier, Karl-Albrecht; Kaup, Franz-Josef

    2005-06-01

    Coat damage has been reported frequently in captive rhesus macaques (Macaca mulatta), and it is a serious health problem because the hair coat functions as an anatomic and physiologic barrier between the animal and the environment. The purpose of this study was to identify the pathogenesis of coat damage in this species and to exclude the most frequent causes of alopecia. The investigation included clinical, hematologic, bacteriologic, mycologic, parasitologic, and histopathologic evaluations. A broad systematic dermatologic investigation was performed on 156 rhesus macaques, kept under variable environmental conditions, at the German Primate Center, Göttingen. In addition, 27 animals from other primate facilities were incorporated into the study. Clinically, 126 animals showed partial alopecia of varying severity, with complete alopecia in the worst cases. In 88% of the cases, the disorder was bilaterally symmetrical. The back and extremities were most commonly affected. No gross clinical changes of the skin surface were detected. Histologic changes consisted predominantly of mild epidermal hyperkeratosis and mild perivascular dermatitis. The presence and severity of histologic lesions were not correlated to coat damage. Parasitic, bacterial, and mycotic causes of alopecia were ruled out. Overviewing these results, disturbances in environment and behavior controlling or influencing hair growth may lead to hair loss in captive rhesus macaques. Future studies should try to identify disturbances in extrinsic or intrinsic factors influencing hair follicle activity in rhesus macaques. PMID:17323563

  13. Spatial Relational Memory in 9-Month-Old Macaque Monkeys

    ERIC Educational Resources Information Center

    Lavenex, Pierre; Lavenex, Pamela Banta

    2006-01-01

    This experiment assesses spatial and nonspatial relational memory in freely moving 9-mo-old and adult (11-13-yr-old) macaque monkeys ("Macaca mulatta"). We tested the use of proximal landmarks, two different objects placed at the center of an open-field arena, as conditional cues allowing monkeys to predict the location of food rewards hidden in…

  14. Visual preferences for sex and status in female rhesus macaques

    PubMed Central

    Ghodasra, Jason H.; Furlong, Melissa A.; Platt, Michael L.

    2012-01-01

    Most primates are both highly visual and highly social. These qualities predict that visual cues to social variables, such as identity, sex, social status, and reproductive quality, would be intrinsically valuable and systematically attract attention. Supporting this idea, thirsty male rhesus macaques (Macaca mulatta) will forego fluid reward to view images of the faces of high-ranking males and the sexual skin of females. Whether female rhesus macaques, who experience dramatically different social pressures and reproductive costs than male macaques, also systematically and spontaneously value visual cues to social information remains untested experimentally. We probed the preferences of female rhesus macaques, given the opportunity to display an image from a known class of social stimuli or touch a second target to display a blank screen. We found that females preferred faces of high-status males and also images of the perinea of both males and females, but were not motivated to display images of subordinate males or control stimuli. These findings endorse the view that both male and female rhesus macaques—and presumably other highly social primates—seek information about other individuals in a way that matches the adaptive value of that information for guiding social behavior. PMID:22160645

  15. Is male rhesus macaque red color ornamentation attractive to females?

    PubMed Central

    Dubuc, Constance; Allen, William L.; Maestripieri, Dario; Higham, James P.

    2014-01-01

    Male sexually-selected traits can evolve through different mechanisms: conspicuous and colorful ornaments usually evolve through inter-sexual selection, while weapons usually evolve through intra-sexual selection. Male ornaments are rare among mammals in comparison to birds, leading to the notion that female mate choice generally plays little role in trait evolution in this taxon. Supporting this view, when ornaments are present in mammals they typically indicate social status and are products of male-male competition. This general mammalian pattern, however, may not apply to rhesus macaques (Macaca mulatta). Males of this species display conspicuous skin coloration, but this expression is not correlated to dominance rank, and is therefore unlikely to have evolved due to male-male competition. Here, we investigate whether male color expression influences female proceptivity towards males in the Cayo Santiago free-ranging rhesus macaque population. We collected face images of 24 adult males varying in dominance rank and age at the peak of the mating season, and modeled these to rhesus macaque visual perception. We also recorded female socio-sexual behaviors towards these males. Results show that dark red males received more sexual solicitations, by more females, than pale pink ones. Together with previous results, our study suggests that male color ornaments are more likely to be a product of inter- rather than intra-sexual selection. This may especially be the case in rhesus macaques due to the particular characteristics of male-male competition in this species. PMID:25246728

  16. Focal damage to macaque photoreceptors produces persistent visual loss

    PubMed Central

    Strazzeri, Jennifer M.; Hunter, Jennifer J.; Masella, Benjamin D.; Yin, Lu; Fischer, William S.; DiLoreto, David A.; Libby, Richard T.; Williams, David R.; Merigan, William H.

    2014-01-01

    Insertion of light-gated channels into inner retina neurons restores neural light responses, light evoked potentials, visual optomotor responses and visually-guided maze behavior in mice blinded by retinal degeneration. This method of vision restoration bypasses damaged outer retina, providing stimulation directly to retinal ganglion cells in inner retina. The approach is similar to that of electronic visual protheses, but may offer some advantages, such as avoidance of complex surgery and direct targeting of many thousands of neurons. However, the promise of this technique for restoring human vision remains uncertain because rodent animal models, in which it has been largely developed, are not ideal for evaluating visual perception. On the other hand, psychophysical vision studies in macaque can be used to evaluate different approaches to vision restoration in humans. Furthermore, it has not been possible to test vision restoration in macaques, the optimal model for human-like vision, because there has been no macaque model of outer retina degeneration. In this study, we describe development of a macaque model of photoreceptor degeneration that can in future studies be used to test restoration of perception by visual prostheses. Our results show that perceptual deficits caused by focal light damage are restricted to locations at which photoreceptors are damaged, that optical coherence tomography (OCT) can be used to track such lesions, and that adaptive optics retinal imaging, which we recently used for in vivo recording of ganglion cell function, can be used in future studies to examine these lesions. PMID:24316158

  17. Focal damage to macaque photoreceptors produces persistent visual loss.

    PubMed

    Strazzeri, Jennifer M; Hunter, Jennifer J; Masella, Benjamin D; Yin, Lu; Fischer, William S; DiLoreto, David A; Libby, Richard T; Williams, David R; Merigan, William H

    2014-02-01

    Insertion of light-gated channels into inner retina neurons restores neural light responses, light evoked potentials, visual optomotor responses and visually-guided maze behavior in mice blinded by retinal degeneration. This method of vision restoration bypasses damaged outer retina, providing stimulation directly to retinal ganglion cells in inner retina. The approach is similar to that of electronic visual protheses, but may offer some advantages, such as avoidance of complex surgery and direct targeting of many thousands of neurons. However, the promise of this technique for restoring human vision remains uncertain because rodent animal models, in which it has been largely developed, are not ideal for evaluating visual perception. On the other hand, psychophysical vision studies in macaque can be used to evaluate different approaches to vision restoration in humans. Furthermore, it has not been possible to test vision restoration in macaques, the optimal model for human-like vision, because there has been no macaque model of outer retina degeneration. In this study, we describe development of a macaque model of photoreceptor degeneration that can in future studies be used to test restoration of perception by visual prostheses. Our results show that perceptual deficits caused by focal light damage are restricted to locations at which photoreceptors are damaged, that optical coherence tomography (OCT) can be used to track such lesions, and that adaptive optics retinal imaging, which we recently used for in vivo recording of ganglion cell function, can be used in future studies to examine these lesions. PMID:24316158

  18. Neonatal Amygdala Lesions Alter Responsiveness to Objects in Juvenile Macaques

    PubMed Central

    Bliss-Moreau, Eliza; Toscano, Jessica E.; Bauman, Melissa; Mason, William A.; Amaral, David G.

    2013-01-01

    The amygdala is widely recognized to play a central role in emotional processing. In nonhuman primates, the amygdala appears to be critical for generating appropriate behavioral responses in emotionally salient contexts. One common finding is that macaque monkeys that receive amygdala lesions as adults are behaviorally uninhibited in the presence of potentially dangerous objects. While control animals avoid these objects, amygdala-lesioned animals readily interact with them. Despite a large literature documenting the role of the amygdala in emotional processing in adult rhesus macaques, little research has assessed the role of the amygdala across the macaque neurodevelopmental trajectory. We assessed the behavioral responses of three-year-old (juvenile) rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at two weeks of age. Animals were presented with salient objects known to produce robust fear-related responses in macaques (e.g., snakes and reptile-like objects), mammal-like objects that included animal-like features (e.g., eyes and mouths) but not reptile-like features (e.g., scales), and non-animal objects. The visual complexity of objects was scaled to vary the objects' salience. In contrast to control and hippocampus-lesioned animals, amygdale-lesioned animals were uninhibited in the presence of potentially dangerous objects. They readily retrieved food rewards placed near these objects and physically explored the objects. Furthermore, while control and hippocampus-lesioned animals differentiated between levels of object complexity, amygdala-lesioned animals did not. Taken together, these findings suggest that early damage to the amygdala, like damage during adulthood, permanently compromises emotional processing. PMID:21215794

  19. Facial expression recognition in crested macaques (Macaca nigra).

    PubMed

    Micheletta, Jérôme; Whitehouse, Jamie; Parr, Lisa A; Waller, Bridget M

    2015-07-01

    Facial expressions are a main communication channel used by many different species of primate. Despite this, we know relatively little about how primates discriminate between different facial expressions, and most of what we do know comes from a restricted number of well-studied species. In this study, three crested macaques (Macaca nigra) took part in matching-to-sample tasks where they had to discriminate different facial expressions. In a first experiment, the macaques had to match a photograph of a facial expression to another exemplar of the same expression produced by a different individual, against examples of one of three other types of expressions and neutral faces. In a second experiment, they had to match a dynamic video recording of a facial expression to a still photograph of another exemplar of the same facial expression produced by another individual, also against one of four other expressions. The macaques performed above chance in both tasks, identifying expressions as belonging to the same category regardless of individual identity. Using matrix correlations and multidimensional scaling, we analysed the pattern of errors to see whether overall similarity between facial expressions and/or specific morphological features caused the macaques to confuse facial expressions. Overall similarity, measured with the macaque facial action coding system (maqFACS), did not correlate with performances. Instead, functional similarities between facial expressions could be responsible for the observed pattern of error. These results expand previous findings to a novel primate species and highlight the potential of using video stimuli to investigate the perception and categorisation of visual signals in primates. PMID:25821924

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

    SciTech Connect

    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.

  1. Evolutionary Distance of Amino Acid Sequence Orthologs across Macaque Subspecies: Identifying Candidate Genes for SIV Resistance in Chinese Rhesus Macaques

    PubMed Central

    Ross, Cody T.; Roodgar, Morteza; Smith, David Glenn

    2015-01-01

    We use the Reciprocal Smallest Distance (RSD) algorithm to identify amino acid sequence orthologs in the Chinese and Indian rhesus macaque draft sequences and estimate the evolutionary distance between such orthologs. We then use GOanna to map gene function annotations and human gene identifiers to the rhesus macaque amino acid sequences. We conclude methodologically by cross-tabulating a list of amino acid orthologs with large divergence scores with a list of genes known to be involved in SIV or HIV pathogenesis. We find that many of the amino acid sequences with large evolutionary divergence scores, as calculated by the RSD algorithm, have been shown to be related to HIV pathogenesis in previous laboratory studies. Four of the strongest candidate genes for SIVmac resistance in Chinese rhesus macaques identified in this study are CDK9, CXCL12, TRIM21, and TRIM32. Additionally, ANKRD30A, CTSZ, GORASP2, GTF2H1, IL13RA1, MUC16, NMDAR1, Notch1, NT5M, PDCD5, RAD50, and TM9SF2 were identified as possible candidates, among others. We failed to find many laboratory experiments contrasting the effects of Indian and Chinese orthologs at these sites on SIVmac pathogenesis, but future comparative studies might hold fertile ground for research into the biological mechanisms underlying innate resistance to SIVmac in Chinese rhesus macaques. PMID:25884674

  2. Evolutionary distance of amino acid sequence orthologs across macaque subspecies: identifying candidate genes for SIV resistance in Chinese rhesus macaques.

    PubMed

    Ross, Cody T; Roodgar, Morteza; Smith, David Glenn

    2015-01-01

    We use the Reciprocal Smallest Distance (RSD) algorithm to identify amino acid sequence orthologs in the Chinese and Indian rhesus macaque draft sequences and estimate the evolutionary distance between such orthologs. We then use GOanna to map gene function annotations and human gene identifiers to the rhesus macaque amino acid sequences. We conclude methodologically by cross-tabulating a list of amino acid orthologs with large divergence scores with a list of genes known to be involved in SIV or HIV pathogenesis. We find that many of the amino acid sequences with large evolutionary divergence scores, as calculated by the RSD algorithm, have been shown to be related to HIV pathogenesis in previous laboratory studies. Four of the strongest candidate genes for SIVmac resistance in Chinese rhesus macaques identified in this study are CDK9, CXCL12, TRIM21, and TRIM32. Additionally, ANKRD30A, CTSZ, GORASP2, GTF2H1, IL13RA1, MUC16, NMDAR1, Notch1, NT5M, PDCD5, RAD50, and TM9SF2 were identified as possible candidates, among others. We failed to find many laboratory experiments contrasting the effects of Indian and Chinese orthologs at these sites on SIVmac pathogenesis, but future comparative studies might hold fertile ground for research into the biological mechanisms underlying innate resistance to SIVmac in Chinese rhesus macaques. PMID:25884674

  3. Heading Tuning in Macaque Area V6

    PubMed Central

    Fan, Reuben H.; Liu, Sheng; DeAngelis, Gregory C.

    2015-01-01

    Cortical areas, such as the dorsal subdivision of the medial superior temporal area (MSTd) and the ventral intraparietal area (VIP), have been shown to integrate visual and vestibular self-motion signals. Area V6 is interconnected with areas MSTd and VIP, allowing for the possibility that V6 also integrates visual and vestibular self-motion cues. An alternative hypothesis in the literature is that V6 does not use these sensory signals to compute heading but instead discounts self-motion signals to represent object motion. However, the responses of V6 neurons to visual and vestibular self-motion cues have never been studied, thus leaving the functional roles of V6 unclear. We used a virtual reality system to examine the 3D heading tuning of macaque V6 neurons in response to optic flow and inertial motion stimuli. We found that the majority of V6 neurons are selective for heading defined by optic flow. However, unlike areas MSTd and VIP, V6 neurons are almost universally unresponsive to inertial motion in the absence of optic flow. We also explored the spatial reference frames of heading signals in V6 by measuring heading tuning for different eye positions, and we found that the visual heading tuning of most V6 cells was eye-centered. Similar to areas MSTd and VIP, the population of V6 neurons was best able to discriminate small variations in heading around forward and backward headings. Our findings support the idea that V6 is involved primarily in processing visual motion signals and does not appear to play a role in visual–vestibular integration for self-motion perception. SIGNIFICANCE STATEMENT To understand how we successfully navigate our world, it is important to understand which parts of the brain process cues used to perceive our direction of self-motion (i.e., heading). Cortical area V6 has been implicated in heading computations based on human neuroimaging data, but direct measurements of heading selectivity in individual V6 neurons have been lacking. We

  4. Visual discrimination of male and female faces by infant rhesus macaques.

    PubMed

    Paukner, Annika; Huntsberry, Mary E; Suomi, Stephen J

    2010-01-01

    Recent studies have revealed that human infants process female faces differently from male faces. To test whether a similar preference for female faces exists in other primates, we presented nursery-reared infant rhesus macaques with photographs of macaque faces and human faces. At <1 month old, infant macaques preferentially oriented towards female macaque faces when faces were presented upright. No preference for female human faces was found. At 9 months old, infants failed to show a visual preference for female macaque faces or female human faces, although they showed significantly more lipsmacking responses at female human faces. Compared to human infants, macaques appear to have stronger predispositions early in life but this preference may nonetheless be amendable to experience. Understanding how innate predispositions and the social rearing environment shape infants' understanding of faces remain important issues to be explored in order to understand facial processing abilities in humans and other primates. PMID:19937740

  5. Genetic studies on the Cayo Santiago rhesus macaques: A review of 40 years of research.

    PubMed

    Widdig, Anja; Kessler, Matthew J; Bercovitch, Fred B; Berard, John D; Duggleby, Christine; Nürnberg, Peter; Rawlins, Richard G; Sauermann, Ulrike; Wang, Qian; Krawczak, Michael; Schmidtke, Jörg

    2016-01-01

    Genetic studies not only contribute substantially to our current understanding of the natural variation in behavior and health in many species, they also provide the basis of numerous in vivo models of human traits. Despite the many challenges posed by the high level of biological and social complexity, a long lifespan and difficult access in the field, genetic studies of primates are particularly rewarding because of the close evolutionary relatedness of these species to humans. The free-ranging rhesus macaque (Macaca mulatta) population on Cayo Santiago (CS), Puerto Rico, provides a unique resource in this respect because several of the abovementioned caveats are of either minor importance there, or lacking altogether, thereby allowing long-term genetic research in a primate population under constant surveillance since 1956. This review summarizes more than 40 years of genetic research carried out on CS, from early blood group typing and the genetic characterization of skeletal material via population-wide paternity testing with DNA fingerprints and short tandem repeats (STRs) to the analysis of the highly polymorphic DQB1 locus within the major histocompatibility complex (MHC). The results of the paternity studies also facilitated subsequent studies of male dominance and other factors influencing male reproductive success, of male reproductive skew, paternal kin bias, and mechanisms of paternal kin recognition. More recently, the CS macaques have been the subjects of functional genetic and gene expression analyses and have played an important role in behavioral and quantitative genetic studies. In addition, the CS colony has been used as a natural model for human adult-onset macular degeneration, glaucoma, and circadian rhythm disorder. Our review finishes off with a discussion of potential future directions of research on CS, including the transition from STRs to single nucleotide polymorphism (SNP) typing and whole genome sequencing. PMID:26031601

  6. IL-4 increases Simian immunodeficiency virus replication despite enhanced SIV immune responses in infected rhesus macaques.

    PubMed

    Boyer, J D; Nath, B; Schumann, K; Curley, E; Manson, K; Kim, J; Weiner, D B

    2002-05-01

    It is widely believed that a Th1 type CD4 response is critical for enhancement of CD8 immunity and for controlling HIV-1 infection. Th2 type responses, such as what might be seen in a chronic parasitic infection, would sacrifice cellular immunity and thus benefit the virus at the expense of the host. However, there has been little direct examination of the hypothesis in a primate model system. Accordingly, the simian immunodeficiency virus (SIV) infected rhesus macaque model was used to investigate the impact of immunisation with SIV expressing DNA constructs and co-injection with IL-4 on the SIV specific immunological responses, lymphocyte cell counts, as well as the impact on viral load. IL-4 is a Th2 type cytokine, which enhances antibody production and inhibits a CD4 Th1 phenotype. Rhesus macaques were infected with 10 AID50 of SIVmac239 and treated with 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) 9 weeks post-infection. During PMPA treatment, animals were immunised with plasmids that expressed the SIV proteins, env, rev, gag and pol. In addition, they were immunised with a construct that encoded the gene for IL-4. IL-4 co-immunisation increased the neutralizing antibody titres in this group. Importantly, the viral loads in animals vaccinated with IL-4 expressing plasmid increased during the immunisation regimens despite the higher neutralizing antibody titres. In addition, neutralizing antibodies did not correlate with viral set point prior to PMPA treatment, however, there was a correlation between viral loads and antibody titres following the treatment with PMPA. Antibody titres decreased following the suppression of viral load. Importantly, vaccination in the absence of IL-4 protected CD4 levels without increasing viral load. The data support the hypothesis that inappropriate immune bias toward a Th2 pathway would ultimately enhance disease progression. PMID:11943227

  7. Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues.

    PubMed Central

    Lackner, A A; Rodriguez, M H; Bush, C E; Munn, R J; Kwang, H S; Moore, P F; Osborn, K G; Marx, P A; Gardner, M B; Lowenstine, L J

    1988-01-01

    Simian acquired immune deficiency syndrome (SAIDS) in rhesus macaques (Macaca mulatta) at the California Primate Research Center is caused by a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). This syndrome is characterized by profound immunosuppression and death associated with opportunistic infections. Neurologic signs and lesions have not been described as part of this syndrome. The distribution of SRV-1 in the salivary glands, lymph nodes, spleens, thymuses, and brains of eight virus-infected rhesus macaques was examined by immunohistochemistry. Electron microscopy, in situ RNA hybridization, and Southern blot hybridization were also performed on selected tissues to detect viral particles, RNA, and DNA, respectively. In seven of eight SRV-1-infected animals, the transmembrane envelope glycoprotein (gp20) of SRV-1 was present in three or more tissues, but never in the brain. In the remaining animal, no viral antigen was detected in any tissue. In this same group of animals, viral nucleic acid was detected in the lymph nodes of six of six animals by Southern blot hybridization, in the salivary glands of two of five animals by both Southern blot and in situ hybridizations, and, surprisingly, in the brains of three of three animals by Southern blot and of three of five animals by in situ hybridization, including the one animal in which viral gp20 was undetectable. None of these animals had neurologic signs or lesions. The detection of viral nucleic acid in the absence of viral antigen in the brain suggests latent SRV-1 infection of the central nervous system. Images PMID:3285033

  8. Brain Abscess in a Rhesus Macaque (Macaca mulatta) with a Cephalic Implant

    PubMed Central

    Leblanc, Mathias; Berry, Kristy; McCort, Holly; Reuter, Jon D

    2013-01-01

    We report a case of brain abscess after craniotomy and the placement of a recording chamber for electrophysiologic records in an adult rhesus macaque (Macaca mulatta) enrolled in visual research. Approximately 2 wk after surgery, the macaque presented with nonspecific gastrointestinal signs and showed no evidence of fever, neurologic deficits, increased intracranial pressure, suggestive alterations in the CBC, or abnormal changes in the recording chamber. The macaque responded to symptomatic and antibiotic treatment and showed no behavioral or abnormal clinical signs for 3 wk before collapsing suddenly. The macaque was euthanized, and pathologic evaluation revealed a large brain abscess immediately under the original craniotomy. PMID:24209974

  9. Macaque–Human Interactions and the Societal Perceptions of Macaques in Singapore

    PubMed Central

    SHA, JOHN CHIH MUN; GUMERT, MICHAEL D.; LEE, BENJAMIN P. Y-H.; JONES-ENGEL, LISA; CHAN, SHARON; FUENTES, AGUSTÍN

    2015-01-01

    Humans and long-tailed macaques (Macaca fascicularis) interface in several locations in Singapore. We investigated six of these interface zones to assess the level of conflict between the two species. We observed macaque-to-human interactions and distributed questionnaires to residents and visitors of nature reserves. We observed an average of two macaque-to-human interactions per hour at the sites, which included affiliative or submissive behaviors (46.9%), aggression (19.1%), taking food and other items (18.5%) searching bins, cars, and houses (13.4%), and nonaggressive contact (2.1%). Two-thirds of interactions occurred when a human was carrying food or food cues, and one-quarter occurred when a human provoked macaques. Only 8% of interactions occurred without a clear human-triggered context. Our interview showed one-third of respondents experienced nuisance problems from macaques. They had items taken from them (50.5%) and received threats (31.9%). Residents reported more nuisance problems than visitors, and their perceptions toward macaques differed. Residents were more aware of the consequences of food provisioning and that there were regulations against feeding. Residents fed macaques less and held more negative sentiments toward macaques. Nearly half of the interviewed people held neutral attitudes toward macaques and only 26.2% of respondents thought conflict with macaques warranted urgent action. Nearly two-thirds of the respondents supported education programs to ameliorate human–macaque conflict, and less than 15% supported removing or eradicating macaques. 87.6% felt that it is importance to conserve and protect macaques. Our results show that human–macaque conflict exists in Singapore, but that it may not be severe. Human behavior is largely responsible for macaque-to-human interactions, and thus could be lessened with management of human behavior in interface zones (i.e. restrict food carrying and provocation). Moreover, our interviews shows

  10. Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

    PubMed

    Lagenaur, Laurel A; Swedek, Iwona; Lee, Peter P; Parks, Thomas P

    2015-01-01

    MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody. PMID:25875100

  11. Robust Vaginal Colonization of Macaques with a Novel Vaginally Disintegrating Tablet Containing a Live Biotherapeutic Product to Prevent HIV Infection in Women

    PubMed Central

    Lagenaur, Laurel A.; Swedek, Iwona; Lee, Peter P.; Parks, Thomas P.

    2015-01-01

    MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody. PMID:25875100

  12. Prevention of SIV Rectal Transmission and Priming of T Cell Responses in Macaques after Local Pre-exposure Application of Tenofovir Gel

    PubMed Central

    Cranage, Martin; Sharpe, Sally; Herrera, Carolina; Cope, Alethea; Dennis, Mike; Berry, Neil; Ham, Claire; Heeney, Jonathan; Rezk, Naser; Kashuba, Angela; Anton, Peter; McGowan, Ian; Shattock, Robin

    2008-01-01

    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 protected from

  13. Congenital malformations in Japanese macaques (Macaca fuscata) at Takasakiyama.

    PubMed

    Sugiyama, Yukimaru; Kurita, Hiroyuki; Matsui, Takeshi; Kimoto, Satoshi; Egawa, Junko

    2014-04-01

    From the late 1960s to the early 1970s, many congenitally malformed infants were born into provisioned Japanese macaque troops. Although the exact cause of this problem was not determined, the occurrence of malformations decreased thereafter. We examined possible factors such as total population size, number of adult females, birth rate, and volume of provisioned food. Agrichemicals attached to provisioned food are suspected as the main cause, as other factors were found to have no influence. Many more malformations were seen in males compared with females, in feet compared with hands, and in the fourth compared with other digits. We confirmed that the frequency of congenital malformation was high during the 1960s through to the mid-1970s when increased levels of provisioned food were given and that the incidence of congenital malformations was also elevated among wild macaques during this time. PMID:24474604

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

    PubMed

    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. PMID:17431167

  15. Otoacoustic Estimates of Cochlear Tuning: Testing Predictions in Macaque

    NASA Astrophysics Data System (ADS)

    Shera, Christopher A.; Bergevin, Christopher; Kalluri, Radha; Mc Laughlin, Myles; Michelet, Pascal; van der Heijden, Marcel; Joris, Philip X.

    2011-11-01

    Otoacoustic estimates of cochlear frequency selectivity suggest substantially sharper tuning in humans. However, the logic and methodology underlying these estimates remain untested by direct measurements in primates. We report measurements of frequency tuning in macaque monkeys, Old-World primates phylogenetically closer to humans than the small laboratory animals often taken as models of human hearing (e.g., cats, guinea pigs, and chinchillas). We find that measurements of tuning obtained directly from individual nerve fibers and indirectly using otoacoustic emissions both indicate that peripheral frequency selectivity in macaques is significantly sharper than in small laboratory animals, matching that inferred for humans at high frequencies. Our results validate the use of otoacoustic emissions for noninvasive measurement of cochlear tuning and corroborate the finding of sharper tuning in humans.

  16. Systemic Spironucleosis In Two Immunodeficient Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Bailey, C; Kramer, J; Mejia, A; MacKey, J; Mansfield, KG; Miller, AD

    2011-01-01

    Spironucleus spp. are parasites of fish and terrestrial vertebrates including mice and turkeys that rarely cause extraintestinal disease. Two rhesus macaques (Macaca mulatta) were experimentally inoculated with simian immunodeficiency virus mac251 (SIVmac251). Both progressed to simian acquired immune deficiency syndrome (SAIDS) within one year of inoculation and, in addition to common opportunistic infections including rhesus cytomegalovirus, rhesus lymphocryptovirus, and rhesus adenovirus, developed systemic protozoal infections. In the first case, the protozoa were associated with colitis, multifocal abdominal abscessation, and lymphadenitis. In the second case they one of a number of organisms associated with extensive pyogranulomatous pneumonia and colitis. Ultrastructural, molecular, and phylogenetic analysis revealed the causative organism to be a species of Spironucleus closely related to Spironucleus meleagridis of turkeys. This is the first report of extraintestinal infection with Spironucleus sp. in higher mammals and further expands the list of opportunistic infections found in immunocompromised rhesus macaques. PMID:20351359

  17. Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis)

    PubMed Central

    Colagross-Schouten, Angela M; Canfield, Don R

    2015-01-01

    A 20-y-old female cynomolgus macaque (Macaca fascicularis) housed in an indoor primate facility presented for poor appetite and acute weakness after several years of no adverse health events. Physical examination revealed a firm, ovoid mass in the caudal abdomen. Further evaluation revealed the mass to be a vaginal calculus composed of calcium carbonate, apatite, and struvite. To our knowledge, this case is the first reported description of a vaginal stone in an NHP. PMID:26678372

  18. Social Interactions through the Eyes of Macaques and Humans

    PubMed Central

    McFarland, Richard; Roebuck, Hettie; Yan, Yin; Majolo, Bonaventura; Li, Wu; Guo, Kun

    2013-01-01

    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 social attention

  19. Analysing Local Sparseness in the Macaque Brain Network

    PubMed Central

    Singh, Raghavendra; Nagar, Seema; Nanavati, Amit A.

    2015-01-01

    Understanding the network structure of long distance pathways in the brain is a necessary step towards developing an insight into the brain’s function, organization and evolution. Dense global subnetworks of these pathways have often been studied, primarily due to their functional implications. Instead we study sparse local subnetworks of the pathways to establish the role of a brain area in enabling shortest path communication between its non-adjacent topological neighbours. We propose a novel metric to measure the topological communication load on a vertex due to its immediate neighbourhood, and show that in terms of distribution of this local communication load, a network of Macaque long distance pathways is substantially different from other real world networks and random graph models. Macaque network contains the entire range of local subnetworks, from star-like networks to clique-like networks, while other networks tend to contain a relatively small range of subnetworks. Further, sparse local subnetworks in the Macaque network are not only found across topographical super-areas, e.g., lobes, but also within a super-area, arguing that there is conservation of even relatively short-distance pathways. To establish the communication role of a vertex we borrow the concept of brokerage from social science, and present the different types of brokerage roles that brain areas play, highlighting that not only the thalamus, but also cingulate gyrus and insula often act as “relays” for areas in the neocortex. These and other analysis of communication load and roles of the sparse subnetworks of the Macaque brain provide new insights into the organisation of its pathways. PMID:26437077

  20. Analysing Local Sparseness in the Macaque Brain Network.

    PubMed

    Singh, Raghavendra; Nagar, Seema; Nanavati, Amit A

    2015-01-01

    Understanding the network structure of long distance pathways in the brain is a necessary step towards developing an insight into the brain's function, organization and evolution. Dense global subnetworks of these pathways have often been studied, primarily due to their functional implications. Instead we study sparse local subnetworks of the pathways to establish the role of a brain area in enabling shortest path communication between its non-adjacent topological neighbours. We propose a novel metric to measure the topological communication load on a vertex due to its immediate neighbourhood, and show that in terms of distribution of this local communication load, a network of Macaque long distance pathways is substantially different from other real world networks and random graph models. Macaque network contains the entire range of local subnetworks, from star-like networks to clique-like networks, while other networks tend to contain a relatively small range of subnetworks. Further, sparse local subnetworks in the Macaque network are not only found across topographical super-areas, e.g., lobes, but also within a super-area, arguing that there is conservation of even relatively short-distance pathways. To establish the communication role of a vertex we borrow the concept of brokerage from social science, and present the different types of brokerage roles that brain areas play, highlighting that not only the thalamus, but also cingulate gyrus and insula often act as "relays" for areas in the neocortex. These and other analysis of communication load and roles of the sparse subnetworks of the Macaque brain provide new insights into the organisation of its pathways. PMID:26437077

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

    PubMed

    McFarland, Richard; Roebuck, Hettie; Yan, Yin; Majolo, Bonaventura; Li, Wu; Guo, Kun

    2013-01-01

    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 social attention

  2. The Organization of Dorsal Frontal Cortex in Humans and Macaques

    PubMed Central

    Mars, Rogier B.; Noonan, MaryAnn P.; Neubert, Franz-Xaver; Jbabdi, Saad; O'Reilly, Jill X.; Filippini, Nicola; Thomas, Adam G.; Rushworth, Matthew F.

    2013-01-01

    The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for “new” regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed. PMID:23884933

  3. Axon diameters and conduction velocities in the macaque pyramidal tract

    PubMed Central

    Firmin, L.; Field, P.; Maier, M. A.; Kraskov, A.; Kirkwood, P. A.; Nakajima, K.; Lemon, R. N.

    2014-01-01

    Small axons far outnumber larger fibers in the corticospinal tract, but the function of these small axons remains poorly understood. This is because they are difficult to identify, and therefore their physiology remains obscure. To assess the extent of the mismatch between anatomic and physiological measures, we compared conduction time and velocity in a large number of macaque corticospinal neurons with the distribution of axon diameters at the level of the medullary pyramid, using both light and electron microscopy. At the electron microscopic level, a total of 4,172 axons were sampled from 2 adult male macaque monkeys. We confirmed that there were virtually no unmyelinated fibers in the pyramidal tract. About 14% of pyramidal tract axons had a diameter smaller than 0.50 μm (including myelin sheath), most of these remaining undetected using light microscopy, and 52% were smaller than 1 μm. In the electrophysiological study, we determined the distribution of antidromic latencies of pyramidal tract neurons, recorded in primary motor cortex, ventral premotor cortex, and supplementary motor area and identified by pyramidal tract stimulation (799 pyramidal tract neurons, 7 adult awake macaques) or orthodromically from corticospinal axons recorded at the mid-cervical spinal level (192 axons, 5 adult anesthetized macaques). The distribution of antidromic and orthodromic latencies of corticospinal neurons was strongly biased toward those with large, fast-conducting axons. Axons smaller than 3 μm and with a conduction velocity below 18 m/s were grossly underrepresented in our electrophysiological recordings, and those below 1 μm (6 m/s) were probably not represented at all. The identity, location, and function of the majority of corticospinal neurons with small, slowly conducting axons remains unknown. PMID:24872533

  4. Distributed acoustic cues for caller identity in macaque vocalization.

    PubMed

    Fukushima, Makoto; Doyle, Alex M; Mullarkey, Matthew P; Mishkin, Mortimer; Averbeck, Bruno B

    2015-12-01

    Individual primates can be identified by the sound of their voice. Macaques have demonstrated an ability to discern conspecific identity from a harmonically structured 'coo' call. Voice recognition presumably requires the integrated perception of multiple acoustic features. However, it is unclear how this is achieved, given considerable variability across utterances. Specifically, the extent to which information about caller identity is distributed across multiple features remains elusive. We examined these issues by recording and analysing a large sample of calls from eight macaques. Single acoustic features, including fundamental frequency, duration and Weiner entropy, were informative but unreliable for the statistical classification of caller identity. A combination of multiple features, however, allowed for highly accurate caller identification. A regularized classifier that learned to identify callers from the modulation power spectrum of calls found that specific regions of spectral-temporal modulation were informative for caller identification. These ranges are related to acoustic features such as the call's fundamental frequency and FM sweep direction. We further found that the low-frequency spectrotemporal modulation component contained an indexical cue of the caller body size. Thus, cues for caller identity are distributed across identifiable spectrotemporal components corresponding to laryngeal and supralaryngeal components of vocalizations, and the integration of those cues can enable highly reliable caller identification. Our results demonstrate a clear acoustic basis by which individual macaque vocalizations can be recognized. PMID:27019727

  5. Auditory artificial grammar learning in macaque and marmoset monkeys.

    PubMed

    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. PMID:24285889

  6. Prevalence of enteric parasites in pet macaques in Sulawesi, Indonesia.

    PubMed

    Jones-Engel, Lisa; Engel, Gregory A; Schillact, Michael A; Froehlich, Jeffery; Paputungan, Umar; Kyes, Randall C

    2004-02-01

    On the Indonesian island of Sulawesi, nonhuman primate pets come into frequent contact with humans, presenting the possibility of zoonotic and anthropozoonotic disease transmission. We collected fecal samples from 88 pet macaques representing six of the seven macaque species currently recognized as endemic to Sulawesi (Macaca nigra, M. nigrescens, M. hecki, M. tonkeana, M. maura, and M. ochreata) as well as two non-endemic species (M. fascicularis and M. nemestrina) in order to determine the prevalence of intestinal parasitic infection in this population. Seven taxa of intestinal protozoa (Blastocystis hominis, Iodamoeba bütschlii, Entamoeba coli, Entamoeba hartmanni, Chilomastrix mesnili, Endolimax nana, and Retortamonas intestinalis) and three taxa of nematodes (hookworm, Trichuris spp., and Ascaris spp.) were detected. The overall parasitization rate was 59.1%. Commensal organisms predominated in this population. Parasitization was not statistically correlated with macaque age group, sex, species, or location, or with the owner's level of education. These findings are discussed in the context of primate pet ownership practices in Sulawesi. PMID:14983465

  7. Distributed acoustic cues for caller identity in macaque vocalization

    PubMed Central

    Doyle, Alex M.; Mullarkey, Matthew P.; Mishkin, Mortimer; Averbeck, Bruno B.

    2015-01-01

    Individual primates can be identified by the sound of their voice. Macaques have demonstrated an ability to discern conspecific identity from a harmonically structured ‘coo’ call. Voice recognition presumably requires the integrated perception of multiple acoustic features. However, it is unclear how this is achieved, given considerable variability across utterances. Specifically, the extent to which information about caller identity is distributed across multiple features remains elusive. We examined these issues by recording and analysing a large sample of calls from eight macaques. Single acoustic features, including fundamental frequency, duration and Weiner entropy, were informative but unreliable for the statistical classification of caller identity. A combination of multiple features, however, allowed for highly accurate caller identification. A regularized classifier that learned to identify callers from the modulation power spectrum of calls found that specific regions of spectral–temporal modulation were informative for caller identification. These ranges are related to acoustic features such as the call’s fundamental frequency and FM sweep direction. We further found that the low-frequency spectrotemporal modulation component contained an indexical cue of the caller body size. Thus, cues for caller identity are distributed across identifiable spectrotemporal components corresponding to laryngeal and supralaryngeal components of vocalizations, and the integration of those cues can enable highly reliable caller identification. Our results demonstrate a clear acoustic basis by which individual macaque vocalizations can be recognized. PMID:27019727

  8. Draft Genome Sequences of Sarcina ventriculi Strains Isolated from Wild Japanese Macaques in Yakushima Island.

    PubMed

    Ushida, Kazunari; Tsuchida, Sayaka; Ogura, Yoshitoshi; Hayashi, Tetsuya; Sawada, Akiko; Hanya, Goro

    2016-01-01

    We report the draft genome sequences of Sarcina ventriculi strains 14 and 17, both isolated from feces of wild Yakushima macaques (Macaca fuscata yakui). These genomic sequences will be helpful for the phylogenetic consideration of the family Clostridiaceae and understanding of the contribution of intestinal microbiota to the survival of Yakushima macaques. PMID:26847899

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

    ERIC Educational Resources Information Center

    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…

  10. Draft Genome Sequences of Sarcina ventriculi Strains Isolated from Wild Japanese Macaques in Yakushima Island

    PubMed Central

    Tsuchida, Sayaka; Ogura, Yoshitoshi; Hayashi, Tetsuya; Sawada, Akiko; Hanya, Goro

    2016-01-01

    We report the draft genome sequences of Sarcina ventriculi strains 14 and 17, both isolated from feces of wild Yakushima macaques (Macaca fuscata yakui). These genomic sequences will be helpful for the phylogenetic consideration of the family Clostridiaceae and understanding of the contribution of intestinal microbiota to the survival of Yakushima macaques. PMID:26847899

  11. Diversity of TRIM5α and TRIMCyp sequences in cynomolgus macaques from different geographical origins.

    PubMed

    Berry, Neil J; Marzetta, Flavia; Towers, Greg J; Rose, Nicola J

    2012-04-01

    The TRIM5α restriction factor can protect some species of monkeys, but not humans, from HIV infection. It has also emerged that some monkeys have a cyclophilin A domain retrotransposed into the TRIM5 locus resulting in the expression of a TRIMCyp protein with anti-retroviral activity. A high degree of sequence variation in the primate TRIM5 gene has been reported that varies between populations of rhesus macaques, a widely used non-human primate model of HIV/AIDS, and recently shown to correlate with susceptibility to simian immunodeficiency viruses in this species. Cynomolgus macaques are also used widely in HIV research. A non-indigenous population on Mauritius has highly restricted genetic diversity compared with macaques from Indonesia. The relative allelic diversity of TRIM5α and TRIMCyp within these two sub-populations may impact on the susceptibility of the macaques to simian immunodeficiency virus thereby influencing the outcome of studies using these monkeys. We sought to establish the genetic diversity of these alleles in cynomolgus macaques. We identified seven TRIM5α alleles in Indonesian macaques, three of which are novel, but only three in the Mauritian-origin macaques. Strikingly, 87% of Indonesian, but none of the Mauritian macaques, possessed a retrotransposed Cyp domain. A splice acceptor site single-nucleotide polymorphism that allows formation of a TRIMCyp protein was absent for the TRIM5α alleles found in the Mauritian macaques. The level of allelic diversity reported here is greater than previously proposed for cynomolgus macaque species. PMID:22124667

  12. Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes

    PubMed Central

    Hughes, Jennifer F.; Skaletsky, Helen; Page, David C.

    2013-01-01

    Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We report that DAZ arrived on the Y chromosome about 36 million years ago via the transposition of at least 1.1 megabases of autosomal DNA. This transposition also brought five additional genes to the Y chromosome, but all five genes were subsequently lost through mutation or deletion. As the only surviving gene, DAZ experienced extensive restructuring, including intragenic amplification and gene duplication, and has been the target of positive selection in the chimpanzee lineage. PMID:23055411

  13. Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques

    PubMed Central

    Suzuki-Hashido, Nami; Hayakawa, Takashi; Matsui, Atsushi; Go, Yasuhiro; Ishimaru, Yoshiro; Misaka, Takumi; Abe, Keiko; Hirai, Hirohisa; Satta, Yoko; Imai, Hiroo

    2015-01-01

    Bitter taste receptors (TAS2R proteins) allow mammals to detect and avoid ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice and are subject to complex natural selection pressures. In our previous study, we examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor for phenylthiocarbamide (PTC), in 333 Japanese macaques (Macaca fuscata) from 9 local populations in Japan. We identified a PTC “non-taster” TAS2R38 allele in Japanese macaques that was caused by a loss of the start codon. This PTC non-taster allele was only found in a limited local population (the Kii area), at a frequency of 29%. In this study, we confirmed that this allele was present in only the Kii population by analyzing an additional 264 individuals from eight new populations. Using cellular and behavioral experiments, we found that this allele lost its receptor function for perceiving PTC. The nucleotide sequences of the allele including flanking regions (of about 10 kb) from 23 chromosomes were identical, suggesting that a non-taster allele arose and expanded in the Kii population during the last 13,000 years. Genetic analyses of non-coding regions in Kii individuals and neighboring populations indicated that the high allele frequency in the Kii population could not be explained by demographic history, suggesting that positive selection resulted in a rapid increase in PTC non-tasters in the Kii population. The loss-of-function that occurred at the TAS2R38 locus presumably provided a fitness advantage to Japanese macaques in the Kii population. Because TAS2R38 ligands are often found in plants, this functional change in fitness is perhaps related to feeding habit specificity. These findings should provide valuable insights for elucidating adaptive evolutionary changes with respect to various environments in wild mammals. PMID:26201026

  14. Genomic Sequencing and Characterization of Cynomolgus Macaque Cytomegalovirus▿

    PubMed Central

    Marsh, Angie K.; Willer, David O.; Ambagala, Aruna P. N.; Dzamba, Misko; Chan, Jacqueline K.; Pilon, Richard; Fournier, Jocelyn; Sandstrom, Paul; Brudno, Michael; MacDonald, Kelly S.

    2011-01-01

    Cytomegalovirus (CMV) infection is the most common opportunistic infection in immunosuppressed individuals, such as transplant recipients or people living with HIV/AIDS, and congenital CMV is the leading viral cause of developmental disabilities in infants. Due to the highly species-specific nature of CMV, animal models that closely recapitulate human CMV (HCMV) are of growing importance for vaccine development. Here we present the genomic sequence of a novel nonhuman primate CMV from cynomolgus macaques (Macaca fascicularis; CyCMV). CyCMV (Ottawa strain) was isolated from the urine of a healthy, captive-bred, 4-year-old cynomolgus macaque of Philippine origin, and the viral genome was sequenced using next-generation Illumina sequencing to an average of 516-fold coverage. The CyCMV genome is 218,041 bp in length, with 49.5% G+C content and 84% protein-coding density. We have identified 262 putative open reading frames (ORFs) with an average coding length of 789 bp. The genomic organization of CyCMV is largely colinear with that of rhesus macaque CMV (RhCMV). Of the 262 CyCMV ORFs, 137 are homologous to HCMV genes, 243 are homologous to RhCMV 68.1, and 200 are homologous to RhCMV 180.92. CyCMV encodes four ORFs that are not present in RhCMV strain 68.1 or 180.92 but have homologies with HCMV (UL30, UL74A, UL126, and UL146). Similar to HCMV, CyCMV does not produce the RhCMV-specific viral homologue of cyclooxygenase-2. This newly characterized CMV may provide a novel model in which to study CMV biology and HCMV vaccine development. PMID:21994460

  15. [Model index observations in SIVmac251-infected rhesus macaques].

    PubMed

    Zhang, Yu; Wang, Jing; Liu, Xiang-mei; Min, Fan-gui; Guo, Peng-jv; Huang, Ren

    2014-11-01

    In this study, five rhesus macaques were inoculated intravenously with SIVmac251 to establish a model of simian autoimmune deficiency syndrome (SAIDS). Peripheral blood samples were collected at different time points to monitor changes in the total T cell number and T lymphocyte subset. Plasma viral loads, cytokine expression levels and anti-SIV antibody levels were also assayed to acquire certain basic indexes to evaluate disease progression in the rhesus macaque SAIDS model. During the acute stage of infection, plasma viral loads reached a peak at week 1 post-inoculation and lasted for approximately 3 to 44 weeks. The CD3+ CD4+ T lymphocyte count in peripheral blood also transitorily decreased. During the same period, the level of interferon-gamma show an increasing trend, whereas IL-12 levels decreased; IL-2, IL-4, IL-10 and TNF-alpha were maintained at normal levels or could not be detected. During the asymptomatic and ARC phases, plasma viral loads persisted above 10(4) RNA copies/mL and either increased or declined during the later stages of disease; CD3+ CD4+ counts showed a steadily declining trend and the ratio of CD4 to CD8 decreased during late-stage disease. Moreover, antibodies against viral proteins were detected in the plasma and showed a significant increasing trend, while there were no apparently changes in the levels of IFN-gamma, IL-12, IL-2, IL-4, IL-10 and TNF-alpha. In conclusion, the characteristics of the SIV animal models in our study are similar to those of patients with AIDS. Therefore, the rhesus macaque SIVmac251 infection models can be applied for further studies into AIDS. PMID:25868283

  16. Intravitreal Injection of AAV2 Transduces Macaque Inner Retina

    PubMed Central

    Yin, Lu; Greenberg, Kenneth; Hunter, Jennifer J.; Dalkara, Deniz; Kolstad, Kathleen D.; Masella, Benjamin D.; Wolfe, Robert; Visel, Meike; Stone, Daniel; Libby, Richard T.; DiLoreto, David; Schaffer, David; Flannery, John; Williams, David R.

    2011-01-01

    Purpose. Adeno-associated virus serotype 2 (AAV2) has been shown to be effective in transducing inner retinal neurons after intravitreal injection in several species. However, results in nonprimates may not be predictive of transduction in the human inner retina, because of differences in eye size and the specialized morphology of the high-acuity human fovea. This was a study of inner retina transduction in the macaque, a primate with ocular characteristics most similar to that of humans. Methods. In vivo imaging and histology were used to examine GFP expression in the macaque inner retina after intravitreal injection of AAV vectors containing five distinct promoters. Results. AAV2 produced pronounced GFP expression in inner retinal cells of the fovea, no expression in the central retina beyond the fovea, and variable expression in the peripheral retina. AAV2 vector incorporating the neuronal promoter human connexin 36 (hCx36) transduced ganglion cells within a dense annulus around the fovea center, whereas AAV2 containing the ubiquitous promoter hybrid cytomegalovirus (CMV) enhancer/chicken-β-actin (CBA) transduced both Müller and ganglion cells in a dense circular disc centered on the fovea. With three shorter promoters—human synapsin (hSYN) and the shortened CBA and hCx36 promoters (smCBA and hCx36sh)—AAV2 produced visible transduction, as seen in fundus images, only when the retina was altered by ganglion cell loss or enzymatic vitreolysis. Conclusions. The results in the macaque suggest that intravitreal injection of AAV2 would produce high levels of gene expression at the human fovea, important in retinal gene therapy, but not in the central retina beyond the fovea. PMID:21310920

  17. Disparate Effects of Acute and Chronic Infection with SIVmac239 or SHIV-89.6P on Macaque Plasmacytoid Dendritic Cells

    PubMed Central

    Reeves, R. Keith; Fultz, Patricia N.

    2007-01-01

    Blood plasmacytoid dendritic cells (pDCs) contribute to both innate and adaptive immune responses by secreting high levels of IFN-α following acute bacterial and viral infections and indirectly by augmenting cell-mediated immunity. Cross-sectional studies have shown that the number of circulating pDCs in HIV patients, compared to that in uninfected individuals, is reduced. However, since the time of infection is usually unknown in HIV-infected patients, pDC-virus interactions that occur immediately after virus exposure are poorly understood. The current study investigated pDC dynamics during acute and chronic infections of macaques with either SIVmac239 or the pathogenic SIV-HIV chimera, SHIV-89.6P, as models for HIV infection. In three rhesus and three pig-tailed macaques infected intravenously with SIVmac239, the percentages of pDCs in blood declined 2- to 6-fold during the first 6 weeks after infection and remained depressed throughout the disease course. Surprisingly, no consistent, comparable decline in peripheral blood pDCs was observed in six macaques infected with SHIV-89.6P. In this latter group, percentages of pDCs did not correlate with CD4+ T cells, but there was an inverse relationship with viral load. In addition, when compared to naïve controls, the percentages of pDCs were reduced in spleens and peripheral lymph nodes of SIVmac239- but not SHIV-89.6P-infected animals that had progressed to AIDS. Proviral DNA was detected during the acute phase in pDCs isolated from macaques infected with either virus. These results imply that, even though macaque pDCs can be infected by both SIVmac239 and SHIV-89.6P, the subsequent effects on in vivo pathogenesis differ. The underlying mechanism(s) for these differences is unclear, but the selection of SIV or SHIV as a challenge virus might influence the outcome of some studies, such as those evaluating vaccines or the therapeutic efficacy of drugs. PMID:17490699

  18. Glucoregulatory Function in Adult Rhesus Macaques (Macaca mulatta) Undergoing Treatment with Medroxyprogesterone Acetate for Endometriosis

    PubMed Central

    Cruzen, Christina L; Baum, Scott T; Colman, Ricki J

    2011-01-01

    Endometriosis affects a large percentage of the rhesus macaques (Macaca mulatta) at our institution. When the disease is diagnosed in macaques on long-term research protocols, the treatment of choice in our facility is monthly administration of medroxyprogesterone acetate (MPA) to decrease estrogen release and subsequently diminish clinical signs associated with the disease. Because hormonal fluctuations associated with the normal menstrual cycle are known to affect parameters of glucoregulatory function in rhesus macaques, we evaluated the effect of MPA treatment on glucoregulatory function cross-sectionally in 6 animals and longitudinally in 4 animals with endometriosis. Our hypothesis was that monthly administration of MPA for the treatment of endometriosis would negatively affect glucoregulatory function in rhesus macaques. We found that adult female rhesus macaques on MPA therapy for 1.4 to 36.1 mo had lower insulin sensitivity than did age- and weight-matched healthy control animals. In addition, glucoregulatory function was reduced after MPA treatment as compared with pretreatment levels in a group of 4 macaques. These data suggest that glucoregulatory function should be considered when endometriosis treatment is planned for rhesus macaques. PMID:22330788

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

    PubMed

    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. PMID:26530218

  20. Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

    PubMed Central

    Embers, Monica E.; Barthold, Stephen W.; Borda, Juan T.; Bowers, Lisa; Doyle, Lara; Hodzic, Emir; Jacobs, Mary B.; Hasenkampf, Nicole R.; Martin, Dale S.; Narasimhan, Sukanya; Phillippi-Falkenstein, Kathrine M.; Purcell, Jeanette E.; Ratterree, Marion S.; Philipp, Mario T.

    2012-01-01

    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. PMID:22253822

  1. Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques

    PubMed Central

    Micci, Luca; Ryan, Emily S.; Fromentin, Rémi; Bosinger, Steven E.; Harper, Justin L.; He, Tianyu; Paganini, Sara; Easley, Kirk A.; Chahroudi, Ann; Benne, Clarisse; Gumber, Sanjeev; McGary, Colleen S.; Rogers, Kenneth A.; Deleage, Claire; Lucero, Carissa; Byrareddy, Siddappa N.; Apetrei, Cristian; Estes, Jacob D.; Lifson, Jeffrey D.; Piatak, Michael; Chomont, Nicolas; Villinger, Francois; Silvestri, Guido; Brenchley, Jason M.; Paiardini, Mirko

    2015-01-01

    Despite successful control of viremia, many HIV-infected individuals given antiretroviral therapy (ART) exhibit residual inflammation, which is associated with non–AIDS-related morbidity and mortality and may contribute to virus persistence during ART. Here, we investigated the effects of IL-21 administration on both inflammation and virus persistence in ART-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through 8 months after ART interruption. Additionally, IL-21, in combination with ART, was associated with reduced levels of SIV RNA in plasma and decreased CD4+ T cell levels harboring replication-competent virus during ART. At the latest experimental time points, which were up to 8 months after ART interruption, plasma viremia and cell-associated SIV DNA levels remained substantially lower than those before ART initiation in IL-21–treated animals but not in controls. Together, these data suggest that IL-21 supplementation of ART reduces residual inflammation and virus persistence in a relevant model of lentiviral disease and warrants further investigation as a potential intervention for HIV infection. PMID:26551680

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

    PubMed Central

    Moukambi, Félicien; Rabezanahary, Henintsoa; Rodrigues, Vasco; Racine, Gina; Robitaille, Lynda; Krust, Bernard; Andreani, Guadalupe; Soundaramourty, Calayselvy; Silvestre, Ricardo; Laforge, Mireille; Estaquier, Jérôme

    2015-01-01

    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. PMID:26640894

  3. Enhanced Antiretroviral Therapy in Rhesus Macaques Improves RT-SHIV Viral Decay Kinetics

    PubMed Central

    North, Thomas W.; Villalobos, Andradi; Hurwitz, Selwyn J.; Deere, Jesse D.; Higgins, Joanne; Chatterjee, Payel; Tao, Sijia; Kauffman, Robert C.; Luciw, Paul A.; Kohler, James J.

    2014-01-01

    Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(−)-FTC], tenofovir (TFV), and efavirenz (EFV). The five-drug combination consisted of one analog for each of the four DNA precursors {using TFV, (−)-FTC, (−)-β-d-(2R,4R)-1,3-dioxolane-2,6-diaminopurine (amdoxovir [DAPD]), and zidovudine (AZT)}, together with EFV. A cohort treated with a three-drug combination of (−)-FTC, TFV, and EFV served as treated controls. Daily administration of a three-, four-, or five-drug combination of antiretroviral agents was initiated at week 6 or 8 after inoculation and continued up to week 50, followed by a rebound period. Plasma samples were collected routinely, and drug levels were monitored using liquid chromatography-tandem mass spectrometry (LC–MS-MS). Viral loads were monitored with a standard TaqMan quantitative reverse transcriptase PCR (qRT-PCR) assay. Comprehensive analyses of replication dynamics were performed. RT-SHIV infection in rhesus macaques produced typical viral infection kinetics, with untreated controls establishing persistent viral loads of >104 copies of RNA/ml. RT-SHIV loads at the start of treatment (V0) were similar in all treated cohorts (P > 0.5). All antiretroviral drug levels were measureable in plasma. The four-drug and five-drug combination regimens (enhanced HAART) improved suppression of the viral load (within 1 week; P < 0.01) and had overall greater potency (P < 0.02) than the three-drug regimen (HAART). Moreover, rebound viremia occurred

  4. A spontaneous depressive pattern in adult female rhesus macaques

    PubMed Central

    Qin, Dongdong; Rizak, Joshua; Chu, Xunxun; Li, Zhifei; Yang, Shangchuan; Lü, Longbao; Yang, Lichuan; Yang, Qing; Yang, Bo; Pan, Lei; Yin, Yong; Chen, Lin; Feng, Xiaoli; Hu, Xintian

    2015-01-01

    Non-human primates offer unique opportunities to study the development of depression rooted in behavioral and physiological abnormalities. This study observed adult female rhesus macaques within social hierarchies and aimed to characterize the physiological and brain abnormalities accompanying depressive-like behavior. The behaviors of 31 female rhesus macaques from 14 different breeding groups were video recorded, and the footage was analyzed using the focal animal technique. There were 13 monkeys who never displayed huddling behavior (non-huddlers). The remaining 18 monkeys were divided into two groups according the mean time spent in the huddle posture. Four monkeys were designated as high huddlers, whereas the other 14 monkeys were low huddlers. An inverse relationship was discovered between social rank and depression. High huddlers spent more time engaging in physical contact and in close proximity to other monkeys, as well as less time spontaneously and reactively locomoting, than low huddlers and/or non-huddlers. Cortisol levels measured from the hair were elevated significantly in high huddlers compared with low huddlers and non-huddlers, and the measured cortisol levels were specifically higher in high huddlers than subordinate or dominant control monkeys. Regional cerebral blood flow data revealed significant and widespread decreases in high huddlers compared with non-huddlers. PMID:26059851

  5. Determinants of immigration strategies in male crested macaques (Macaca nigra).

    PubMed

    Marty, Pascal R; Hodges, Keith; Agil, Muhammad; Engelhardt, Antje

    2016-01-01

    Immigration into a new group can produce substantial costs due to resistance from residents, but also reproductive benefits. Whether or not individuals base their immigration strategy on prospective cost-benefit ratios remains unknown. We investigated individual immigration decisions in crested macaques, a primate species with a high reproductive skew in favour of high-ranking males. We found two different strategies. Males who achieved low rank in the new group usually immigrated after another male had immigrated within the previous 25 days and achieved high rank. They never got injured but also had low prospective reproductive success. We assume that these males benefitted from immigrating into a destabilized male hierarchy. Males who achieved high rank in the new group usually immigrated independent of previous immigrations. They recieved injuries more frequently and therefore bore immigration costs. They, however, also had higher reproductive success prospects. We conclude that male crested macaques base their immigration strategy on relative fighting ability and thus potential rank in the new group i.e. potential reproductive benefits, as well as potential costs of injury. PMID:27535622

  6. Improved collection and developmental competence of immature macaque oocytes.

    PubMed

    VandeVoort, C A; Leibo, S P; Tarantal, A F

    2003-02-01

    Methods previously described to aspirate immature oocytes from ovaries of macaques result in approximately half the oocytes being stripped of cumulus cells. Here, we describe modifications of the needle aspiration assembly that yield much higher percentages of cumulus-intact oocytes when used with an ultrasound-guided method for oocyte recovery in monkeys. Sealing of the needle assembly appears to stabilize vacuum pressure at the needle tip and prevents air from entering the tubing. Reduction of the vacuum pressure from -100 to -20 kPa resulted in a significant decrease of denuded oocytes from over 50% to fewer than 10%. This was accompanied by a significant increase in the percentage of oocytes that developed into blastocysts after in vitro fertilization. Reduction of the aspiration pressure below -20 kPa significantly reduced the total number of oocytes recovered. We concluded that these modifications represent the best compromise to collect the largest number of cumulus-intact oocyte complexes from macaques. PMID:12517374

  7. Neonatal amygdala lesions advance pubertal timing in female rhesus macaques

    PubMed Central

    Stephens, Shannon B.Z.; Raper, Jessica; Bachevalier, Jocelyne; Wallen, Kim

    2014-01-01

    Summary Social context influences the timing of puberty in both humans and nonhuman primates, such as delayed first ovulation in low-ranking rhesus macaques, but the brain region(s) mediating the effects of social context on pubertal timing are unknown. The amygdala is important for responding to social information and thus, is a potential brain region mediating the effects of social context on pubertal timing. In this study, female rhesus macaques living in large, species-typical, social groups received bilateral neurotoxic amygdala lesions at one month of age and pubertal timing was examined beginning at 14 months of age. Pubertal timing was affected in neonatal amygdala-lesioned females (Neo-A), such that they experienced significantly earlier menarche and first ovulation than did control females (Neo-C). Duration between menarche and first ovulation did not differ between Neo-A and Neo-C females, indicating earlier first ovulation in Neo-A females was likely a consequence of earlier menarche. Social rank of Neo-A females was related to age at menarche, but not first ovulation, and social rank was not related to either event in Neo-C females. It is more likely that amygdalectomy affects pubertal timing through its modulation of GABA-ergic mechanisms rather than as a result of the removal of a social-contextual inhibition on pubertal timing. PMID:25462903

  8. Macaques can predict social outcomes from facial expressions.

    PubMed

    Waller, Bridget M; Whitehouse, Jamie; Micheletta, Jérôme

    2016-09-01

    There is widespread acceptance that facial expressions are useful in social interactions, but empirical demonstration of their adaptive function has remained elusive. Here, we investigated whether macaques can use the facial expressions of others to predict the future outcomes of social interaction. Crested macaques (Macaca nigra) were shown an approach between two unknown individuals on a touchscreen and were required to choose between one of two potential social outcomes. The facial expressions of the actors were manipulated in the last frame of the video. One subject reached the experimental stage and accurately predicted different social outcomes depending on which facial expressions the actors displayed. The bared-teeth display (homologue of the human smile) was most strongly associated with predicted friendly outcomes. Contrary to our predictions, screams and threat faces were not associated more with conflict outcomes. Overall, therefore, the presence of any facial expression (compared to neutral) caused the subject to choose friendly outcomes more than negative outcomes. Facial expression in general, therefore, indicated a reduced likelihood of social conflict. The findings dispute traditional theories that view expressions only as indicators of present emotion and instead suggest that expressions form part of complex social interactions where individuals think beyond the present. PMID:27155662

  9. Opposite-sex social bonding in wild Assamese macaques.

    PubMed

    Haunhorst, Christine B; Schülke, Oliver; Ostner, Julia

    2016-08-01

    In large multimale-multifemale primate groups, individual adult males and females may form close social relationships that extend beyond the mating context, a surprising finding for polygynandrous mammals. The patterns of these associations can be relatively stable across time. Here we investigate whether dyadic social relationships between the sexes transcend mere association in wild Assamese macaques and may be characterized as strong, equitable, and stable affiliative relationships or social bonds. We collected >9,000 hr of focal animal data on adult males and females from two groups of wild Assamese macaques (Macaca assamensis) at Phu Khieo Wildlife Sanctuary, Thailand. Using dyadic composite sociality indices, we found male-female affiliative relationships to be highly differentiated. The stronger the relationships were, the more likely partners were to reciprocate grooming and the more stable were the relationships. In addition, the strongest dyadic relationships remained stable over multiple years as long as both partners remained in the group. These results indicate that in a polygynous species particular males and females form strong, equitable, and enduring affiliative relationships qualitatively similar to the same-sex bonds described for female baboons and male chimpanzees. Am. J. Primatol. 78:872-882, 2016. © 2016 Wiley Periodicals, Inc. PMID:27120312

  10. Invasive Ductular Carcinoma in 2 Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Beck, Amanda P; Brooks, Amos; Zeiss, Caroline J

    2014-01-01

    In the United States, breast cancer is the most common malignancy among women, with an estimated lifetime incidence of approximately 12% in American women. Invasive ductal carcinoma is the most common form of breast cancer in women, accounting for approximately 60% of all breast carcinomas. Prognostic markers are used to assess aggressiveness, invasiveness, and extent of spread of a neoplasm and thus may be correlated with patient survival. Immunohistochemistry is currently widely used for this purpose, with a variety of prognostication markers available. Classic markers for breast cancer in women include estrogen and progesterone receptor steroid hormone proteins and human epidermal growth factor receptor 2. Many additional markers have been used in diagnosis and prognostication, including p53, p63, and E-cadherin and cell proliferation markers such as Ki67. Despite an estimated lifetime incidence of approximately 6.1%, naturally occurring mammary neoplasms in nonhuman primates are uncommonly reported, with only sporadic references over the past 75 y. The majority of reported tumors occur in rhesus macaques, although this prevalence has been suggested to be a consequence of their high frequency of usage in biomedical research. Here we present 2 cases of mammary carcinoma in adult female intact rhesus macaques, with cytology, histopathology, and extensive immunohistochemical analysis. According to current classifications for human breast tumors, both tumors were classified as invasive ductal carcinoma. The prognostic value of immunohistochemical markers in human breast cancer and in reported cases in nonhuman primates is discussed. PMID:25296018

  11. Visceral and Neural Larva Migrans in Rhesus Macaques

    PubMed Central

    Gozalo, Alfonso S; Maximova, Olga A; StClaire, Marisa C; Montali, Richard J; Ward, Jerrold M; Cheng, Lily I; Elkins, William R; Kazacos, Kevin R

    2008-01-01

    Large ascarid larvae within granulomas were noted histologically in the mesenteric and pancreatic lymph nodes of 13 of 21 rhesus macaques (Macaca mulatta) euthanized as part of an experimental viral pathogenesis study. In addition, 7 of the 13 monkeys had cerebral granulomas, which in 4 animals contained nematode larvae similar to those within the lymph nodes. Despite the lesions, the animals did not show clinical signs associated with the parasitic infections. Characteristics of the larvae included, on cross-section, a midbody diameter of approximately 60 to 80 µm, a centrally located and slightly compressed intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. The morphology of the larvae was compatible with Baylisascaris spp. Baylisascariasis is a well-described infection of animals and humans that is caused by migrating larvae of the raccoon roundworm, Baylisascaris procyonis. A similar species, B. columnaris, is found in skunks and can cause cerebrospinal nematodiasis, but most reported cases of baylisascariasis have been due to B. procyonis. Our macaques were born free-ranging on an island in the southeastern United States where raccoons, but not skunks, were found to be common inhabitants, indicating that B. procyonis was the most likely parasite involved. These cases are similar to the low-level or covert cases of Baylisascaris infection described to occur in humans and provide further evidence of the existence of this parasite in the southeastern United States. PMID:18702454

  12. A spontaneous depressive pattern in adult female rhesus macaques.

    PubMed

    Qin, Dongdong; Rizak, Joshua; Chu, Xunxun; Li, Zhifei; Yang, Shangchuan; Lü, Longbao; Yang, Lichuan; Yang, Qing; Yang, Bo; Pan, Lei; Yin, Yong; Chen, Lin; Feng, Xiaoli; Hu, Xintian

    2015-01-01

    Non-human primates offer unique opportunities to study the development of depression rooted in behavioral and physiological abnormalities. This study observed adult female rhesus macaques within social hierarchies and aimed to characterize the physiological and brain abnormalities accompanying depressive-like behavior. The behaviors of 31 female rhesus macaques from 14 different breeding groups were video recorded, and the footage was analyzed using the focal animal technique. There were 13 monkeys who never displayed huddling behavior (non-huddlers). The remaining 18 monkeys were divided into two groups according the mean time spent in the huddle posture. Four monkeys were designated as high huddlers, whereas the other 14 monkeys were low huddlers. An inverse relationship was discovered between social rank and depression. High huddlers spent more time engaging in physical contact and in close proximity to other monkeys, as well as less time spontaneously and reactively locomoting, than low huddlers and/or non-huddlers. Cortisol levels measured from the hair were elevated significantly in high huddlers compared with low huddlers and non-huddlers, and the measured cortisol levels were specifically higher in high huddlers than subordinate or dominant control monkeys. Regional cerebral blood flow data revealed significant and widespread decreases in high huddlers compared with non-huddlers. PMID:26059851

  13. Feedback loop between kinship and dominance: the macaque model.

    PubMed

    Thierry, B

    1990-08-23

    There is growing evidence that macaque social systems represent sets of coadapted traits in which strength of hierarchies and degree of nepotism covary. A framework is developed to explain the link between dominance and kinship phenomena, assuming that power brought by alliances among non-kin is allometrically related to those involving relatives. This can account for the type of social relationships observed in "despotic" systems vs. "egalitarian" ones. When social bonds are mostly founded on kinship, lineages are closed and social power generated by coalitions among relatives may reach high levels; social power frequently outweighs the fighting abilities of single individuals, and asymmetry of dominance between group members may be marked. When lineages are more open, social bonds and alliances are less kin-biased, social relationships are more equal, and as the influence of coalitions is less important, the individual retains a certain degree of freedom in relation to the power of kin-networks. Acknowledging that the balance between individual and social power is not set at the same level across different species can explain a number of variations in rules of rank inheritance and relative dominance of males and females among macaques. The framework illustrates how epigenetic processes may shape complex features of primate social systems, and offers opportunities for testing. PMID:2246899

  14. Rudimentary empathy in macaques' social decision-making.

    PubMed

    Ballesta, Sebastien; Duhamel, Jean-René

    2015-12-15

    Primates live in highly social environments, where prosocial behaviors promote social bonds and cohesion and contribute to group members' fitness. Despite a growing interest in the biological basis of nonhuman primates' social interactions, their underlying motivations remain a matter of debate. We report that macaque monkeys take into account the welfare of their peers when making behavioral choices bringing about pleasant or unpleasant outcomes to a monkey partner. Two macaques took turns in making decisions that could impact their own welfare or their partner's. Most monkeys were inclined to refrain from delivering a mildly aversive airpuff and to grant juice rewards to their partner. Choice consistency between these two types of outcome suggests that monkeys display coherent motivations in different social interactions. Furthermore, spontaneous affilitative group interactions in the home environment were mostly consistent with the measured social decisions, thus emphasizing the impact of preexisting social bonds on decision-making. Interestingly, unique behavioral markers predicted these decisions: benevolence was associated with enhanced mutual gaze and empathic eye blinking, whereas indifference or malevolence was associated with lower or suppressed such responses. Together our results suggest that prosocial decision-making is sustained by an intrinsic motivation for social affiliation and controlled through positive and negative vicarious reinforcements. PMID:26621711

  15. Physiology and Endocrinology of the Ovarian Cycle in Macaques

    PubMed Central

    Weinbauer, Gerhard F.; Niehoff, Marc; Niehaus, Michael; Srivastav, Shiela; Fuchs, Antje; Van Esch, Eric; Cline, J. Mark

    2009-01-01

    Macaques provide excellent models for preclinical testing and safety assessment of female reproductive toxicants. Currently, cynomolgus monkeys are the predominant species for (reproductive) toxicity testing. Marmosets and rhesus monkeys are being used occasionally. The authors provide a brief review on physiology and endocrinology of the cynomolgus monkey ovarian cycle, practical guidance on assessment and monitoring of ovarian cyclicity, and new data on effects of social housing on ovarian cyclicity in toxicological studies. In macaques, cycle monitoring is achieved using daily vaginal smears for menstruation combined with cycle-timed frequent sampling for steroid and peptide hormone analysis. Owing to requirements of frequent and timed blood sampling, it is not recommended to incorporate these special evaluations into a general toxicity study design. Marmosets lack external signs of ovarian cyclicity, and cycle monitoring is done by regular determinations of progesterone. Cynomolgus and marmoset monkeys do not exhibit seasonal variations in ovarian activity, whereas such annual rhythm is pronounced in rhesus monkeys. Studies on pair- and group-housed cynomolgus monkeys revealed transient alterations in the duration and endocrinology of the ovarian cycle followed by return to normal cyclicity after approximately six months. This effect is avoided if the animals had contact with each other prior to mingling. These experiments also demonstrated that synchronization of ovarian cycles did not occur. PMID:20852722

  16. Familiar and unfamiliar face recognition in crested macaques (Macaca nigra)

    PubMed Central

    Micheletta, Jérôme; Whitehouse, Jamie; Parr, Lisa A.; Marshman, Paul; Engelhardt, Antje; Waller, Bridget M.

    2015-01-01

    Many species use facial features to identify conspecifics, which is necessary to navigate a complex social environment. The fundamental mechanisms underlying face processing are starting to be well understood in a variety of primate species. However, most studies focus on a limited subset of species tested with unfamiliar faces. As well as limiting our understanding of how widely distributed across species these skills are, this also limits our understanding of how primates process faces of individuals they know, and whether social factors (e.g. dominance and social bonds) influence how readily they recognize others. In this study, socially housed crested macaques voluntarily participated in a series of computerized matching-to-sample tasks investigating their ability to discriminate (i) unfamiliar individuals and (ii) members of their own social group. The macaques performed above chance on all tasks. Familiar faces were not easier to discriminate than unfamiliar faces. However, the subjects were better at discriminating higher ranking familiar individuals, but not unfamiliar ones. This suggests that our subjects applied their knowledge of their dominance hierarchies to the pictorial representation of their group mates. Faces of high-ranking individuals garner more social attention, and therefore might be more deeply encoded than other individuals. Our results extend the study of face recognition to a novel species, and consequently provide valuable data for future comparative studies. PMID:26064665

  17. MHC and KIR Polymorphisms in Rhesus Macaque SIV Infection

    PubMed Central

    Walter, Lutz; Ansari, Aftab A.

    2015-01-01

    Natural killer lymphocytes are essentially involved as the first line of defense against agents such as viruses and malignant cells. The activity of these cells is regulated via interaction of specific and diverse killer cell immunoglobulin-like receptors (KIR) with the highly polymorphic cognate MHC class I proteins on target cells. Genetic variability of both KIR and MHC-I ligands has been shown to be associated with resistance to many diseases, including infection with the immunodeficiency virus. Disease course and progression to AIDS after infection with human immunodeficiency virus-1 (HIV-1) is essentially influenced by the presence of the stimulatory KIR3DS1 receptor in combination with HLA-Bw4. Knowledge of such genetic interactions that contribute to not only disease resistance but also susceptibility are just as important. Such combined genetic factors were recently reported in the rhesus macaque AIDS model. Here, we review the rhesus macaque MHC class I and KIR gene systems and the role of their polymorphisms in the SIV infection model. PMID:26557119

  18. Visceral and neural larva migrans in rhesus macaques.

    PubMed

    Gozalo, Alfonso S; Maximova, Olga A; StClaire, Marisa C; Montali, Richard J; Ward, Jerrold M; Cheng, Lily I; Elkins, William R; Kazacos, Kevin R

    2008-07-01

    Large ascarid larvae within granulomas were noted histologically in the mesenteric and pancreatic lymph nodes of 13 of 21 rhesus macaques (Macaca mulatta) euthanized as part of an experimental viral pathogenesis study. In addition, 7 of the 13 monkeys had cerebral granulomas, which in 4 animals contained nematode larvae similar to those within the lymph nodes. Despite the lesions, the animals did not show clinical signs associated with the parasitic infections. Characteristics of the larvae included, on cross-section, a midbody diameter of approximately 60 to 80 mum, a centrally located and slightly compressed intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. The morphology of the larvae was compatible with Baylisascaris spp. Baylisascariasis is a well-described infection of animals and humans that is caused by migrating larvae of the raccoon roundworm, Baylisascaris procyonis. A similar species, B. columnaris, is found in skunks and can cause cerebrospinal nematodiasis, but most reported cases of baylisascariasis have been due to B. procyonis. Our macaques were born free-ranging on an island in the southeastern United States where raccoons, but not skunks, were found to be common inhabitants, indicating that B. procyonis was the most likely parasite involved. These cases are similar to the low-level or covert cases of Baylisascaris infection described to occur in humans and provide further evidence of the existence of this parasite in the southeastern United States. PMID:18702454

  19. Oxytocin blunts social vigilance in the rhesus macaque

    PubMed Central

    Ebitz, R. Becket; Watson, Karli K.; Platt, Michael L.

    2013-01-01

    Exogenous application of the neuromodulatory hormone oxytocin (OT) promotes prosocial behavior and can improve social function. It is unclear, however, whether OT promotes prosocial behavior per se, or whether it facilitates social interaction by reducing a state of vigilance toward potential social threats. To disambiguate these two possibilities, we exogenously delivered OT to male rhesus macaques, which have a characteristic pattern of species-typical social vigilance, and examined their performance in three social attention tasks. We first determined that, in the absence of competing task demands or goals, OT increased attention to faces and eyes, as in humans. By contrast, OT reduced species typical social vigilance for unfamiliar, dominant, and emotional faces in two additional tasks. OT eliminated the emergence of a typical state of vigilance when dominant face images were available during a social image choice task. Moreover, OT improved performance on a reward-guided saccade task, despite salient social distractors: OT reduced the interference of unfamiliar faces, particularly emotional ones, when these faces were task irrelevant. Together, these results demonstrate that OT suppresses vigilance toward potential social threats in the rhesus macaque. We hypothesize that a basic role for OT in regulating social vigilance may have facilitated the evolution of prosocial behaviors in humans. PMID:23798448

  20. Determinants of immigration strategies in male crested macaques (Macaca nigra)

    PubMed Central

    Marty, Pascal R.; Hodges, Keith; Agil, Muhammad; Engelhardt, Antje

    2016-01-01

    Immigration into a new group can produce substantial costs due to resistance from residents, but also reproductive benefits. Whether or not individuals base their immigration strategy on prospective cost-benefit ratios remains unknown. We investigated individual immigration decisions in crested macaques, a primate species with a high reproductive skew in favour of high-ranking males. We found two different strategies. Males who achieved low rank in the new group usually immigrated after another male had immigrated within the previous 25 days and achieved high rank. They never got injured but also had low prospective reproductive success. We assume that these males benefitted from immigrating into a destabilized male hierarchy. Males who achieved high rank in the new group usually immigrated independent of previous immigrations. They recieved injuries more frequently and therefore bore immigration costs. They, however, also had higher reproductive success prospects. We conclude that male crested macaques base their immigration strategy on relative fighting ability and thus potential rank in the new group i.e. potential reproductive benefits, as well as potential costs of injury. PMID:27535622

  1. How posture affects macaques' reach-to-grasp movements.

    PubMed

    Sartori, Luisa; Camperio-Ciani, Andrea; Bulgheroni, Maria; Castiello, Umberto

    2014-03-01

    Although there is a wealth of behavioral data regarding grasping movements in non-human primates, how posture influences the kinematics of prehensile behavior is not yet clearly understood. The purpose of this study was to examine and compare kinematic descriptions of grip behaviors while primates (macaque monkeys) were in a sitting posture or when stopping after quadrupedal locomotion (i.e., tripedal stance). Video footage taken while macaques grasped objects was analyzed frame-by-frame using digitalization techniques. Each of the two grip types considered (power and precision grips) was found to be characterized by specific, distinct kinematic signatures for both the reaching and the grasping components when those actions were performed in a sitting position. The grasping component did not differentiate in relation to the type of grip that was needed when, instead, the prehensile action took place in a tripedal stance. Quadrupedal locomotion affected the concomitant organization of prehensile activities determining in fact a similar kinematic patterning for the two grips regardless of the size of the object to be grasped. It is suggested that using a single kinematic grip patterning for all prehensile activities might be both the by-product of planning a grasping action while walking and a way to simplify motor programming during unstable tripedal stance. PMID:24337352

  2. Corynebacterium faecale sp. nov., isolated from the faeces of Assamese macaque.

    PubMed

    Chen, Xiu; Li, Gui-Ding; Li, Qin-Yuan; Hu, Cai-Juan; Liu, Cheng-Bin; Jiang, Yi; Jiang, Cheng-Lin; Han, Li; Huang, Xue-Shi

    2016-07-01

    A Gram-stain-positive, facultatively anaerobic, short rod-shaped, oxidase-negative and non-motile novel strain, designated YIM 101505T, was isolated from the faeces of a primate, Assamese macaque, and was studied to determine its taxonomic position. The cell wall contained meso-diaminopimelic acid and short-chain mycolic acids. Whole cell sugars were mannose, galactose and arabinose as major components. The major fatty acids (>10 %) were C18 : 1ω9c, C16 : 0 and C17 : 1ω8c and the major menaquinone was MK-9(H2). The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, glycolipid and six unidentified lipids. The new isolate shared most of the typical chemotaxonomic characteristics of members of the genus Corynebacterium. The closest related species was Corynebacterium efficiens based on 16S rRNA gene (98.1 % similarity) and partial rpoB gene (91.4 % similarity) sequences. Similarities with other species of this genus were below 97 % based on the 16S rRNA gene. The DNA-DNA hybridization value between YIM 101505T and C. efficiens DSM 44549T was 47.7±3.6 %. Moreover, the physiological and biochemical characteristics of YIM 101505T and C. efficiens DSM 44549T were different. Thus, strain YIM 101505T is considered to represent a novel member of the genus Corynebacterium, for which the name Corynebacterium faecale sp. nov. is proposed. The type strain is YIM 101505T (=DSM 45971T=CCTCC AB 2013226T). PMID:27073837

  3. Enhanced cell immune responses to hepatitis C virus core by novel heterologous DNA prime/lambda nanoparticles boost in mice.

    PubMed

    Saeedi, Atefeh; Ghaemi, Amir; Tabarraei, Alijan; Moradi, Abdolvahab; Gorji, Ali; Semnani, Shahryar; Soleimanjahi, Hoorieh; Adli, Ahmad Hosseinzadeh; Hosseini, Seyed Yones; Vakili, Mohammad Ali

    2014-08-01

    Hepatitis C virus (HCV) is a worldwide problem which does not have an effective vaccine and more than 170 million people worldwide are chronically infected by HCV. T cell responses are associated with spontaneous clearance of HCV infection. We report here the development of recombinant Lambda bacteriophage nanoparticles encoding HCV Core antigen. The aim of this study was to investigate the antigen-specific immune responses triggered in mice by different prime-boost combinations of DNA and Lambda phage nanoparticles encoding the HCV Core. The homologous prime/boost with recombinant Lambda nanoparticles induced higher levels of cellular and humoral immune response than the DNA vaccines. However, a heterologous prime/boost of HCV Core protein, using DNA vaccine priming followed by Lambda boost, induced highest level of lymphocyte proliferation, CD8 lymphocytes with cytotoxic function, and shifting the immune response toward a T helper (Th1) pattern and in overall improved immunity. Our study provides a new, safe, and effective vaccine for the prime-boost regimen which augments robust immunity and highlights novel promising strategies in HCV vaccine development. PMID:24752903

  4. A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus.

    PubMed

    Martín-Acebes, Miguel A; Blázquez, Ana-Belén; Cañas-Arranz, Rodrigo; Vázquez-Calvo, Ángela; Merino-Ramos, Teresa; Escribano-Romero, Estela; Sobrino, Francisco; Saiz, Juan-Carlos

    2016-04-19

    Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus-host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (-/-) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model, a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPs). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (-/-) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (-/-) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen. PMID:26993334

  5. Faces in Motion: Selectivity of Macaque and Human Face Processing Areas for Dynamic Stimuli

    PubMed Central

    Polosecki, Pablo; Moeller, Sebastian; Schweers, Nicole; Romanski, Lizabeth M.; Tsao, Doris Y.

    2013-01-01

    Face recognition mechanisms need to extract information from static and dynamic faces. It has been hypothesized that the analysis of dynamic face attributes is performed by different face areas than the analysis of static facial attributes. To date, there is no evidence for such a division of labor in macaque monkeys. We used fMRI to determine specializations of macaque face areas for motion. Face areas in the fundus of the superior temporal sulcus responded to general object motion; face areas outside of the superior temporal sulcus fundus responded more to facial motion than general object motion. Thus, the macaque face-processing system exhibits regional specialization for facial motion. Human face areas, processing the same stimuli, exhibited specializations for facial motion as well. Yet the spatial patterns of facial motion selectivity differed across species, suggesting that facial dynamics are analyzed differently in humans and macaques. PMID:23864665

  6. Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV).

    PubMed Central

    Chalifoux, L. V.; Ringler, D. J.; King, N. W.; Sehgal, P. K.; Desrosiers, R. C.; Daniel, M. D.; Letvin, N. L.

    1987-01-01

    A T-cell tropic lentivirus of macaques the simian immunodeficiency virus (SIV), has morphologic, growth, and antigenic properties that indicate that it is related to the human immunodeficiency virus (HIV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Six juvenile macaques developed persistent lymphadenopathy (greater than 3 months in duration) after inoculation with SIV. The histologic appearance of the lymph nodes was characterized by marked follicular hyperplasia with abundant proliferative B cells infiltrating into the paracortex. The number of T8-positive lymphocytes equaled or exceeded the number of T4-positive lymphocytes in the paracortex. These findings, in association with immunologic abnormalities and a previously observed fatal immunodeficiency syndrome in SIV-infected macaques, provide further evidence of the importance of SIV-induced disease in macaques as a model for the study of AIDS. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3037910

  7. A Chinese rhesus macaque (Macaca mulatta) model for vaginal Lactobacillus colonization and live microbicide development

    PubMed Central

    Yu, Rosa R.; Cheng, Andrew T.; Lagenaur, Laurel A.; Huang, Wenjun; Weiss, Deborah E.; Treece, Jim; Sanders-Beer, Brigitte E.; Hamer, Dean H.; Lee, Peter P.; Xu, Qiang; Liu, Yang

    2015-01-01

    Background We sought to establish a nonhuman primate model of vaginal Lactobacillus colonization suitable for evaluating live microbial microbicide candidates. Methods Vaginal and rectal microflora in Chinese rhesus macaques (Macaca mulatta) were analyzed, with cultivable bacteria identified by 16S rRNA gene sequencing. Live lactobacilli were intravaginally administered to evaluate bacterial colonization. Results Chinese rhesus macaques harbored abundant vaginal Lactobacillus, with Lactobacillus johnsonii as the predominant species. Like humans, most examined macaques harbored only one vaginal Lactobacillus species. Vaginal and rectal Lactobacillus isolates from the same animal exhibited different genetic and biochemical profiles. Vaginal Lactobacillus was cleared by a vaginal suppository of azithromycin, and endogenous L. johnsonii was subsequently restored by intravaginal inoculation. Importantly, prolonged colonization of a human vaginal Lactobacillus jensenii was established in these animals. Conclusions The Chinese rhesus macaque harbors vaginal Lactobacillus and is a potentially useful model to support the pre-clinical evaluation of Lactobacillus-based topical microbicides. PMID:19367737

  8. Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host

    PubMed Central

    Okamoto, Munehiro; Miyazawa, Takayuki; Morikawa, Shigeru; Ono, Fumiko; Nakamura, Shota; Sato, Eiji; Yoshida, Tomoyuki; Yoshikawa, Rokusuke; Sakai, Kouji; Mizutani, Tetsuya; Nagata, Noriyo; Takano, Jun-ichiro; Okabayashi, Sachi; Hamano, Masataka; Fujimoto, Koji; Nakaya, Takaaki; Iida, Tetsuya; Horii, Toshihiro; Miyabe-Nishiwaki, Takako; Watanabe, Akino; Kaneko, Akihisa; Saito, Akatsuki; Matsui, Atsushi; Hayakawa, Toshiyuki; Suzuki, Juri; Akari, Hirofumi; Matsuzawa, Tetsuro; Hirai, Hirohisa

    2015-01-01

    We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers. PMID:25743183

  9. Evidence That Emotion Mediates Social Attention in Rhesus Macaques

    PubMed Central

    Bethell, Emily J.; Holmes, Amanda; MacLarnon, Ann; Semple, Stuart

    2012-01-01

    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 provides novel

  10. Temperament in rhesus, long-tailed, and pigtailed macaques varies by species and sex

    PubMed Central

    Sussman, Adrienne F.; Ha, James C.; Bentson, Kathy L.; Crockett, Carolyn M.

    2012-01-01

    Temperament differs among individuals both within and between species. Evidence suggests that differences in temperament of group members may parallel differences in social behavior among groups or between species. Here, we compared temperament between three closely related species of monkey - rhesus (Macaca mulatta), long-tailed (M. fascicularis), and pigtailed (M. nemestrina) macaques - using cage-front behavioral observations of individually housed monkeys at a National Primate Research Center. Frequencies of 12 behaviors in 899 subjects were analyzed using a PCA to identify temperament components. The analysis identified four components, which we interpreted as Sociability towards humans, Cautiousness, Aggressiveness, and Fearfulness. Species and sexes differed in their average scores on these components, even after controlling for differences in age and early-life experiences. Our results suggest that rhesus macaques are especially aggressive and unsociable towards humans, long-tailed macaques are more cautious and fearful, and pigtailed macaques are more sociable towards humans and less aggressive than the other species. Pigtailed males were notably more sociable than any other group. The differences observed are consistent with reported variation in these species’ social behaviors, as rhesus macaques generally engage in more social aggression and pigtailed macaques engage in more male-male affiliative behaviors. Differences in predation risks are among the socioecological factors that might make these species-typical behaviors adaptive. Our results suggest that adaptive species-level social differences may be encoded in individual-level temperaments, which are manifested even outside of a social context. PMID:23225368

  11. Glial cell morphological and density changes through the lifespan of rhesus macaques.

    PubMed

    Robillard, Katelyn N; Lee, Kim M; Chiu, Kevin B; MacLean, Andrew G

    2016-07-01

    How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging. The present study analyzed changes in glial morphology and density through the entire lifespan of rhesus macaques, which are physiologically and anatomically similar to humans. We observed apparent increases in gray matter astrocytic process length and process complexity as rhesus macaques matured from juveniles through adulthood. These changes were not attributed to cell enlargement because they were not accompanied by proportional changes in soma or process volume. There was a decrease in white matter microglial process length as rhesus macaques aged. Aging was shown to have a significant effect on gray matter microglial density, with a significant increase in aged macaques compared with adults. Overall, we observed significant changes in glial morphology as macaques age indicative of astrocytic activation with subsequent increase in microglial density in aged macaques. PMID:26851132

  12. Dietary adaptations of Assamese macaques (Macaca assamensis) in limestone forests in Southwest China.

    PubMed

    Huang, Zhonghao; Huang, Chengming; Tang, Chuangbin; Huang, Libin; Tang, Huaxing; Ma, Guangzhi; Zhou, Qihai

    2015-02-01

    Limestone hills are an unusual habitat for primates, prompting them to evolve specific behavioral adaptations to the component karst habitat. From September 2012 to August 2013, we collected data on the diet of one group of Assamese macaques living in limestone forests at Nonggang National Nature Reserve, Guangxi Province, China, using instantaneous scan sampling. Assamese macaques were primarily folivorous, young leaves accounting for 75.5% and mature leaves an additional 1.8% of their diet. In contrast, fruit accounted for only 20.1%. The young leaves of Bonia saxatilis, a shrubby, karst-endemic bamboo that is superabundant in limestone hills, comprised the bulk of the average monthly diet. Moreover, macaques consumed significantly more bamboo leaves during the season when the availability of fruit declined, suggesting that bamboo leaves are an important fallback food for Assamese macaques in limestone forests. In addition, diet composition varied seasonally. The monkeys consumed significantly more fruit and fewer young leaves in the fruit-rich season than in the fruit-lean season. Fruit consumption was positively correlated with fruit availability, indicating that fruit is a preferred food for Assamese macaques. Of seventy-eight food species, only nine contributed >0.5% of the annual diet, and together these nine foods accounted for 90.7% of the annual diet. Our results suggest that bamboo consumption represents a key factor in the Assamese macaque's dietary adaptation to limestone habitat. PMID:25231871

  13. Antemortem Screening for Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta).

    PubMed

    Haertel, Andrew J; Stern, Joshua A; Reader, J Rachel; Spinner, Abigail; Roberts, Jeffrey A; Christe, Kari L

    2016-01-01

    Concentric left ventricular hypertrophy (LVH) is a hallmark finding in hypertrophic cardiomyopathy that leads to diastolic dysfunction and variable cardiac consequences as severe as congestive heart failure and sudden cardiac death. LVH was diagnosed postmortem in a large colony of rhesus macaques (Macaca mulatta), but methods to screen and diagnose LVH in living animals are desired. We hypothesized that targeted echocardiography of macaques with a familial association of LVH would yield antemortem LVH diagnoses. We also hypothesized that cardiac biomarker levels would be higher in sudden-death LVH or occult LVH than controls and that cardiac troponin I (cTnI) levels would be higher in macaques housed outdoors than indoors. Sera were assayed for cardiac biomarkers (cTnI, C-reactive protein, creatinine kinase-MB, creatine phosphokinase, and LDH), in conjunction with echocardiography, after diagnosis by postmortem exam or from animals with different levels of exercise due to indoor compared with outdoor housing. None of the investigated biomarkers were associated with LVH. cTnI levels were significantly higher in serum collected from outdoor than indoor macaques. In addition, LVH was diagnosed in 29.4% of subjects with a familial association of LVH. These findings suggest that exercise may increase cTnI levels in rhesus macaques and that targeted echocardiography of rhesus macaques with a familial association of LVH was the most useful variable examined for disease surveillance. PMID:27538864

  14. Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques

    PubMed Central

    2013-01-01

    Background Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viability in vivo, however, as well as immunogenicity and antibody persistence, were unknown. Results This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustly in vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells. Conclusions Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge. PMID:24041113

  15. Cloning and characterization of equine CD89 and identification of the CD89 gene in chimpanzees and rhesus macaques.

    PubMed

    Morton, H Craig; Pleass, Richard J; Storset, Anne K; Brandtzaeg, Per; Woof, Jenny M

    2005-05-01

    Immunoglobulin A (IgA) is the major antibody class present in external secretions of mammals. At the vulnerable mucosal surfaces, IgA provides a crucial first-line defence by neutralizing pathogens. Primates also have a substantial level of IgA in serum and although not well understood, the biological role of this IgA depends, at least partly, on its ability to interact with specific receptors (FcalphaRs) on the surface of leucocytes. The human FcalphaR, CD89, was the first IgA Fc receptor to be identified and binding of IgA-coated particles to CD89 triggers numerous cellular effector functions, including phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators, all of which may play an important role in both systemic and mucosal immunity. For many years humans were the only species known to express CD89, however, it has recently been cloned from cows and rats. Here, we describe the identification of the CD89 gene in three additional species: horses, chimpanzees, and Rhesus macaques. Equine CD89 was identified at the cDNA level, whereas the chimpanzee and Rhesus macaque genes were identified from the available draft genomic sequence. Interestingly, when compared with humans and other primates, horses, cows and rats have a relatively low concentration of serum IgA, so the role of CD89 in these species is of particular interest. The identification and characterization of CD89 in different species will contribute to a greater understanding of the biological role of IgA and CD89 in mucosal and systemic immunity throughout evolution. PMID:15819699

  16. Semen CD4+ T Cells and Macrophages Are Productively Infected at All Stages of SIV infection in Macaques

    PubMed Central

    Bernard-Stoecklin, Sibylle; Gommet, Céline; Corneau, Aurélien B.; Guenounou, Sabrina; Torres, Claire; Dejucq-Rainsford, Nathalie; Cosma, Antonio; Dereuddre-Bosquet, Nathalie; Le Grand, Roger

    2013-01-01

    The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4+ T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4+ T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure. PMID:24348253

  17. Mixed Fortunes: Ancient Expansion and Recent Decline in Population Size of a Subtropical Montane Primate, the Arunachal Macaque Macaca munzala

    PubMed Central

    Chakraborty, Debapriyo; Sinha, Anindya; Ramakrishnan, Uma

    2014-01-01

    Quaternary glacial oscillations are known to have caused population size fluctuations in many temperate species. Species from subtropical and tropical regions are, however, considerably less studied, despite representing most of the biodiversity hotspots in the world including many highly threatened by anthropogenic activities such as hunting. These regions, consequently, pose a significant knowledge gap in terms of how their fauna have typically responded to past climatic changes. We studied an endangered primate, the Arunachal macaque Macaca munzala, from the subtropical southern edge of the Tibetan plateau, a part of the Eastern Himalaya biodiversity hotspot, also known to be highly threatened due to rampant hunting. We employed a 534 bp-long mitochondrial DNA sequence and 22 autosomal microsatellite loci to investigate the factors that have potentially shaped the demographic history of the species. Analysing the genetic data with traditional statistical methods and advance Bayesian inferential approaches, we demonstrate a limited effect of past glacial fluctuations on the demographic history of the species before the last glacial maximum, approximately 20,000 years ago. This was, however, immediately followed by a significant population expansion possibly due to warmer climatic conditions, approximately 15,000 years ago. These changes may thus represent an apparent balance between that displayed by the relatively climatically stable tropics and those of the more severe, temperate environments of the past. This study also draws attention to the possibility that a cold-tolerant species like the Arunachal macaque, which could withstand historical climate fluctuations and grow once the climate became conducive, may actually be extremely vulnerable to anthropogenic exploitation, as is perhaps indicated by its Holocene ca. 30-fold population decline, approximately 3,500 years ago. Our study thus provides a quantitative appraisal of these demographically important

  18. Cerebral Baylisascaris larva migrans in a cynomolgus macaque (Macaca fascicularis).

    PubMed

    Shoieb, Ahmed; Radi, Zaher A

    2014-08-01

    An incidental, asymptomatic, focal inflammatory lesion was detected in brain cerebrum of an approximately 6-year-old, female cynomolgus macaque from a chronic toxicology study. No gross lesions were noted at necropsy. Microscopically, the lesion contained a cross-section of larvae approximately 70-80 μm in diameter, a centrally located intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. Mixed inflammatory cells of eosinophils, macrophages, and lymphocytes admixed with abundant connective tissue stroma and necrosis surrounded the larvae. Histochemical stains for trichrome revealed significant amount of fibrous connective tissue. The morphology of the larvae was compatible with Baylisascaris spp. Based on the microscopic and histochemical examination, a diagnosis of neural Baylisascaris spp. larva migrans was made. PMID:24795276

  19. Variation in Clitoral Length in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Goldschmidt, Beatriz; Cabello, Pedro H; Kugelmeier, Tatiana; Pereira, Barbara B; Lopes, Claudia A; Fasano, Daniele M; Andrade, Marcia C; Santos, Joice S; Marinho, Antonio M

    2009-01-01

    Clitoromegaly in the neonatal period is an important morphologic sign that can be useful for sexual determination in aberrant cases. In rhesus monkeys, differentiation of the external genitalia occurs early during gestation (at 55 to 60 d) and is complete by approximately 80 d. Most of the critical steps in genital differentiation in primates occur prenatally. We sought to determine clitoral size in normal rhesus monkeys (Macaca mulatta) and possible effects of age and inheritance. Clitoral length was highly variable and had no relationship to fertility. Statistical evaluation revealed no association in the distribution of daughters with and without clitoris between mothers with and without clitoris. However, even when mated with several female monkeys, some male macaques produced primarily daughters without clitoris. PMID:19807967

  20. State dependence of noise correlations in macaque primary visual cortex

    PubMed Central

    Ecker, Alexander S.; Berens, Philipp; Cotton, R. James; Subramaniyan, Manivannan; Denfield, George H.; Cadwell, Cathryn R.; Smirnakis, Stelios M.; Bethge, Matthias; Tolias, Andreas S.

    2014-01-01

    Shared, trial-to-trial variability in neuronal populations has a strong impact on the accuracy of information processing in the brain. Estimates of the level of such noise correlations are diverse, ranging from 0.01 to 0.4, with little consensus on which factors account for these differences. Here we addressed one important factor that varied across studies, asking how anesthesia affects the population activity structure in macaque primary visual cortex. We found that under opioid anesthesia, activity was dominated by strong coordinated fluctuations on a timescale of 1–2 Hz, which were mostly absent in awake, fixating monkeys. Accounting for these global fluctuations markedly reduced correlations under anesthesia, matching those observed during wakefulness and reconciling earlier studies conducted under anesthesia and in awake animals. Our results show that internal signals, such as brain state transitions under anesthesia, can induce noise correlations, but can also be estimated and accounted for based on neuronal population activity. PMID:24698278

  1. Comparison of discrete ratios by rhesus macaques (Macaca mulatta).

    PubMed

    Drucker, Caroline B; Rossa, Marley A; Brannon, Elizabeth M

    2016-01-01

    Perceiving and comparing ratios are crucial skills for humans. Little is known about whether other animals can compare ratios. We trained two rhesus macaques (Macaca mulatta) to choose arrays that contained the greater ratio of positive to negative stimuli, regardless of the absolute number of stimuli in each of the two choice arrays. Subjects learned this task, and their performance generalized to novel ratios. Moreover, performance was modulated by the ratio between ratios; subjects responded more quickly and accurately when the ratio between ratios was higher. Control conditions ruled out the possibility that subjects were relying on surface area, although the ratio between ratios of surface area did seem to influence their choices. Our results demonstrate that rhesus monkeys can compare discrete ratios, demonstrating not only proportional reasoning ability but also the ability to reason about relations between relations. PMID:26286201

  2. Optogenetic activation of normalization in alert macaque visual cortex

    PubMed Central

    Nassi, Jonathan J.; Avery, Michael C.; Cetin, Ali H.; Roe, Anna W.; Reynolds, John H.

    2015-01-01

    Summary Normalization has been proposed as a canonical computation that accounts for a variety of nonlinear neuronal response properties associated with sensory processing and higher cognitive functions. A key premise of normalization is that the excitability of a neuron is inversely proportional to the overall activity level of the network. We tested this by optogenetically activating excitatory neurons in alert macaque primary visual cortex and measuring changes in neuronal activity as a function of stimulation intensity, with or without variable-contrast visual stimulation. Optogenetic depolarization of excitatory neurons either facilitated or suppressed baseline activity, consistent with indirect recruitment of inhibitory networks. As predicted by the normalization model, neurons exhibited sub-additive responses to optogenetic and visual stimulation, which depended lawfully on stimulation intensity and luminance contrast. We conclude that the normalization computation persists even under the artificial conditions of optogenetic stimulation, underscoring the canonical nature of this form of neural computation. PMID:26087167

  3. Spatial and temporal vision of macaques after central retinal lesions

    SciTech Connect

    Merigan, W.H.; Pasternak, T.; Zehl, D.

    1981-07-01

    Spatial contrast and temporal modulation sensitivity of two macaque monkeys were measured at three luminance levels before and after binocular laser coagulation of the fovea. The radius of the lesions ranged from 1.6 to 2.2 degree from the center of the fovea. After placement of the lesions, the visibility of high spatial frequencies was greatly reduced, although sensitivity at middle and low spatial frequencies was unaffected. No loss of spatial resolution was found at the lowest luminance tested. When temporal modulation sensitivity was tested with 4 deg targets, foveal lesions had no effect at any temporal frequency or luminance. However, with a 0.57 degree target, sensitivity to lower temporal frequencies was impaired. Thus visual loss after destruction of the fovea is limited to high luminance, small targets, and the resolution of fine detail.

  4. Measurement of Blood Volume in Adult Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Hobbs, Theodore R; Blue, Steven W; Park, Byung S; Greisel, Jennifer J; Conn, P Michael; Pau, Francis K-Y

    2015-01-01

    Most biomedical facilities that use rhesus macaques (Macaca mulatta) limit the amount of blood that may be collected for experimental purposes. These limits typically are expressed as a percentage of blood volume (BV), estimated by using a fixed ratio of blood (mL) per body weight (kg). BV estimation ratios vary widely among facilities and typically do not factor in variables known to influence BV in humans: sex, age, and body condition. We used indicator dilution methodology to determine the BV of 20 adult rhesus macaques (10 male, 10 female) that varied widely in body condition. We measured body composition by using dual-energy X-ray absorptiometry, weight, crown-to-rump length, and body condition score. Two indicators, FITC-labeled hydroxyethyl starch (FITC–HES) and radioiodinated rhesus serum albumin (125I-RhSA), were injected simultaneously, followed by serial blood collection. Plasma volume at time 0 was determined by linear regression. BV was calculated from the plasma volume and Hct. We found that BV calculated by using FITC–HES was consistently lower than BV calculated by using 125I-RhSA. Sex and age did not significantly affect BV. Percentage body fat was significantly associated with BV. Subjects categorized as having ‘optimal’ body condition score had 18% body fat and 62.1 mL/kg BV (by FITC–HES; 74.5 mL/kg by 125I-RhSA). Each 1% increase in body fat corresponded to approximately 1 mL/kg decrease in BV. Body condition score correlated with the body fat percentage (R2 = 0.7469). We provide an equation for calculating BV from weight and body condition score. PMID:26632777

  5. Discovery of a secular trend in Cayo Santiago macaque reproduction.

    PubMed

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

    2016-02-01

    Reproductive synchrony and the consequent clustering of births are hypothesized to be regulated by seasonal changes in rainfall and food availability. Such climate-related seasonality is, however, questionable in tropical populations occupying temporally invariant habitats year round. Using the long-term data of the Cayo Santiago rhesus macaques from 1973 to 2013, this study distinguishes synchrony (a greater than chance clustering of births) from seasonality (a cluster of births during a period of the year when abiotic conditions are favorable) and shows that females are highly synchronized (>72% of births in a 3-month period) but the effects of environmental zeitgebers on reproduction are overridden by biological factors. Specifically, biotic and abiotic factors including (i) loss of immature offspring; (ii) population density; (iii) age at delivery; (iv) rainfall; and (v) changes in colony management were modeled in relation to the annual onset of births and the median birth date. Females experiencing loss of immature offspring had an interbirth interval of <365 days in average and the proportion of these females increased up to 48% due to changes in colony management overtime, although reproductive synchrony increased with increasing population density. A secular trend in both the onset of births and the median date of birth is documented and the model predicts that the median birth date will advance across all calendar-based seasons by 2050. The secular trend in reproduction appears to be triggered by changes in the age at delivery of females, the absence of physiological constraints from maternal investment due to offspring loss, shorter interbirth interval, and a higher degree of coordination due to increasing population density. This study challenges the reproductive phenology previously described for rhesus macaques highlighting the importance of long-term studies in addressing the ultimate causes of reproductive synchrony. PMID:26540010

  6. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    PubMed

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  7. Psychophysics of electrical stimulation of striate cortex in macaques.

    PubMed

    Bartlett, John R; DeYoe, Edgar A; Doty, Robert W; Lee, Barry B; Lewine, Jeffrey D; Negrão, Nubio; Overman, William H

    2005-11-01

    Macaques indicated their detection of onset or alteration of 0.2-ms pulses applied in various configurations through electrodes implanted in striate cortex. When microelectrodes were introduced and left in place, the threshold for detection of 100-Hz pulses nearly doubled within 24 h. However, for chronically implanted platinum-alloy macroelectrodes detection thresholds usually remained stable for many months, independently of location within striate cortex or its immediately subjacent white matter. Thresholds were unaffected by the visual conditions, such as light versus darkness, or movement of the eyes; but in one animal blind after acute glaucoma thresholds for loci in striate cortex were permanently decreased by about 50%. Learning to respond to electrical stimulation of the optic tract produced no tendency to respond to such stimulation of striate cortex. Onset of stimulation at a given locus could be detected even in the face of continuous supraliminal stimulation at four surrounding loci on a 3-mm radius. The surround stimulation did alter the threshold of the central locus, but such stimuli could not summate if they were subliminal by some 10%. Cessation of stimulation that had been continuing for 1 min to 1 h could be detected if it were being applied at a level 20-75% above that needed for detection of stimulus onset. Continuous stimulation had a pronounced "priming" effect, in that modulation of frequency or intensity of such stimulation by as little as 5% could be detected (e.g., 20 microA in a background of 500 microA, or <2-ms interpulse interval with pulses at 50 Hz). Using pulses inserted in various phase relations to ongoing pulses at 2-5 Hz, it could be determined that stimulus pulses were surrounded by a strong facilitatory period for about 30 ms, which was then replaced by refractoriness. Given the congruence of macaque and human visual anatomy and psychophysics, these results further encourage efforts to develop a cortical prosthesis for the

  8. Measurement of Blood Volume in Adult Rhesus Macaques (Macaca mulatta).

    PubMed

    Hobbs, Theodore R; Blue, Steven W; Park, Byung S; Greisel, Jennifer J; Conn, P Michael; Pau, Francis K-Y

    2015-11-01

    Most biomedical facilities that use rhesus macaques (Macaca mulatta) limit the amount of blood that may be collected for experimental purposes. These limits typically are expressed as a percentage of blood volume (BV), estimated by using a fixed ratio of blood (mL) per body weight (kg). BV estimation ratios vary widely among facilities and typically do not factor in variables known to influence BV in humans: sex, age, and body condition. We used indicator dilution methodology to determine the BV of 20 adult rhesus macaques (10 male, 10 female) that varied widely in body condition. We measured body composition by using dual-energy X-ray absorptiometry, weight, crown-to-rump length, and body condition score. Two indicators, FITC-labeled hydroxyethyl starch (FITC-HES) and radioiodinated rhesus serum albumin ((125)I-RhSA), were injected simultaneously, followed by serial blood collection. Plasma volume at time 0 was determined by linear regression. BV was calculated from the plasma volume and Hct. We found that BV calculated by using FITC-HES was consistently lower than BV calculated by using (125)I-RhSA. Sex and age did not significantly affect BV. Percentage body fat was significantly associated with BV. Subjects categorized as having 'optimal' body condition score had 18% body fat and 62.1 mL/kg BV (by FITC-HES; 74.5 mL/kg by (125)I-RhSA). Each 1% increase in body fat corresponded to approximately 1 mL/kg decrease in BV. Body condition score correlated with the body fat percentage (R(2) = 0.7469). We provide an equation for calculating BV from weight and body condition score. PMID:26632777

  9. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

    SciTech Connect

    Kaur, Amitinder . E-mail: amitinder_kaur@hms.harvard.edu; Sanford, Hannah B.; Garry, Deirdre; Lang, Sabine; Klumpp, Sherry A.; Watanabe, Daisuke; Bronson, Roderick T.; Lifson, Jeffrey D.; Rosati, Margherita; Pavlakis, George N.; Felber, Barbara K.; Knipe, David M.; Desrosiers, Ronald C.

    2007-01-20

    The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.

  10. Clinical and Parasitological Protection in a Leishmania infantum-Macaque Model Vaccinated with Adenovirus and the Recombinant A2 Antigen

    PubMed Central

    Grimaldi, Gabriel; Teva, Antonio; Porrozzi, Renato; Pinto, Marcelo A.; Marchevsky, Renato S.; Rocha, Maria Gabrielle L.; Dutra, Miriam S.; Bruña-Romero, Oscar; Fernandes, Ana-Paula; Gazzinelli, Ricardo T.

    2014-01-01

    Background Visceral leishmaniasis (VL) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites. Approximately 0.2 to 0.4 million new human VL cases occur annually worldwide. In the new world, these alarming numbers are primarily due to the impracticality of current control methods based on vector reduction and dog euthanasia. Thus, a prophylactic vaccine appears to be essential for VL control. The current efforts to develop an efficacious vaccine include the use of animal models that are as close to human VL. We have previously reported a L. infantum-macaque infection model that is reliable to determine which vaccine candidates are most worthy for further development. Among the few amastigote antigens tested so far, one of specific interest is the recombinant A2 (rA2) protein that protects against experimental L. infantum infections in mice and dogs. Methodology/Principal Findings Primates were vaccinated using three rA2-based prime-boost immunization regimes: three doses of rA2 plus recombinant human interleukin-12 (rhIL-12) adsorbed in alum (rA2/rhIL-12/alum); two doses of non-replicative adenovirus recombinant vector encoding A2 (Ad5-A2) followed by two boosts with rA2/rhIL-12/alum (Ad5-A2+rA2/rhIL12/alum); and plasmid DNA encoding A2 gene (DNA-A2) boosted with two doses of Ad5-A2 (DNA-A2+Ad5-A2). Primates received a subsequent infectious challenge with L. infantum. Vaccines, apart from being safe, were immunogenic as animals responded with increased pre-challenge production of anti-A2-specific IgG antibodies, though with some variability in the response, depending on the vaccine formulation/protocol. The relative parasite load in the liver was significantly lower in immunized macaques as compared to controls. Protection correlated with hepatic granuloma resolution, and reduction of clinical symptoms, particularly when primates were vaccinated with the Ad5-A2+rA2/rhIL12/alum protocol. Conclusions/Significance The

  11. Cloning, sequencing, and polymorphism analysis of novel classical MHC class I alleles in northern pig-tailed macaques (Macaca leonina).

    PubMed

    Lian, Xiao-Dong; Zhang, Xi-He; Dai, Zheng-Xi; Zheng, Yong-Tang

    2016-04-01

    The northern pig-tailed macaque (Macaca leonina) has been confirmed to be an independent species from the pig-tailed macaque group of Old World monkey. We have previously reported that the northern pig-tailed macaques were also susceptible to HIV-1. Here, to make this animal a potential HIV/AIDS model and to discover the mechanism of virus control, we attempted to assess the role of major histocompatibility complex (MHC) class I-restricted immune responses to HIV-1 infection, which was associated with viral replication and disease progression. As an initial step, we first cloned and characterized the classical MHC class I gene of northern pig-tailed macaques. In this study, we identified 39 MHC class I alleles including 17 MHC-A and 22 MHC-B alleles. Out of these identified alleles, 30 were novel and 9 were identical to alleles previously reported from other macaque species. The MHC-A and MHC-B loci were both duplicates as rhesus macaques and southern pig-tailed macaques. In addition, we also detected the patterns of positive selection in northern pig-tailed macaques and revealed the existence of balance selection with 20 positive selection sites in the peptide binding region. The analysis of B and F peptide binding pockets in northern and southern pig-tailed macaques and rhesus macaques suggested that they were likely to share a few common peptides to present. Thus, this study provides important MHC immunogenetics information and adds values to northern pig-tailed macaques as a promising HIV/AIDS model. PMID:26782049

  12. Metabolism of arachidonic acid by macaque platelets. Implications for studies on atherosclerosis.

    PubMed

    Beatty, C H; Howard, C F; Hoskins, M K; Herrington, P T

    1985-04-01

    The metabolism of [1-14C]arachidonic acid [( 1-14C]AA) by washed platelets from macaques and human subjects was investigated. The results were as follows: At substrate levels of 1 microM, similar amounts of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), and thromboxane A2 (TXA2), measured as thromboxane B2 (TXB2), were produced from [1-14C]AA by platelets from rhesus, Celebes black, and cynomolgus macaques and humans. An increase in the AA concentration from 1 microM to 20 microM decreased the TXB2: PGD2 ratio (aggregator: antiaggregator) from greater than 5 to less than 2 in all series. In the human series, the ratio decrease was due to an increase in PGD2 production; in the macaque series, PGD2 production increased and TXB2 production decreased. Under basal conditions and at 1 microM AA concentrations, the amounts of prostaglandins and thromboxanes produced by platelets from male and female rhesus macaques were the same. An increase in substrate concentration from 1 microM to 20 microM AA decreased TXB2 production and increased PGD2 production to the same extent in platelets from male and female rhesus macaques. Imidazole increased prostaglandin production and decreased TXB2 production by platelets from both male and female rhesus macaques. The TXB2: PGD2 ratios were reduced below 1.5; there was no difference between the ratios in the two series. In the presence of 1 mM imidazole, greater amounts of prostaglandins and thromboxanes were produced in the male than in the female series. These data indicate that macaque's platelets are a suitable model for the study of AA metabolism in human platelets. PMID:3924062

  13. Comparative locomotor ecology of gibbons and macaques: selection of canopy elements for crossing gaps.

    PubMed

    Cannon, C H; Leighton, M

    1994-04-01

    To examine functional questions of arboreal locomotor ecology, the selection of canopy elements by Bornean agile gibbons (Hylobates agilis) and long-tailed macaques (Macaca fascicularis) was contrasted, and related to locomotor behaviors. The two species, and in some cases, the macaque sexes, varied in their use of most structural elements. Although both species traveled most frequently in the main canopy layer (macaques: 56%, gibbons: 48%), the gibbons strongly preferred the emergent canopy layer and traveled higher than the macaques (31 vs. 23 m above ground) in larger trees (48 vs. 26 cm dbh). Macaques preferred to cross narrower gaps (50% were in the class 0.1-0.5 m wide) than gibbons (42% were 1.6-3.0 m wide), consistent with the maximum gap width each crossed (3.5 m for macaques, 9 m for gibbons). Macaques could cross only 12% of the gaps encountered in the main canopy, and < 5% of the gaps in each of the other four layers. In contrast, all layers appear relatively continuous for gibbons. Specialized locomotor modes were used disproportionately at the beginning and end of travel segments, further indicating that behavior was organized around gap crossings. A model is defined, the Perceived Continuity Index (PCI), which predicts the relative use of canopy strata for each species, based on the percentage of gaps a species can cross, the frequency of gaps, and median length of continuous canopy structure in each canopy layer. The results support the hypothesis that locomotor behaviors, and strategies of selecting canopy strata for travel, are strongly constrained by wide gaps between trees and are ultimately based on selection for efficient direct line travel between distant points. PMID:8048471

  14. Glucocorticoid treatment at moderate doses of SIVmac251-infected rhesus macaques decreases the frequency of circulating CD14+CD16++ monocytes but does not alter the tissue virus reservoir.

    PubMed

    Moniuszko, Marcin; Liyanage, Namal P M; Doster, Melvin N; Parks, Robyn Washington; Grubczak, Kamil; Lipinska, Danuta; McKinnon, Katherine; Brown, Charles; Hirsch, Vanessa; Vaccari, Monica; Gordon, Shari; Pegu, Poonam; Fenizia, Claudio; Flisiak, Robert; Grzeszczuk, Anna; Dabrowska, Milena; Robert-Guroff, Marjorie; Silvestri, Guido; Stevenson, Mario; McCune, Joseph; Franchini, Genoveffa

    2015-01-01

    Subsets of CD16-positive monocytes produce proinflammatory cytokines and expand during chronic infection with the human immunodeficiency virus type 1 (HIV). HIV-infected macrophage in tissues may be long lived and contribute to the establishment and maintenance of the HIV reservoir. We found that the (intermediate) CD14(++)CD16(+) and (nonclassical) CD14(+)CD16(++) monocyte subsets are significantly expanded during infection of Rhesus macaques with pathogenic SIV(mac251) but not during infection of sooty mangabeys with the nonpathogenic isolate SIVSM. In vitro glucocorticoid (GC) treatment of peripheral blood mononuclear cells (PBMCs) from uninfected or SIV(mac251)-infected Rhesus macaques and HIV-infected patients treated or not with antiretroviral therapy (ART) resulted in a significant decrease in the frequency of both CD16-positive monocyte subsets. Short-term in vivo treatment with high doses of GC of chronically SIV(mac251)-infected macaques resulted in a significant decrease in the CD14(+)CD16(++) population and, to a lesser extent, in the CD14(++)CD16(+) monocytes, as well as a significant decrease in the number of macrophages in tissues. Surprisingly, treatment of SIV(mac251)-infected macaques with ART significantly increased the CD14(++)CD16(+) population and the addition of GC resulted in a significant decrease in only the CD14(+)CD16(++) subset. No difference in SIV DNA levels in blood, lymph nodes, gut, and spleen was found between the groups treated with ART or ART plus GC. Thus, it appears that high doses of GC treatment in the absence of ART could affect both CD16-positive populations in vivo. Whether the efficacy of this treatment at higher doses to decrease virus levels outweighs its risks remains to be determined. PMID:24432835

  15. Oligonucleotide fingerprinting of free-ranging and captive rhesus macaques from Cayo Santiago: paternity assignment and comparison of heterozygosity.

    PubMed

    Nürnberg, P; Berard, J D; Bercovitch, F; Epplen, J T; Schmidtke, J; Krawczak, M

    1993-01-01

    Multilocus DNA fingerprinting with oligonucleotide probes (GTG)5, (GATA)4, and (CA)8 was applied in order to determine paternity in one birth cohort (15 infants) of social group (S) from the free-ranging colony of rhesus macaques (Macaca mulatta) on Cayo Santiago. While sires could be identified in 11 cases, all males tested (N = 19) could be excluded from paternity for the remaining four infants. Data revealed marked discrepancies between actual paternity and paternity as inferred from the observation of copulation behavior. Thus, a dominant social rank does not appear to be strongly associated with reproductive success. Furthermore, alternative reproductive strategies were found to yield comparable net benefits in reproduction. A second group of animals (M) was translocated from Cayo Santiago to the Sabana Seca Field Station in 1984. They have continuously resided together in a large outdoor enclosure since then. Here paternity assessment was seriously impeded by a reduced number of discriminating bands, i.e. offspring bands which were unequivocally derived from the sires. This was initially held to be indicative of a smaller degree of heterozygosity in Group M, and was attributed to inbreeding due to a lack of male immigration or extra-group fertilizations. However, a comparison of the DNA fingerprint patterns obtained in Group S and Group M lends only partial support to this idea. PMID:8400713

  16. Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy: oral 3'-azido-3'-deoxythymidine prevents SIV infection.

    PubMed Central

    Van Rompay, K K; Marthas, M L; Ramos, R A; Mandell, C P; McGowan, E K; Joye, S M; Pedersen, N C

    1992-01-01

    The prophylactic and therapeutic properties of 3'-azido-3'-deoxythymidine (AZT) against simian immunodeficiency virus (SIV) infection were tested in four 3-month-old rhesus macaques. The infant monkeys were inoculated intravenously with a low dose (1 to 10 100% animal infectious doses) of uncloned SIVmac. The monkeys were treated orally with 50 mg of AZT per kg of body weight every 8 h; two animals were started on treatment 2 h prior to virus inoculation, and two animals were started on treatment 6 weeks later. All four animals were treated for a period of 6 to 10 weeks. Outward signs of AZT toxicity were absent, but a mild macrocytic anemia occurred soon after therapy was started and resolved shortly after it was discontinued. The two infants that were begun on AZT treatment 2 h prior to virus inoculation never became infected, as demonstrated by the inability to detect cell-free or cell-associated virus in the blood, proviral DNA in peripheral blood mononuclear cells, or anti-SIV antibodies. AZT administration over a 10-week period had no detectable effect on the course of disease in the two animals that were begun on treatment after the infection had been established. In addition to demonstrating the prophylactic effect of AZT against low-dose SIV exposure, the study demonstrated the ease with which infant rhesus macaques can be used for antiretroviral drug testing. Images PMID:1489181

  17. Comparable Genital Tract Infection, Pathology, and Immunity in Rhesus Macaques Inoculated with Wild-Type or Plasmid-Deficient Chlamydia trachomatis Serovar D

    PubMed Central

    Qu, Yanyan; Frazer, Lauren C.; O'Connell, Catherine M.; Tarantal, Alice F.; Andrews, Charles W.; O'Connor, Shelby L.; Russell, Ali N.; Sullivan, Jeanne E.; Poston, Taylor B.; Vallejo, Abbe N.

    2015-01-01

    Rhesus macaques were studied to directly address the potential for plasmid-deficient Chlamydia trachomatis to serve as a live attenuated vaccine in the genital tract. Five repeated cervical inoculations of rhesus macaques with wild-type serovar D strain D/UW-3/Cx or a plasmid-deficient derivative of this strain, CTD153, resulted in infections with similar kinetics and induced comparable levels of protective immunity. After all animals received five challenges with D/UW-3/Cx, levels of inflammation observed grossly and histologically were similar between the groups. Animals in both groups developed evidence of oviduct dilatation; however, reduced oviduct dilatation was observed for “controllers,” i.e., animals without detectable chlamydial DNA in the fimbriae at weeks 5 and 12. Grouping animals into “ascenders” and “controllers” revealed that elevated early T cell responses were associated with protection, whereas higher antibody responses were associated with ascension. Protected animals shared common major histocompatibility complex (MHC) alleles. Overall, genetic differences of individual animals, rather than the presence or absence of the chlamydial plasmid in the primary infecting strain, appeared to play a role in determining the outcome of infection. PMID:26216426

  18. Preclinical Evaluation of HIV Eradication Strategies in the Simian Immunodeficiency Virus-Infected Rhesus Macaque: A Pilot Study Testing Inhibition of Indoleamine 2,3-Dioxygenase

    PubMed Central

    Dunham, Richard M.; Gordon, Shari N.; Vaccari, Monica; Piatak, Michael; Huang, Yong; Deeks, Steven G.; Lifson, Jeffrey; Franchini, Genoveffa

    2013-01-01

    Abstract Even in the setting of maximally suppressive antiretroviral therapy (ART), HIV persists indefinitely. Several mechanisms might contribute to this persistence, including chronic inflammation and immune dysfunction. In this study, we have explored a preclinical model for the evaluation of potential interventions that might serve to eradicate or to minimize the level of persistent virus. Given data that metabolic products of the inducible enzyme indoleamine 2,3-dioxygeanse (IDO) might foster inflammation and viral persistence, chronically simian immunodeficiency virus (SIV)-infected, ART-treated rhesus macaques were treated with the IDO inhibitor 1-methyl tryptophan (1mT). Orally administered 1mT achieved targeted plasma levels, but did not impact tryptophan metabolism or decrease viral RNA or DNA in plasma or in intestinal tissues beyond levels achieved by ART alone. Animals treated with 1mT showed no difference in the levels of T cell activation or differentiation, or in the kinetics or magnitude of viral rebound following cessation of ART. Notwithstanding these negative results, our observations suggest that the chronically SIV-infected rhesus macaque on suppressive ART can serve as a tractable model in which to test and to prioritize the selection of other potential interventions designed to eradicate HIV in vivo. In addition, this model might be used to optimize the route and dose by which such interventions are administered and the methods by which their effects are monitored. PMID:22924680

  19. Longitudinal assessment of pigtailed macaque lower genital tract microbiota by pyrosequencing reveals dissimilarity to the genital microbiota of healthy humans.

    PubMed

    Spear, Gregory T; Kersh, Ellen; Guenthner, Patricia; Vishwanathan, Sundaram Ajay; Gilbert, Douglas; Zariffard, M Reza; Mirmonsef, Paria; Landay, Alan; Zheng, Luyang; Gillevet, Patrick

    2012-10-01

    Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection. PMID:22264029

  20. Longitudinal Assessment of Pigtailed Macaque Lower Genital Tract Microbiota by Pyrosequencing Reveals Dissimilarity to the Genital Microbiota of Healthy Humans

    PubMed Central

    Kersh, Ellen; Guenthner, Patricia; Vishwanathan, Sundaram Ajay; Gilbert, Douglas; Zariffard, M. Reza; Mirmonsef, Paria; Landay, Alan; Zheng, Luyang; Gillevet, Patrick

    2012-01-01

    Abstract Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection. PMID:22264029

  1. The mucosal expression pattern of interferon-ε in rhesus macaques

    PubMed Central

    Demers, Andrew; Kang, Guobin; Ma, Fungrui; Lu, Wuxun; Yuan, Zhe; Li, Yue; Lewis, Mark; Kraiselburd, Edmundo N.; Montaner, Luis; Li, Qingsheng

    2014-01-01

    Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-ε, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-ε in tissues remain uncertain. In addition, the expression of IFN-ε in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-ε expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the detection of IFN-ε expression in situ in the lung, foreskin, vaginal, cervical, and small and large intestinal mucosae of rhesus macaques. We found that the expression of IFN-ε was exclusive to the epithelial cells in all of the aforementioned mucosal tissues. Furthermore, the macaque IFN-ε sequence in this study revealed that macaque IFN-ε is highly conserved among human and other nonhuman primates. Lastly, SIV rectal infection did not significantly alter the expression of IFN-ε in rectal mucosae. Together, these findings indicate that IFN-ε may function as the first line of defense against the invasion of mucosal pathogens. Further studies should be conducted to examine IFN-ε protection against gastrointestinal as well as respiratory infections. PMID:25139290

  2. Parvalbumin increases in the medial and lateral geniculate nuclei of aged rhesus macaques

    PubMed Central

    Gray, Daniel T.; Rudolph, Megan L.; Engle, James R.; Recanzone, Gregg H.

    2013-01-01

    Subcortical auditory structures in the macaque auditory system increase their densities of neurons expressing the calcium binding protein parvalbumin (PV) with age. However, it is unknown whether these increases occur in the thalamic division of the auditory system, the medial geniculate nucleus (MGN). Furthermore, it is also unclear whether these age-related changes are specific to the macaque auditory system or are generalized to other sensory systems. To address these questions, the PV immunoreactivity of the medial and lateral geniculate nuclei (LGN) from seven rhesus macaques ranging in age from 15 to 35 was assessed. Densities of PV expressing neurons in the three subdivisions of the MGN and the six layers of the LGN were calculated separately using unbiased stereological sampling techniques. We found that the ventral and magnocellular subdivisions of the MGN and all six layers of the LGN increased their expressions of PV with age, although increases in the MGN were greater in magnitude than in the LGN. Together, these results suggest that the MGN shows age-related increases in PV expression as is seen throughout the macaque ascending auditory system, and that the analogous region of the visual system shows smaller increases. We conclude that, while there are some similarities between sensory systems, the age-related neurochemical changes seen throughout the macaque auditory system cannot be fully generalized to other sensory systems. PMID:24265617

  3. BETA-ENDORPHIN LEVELS IN LONGTAILED AND PIGTAILED MACAQUES VARY BY ABNORMAL BEHAVIOR RATING AND SEX

    PubMed Central

    Crockett, Carolyn M.; Sackett, Gene P.; Sandman, Curt A.; Chicz-DeMet, Aleksandra; Bentson, Kathleen L.

    2007-01-01

    Frequent or severe abnormal behavior may be associated with the release of endorphins that positively reinforce the behavior with an opiate euphoria or analgesia. One line of research exploring this association involves the superhormone, proopiomelanocortin (POMC). The products of POMC appear to be dysregulated in some human subjects who exhibit self-injurious behavior (SIB). Macaque monkeys have POMC very similar to humans, and some laboratory macaques display SIB or frequent stereotypies. We investigated associations between plasma levels of three immunoreactive POMC fragments with possible opioid action and abnormal behavior ratings in macaques. In 58 adult male and female macaques (24 Macaca fascicularis and 34 M. nemestrina), plasma levels of intact beta-endorphin (βE) and the N-terminal fragment (BEN) were significantly higher in animals with higher levels of abnormal behavior. The C-terminal fragment (BEC) was significantly higher in males but unrelated to ratings of abnormal behavior. Levels of ACTH, cortisol, and (βE-ACTH)/βE dysregulation index were unrelated to abnormal behavior. None of the POMC products differed significantly by subjects' species, age, or weight. The finding that intact beta-endorphin is positively related to abnormal behavior in two species of macaque is consistent with some previous research on human subjects and nonprimates. The positive relation of the N-terminal fragment of βE to abnormal behavior is a new finding. PMID:17719139

  4. Comparative Proteomics of Human and Macaque Milk Reveals Species-Specific Nutrition during Postnatal Development.

    PubMed

    Beck, Kristen L; Weber, Darren; Phinney, Brett S; Smilowitz, Jennifer T; Hinde, Katie; Lönnerdal, Bo; Korf, Ian; Lemay, Danielle G

    2015-05-01

    Milk has been well established as the optimal nutrition source for infants, yet there is still much to be understood about its molecular composition. Therefore, our objective was to develop and compare comprehensive milk proteomes for human and rhesus macaques to highlight differences in neonatal nutrition. We developed a milk proteomics technique that overcomes previous technical barriers including pervasive post-translational modifications and limited sample volume. We identified 1606 and 518 proteins in human and macaque milk, respectively. During analysis of detected protein orthologs, we identified 88 differentially abundant proteins. Of these, 93% exhibited increased abundance in human milk relative to macaque and include lactoferrin, polymeric immunoglobulin receptor, alpha-1 antichymotrypsin, vitamin D-binding protein, and haptocorrin. Furthermore, proteins more abundant in human milk compared with macaque are associated with development of the gastrointestinal tract, the immune system, and the brain. Overall, our novel proteomics method reveals the first comprehensive macaque milk proteome and 524 newly identified human milk proteins. The differentially abundant proteins observed are consistent with the perspective that human infants, compared with nonhuman primates, are born at a slightly earlier stage of somatic development and require additional support through higher quantities of specific proteins to nurture human infant maturation. PMID:25757574

  5. Survey of prevalence of overweight body condition in laboratory-housed cynomolgus macaques (Macaca fascicularis).

    PubMed

    Bauer, Sharon A; Leslie, Ken E; Pearl, David L; Fournier, Jocelyn; Turner, Patricia V

    2010-07-01

    Excessive weight gain has been reported to occur in captive cynomolgus macaques with little to no change in diet. Overweight body condition can result in development of hyperglycemia and type 2 diabetes and should be avoided. The purpose of this survey was to assess the prevalence of overweight cynomolgus macaques in North American research facilities, including breeding colonies and short-term and long-term facilities, and to describe current methods used to assess body condition. The survey consisted of 51 questions covering animal population demographics, body weight and body condition scoring, feeding, and behavior. Voluntary participants included veterinarians and animal care managers. Respondents from 13 facilities completed the survey, and information was collected on 17,500 cynomolgus macaques. The majority of surveyed facilities housed juvenile and young adult macaques. The reported prevalence of overweight (greater than 10% of ideal body weight) animals ranged between 0% and 20% and reportedly was more frequent in animals younger than 10 y. Most facilities had weight reduction strategies in place. Despite these programs, a significant proportion of animals were reported as being overweight. The results of this survey demonstrate that most North American facilities housing cynomolgus macaques recognize the importance of tracking body condition regularly. However, implementing effective weight reduction programs may be difficult in captive housing environments. Because of the potential for adverse health effects, facilities should have a means of regularly tracking body weight as well as an action plan for managing overweight animals. PMID:20819384

  6. Pharmacokinetics of Oxymorphone in Titi Monkeys (Callicebus spp.) and Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R; Pypendop, Bruno H; Grayson, J Kevin; Stanley, Scott D; Christe, Kari L; Summers, Laura M; Lerche, Nicholas W

    2011-01-01

    Oxymorphone is a pure μ-opioid receptor agonist that is commonly used in nonhuman primate medicine and surgery to minimize pain ranging in intensity from moderate to severe. We compared pharmacokinetic profiles and physiologic and behavioral responses to oxymorphone between titi monkeys (Callicebus spp.) and rhesus macaques (Macaca mulatta). Titi monkeys (n = 4) and rhesus macaques (n = 4) were injected intravenously with either a bolus of 0.075 mg/kg oxymorphone or placebo on multiple occasions, with a minimal washout period of 14 d between trials. Blood collection was limited to no more than 3 samples per trial, with samples collected at multiple time points until 10 h after injection. Collection periods, animal order, and testing day were randomized. In addition, macaques underwent a single serial collection at all time points to validate study design. A 2-compartment model best described the disposition of oxymorphone in both species. Clearance was faster in macaques than titi monkeys, in which terminal half-life was longer. Statistically significant physiologic differences were found between species and between treatments within species. Apart from these effects, oxymorphone did not significantly change physiologic parameters over time. After oxymorphone treatment, macaques demonstrated behaviors reflecting pruritis, whereas titi monkeys exhibited sedation. Despite its mild side effects, we recommend the consideration of oxymorphone for pain management protocols in both Old and New World nonhuman primates. PMID:21439215

  7. Mapping the contribution of single muscles to facial movements in the Rhesus Macaque

    PubMed Central

    Waller, B.M.; Parr, L.A.; Gothard, K.M.; Burrows, A.M.; Fuglevand, A.J.

    2008-01-01

    The rhesus macaque (Macaca mulatta) is the most utilized primate model in the biomedical and psychological sciences. Expressive behavior is of interest to scientists studying these animals, both as a direct variable (modeling neuropsychiatric disease, where expressivity is a primary deficit), as an indirect measure of health and welfare, and also in order to understand the evolution of communication. Here, intramuscular electrical stimulation of facial muscles was conducted in the rhesus macaque in order to document the relative contribution of each muscle to the range of facial movements and to compare the expressive function of homologous muscles in humans and macaques. Despite published accounts that monkeys possess less differentiated and less complex facial musculature, the majority of muscles previously identified in humans were stimulated successfully in the rhesus macaque and caused similar appearance changes to human facial movements. These observations suggest that the facial muscular apparatus of the monkey has extensive homology to the human face. The muscles of the human face, therefore, do not represent a significant evolutionary departure from that of monkey species. Thus, facial expressions can be compared between humans and rhesus macaques at the level of the facial musculature, facilitating the systematic investigation of comparative facial communication. PMID:18582909

  8. Buton macaques (Macaca ochreata brunnescens): crops, conflict, and behavior on farms.

    PubMed

    Priston, Nancy E C; Wyper, Rebecca M; Lee, Phyllis C

    2012-01-01

    One consequence of anthropogenic habitat alteration is that many nonhuman primates are forced into conflict interactions with humans and their livelihood activities, especially through crop raiding. These problems are particularly acute for the endemic and threatened Buton Island macaque (Macaca ochreata brunnescens), in southeast Sulawesi, Indonesia. Our study investigated the crop raiding behavior of this species over time. Foods eaten and the behavioral repertoire exhibited by macaques during crop raiding at and inside farm perimeters were observed over a period of 8 years (2002-2009). Storage organ crops (e.g. sweet potato) were abundant and most frequently raided by macaques. Individual macaques were most commonly observed to raid close (0-10 m) to farm perimeters. Activities such as feeding, resting, moving, and social interaction varied significantly as a function of penetration distance into the farm, but only marginally between age-sex classes. The annual average raid frequency per farm decreased over the latter years of the study period, raising questions about changes in macaque foraging and ranging behavior over time and their response to farm management and mitigation strategies. PMID:22025206

  9. Intranasal HIV-1-gp160-DNA/gp41 peptide prime-boost immunization regimen in mice results in long-term HIV-1 neutralizing humoral mucosal and systemic immunity.

    PubMed

    Devito, Claudia; Zuber, Bartek; Schröder, Ulf; Benthin, Reinhold; Okuda, Kenji; Broliden, Kristina; Wahren, Britta; Hinkula, Jorma

    2004-12-01

    An intranasal DNA vaccine prime followed by a gp41 peptide booster immunization was compared with gp41 peptide and control immunizations. Serum HIV-1-specific IgG and IgA as well as IgA in feces and vaginal and lung secretions were detected after immunizations. Long-term humoral immunity was studied for up to 12 mo after the booster immunization by testing the presence of HIV-1 gp41- and CCR5-specific Abs and IgG/IgA-secreting B lymphocytes in spleen and regional lymph nodes in immunized mice. A long-term IgA-specific response in the intestines, vagina, and lungs was obtained in addition to a systemic immune response. Mice immunized only with gp41 peptides and L3 adjuvant developed a long-term gp41-specific serum IgG response systemically, although over a shorter period (1-9 mo), and long-term mucosal gp41-specific IgA immunity. HIV-1-neutralizing serum Abs were induced that were still present 12 mo after booster immunization. HIV-1 SF2-neutralizing fecal and lung IgA was detectable only in the DNA-primed mouse groups. Intranasal DNA prime followed by one peptide/L3 adjuvant booster immunization, but not a peptide prime followed by a DNA booster, was able to induce B cell memory and HIV-1-neutralizing Abs for at least half of a mouse's life span. PMID:15557206

  10. Characterization of the Kynurenine Pathway and Quinolinic Acid Production in Macaque Macrophages

    PubMed Central

    Lim, Chai K.; Yap, Margaret M.C.; Kent, Stephen J.; Gras, Gabriel; Samah, Boubekeur; Batten, Jane C.; De Rose, Robert; Heng, Benjamin; Brew, Bruce J.; Guillemin, Gilles J.

    2013-01-01

    The kynurenine pathway (KP) and one of its end-products, the excitotoxin quinolinic acid (QUIN), are involved in the pathogenesis of several major neuroinflammatory brain diseases. A relevant animal model to study KP metabolism is now needed to assess whether intervention in this pathway may improve the outcome of such diseases. Humans and macaques share a very similar genetic makeup. In this study, we characterized the KP metabolism in macaque primary macrophages of three different species in comparison to human cells. We found that the KP profiles in simian macrophages were very similar to those in humans when challenged with inflammatory cytokines. Further, we found that macaque macrophages are capable of producing a pathophysiological concentration of QUIN. Our data validate the simian model as a relevant model to study the human cellular KP metabolism in the context of inflammation. PMID:23761975

  11. Comparative Analysis of the Macroscale Structural Connectivity in the Macaque and Human Brain

    PubMed Central

    Bezgin, Gleb; Uylings, Harry B. M.; Roebroeck, Alard; Stiers, Peter

    2014-01-01

    The macaque brain serves as a model for the human brain, but its suitability is challenged by unique human features, including connectivity reconfigurations, which emerged during primate evolution. We perform a quantitative comparative analysis of the whole brain macroscale structural connectivity of the two species. Our findings suggest that the human and macaque brain as a whole are similarly wired. A region-wise analysis reveals many interspecies similarities of connectivity patterns, but also lack thereof, primarily involving cingulate regions. We unravel a common structural backbone in both species involving a highly overlapping set of regions. This structural backbone, important for mediating information across the brain, seems to constitute a feature of the primate brain persevering evolution. Our findings illustrate novel evolutionary aspects at the macroscale connectivity level and offer a quantitative translational bridge between macaque and human research. PMID:24676052

  12. Pregnancy diagnosis by laparoscopy in free range rhesus macaques (Macaca mulatta)

    PubMed Central

    Kumar, V.; Raj, A.; Kumar, P.

    2011-01-01

    The present study involved 50 adult female rhesus macaques (Macaca mulatto) of age ranging between 4 to 15 years. Pregnancy diagnosis was done by using laparoscopic method. Anesthesia was achieved by using xylazine (2mg/kg) and ketamine (10mg/kg) intramuscularly. The gravid uterus was located close to the urinary bladder in early pregnancy and in abdominal cavity in the mid and late stage of pregnancy. The procedure was completed within 10 - 12 minutes. There were no complications after the surgery and recovery of animal was smooth and uneventful. The results of this study showed that laparoscopic method is also one of the methods of pregnancy diagnosis in rhesus macaques and it can be a precise and a reliable method of pregnancy diagnosis in rhesus macaques. PMID:26623277

  13. The complete mitochondrial genome of Assamese Macaques (Macaca assamensis).

    PubMed

    Jiang, Juan; Li, Peng; Yu, Jianqiu; Zhao, Guang; Yi, Yong; Yue, Bisong; Li, Jing

    2016-01-01

    The complete mitochondrial genome of Assamese macaques (Macaca assamensis) was sequenced in this study. The genome is 16,542 bp long, consisting of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes and 2 non-coding areas. Eight PCGs (COI, COII, ATP6, COIII, ND4L, ND4, ND6, CYTB) initiate with the start codon ATG and another two genes (ND1, ATP8) use GTG, while ND2, ND3 and ND5 start with ATT, ATC and ATA, respectively. Five genes (COII, ATP8, ATP6, ND4L and ND5) use the complete stop codon TAA, whereas four genes have incomplete stop codons, TA- (COIII) and T- - (ND3, ND4, CYTB), while others use standard canonical TAA as their termination codons. The largest non-coding control region with the length of 1091 bp is located between the tRNA-Pro and tRNA-Phe genes. PMID:24495139

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

    PubMed Central

    Blomquist, Gregory E.

    2012-01-01

    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 pre-reproductive age classes in the semi-free ranging Cayo Santiago rhesus macaques. Using a large set of records (max. n=977 mothers, 6240 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. PMID:23315583

  15. Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

    PubMed Central

    Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F.; Ebihara, Hideki; Scott, Dana P.; Hjelle, Brian; Feldmann, Heinz

    2014-01-01

    The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. PMID:24778254

  16. Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.

    PubMed

    Safronetz, David; Prescott, Joseph; Feldmann, Friederike; Haddock, Elaine; Rosenke, Rebecca; Okumura, Atsushi; Brining, Douglas; Dahlstrom, Eric; Porcella, Stephen F; Ebihara, Hideki; Scott, Dana P; Hjelle, Brian; Feldmann, Heinz

    2014-05-13

    The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases. PMID:24778254

  17. Selectivity and tolerance for visual texture in macaque V2

    PubMed Central

    Ziemba, Corey M.; Freeman, Jeremy; Movshon, J. Anthony; Simoncelli, Eero P.

    2016-01-01

    As information propagates along the ventral visual hierarchy, neuronal responses become both more specific for particular image features and more tolerant of image transformations that preserve those features. Here, we present evidence that neurons in area V2 are selective for local statistics that occur in natural visual textures, and tolerant of manipulations that preserve these statistics. Texture stimuli were generated by sampling from a statistical model, with parameters chosen to match the parameters of a set of visually distinct natural texture images. Stimuli generated with the same statistics are perceptually similar to each other despite differences, arising from the sampling process, in the precise spatial location of features. We assessed the accuracy with which these textures could be classified based on the responses of V1 and V2 neurons recorded individually in anesthetized macaque monkeys. We also assessed the accuracy with which particular samples could be identified, relative to other statistically matched samples. For populations of up to 100 cells, V1 neurons supported better performance in the sample identification task, whereas V2 neurons exhibited better performance in texture classification. Relative to V1, the responses of V2 show greater selectivity and tolerance for the representation of texture statistics. PMID:27173899

  18. Postdispersal nepotism in male long-tailed macaques (Macaca fascicularis).

    PubMed

    Gerber, Livia; Krützen, Michael; de Ruiter, Jan R; van Schaik, Carel P; van Noordwijk, Maria A

    2016-01-01

    Cooperative behaviors are promoted by kin selection if the costs to the actor are smaller than the fitness benefits to the recipient, weighted by the coefficient of relatedness. In primates, cooperation occurs primarily among female dyads. Due to male dispersal before sexual maturity in many primate species, however, it is unknown whether there are sufficient opportunities for selective tolerance and occasional coalitionary support for kin selection to favor male nepotistic support. We studied the effect of the presence of male kin on correlates of male reproductive success (residence time, duration of high dominance rank) in non-natal male long-tailed macaques (Macaca fascicularis). We found that "related" (i.e., related at the half-sibling level or higher) males in a group have a significantly higher probability to remain in the non-natal group compared to males without relatives. Moreover, males stayed longer in a group when a relative was present at group entry or joined the same group within 3 months upon arrival. Males with co-residing relatives also maintained a high rank for longer than those without. To our knowledge, this is the first demonstration of a potential nepotistic effect on residence and rank maintenance among non-natal males in a social system without long-term alliances. PMID:26811773

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

    PubMed Central

    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 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. PMID:25027164

  20. Subcortical connections of area V4 in the macaque

    PubMed Central

    Gattass, Ricardo; Galkin, Thelma W; Desimone, Robert; Ungerleider, Leslie G

    2014-01-01

    Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4’s connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific. J. Comp. Neurol. 522:1941–1965, 2014. PMID:24288173

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

    PubMed

    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 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. PMID:25027164

  2. Selectivity and tolerance for visual texture in macaque V2.

    PubMed

    Ziemba, Corey M; Freeman, Jeremy; Movshon, J Anthony; Simoncelli, Eero P

    2016-05-31

    As information propagates along the ventral visual hierarchy, neuronal responses become both more specific for particular image features and more tolerant of image transformations that preserve those features. Here, we present evidence that neurons in area V2 are selective for local statistics that occur in natural visual textures, and tolerant of manipulations that preserve these statistics. Texture stimuli were generated by sampling from a statistical model, with parameters chosen to match the parameters of a set of visually distinct natural texture images. Stimuli generated with the same statistics are perceptually similar to each other despite differences, arising from the sampling process, in the precise spatial location of features. We assessed the accuracy with which these textures could be classified based on the responses of V1 and V2 neurons recorded individually in anesthetized macaque monkeys. We also assessed the accuracy with which particular samples could be identified, relative to other statistically matched samples. For populations of up to 100 cells, V1 neurons supported better performance in the sample identification task, whereas V2 neurons exhibited better performance in texture classification. Relative to V1, the responses of V2 show greater selectivity and tolerance for the representation of texture statistics. PMID:27173899

  3. Reconciliation and relationship quality in Assamese macaques (Macaca assamensis).

    PubMed

    Cooper, Matthew A; Berntein, Irwin S; Hemelrijk, Charlotte K

    2005-03-01

    A consistent conclusion in reconciliation research is that animals that reconcile are likely to have strong social bonds. This has led to the hypothesis that reconciliation occurs most often between valuable social partners. We tested this hypothesis in a group of Assamese macaques (Macaca assamensis) living near a temple in Assam, India. Using focal sample and ad libitum data collection, we recorded the occurrence of reconciliation, grooming, and agonistic aiding, and the outcomes of approach. We used matrix association methods (TauKr correlation) to correlate reconciliation with grooming, aiding, and approach outcome. Females reconciled more often with females with which they had stronger grooming and aiding relationships. The correlation between reconciliation and aiding was significant for support to the aggressor and the victim. In contrast, no such correlations with reconciliation were found for males. This study provides evidence that females reconcile most often with valuable and compatible social partners. The results do not support the relationship-quality hypothesis for males, and we suggest that future studies give more consideration to the possibility that males reconcile for reasons other than to repair relationships with valuable partners. PMID:15772987

  4. Gain Modulation by Nicotine in Macaque V1

    PubMed Central

    Disney, Anita A.; Aoki, Chiye; Hawken, Michael J.

    2010-01-01

    SUMMARY Acetylcholine is a ubiquitous cortical neuromodulator implicated in cognition. In order to understand the potential for acetylcholine to play a role in visual attention, we studied nicotinic acetylcholine receptor (nAChR) localization and function in area V1 of the macaque. We found nAChRs presynaptically at thalamic synapses onto excitatory, but not inhibitory, neurons in the primary thalamorecipient layer 4c. Furthermore, consistent with the release enhancement suggested by this localization, we discovered that nicotine increases responsiveness and lowers contrast threshold in layer 4c neurons. We also found that nAChRs are expressed by GABAergic interneurons in V1 but rarely by pyramidal neurons, and that nicotine suppresses visual responses outside layer 4c. All sensory systems incorporate gain control mechanisms, or processes which dynamically alter input/output relationships. We demonstrate that at the site of thalamic input to visual cortex, the effect of this nAChR-mediated gain is an enhancement of the detection of visual stimuli. PMID:18031686

  5. Copying hierarchical leaders’ voices? Acoustic plasticity in female Japanese macaques

    PubMed Central

    Lemasson, Alban; Jubin, Ronan; Masataka, Nobuo; Arlet, Malgorzata

    2016-01-01

    It has been historically claimed that call production in nonhuman primates has been shaped by genetic factors, although, recently socially-guided plasticity and cortical control during vocal exchanges have been observed. In humans, context-dependent vocal convergence with relatives, friends or leaders’ voices can be found. Comparative studies with monkeys and apes presenting tolerant social organizations have demonstrated that affiliative bonding is the determining factor of convergence. We tested whether vocal copying could also exist in a primate species with a despotic social organization. We compared the degree of inter-individual similarity of contact calls in two groups of Japanese macaques as a function of age, dominance rank, maternal kin and affiliative bonds. We found a positive relationship between dyadic acoustic similarity and female rank differences. Since most call exchanges were initiated by dominant females and since this species is known for the ability of responders to acoustically match initiators’ calls, we conclude that high social status may motivate vocal convergence in this despotic society. Accordingly, intra-individual comparisons showed that isolated calls were more stereotyped than exchanged calls, and that dominants had more stereotyped voices than subordinates. This opens new lines of research with regard to social motivation guiding acoustic plasticity in primates. PMID:26880673

  6. Neural Representation of Concurrent Vowels in Macaque Primary Auditory Cortex.

    PubMed

    Fishman, Yonatan I; Micheyl, Christophe; Steinschneider, Mitchell

    2016-01-01

    Successful speech perception in real-world environments requires that the auditory system segregate competing voices that overlap in frequency and time into separate streams. Vowels are major constituents of speech and are comprised of frequencies (harmonics) that are integer multiples of a common fundamental frequency (F0). The pitch and identity of a vowel are determined by its F0 and spectral envelope (formant structure), respectively. When two spectrally overlapping vowels differing in F0 are presented concurrently, they can be readily perceived as two separate "auditory objects" with pitches at their respective F0s. A difference in pitch between two simultaneous vowels provides a powerful cue for their segregation, which in turn, facilitates their individual identification. The neural mechanisms underlying the segregation of concurrent vowels based on pitch differences are poorly understood. Here, we examine neural population responses in macaque primary auditory cortex (A1) to single and double concurrent vowels (/a/ and /i/) that differ in F0 such that they are heard as two separate auditory objects with distinct pitches. We find that neural population responses in A1 can resolve, via a rate-place code, lower harmonics of both single and double concurrent vowels. Furthermore, we show that the formant structures, and hence the identities, of single vowels can be reliably recovered from the neural representation of double concurrent vowels. We conclude that A1 contains sufficient spectral information to enable concurrent vowel segregation and identification by downstream cortical areas. PMID:27294198

  7. Social and ecological factors influencing offspring survival in wild macaques

    PubMed Central

    Kerhoas, Daphne; Perwitasari-Farajallah, Dyah; Agil, Muhammad; Widdig, Anja

    2014-01-01

    Premature loss of offspring decreases direct fitness of parents. In gregarious mammals, both ecological and social variables impact offspring survival and may interact with each other in this regard. Although a number of studies have investigated factors influencing offspring loss in mammals, we still know very little on how different factors interact with one another. We therefore investigated fetal and infant mortality in 3 large groups of wild crested macaques (Macaca nigra) over a period of up to 5 years by including potential social causes such as maternal dominance rank, male immigration, between group encounters, and ecological conditions such as rainfall in a multivariate survival analysis using Cox proportional hazards model. Infant but not fetal survival was most impaired after a recent takeover of the alpha-male position by an immigrant male. Furthermore, infant survival probability increased when there was an increase in number of group adult females and rainfall. Fetal survival probability also increased with an increase of these 2 factors, but more in high-ranking than low-ranking females. Fetal survival, unlike that of infants, was also improved by an increase of intergroup encounter rates. Our study thus stresses the importance of survival analyses using a multivariate approach and encompassing more than a single offspring stage to investigate the determinants of female direct fitness. We further provide evidence for fitness costs and benefits of group living, possibly deriving from high pressures of both within- and between-group competition, in a wild primate population. PMID:25214754

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

    PubMed

    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. PMID:23315583

  9. Admixture in Humans of Two Divergent Plasmodium knowlesi Populations Associated with Different Macaque Host Species

    PubMed Central

    Divis, Paul C. S.; Singh, Balbir; Anderios, Fread; Hisam, Shamilah; Matusop, Asmad; Kocken, Clemens H.; Assefa, Samuel A.; Duffy, Craig W.; Conway, David J.

    2015-01-01

    Human malaria parasite species were originally acquired from other primate hosts and subsequently became endemic, then spread throughout large parts of the world. A major zoonosis is now occurring with Plasmodium knowlesi from macaques in Southeast Asia, with a recent acceleration in numbers of reported cases particularly in Malaysia. To investigate the parasite population genetics, we developed sensitive and species-specific microsatellite genotyping protocols and applied these to analysis of samples from 10 sites covering a range of >1,600 km within which most cases have occurred. Genotypic analyses of 599 P. knowlesi infections (552 in humans and 47 in wild macaques) at 10 highly polymorphic loci provide radical new insights on the emergence. Parasites from sympatric long-tailed macaques (Macaca fascicularis) and pig-tailed macaques (M. nemestrina) were very highly differentiated (FST = 0.22, and K-means clustering confirmed two host-associated subpopulations). Approximately two thirds of human P. knowlesi infections were of the long-tailed macaque type (Cluster 1), and one third were of the pig-tailed-macaque type (Cluster 2), with relative proportions varying across the different sites. Among the samples from humans, there was significant indication of genetic isolation by geographical distance overall and within Cluster 1 alone. Across the different sites, the level of multi-locus linkage disequilibrium correlated with the degree of local admixture of the two different clusters. The widespread occurrence of both types of P. knowlesi in humans enhances the potential for parasite adaptation in this zoonotic system. PMID:26020959

  10. Increased Mucosal CD4+ T Cell Activation in Rhesus Macaques following Vaccination with an Adenoviral Vector

    PubMed Central

    Bukh, Irene; Calcedo, Roberto; Roy, Soumitra; Carnathan, Diane G.; Grant, Rebecca; Qin, Qiuyue; Boyd, Surina; Ratcliffe, Sarah J.; Veeder, Christin L.; Bellamy, Scarlett L.; Betts, Michael R.

    2014-01-01

    ABSTRACT The possibility that vaccination with adenovirus (AdV) vectors increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of HIV acquisition within the Step trial. Modeling this within rhesus macaques is complicated because human adenoviruses, including human adenovirus type 5 (HAdV-5), are not endogenous to macaques. Here, we tested whether vaccination with a rhesus macaque-derived adenoviral vector (simian adenovirus 7 [SAdV-7]) enhances mucosal T cell activation within rhesus macaques. Following intramuscular SAdV-7 vaccination, we observed a pronounced increase in SAdV-7-specific CD4+ T cell responses in peripheral blood and, more dramatically, in rectal mucosa tissue. Vaccination also induced a significant increase in the frequency of activated memory CD4+ T cells in SAdV-7- and HAdV-5-vaccinated animals in the rectal mucosa but not in peripheral blood. These fluctuations within the rectal mucosa were also associated with a pronounced decrease in the relative frequency of naive resting CD4+ T cells. Together, these results indicate that peripheral vaccination with an AdV vector can increase the activation of mucosal CD4+ T cells, potentially providing an experimental model to further evaluate the role of host-vector interactions in increased HIV acquisition after AdV vector vaccination. IMPORTANCE The possibility that vaccination with a human adenovirus 5 vector increased mucosal T cell activation remains a central hypothesis to explain the potential enhancement of human immunodeficiency virus (HIV) acquisition within the Step trial. In this study, we tested whether vaccination with a rhesus macaque-derived adenoviral vector in rhesus macaques enhances mucosal CD4+ T cell activation, the main cell target of simian immunodeficiency virus (SIV)/HIV. The results showed that vaccination with an adenoviral vector indeed increases activation of mucosal CD4+ T cells and potentially increases susceptibility to SIV

  11. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

    PubMed

    McCarthy, Kevin R; Johnson, Welkin E; Kirmaier, Andrea

    2016-01-01

    In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery. PMID:27415779

  12. Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa

    PubMed Central

    Johnson, Welkin E.

    2016-01-01

    In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery. PMID:27415779

  13. Clinical Allograft of a Calcaneal Tendon in a Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Lemoy, Marie-Josee; Summers, Laura; Colagross-Schouten, Angela

    2014-01-01

    A 5.5-y-old male rhesus monkey (Macaca mulatta) housed in an outdoor field cage presented for severe trauma involving the left calcaneal tendon. Part of the management of this wound included an allograft of the calcaneal tendon from an animal that was euthanized for medical reasons. This case report describes the successful medical and surgical management of a macaque with a significant void of the calcaneal tendon. To our knowledge, this report is the first description of a successful tendon allograft in a rhesus macaque for clinical purposes. PMID:25255076

  14. A Method for Recording Single-cell Activity in the Frontal Pole Cortex of Macaque Monkeys

    PubMed Central

    Mitz, Andrew R.; Tsujimoto, Satoshi; MacLarty, Arthur J.; Wise, Steven P.

    2009-01-01

    Neurophysiological research has explored most of the prefrontal cortex of macaque monkeys, but the relatively inaccessible frontal pole cortex remains unexamined. Here we describe a method for gaining access to the frontal pole cortex with moveable microelectrodes. The key innovation is a direct approach through the frontal air sinus. In addition, the small size of the frontal pole cortex in macaques led to the design of a smaller recording chamber than typically used in behavioral neurophysiology. The method has proven successful in two subjects, with no adverse health consequences. PMID:18977387

  15. What studies of macaque monkeys have told us about human color vision

    PubMed Central

    Horwitz, Gregory D.

    2014-01-01

    Animal models are a necessary component of systems neuroscience research. Determining which animal model to use for a given study involves a complicated calculus. Some experimental manipulations are easily made in some animal models but impossible in others. Some animal models are similar to humans with respect to particular scientific questions, and others are less so. In this review, I discuss work done in my laboratory to investigate the neural mechanisms of color vision in the rhesus macaque. The emphasis is on the strengths of the macaque model, but shortcomings are also discussed. PMID:25445192

  16. Hepatic Cells Derived from Induced Pluripotent Stem Cells of Pigtail Macaques Support Hepatitis C Virus infection

    PubMed Central

    Sourisseau, Marion; Goldman, Orit; He, Wenqian; Gori, Jennifer L.; Kiem, Hans-Peter; Gouon-Evans, Valerie; Evans, Matthew J.

    2013-01-01

    The narrow species tropism of hepatitis C virus (HCV) limits animal studies. We found that pigtail macaque (Macaca nemestrina) hepatic cells derived from induced pluripotent stem cells support the entire HCV life cycle, although infection efficiency was limited by defects in the HCV cell entry process. This block was overcome by either increasing occludin expression, complementing the cells with human CD81, or infecting them with a strain of HCV with less-restricted requirements for CD81. Using this system, we can modify viral and host cell genetics to make pigtail macaques a suitable, clinically relevant model for the study of HCV infection. PMID:23891978

  17. C5A Protects Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge

    PubMed Central

    Veazey, Ronald S.; Chatterji, Udayan; Bobardt, Michael; Russell-Lodrigue, Kasi E.; Li, Jian; Wang, Xiaolei

    2015-01-01

    A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian-human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate. PMID:26552985

  18. C5A Protects Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge.

    PubMed

    Veazey, Ronald S; Chatterji, Udayan; Bobardt, Michael; Russell-Lodrigue, Kasi E; Li, Jian; Wang, Xiaolei; Gallay, Philippe A

    2016-01-01

    A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian-human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate. PMID:26552985

  19. Protection of macaques from vaginal SHIV challenge by an orally delivered CCR5 inhibitor.

    PubMed

    Veazey, Ronald S; Springer, Martin S; Marx, Preston A; Dufour, Jason; Klasse, Per Johan; Moore, John P

    2005-12-01

    Pre-exposure oral prophylaxis with antiviral drugs is a potential method for preventing transmission of human immunodeficiency virus type 1 (HIV-1). We show that oral delivery of CMPD167, a small molecule that binds to the CCR5 coreceptor, for 10-14 d can protect a substantial proportion of macaques from vaginal infection with a CCR5-using virus (SHIV-162P3). The macaques that became infected despite receiving CMPD167 had reduced plasma viremia levels during the earliest stages of infection. PMID:16273102

  20. Multiple sirehood in free-ranging twin rhesus macaques (Macaca mulatta).

    PubMed

    Bercovitch, Fred B; Widdig, Anja; Berard, John D; Nürnberg, Peter; Kessler, Matt J; Schmidtke, Jörg; Trefilov, Andrea; Krawczak, Michael

    2002-05-01

    Rhesus macaque females regularly copulate with a number of partners, and produce a single offspring per reproductive cycle in over 99% of cases. We used genotyping of 10 STR markers to determine paternity in the Cayo Santiago population of rhesus macaques. About 1,500 monkeys have been analyzed to date, with their marker genotypes entered into a computerized database. These data enable us to report the first documented case in any cercopithecine nonhuman primate species of the production of twin offspring sired by different males. PMID:11977124

  1. Natural Infection of Burkholderia pseudomallei in an Imported Pigtail Macaque (Macaca nemestrina) and Management of the Exposed Colony

    PubMed Central

    Johnson, Crystal H; Skinner, Brianna L; Dietz, Sharon M; Blaney, David; Engel, Robyn M; Lathrop, George W; Hoffmaster, Alex R; Gee, Jay E; Elrod, Mindy G; Powell, Nathaniel; Walke, Henry

    2013-01-01

    Identification of the select agent Burkholderia pseudomallei in macaques imported into the United States is rare. A purpose-bred, 4.5-y-old pigtail macaque (Macaca nemestrina) imported from Southeast Asia was received from a commercial vendor at our facility in March 2012. After the initial acclimation period of 5 to 7 d, physical examination of the macaque revealed a subcutaneous abscess that surrounded the right stifle joint. The wound was treated and resolved over 3 mo. In August 2012, 2 mo after the stifle joint wound resolved, the macaque exhibited neurologic clinical signs. Postmortem microbiologic analysis revealed that the macaque was infected with B. pseudomallei. This case report describes the clinical evaluation of a B. pseudomallei-infected macaque, management and care of the potentially exposed colony of animals, and protocols established for the animal care staff that worked with the infected macaque and potentially exposed colony. This article also provides relevant information on addressing matters related to regulatory issues and risk management of potentially exposed animals and animal care staff. PMID:24326230

  2. A critical analysis of the cynomolgus macaque, Macaca fascicularis, as a model to test HIV-1/SIV vaccine efficacy.

    PubMed

    Antony, Joseph M; MacDonald, Kelly S

    2015-06-17

    The use of a number of non-rhesus macaque species, but especially cynomolgus macaques as a model for HIV-1 vaccine development has increased in recent years. Cynomolgus macaques have been used in the United Kingdom, Europe, Canada and Australia as a model for HIV vaccine development for many years. Unlike rhesus macaques, cynomolgus macaques infected with SIV show a pattern of disease pathogenesis that more closely resembles that of human HIV-1 infection, exhibiting lower peak and set-point viral loads and slower progression to disease with more typical AIDS defining illnesses. Several advances have been made recently in the use of the cynomolgus macaque SIV challenge model that allow the demonstration of vaccine efficacy using attenuated viruses and vectors that are both viral and non-viral in origin. This review aims to probe the details of various vaccination trials carried out in cynomolgus macaques in the context of our modern understanding of the highly diverse immunogenetics of this species with a view to understanding the species-specific immune correlates of protection and the efficacy of vectors that have been used to design vaccines. PMID:25510387

  3. Human behavior and opportunities for parasite transmission in communities surrounding long-tailed macaque populations in Bali, Indonesia.

    PubMed

    Lane-DeGraaf, Kelly E; Putra, I G A Arta; Wandia, I Nengah; Rompis, Aida; Hollocher, Hope; Fuentes, Agustin

    2014-02-01

    Spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (Macaca fascicularis), concentrating them in areas in close proximity to humans. In this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestinal parasites to understand if age, education level, or occupation are significant determinants of exposure behaviors. These exposure risk behaviors and attitudes include fear of macaques, direct contact with macaques, owning pet macaques, hunting and eating macaques, and overlapping water uses. We find that willingness to participate in exposure risk behaviors are correlated with an individual's occupation, age, and/or education level. We also found that because the actual risk of infection varies across populations, activities such as direct macaque contact and pet ownership, could be putting individuals at real risk in certain contexts. Thus, we show that human demographics and social structure can influence willingness to participate in behaviors putting them at increased risk for exposure to parasites. PMID:24123083

  4. Molecular detection and prevalence of Giardia duodenalis and Cryptosporidium spp. among long-tailed macaques (Macaca fascicularis) in Thailand.

    PubMed

    Sricharern, Wanat; Inpankaew, Tawin; Keawmongkol, Sarawan; Supanam, Juthamas; Stich, Roger W; Jittapalapong, Sathaporn

    2016-06-01

    Giardia duodenalis and Cryptosporidium spp. are divergent protozoal intestinal parasites that infect human beings and other animals, including non-human primates. Although long-tailed macaques (Macaca fascicularis) reside in human communities in Thailand, the prevalence of Giardia spp. and Cryptosporidium spp. in these primates has not been previously investigated. The objective of this study was to evaluate long-tailed macaques living near human communities as possible hosts of these intestinal parasites. In 2014, 200 fecal samples were randomly collected from long-tailed macaques living in different areas of Lopburi province, Thailand, and tested with a panel of PCR assays for Giardia spp. and Cryptosporidium spp. G. duodenalis assemblage B was most frequently detected (6%), while assemblage A and an inconclusive assemblage were detected in single samples, for a total G. duodenalis infection rate of 7%. Two samples (1%) tested positive for Cryptosporidium spp., which were both classified as monkey genotypes. No significant associations were found between G. duodenalis infection and sex or location of macaques. This study indicates that long-tailed macaques can carry G. duodenalis and, to a lesser extent, Cryptosporidium spp. monkey genotype. These results warrant education of residents and tourists to limit contact with long-tailed macaques and to take hygienic precautions to mitigate risk of zoonotic and anthroponotic transmission of these parasites between people and macaques. PMID:26892616

  5. A Long-Acting Integrase Inhibitor Protects Female Macaques from Repeated High-Dose Intravaginal SHIV Challenge

    PubMed Central

    Andrews, Chasity D.; Yueh, Yun Lan; Spreen, William R.; St. Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D.; Markowitz, Martin

    2015-01-01

    GSK1265744 long-acting (GSK744 LA) is a strand-transfer inhibitor of HIV/SIV integrase and was shown to be an effective pre-exposure prophylaxis agent in a low-dose intrarectal SHIV rhesus macaque challenge model. Here, we examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with 50 mg/kg of GSK744 LA monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were 5-fold lower on average in cervical tissues than rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected 6 of 8 female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for pre-exposure prophylaxis. PMID:25589630

  6. Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes.

    PubMed

    Hughes, Jennifer F; Skaletsky, Helen; Page, David C

    2012-12-01

    Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We report that DAZ arrived on the Y chromosome about 38 million years ago via the transposition of at least 1.1 megabases of autosomal DNA. This transposition also brought five additional genes to the Y chromosome, but all five genes were subsequently lost through mutation or deletion. As the only surviving gene, DAZ experienced extensive restructuring, including intragenic amplification and gene duplication, and has been the target of positive selection in the chimpanzee lineage. Editor's suggested further reading in BioEssays Should Y stay or should Y go: The evolution of non-recombining sex chromosomes Abstract. PMID:23055411

  7. A chimeric Sindbis-based vaccine protects cynomolgus macaques against a lethal aerosol challenge of eastern equine encephalitis virus

    PubMed Central

    Roy, Chad J.; Adams, A. Paige; Wang, Eryu; Leal, Grace; Seymour, Robert L.; Sivasubramani, Satheesh K.; Mega, William; Frolov, Ilya; Didier, Peter J.; Weaver, Scott C.

    2013-01-01

    Eastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus that causes sporadic, often fatal disease outbreaks in humans and equids, and is also a biological threat agent. Two chimeric vaccine candidates were constructed using a cDNA clone with a Sindbis virus (SINV) backbone and structural protein genes from either a North (SIN/NAEEEV) or South American (SIN/SAEEEV) strain of EEEV. The vaccine candidates were tested in a nonhuman primate (NHP) model of eastern equine encephalitis (EEE). Cynomolgus macaques were either sham-vaccinated, or vaccinated with a single dose of either SIN/NAEEEV or SIN/SAEEEV. After vaccination, animals were challenged by aerosol with a virulent North American strain of EEEV (NA EEEV). The SIN/NAEEEV vaccine provided significant protection, and most vaccinated animals survived EEEV challenge (82%) with little evidence of disease, whereas most SIN/SAEEEV-vaccinated (83%) and control (100%) animals died. Protected animals exhibited minimal changes in temperature and cardiovascular rhythm, whereas unprotected animals showed profound hyperthermia and changes in heart rate post-exposure. Acute inflammation and neuronal necrosis were consistent with EEEV-induced encephalitis in unprotected animals, whereas no encephalitis-related histopathologic changes were observed in the SIN/NAEEEV-vaccinated animals. These results demonstrate that the chimeric SIN/NAEEEV vaccine candidate protects against an aerosol EEEV exposure. PMID:23333212

  8. Phylogenetic relationships of Malaysia's pig-tailed macaque Macaca nemestrina based on D-loop region sequences

    NASA Astrophysics Data System (ADS)

    Abdul-Latiff M. A., B.; Ampeng, A.; Yaakop, S.; Md-Zain B., M.

    2014-09-01

    Phylogenetic relationships among Malaysian pig-tailed macaques have never been established even though the data are crucial in aiding conservation plan for the species. The aims of this study is to establish the phylogenetic relationships of Macaca nemestrina in Malaysia. A total of 21 genetic samples of M. nemestrina yielding 458 bp of D-loop sequences were used in phylogenetic analyses, in addition to one sample of M. fascicularis which was used as an outgroup. Sequence character analysis revealed that D-loop locus contains 23% parsimony informative character detected among the ingroups. Further analysis indicated a clear separation between populations originating from different regions; the Malay Peninsula populations are separated from Borneo Insular population; and Perak population formed a distinctive clade within Peninsular Malaysia populations. Phylogenetic trees (NJ, MP and Bayesian) portray a consistent clustering paradigm as Borneo population was distinguished from Peninsula population (100% bootstrap value in the NJ, MP, 1.00 posterior probability in Bayesian trees). Perak's population was separated from other Peninsula populations (100% in NJ, 99% in MP and 1.00 in Bayesian). D-loop region of mtDNA is proven to be a suitable locus in studying the separation of M. nemestrina at population level. These findings are crucial in aiding the conservation management and translocation process of M. fascicularis populations in Malaysia.

  9. Neurobiology of Stress-Induced Reproductive Dysfunction In Female Macaques

    PubMed Central

    Bethea, Cynthia L.; Centeno, Maria Luisa; Cameron, Judy L.

    2012-01-01

    It is now well accepted that stress can precipitate mental and physical illness. However, it is becoming clear that given the same stress, some individuals are very vulnerable and will succumb to illness while others are more resilient and cope effectively, rather than becoming ill. This difference between individuals is called stress sensitivity. Stress-sensitivity of an individual appears to be influenced by genetically inherited factors, early life (even prenatal) stress, and by the presence or absence of factors that provide protection from stress. In comparison to other stress-related diseases, the concept of sensitivity versus resilience to stress-induced reproductive dysfunction has received relatively little attention. The studies presented herein were undertaken to begin to identify stable characteristics and the neural underpinnings of individuals with sensitivity to stress-induced reproductive dysfunction. Female cynomolgus macaques with normal menstrual cycles either stop ovulating (Stress Sensitive) or to continue to ovulate (Stress Resilient) upon exposure to a combined metabolic and psychosocial stress. However, even in the absence of stress, the stress sensitive animals have lower secretion of the ovarian steroids, estrogen and progesterone, have higher heart rates, have lower serotonin function, have fewer serotonin neurons and lower expression of pivotal serotonin-related genes, have lower expression of 5HT2A and 2C genes in the hypothalamus, have higher gene expression of GAD67 and CRH in the hypothalamus and have reduced GnRH transport to the anterior pituitary. Altogether, the results suggest that the neurobiology of reproductive circuits in stress sensitive individuals is compromised. We speculate that with the application of stress, the dysfunction of these neural systems becomes exacerbated and reproductive function ceases. PMID:18931961

  10. Spatiotemporal structure of visual receptive fields in macaque superior colliculus.

    PubMed

    Churan, Jan; Guitton, Daniel; Pack, Christopher C

    2012-11-01

    Saccades are useful for directing the high-acuity fovea to visual targets that are of behavioral relevance. The selection of visual targets for eye movements involves the superior colliculus (SC), where many neurons respond to visual stimuli. Many of these neurons are also activated before and during saccades of specific directions and amplitudes. Although the role of the SC in controlling eye movements has been thoroughly examined, far less is known about the nature of the visual responses in this area. We have, therefore, recorded from neurons in the intermediate layers of the macaque SC, while using a sparse-noise mapping procedure to obtain a detailed characterization of the spatiotemporal structure of visual receptive fields. We find that SC responses to flashed visual stimuli start roughly 50 ms after the onset of the stimulus and last for on average ~70 ms. About 50% of these neurons are strongly suppressed by visual stimuli flashed at certain locations flanking the excitatory center, and the spatiotemporal pattern of suppression exerts a predictable influence on the timing of saccades. This suppression may, therefore, contribute to the filtering of distractor stimuli during target selection. We also find that saccades affect the processing of visual stimuli by SC neurons in a manner that is quite similar to the saccadic suppression and postsaccadic enhancement that has been observed in the cortex and in perception. However, in contrast to what has been observed in the cortex, decreased visual sensitivity was generally associated with increased firing rates, while increased sensitivity was associated with decreased firing rates. Overall, these results suggest that the processing of visual stimuli by SC receptive fields can influence oculomotor behavior and that oculomotor signals originating in the SC can shape perisaccadic visual perception. PMID:22933722

  11. Pupil size and social vigilance in rhesus macaques

    PubMed Central

    Ebitz, R. Becket; Pearson, John M.; Platt, Michael L.

    2014-01-01

    Complex natural environments favor the dynamic alignment of neural processing between goal-relevant stimuli and conflicting but biologically salient stimuli like social competitors or predators. The biological mechanisms that regulate dynamic changes in vigilance have not been fully elucidated. Arousal systems that ready the body to respond adaptively to threat may contribute to dynamic regulation of vigilance. Under conditions of constant luminance, pupil diameter provides a peripheral index of arousal state. Although pupil size varies with the processing of goal-relevant stimuli, it remains unclear whether pupil size also predicts attention to biologically salient objects and events like social competitors, whose presence interferes with current goals. Here we show that pupil size in rhesus macaques both reflects the biological salience of task-irrelevant social distractors and predicts vigilance for these stimuli. We measured pupil size in monkeys performing a visual orienting task in which distractors—monkey faces and phase-scrambled versions of the same images—could appear in a congruent, incongruent, or neutral position relative to a rewarded target. Baseline pupil size under constant illumination predicted distractor interference, consistent with the hypothesis that pupil-linked arousal mechanisms regulate task engagement and distractibility. Notably, pupil size also predicted enhanced vigilance for social distractors, suggesting that pupil-linked arousal may adjust the balance of processing resources between goal-relevant and biologically important stimuli. The magnitude of pupil constriction in response to distractors closely tracked distractor interference, saccade planning and the social relevance of distractors, endorsing the idea that the pupillary light response is modulated by attention. These findings indicate that pupil size indexes dynamic changes in attention evoked by both the social environment and arousal. PMID:24834026

  12. Sleeping site selection and presleep behavior in wild pigtailed macaques.

    PubMed

    Albert, Aurélie; Savini, Tommaso; Huynen, Marie-Claude

    2011-12-01

    Several factors are likely to control sleeping site selection and presleep behavior in nonhuman primates, including predation risk and location of food resources. We examined the effects of these factors on the sleeping behavior of northern pigtailed macaques (Macaca leonina). While following a troop living in the surroundings of the Visitor Center of Khao Yai National Park (Thailand), we recorded the physical characteristics and location of each sleeping site, tree, the individuals' place in the tree, posture, and behavior. We collected data for 154 nights between April 2009 and November 2010. The monkeys preferred tall sleeping trees (20.9 ± SD 4.9 m) and high sleeping places (15.8 ± SD 4.3 m), which may be an antipredator strategy. The choice of sleeping trees close to the last (146.7 ± SD 167.9 m) or to the first (150.4 ± SD 113.0 m) feeding tree of the day may save energy and decrease predation risk when monkeys are searching for food. Similarly, the choice of sleeping sites close to human settlements eases the access to human food during periods of fruit scarcity. Finally, the temporal pattern of use of sleeping sites, with a preference for four of the sleeping sites but few reuses during consecutive nights, may be a trade-off between the need to have several sleeping sites (decreasing detection by predators and travel costs to feeding sites), and the need to sleep in well-known sites (guaranteeing a faster escape in case of predator attack). PMID:21898516

  13. Visual signal processing in the macaque lateral geniculate nucleus.

    PubMed

    Seim, Thorstein; Valberg, Arne; Lee, Barry B

    2012-03-01

    Comparisons of S- or prepotential activity, thought to derive from a retinal ganglion cell afferent, with the activity of relay cells of the lateral geniculate nucleus (LGN) have sometimes implied a loss, or leak, of visual information. The idea of the "leaky" relay cell is reconsidered in the present analysis of prepotential firing and LGN responses of color-opponent cells of the macaque LGN to stimuli varying in size, relative luminance, and spectral distribution. Above a threshold prepotential spike frequency, called the signal transfer threshold (STT), there is a range of more than 2 log units of test field luminance that has a 1:1 relationship between prepotential- and LGN-cell firing rates. Consequently, above this threshold, the LGN cell response can be viewed as an extension of prepotential firing (a "nonleaky relay cell"). The STT level decreased when the size of the stimulus increased beyond the classical receptive field center, indicating that the LGN cell is influenced by factors other than the prepotential input. For opponent ON cells, both the excitatory and the inhibitory response decreased similarly when the test field size increased beyond the center of the receptive field. These findings have consequences for the modeling of LGN cell responses and transmission of visual information, particularly for small fields. For instance, for LGN ON cells, information in the prepotential intensity-response curve for firing rates below the STT is left to be discriminated by OFF cells. Consequently, for a given light adaptation, the STT improves the separation of the response range of retinal ganglion cells into "complementary" ON and OFF pathways. PMID:22391245

  14. Immune biology of macaque lymphocyte populations during mycobacterial infection

    PubMed Central

    LAI, X; SHEN, Y; ZHOU, D; SEHGAL, P; SHEN, L; SIMON, M; QIU, L; LETVIN, N L; CHEN, Z W

    2003-01-01

    Immune responses of lymphocyte populations during early phases of mycobacterial infection and reinfection have not been well characterized in humans. A non-human primate model of Mycobacterium bovis bacille Calmette–Guerin (BCG) infection was employed to characterize optimally the immune responses of mycobacteria-specific T cells. Primary BCG infection induced biphasic immune responses, characterized by initial lymphocytopenia and subsequent expansion of CD4+, CD8+ and γδ T cell populations in the blood, lymph nodes and the pulmonary compartment. The potency of detectable T cell immune responses appears to be influenced by the timing and route of infection as well as challenge doses of BCG organisms. Systemic BCG infection introduced by intravenous challenge induced a dose-dependent expansion of circulating CD4+, CD8+ and γδ T cells whereas, in the pulmonary compartment, the systemic infection resulted in a predominant increase in numbers of γδ T cells. In contrast, pulmonary exposure to BCG through the bronchial route induced detectable expansions of CD4+, CD8+ and γδ T cell populations in only the lung but not in the blood. A rapid recall expansion of these T cell populations was seen in the macaques reinfected intravenously and bronchially with BCG. The expanded αβ and γδ T cell populations exhibited their antigen specificity for mycobacterial peptides and non-peptide phospholigands, respectively. Finally, the major expansion of T cells was associated with a resolution of active BCG infection and reinfection. The patterns and kinetics of CD4+, CD8+ and γδ T cell immune responses during BCG infection might contribute to characterizing immune protection against tuberculosis and testing new tuberculosis vaccines in primates. PMID:12869023

  15. Crossmodal integration of conspecific vocalizations in rhesus macaques.

    PubMed

    Payne, Christa; Bachevalier, Jocelyne

    2013-01-01

    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. PMID:24236218

  16. Vaccination of calves using the BRSV nucleocapsid protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects the lungs against BRSV replication and pathology.

    PubMed

    Letellier, Carine; Boxus, Mathieu; Rosar, Laurent; Toussaint, Jean-François; Walravens, Karl; Roels, Stefan; Meyer, Gilles; Letesson, Jean-Jacques; Kerkhofs, Pierre

    2008-09-01

    Respiratory syncytial virus (RSV) is a major cause of respiratory disease in both cattle and young children. Despite the development of vaccines against bovine (B)RSV, incomplete protection and exacerbation of subsequent RSV disease have occurred. In order to circumvent these problems, calves were vaccinated with the nucleocapsid protein, known to be a major target of CD8(+) T cells in cattle. This was performed according to a DNA prime-protein boost strategy. The results showed that DNA vaccination primed a specific T-cell-mediated response, as indicated by both a lymphoproliferative response and IFN-gamma production. These responses were enhanced after protein boost. After challenge, mock-vaccinated calves displayed gross pneumonic lesions and viral replication in the lungs. In contrast, calves vaccinated by successive administrations of plasmid DNA and protein exhibited protection against the development of pneumonic lesions and the viral replication in the BAL fluids and the lungs. The protection correlated to the cell-mediated immunity and not to the antibody response. PMID:18644416

  17. The effects of TRIM5α polymorphism on HIV-2ROD and SIVmac239 replication in PBMCs from Chinese rhesus macaques and Vietnamese-origin cynomolgus macaques.

    PubMed

    Zhang, Hui-Ling; Liu, Feng-Liang; Jin, Ya-Bin; Deng, Qing; Liu, Bei-Lei; Zhuo, Min; Liu, Xiao-Hui; Zheng, Yong-Tang; Ling, Fei

    2016-01-01

    Because of the difficulty of obtaining Indian-origin rhesus macaques, Chinese-origin rhesus macaques (CR) and Vietnamese-origin cynomolgus macaques (CM) are now used frequently in HIV/AIDS research. Nonetheless, the effects of TRIM5α polymorphism on viral replication in both CR and CM are unclear. To address these questions, we recruited 70 unrelated CR and 40 unrelated CM and studied the effect of TRIM5α polymorphism on HIV-2ROD and SIVmac239 replication in PBMCs. We found that 3 polymorphisms, located in the B30.2 domain of CR TRIM5α formed a haplotype and affected HIV-2ROD replication. In addition, we found that the variant Y178H, located in the Coiled-coil domain of CM TRIM5α, affected TRIM5α-mediated HIV-2ROD restriction. Finally, two polymorphisms, located in the Coiled-coil domain, altered anti-SIVmac239 activity in CR. We concluded that, CM TRIM5α polymorphism could alter HIV-2ROD infection; however, a different domain of CR TRIM5α was responsible for restricting different virus replication. PMID:26550946

  18. A Generalizability Analysis of Subjective Personality Assessments in the Stumptail Macaque and the Zebra Finch.

    ERIC Educational Resources Information Center

    Figueredo, Aurelio Jose; And Others

    1995-01-01

    Two longitudinal studies involving 29 raters concerning the construct validity, temporal stability, and interrater reliability of the latent common factors underlying subjective assessments by human raters of personality traits in the stumptail macaque and the zebra finch illustrate the use of generalizability analysis to test prespecified…

  19. Effects of Category Learning on the Stimulus Selectivity of Macaque Inferior Temporal Neurons

    ERIC Educational Resources Information Center

    De Baene, Wouter; Ons, Bart; Wagemans, Johan; Vogels, Rufin

    2008-01-01

    Primates can learn to categorize complex shapes, but as yet it is unclear how this categorization learning affects the representation of shape in visual cortex. Previous studies that have examined the effect of categorization learning on shape representation in the macaque inferior temporal (IT) cortex have produced diverse and conflicting results…

  20. Trisomy 16 in a Pigtailed Macaque ("M. nemestrina") with Multiple Anomalies and Developmental Delays

    ERIC Educational Resources Information Center

    Ruppenthal, Gerald C.; Moore, Charleen M.; Best, Robert G.; Walker-Gelatt, Coleen G.; Delio, Patrick J.; Sackett, Gene P.

    2004-01-01

    A female pigtailed macaque ("Macaca nemestrina") with unusual physical characteristics, deficits in learning and cognitive tasks, abnormal social behavior, and abnormal reflexes and motor control was followed from birth until 3 years of age and found to have trisomy 16, which is homologous to trisomy 13 in humans. The animal described here showed…

  1. Infant Abuse Runs in Families of Group-Living Pigtail Macaques.

    ERIC Educational Resources Information Center

    Maestripieri, Dario; And Others

    1997-01-01

    Infant abuse and neglect were investigated in five families of group-living pigtail macaques over five generations. Neglect was mostly limited to first-born and newborns; closely related rather than distantly related females were more prone to abuse; and infants with siblings previously abused were at highest risk. Results provide evidence of…

  2. The vocal repertoire of Tibetan macaques (Macaca thibetana): A quantitative classification.

    PubMed

    Bernstein, Sofia K; Sheeran, Lori K; Wagner, R Steven; Li, Jin-Hua; Koda, Hiroki

    2016-09-01

    Vocal repertoires are basic and essential components for describing vocal communication in animals. Studying the entire suite of vocal signals aids investigations on the variation of acoustic structure across social contexts, comparisons on the complexity of communication systems across taxa, and in exploration of the evolutionary origins of species-specific vocalizations. Here, we describe the vocal repertoire of the largest species in the macaque genus, Macaca thibetana. We extracted thirty acoustic parameters from call recordings. Post hoc validation through quantitative analyses of the a priori repertoire classified eleven call types: coo, squawk, squeal, noisy scream, growl, bark, compound squeak, leap coo, weeping, modulated tonal scream, and pant. In comparison to the rest of the genus, Tibetan macaques uttered a wider array of vocalizations in the context of copulations. Previous reports did not include modulated tonal screams and pants during harassment of copulatory dyads. Furthermore, in comparison to the rest of the genus, Tibetan macaque females emit acoustically distinct copulation calls. The vocal repertoire of Tibetan macaques contributes to the literature on the emergence of species-specific calls in the genus Macaca with potential insights from social, reproductive, and ecological comparisons across species. Am. J. Primatol. 78:937-949, 2016. © 2016 Wiley Periodicals, Inc. PMID:27243451

  3. Spontaneous Representations of Small Numbers of Objects by Rhesus Macaques: Examinations of Content and Format

    ERIC Educational Resources Information Center

    Hauser, Marc D.; Carey, Susan

    2003-01-01

    The project of comparative cognition benefits from common measures across species. We report here on five experiments using the violation of expectancy looking time measure with free-ranging rhesus macaques ("Macaca mulatta"), each designed to build on current knowledge concerning spontaneous representations of number. Each subject, tested in only…

  4. Social Preferences by and for Pigtailed Macaques (Macaca Nemestrina) with Trisomy 18.

    ERIC Educational Resources Information Center

    Swartz, Karyl B.; Sackett, Gene P.

    1994-01-01

    Comparison of social choices of trisomic macaques and of control groups found that groups showed few differences in preferences for stimulus animals with and without disabilities. Results suggest that the avoidance of individuals with disabilities is not a general primate trait and the presence of mental retardation and physical handicaps need not…

  5. Development and Characterization of a Macaque Model of Focal Internal Capsular Infarcts

    PubMed Central

    Murata, Yumi; Higo, Noriyuki

    2016-01-01

    Several studies have used macaque monkeys with lesions induced in the primary motor cortex (M1) to investigate the recovery of motor function after brain damage. However, in human stroke patients, the severity and outcome of motor impairments depend on the degree of damage to the white matter, especially that in the posterior internal capsule, which carries corticospinal tracts. To bridge the gap between results obtained in M1-lesioned macaques and the development of clinical intervention strategies, we established a method of inducing focal infarcts at the posterior internal capsule of macaque monkeys by injecting endothelin-1 (ET-1), a vasoconstrictor peptide. The infarcts expanded between 3 days and 1 week after ET-1 injection. The infarct volume in each macaque was negatively correlated with precision grip performance 3 days and 1 week after injection, suggesting that the degree of infarct expansion may have been a cause of the impairment in hand movements during the early stage. Although the infarct volume decreased and gross movement improved, impairment of dexterous hand movements remained until the end of the behavioral and imaging experiments at 3 months after ET-1 injection. A decrease in the abundance of large neurons in M1, from which the descending motor tracts originate, was associated with this later-stage impairment. The present model is useful not only for studying neurological changes underlying deficits and recovery but also for testing therapeutic interventions after white matter infarcts in primates. PMID:27149111

  6. Tetanus as cause of mass die-off of captive Japanese macaques, Japan, 2008.

    PubMed

    Nakano, Tomomi; Nakamura, Shin-ichi; Yamamoto, Akihiko; Takahashi, Motohide; Une, Yumi

    2012-10-01

    In 2008 in Japan, 15/60 captive Japanese macaques died. Clostridium tetani was isolated from 1 monkey, and 11 had tetanus-specific symptoms. We conclude the outbreak resulted from severe environmental C. tetani contamination. Similar outbreaks could be prevented by vaccinating all monkeys, disinfecting housing areas/play equipment, replacing highly C. tetani-contaminated soil, and conducting epidemiologic surveys. PMID:23017658

  7. Coagulation Biomarkers in Healthy Chinese-Origin Rhesus Macaques (Macaca mulatta).

    PubMed

    Frydman, Galit H; Bendapudi, Pavan K; Marini, Robert P; Vanderburg, Charles R; Tompkins, Ronald G; Fox, James G

    2016-01-01

    Rhesus macaques (Macaca mulatta) are a common model for the study of human biology and disease. To manage coagulopathies in these animals and to study their clotting changes, the ability to measure coagulation biomarkers is necessary. Currently, few options for coagulation testing in NHP are commercially available. In this study, assays for 4 coagulation biomarkers-D-dimer, antithrombin III, protein C, and soluble P-selectin-were developed and optimized for rhesus macaques. Whole blood was collected from 28 healthy Chinese-origin rhesus macaques (11 male; 17 female) ranging in age from 5 to 20 y. Coagulation biomarkers were measured by using bead-based sandwich ELISA technology. The ranges (mean ± 90% confidence interval) for these biomarkers were: antithrombin III, 124.2 to 133.4 μg/mL; protein C, 3.2 to 3.6 μg/mL; D-dimer, 110.3 to 161.3 ng/mL; soluble P-selectin, 0.12 to 0.14 ng/10(6) platelets. These reference values did not differ significantly according to sex or age. These new assays for coagulation biomarkers in rhesus macaques will facilitate the evaluation of in vivo hemostasis. PMID:27177557

  8. Plasticity of Ability to Form Cross-Modal Representations in Infant Japanese Macaques

    ERIC Educational Resources Information Center

    Adachi, Ikuma; Kuwahata, Hiroko; Fujita, Kazuo; Tomonaga, Masaki; Matsuzawa, Tetsuro

    2009-01-01

    In a previous study, Adachi, Kuwahata, Fujita, Tomonaga & Matsuzawa demonstrated that infant Japanese macaques (Macaca fuscata) form cross-modal representations of conspecifics but not of humans. However, because the subjects in the experiment were raised in a large social group and had considerably less exposure to humans than to conspecifics, it…

  9. Influence of sexual competition and social context on homosexual behavior in adolescent female Japanese macaques.

    PubMed

    Gunst, Noëlle; Leca, Jean-Baptiste; Vasey, Paul L

    2015-05-01

    We explored the role that sexual and social partners play in the expression of female homosexual behavior among adolescent female Japanese macaques at Arashiyama, Japan. Our data fully or partially supported all the predictions related to four non-mutually exclusive hypotheses, namely the "adult male disinterest in adolescent females" hypothesis, the "numerous homosexual adult females" hypothesis, the "safer homosexual interactions" hypothesis and the "same-sex sexual interactions" hypothesis. Our results show that both sexual context (e.g., lack of adolescent female attractivity toward adult males, presence of motivated same-sex sexual partners), and social context (e.g., risk of aggression) help explain the high frequency and prevalence of homosexual behavior in adolescent females in the Arashiyama group of Japanese macaques. As with adult females, whose homosexual consortships do not reflect generalized patterns of social affiliation or kinship, we found that adolescent females' same-sex sexual partners were neither kin, nor were they non-kin individuals with whom adolescent females were closely affiliated outside of a consortship context. Our study furthers the growing database of female homosexual behavior in Japanese macaques and provides additional evidence that homosexual behavior as expressed by adolescent female Japanese macaques is, like heterosexual behavior, sexual in nature. We discuss the relevance of our findings to a broader comparative approach that may shed light upon the development and evolution of human homosexuality. PMID:25597406

  10. Developmental and Cross-Situational Stability in Infant Pigtailed Macaque Temperament

    ERIC Educational Resources Information Center

    Sussman, Adrienne; Ha, James

    2011-01-01

    We assessed developmental stability and context generalizability of temperament in pigtailed macaques ("Macaca nemestrina") from the University of Washington Infant Primate Research Lab. A principal components analysis condensed 6 behavioral measures into 2 components, interpreted as reactivity and boldness. Changes in these measures over the 1st…

  11. Coats-like retinopathy in a Young Indian Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Liu, David X.; Gilbert, Margaret H.; Wang, Xiaolei; Didier, Peter J.; Shields, Carol L.; Lackner, Andrew A.

    2015-01-01

    A 1-year-old male Indian rhesus macaque presented with a bilateral blindness. Ocular examination, gross and histopathological evaluation, and immunohistochemistry were performed. The major findings were retinal telangiectasia, accumulation of exudate in the intraretinal and subretinal space, and retinal detachment. Coat-like retinopathy was diagnosed, and it has not been previously reported in veterinary medicine. PMID:25656754

  12. Can Gender Differences Be Evaluated in a Rhesus Macaque (Macaca mulatta) Model of Focal Cerebral Ischemia?

    PubMed Central

    Murphy, Stephanie J; Kirsch, Jeffrey R; Zhang, Wenri; Grafe, Marjorie R; West, G Alex; del Zoppo, Gregory J; Traystman, Richard J; Hurn, Patricia D

    2008-01-01

    Gender differences, sex steroid effects, and sex-specific candidate therapeutics in ischemic stroke have been studied in rodents but not in nonhuman primates. In this feasibility study (n = 3 per group), we developed a model of transient focal cerebral ischemia in adult male and female rhesus macaques that consistently includes white matter injury. The animals also were used to determine whether gender-linked differences in histopathologic outcomes could be evaluated in this model in future, larger preclinical trials. Histologic brain pathology was evaluated at 4 d after 90 min of reversible occlusion of the middle cerebral artery (MCA). MCA occlusion was accomplished by using a transorbital approach and temporary placement of an aneurysm clip. Male and female rhesus macaques 7 to 11 y of age were studied. Baseline and intraischemic blood glucose, systolic blood pressure, heart rate, oxygen saturation, end-tidal CO2, and rectal temperatures were not different among groups. The variability in injury volume was comparable to that observed in human focal cerebrovascular ischemia and in other nonhuman primate models using proximal MCA occlusion. In this small sample, the volume of injury was not different between male and female subjects, but observed variability was higher in female caudate nucleus, putamen, and hemisphere. This report is the first to compare cerebral ischemic outcomes in female and male rhesus macaques. The female rhesus macaque ischemic stroke model could be used after rodent studies to provide preclinical data for clinical trials in women. PMID:19149416

  13. Biological variables in the hair uptake of methylmercury from blood in the Macaque monkey

    SciTech Connect

    Mottet, N.K.; Body, R.L.; Wilkens, V.; Burbacher, T.M.

    1987-04-01

    The total mercury (Hg) in hair and blood of 45 young healthy adult female Macaque fascicularis given 0, 50, 70, or 90 ..mu..g MeHg/kg body wt orally in apple juice daily revealed a close and constant ratio between blood Hg and hair. The amount of hair Hg does not increase with time (maximum period of observation 490 days) at a given dose level. Also the ratio was unchanged between background and subtoxic dose levels. Individuals at a given dose level with a higher-than-average blood level had a proportionately higher hair level. The Macaque blood/hair ratio is markedly lower than that reported for humans. Pregnancy did not have an appreciable effect on the hair mercury level. Review of the known variables in human and Macaque hair growth and structures does not provide an explanation for the difference. They suggest that an as yet unidentified biological variable(s), possibly circumfollicular blood flow, could account for the difference. This ratio difference notwithstanding, controlled studies on Macaque hair such as this add support for the validity of terminal hair as a trace metal exposure indicator.

  14. Pirate primates in uncharted waters: lymphocyte transfers in unrelated, MHC-matched macaques.

    PubMed

    Burwitz, Benjamin J; Greene, Justin M; O'Connor, David H

    2009-01-01

    An HIV vaccine remains elusive despite the concerted efforts of investigators and clinicians over the past two decades. Animal models are regularly used to obtain new insights on disease pathogenesis and have become invaluable tools in the translation of treatments from basic research laboratories to the clinic. Vaccination of macaques with live, attenuated simian immunodeficiency virus is currently the most effective method of garnering protection against subsequent pathogenic SIV challenge. However, immunization of humans with live, attenuated HIV is not feasible due to safety concerns. Therefore, clues to an effective and safe vaccine against HIV may be found by studying immune correlates of protection in the live, attenuated, vaccinated macaque model. Previous studies have identified the immune correlates of protection against Friend retrovirus in live, attenuated vaccinated mice using allogeneic adoptive transfers. Similar experiments in macaques have thus far been hindered due to the vast genetic diversity found within outbred populations. Here we review the current state of SIV adoptive transfer research and present a novel macaque model that allows for allogeneic adoptive transfers. PMID:19149554

  15. An Automated ELISA Using Recombinant Antigens for Serologic Diagnosis of B Virus Infections in Macaques

    PubMed Central

    Katz, David; Shi, Wei; Patrusheva, Irina; Perelygina, Ludmila; Gowda, Manjunath S; Krug, Peter W; Filfili, Chadi N; Ward, John A; Hilliard, Julia K

    2012-01-01

    B virus (Macacine herpesvirus 1) occurs naturally in macaques and can cause lethal zoonotic infections in humans. Detection of B virus (BV) antibodies in macaques is essential for the development of SPF breeding colonies and for diagnosing infection in macaques that are involved in human exposures. Traditionally, BV infections are monitored for presence of antibodies by ELISA (a screening assay) and western blot analysis (WBA; a confirmatory test). Both tests use lysates of infected cells as antigens. Because WBA often fails to confirm the presence of low-titer serum antibodies detected by ELISA, we examined a recombinant-based ELISA as a potential alternative confirmatory test. We compared a high-throughput ELISA using 384-well plates for simultaneous antibody screening against 4 BV-related, recombinant proteins with the standard ELISA and WBA. The recombinant ELISA results confirmed more ELISA-positive sera than did WBA. The superiority of the recombinant ELISA over WBA was particularly prominent for sera with low (<500 ELISA units) antibody titers. Among low-titer sera, the relative sensitivity of the recombinant ELISA ranged from 36.7% to 45.0% as compared with 3.3% to 10.0% for WBA. In addition, the screening and confirmatory assays can be run simultaneously, providing results more rapidly. We conclude that the recombinant ELISA is an effective replacement for WBA as a confirmatory assay for the evaluation of macaque serum antibodies to BV. PMID:23561887

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

    SciTech Connect

    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.

  17. Effects of seasonal changes in dietary energy on body weight of captive Japanese macaques (Macaca fuscata).

    PubMed

    Aoki, Kouhei; Mitsutsuka, Syuuhei; Yamazaki, Ato; Nagai, Kazumi; Tezuka, Atsuko; Tsuji, Yamato

    2015-01-01

    Food availability varies seasonally for wild animals, and body weight fluctuates accordingly in the wild. In contrast, controlling availability of diet under captive condition is difficult from keepers' standpoint, and monotonous diet often causes health problems in captive animals. We evaluated the effects of a seasonally controlled diet on body weight of captive Japanese macaques (Macaca fuscata) in an outside enclosure at Ueno Zoo, Tokyo, Japan. We fed a high-energy diet in spring and fall, and a more restricted diet in summer and winter for 3 years (2011-2013). Seasonal changes in body weight were similar to those that occur in wild macaques: for both sexes, body weight was higher in spring and fall and lower in winter. A decrease in body weight between fall and winter occurred only in adults, which implied that reducing dietary intake in winter had a more severe effect on adults than on juveniles. Different from wild populations, the body weight of captive macaques did not decrease between spring and summer, which we attributed to a lack of movement within the enclosure and to excess energy intake in summer. In addition to controlling dietary composition, providing large enclosure with complex structure and making efforts of giving unpredictability in feeding are necessary to motivate the captive animals to be more active, which would cause the macaques to show seasonal change in body weight, which is found in wild. PMID:25823966

  18. Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment.

    PubMed

    Mangus, Lisa M; Dorsey, Jamie L; Weinberg, Rachel L; Ebenezer, Gigi J; Hauer, Peter; Laast, Victoria A; Mankowski, Joseph L

    2016-08-01

    Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus-associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies. Although initially developed for studies of HIV-SN in the SIV-infected macaque model, these methods could be readily translated to a range of studies involving peripheral nerve degeneration and neurotoxicity in nonhuman primates as well as preclinical investigations of agents aimed at neuroprotection and regeneration. PMID:27235324

  19. Spontaneous Nocardial Brain Abscess in a Juvenile Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Ferrecchia, Christie E.; Ducore, Rebecca M.; Colgin, Lois M.A.; Lewis, Anne D.

    2015-01-01

    Background A juvenile rhesus macaque presented with blindness, ataxia, and head tilt. Methods Postmortem gross and microscopic examination, histochemical staining and bacterial culture were performed. Results Nocardia sp. was identified as the etiologic agent of a primary pneumonia with secondary cerebral abscessation. Conclusions Nocardiosis should be a differential diagnosis for patients with neurologic disease. PMID:25470211

  20. Inefficient use of inverted pendulum mechanism during quadrupedal walking in the Japanese macaque.

    PubMed

    Ogihara, Naomichi; Makishima, Haruyuki; Hirasaki, Eishi; Nakatsukasa, Masato

    2012-01-01

    In animal walking, the gravitational potential and kinetic energy of the center of mass (COM) fluctuates out-of-phase to reduce the energetic cost of locomotion via an inverted pendulum mechanism, and, in canine quadrupedal walking, up to 70% of the mechanical energy can be recovered. However, the rate of energy recovery for quadrupedal walking in primates has been reported to be comparatively lower. The present study analyzed fluctuations in the potential and kinetic energy of the COM during quadrupedal walking in the Japanese macaque to clarify the mechanisms underlying this inefficient utilization of the inverted pendulum mechanism in primates. Monkeys walked on a wooden walkway at a self-selected speed, and ground reaction forces were measured, using a force platform, to calculate patterns of mechanical energy fluctuation and rates of energy recovery. Our results demonstrated that rates of energy recovery for quadrupedal walking in Japanese macaques were approximately 30-50%, much smaller than those reported for dogs. Comparisons of the patterns of mechanical energy fluctuation suggested that the potential and kinetic energies oscillated relatively more in-phase, and amplitudes did not attain near equality during quadrupedal walking in Japanese macaques, possibly because of greater weight support (reaction force) of the hindlimbs and more protracted forelimbs at touchdown in the Japanese macaque, two of the three commonly accepted locomotor characteristics distinguishing primates from non-primate mammals. PMID:21874286

  1. Mitochondrial Genome and Nuclear Markers Provide New Insight into the Evolutionary History of Macaques.

    PubMed

    Jiang, Juan; Yu, Jianqiu; Li, Jing; Li, Peng; Fan, Zhenxin; Niu, Lili; Deng, Jiabo; Yue, Bisong; Li, Jing

    2016-01-01

    The evolutionary history of macaques, genus Macaca, has been under debate due to the short times of divergence. In this study, maternal, paternal, and biparental genetic systems were applied to infer phylogenetic relationships among macaques and to trace ancient hybridization events in their evolutionary history. Using a PCR display method, 17 newly phylogenetically informative Alu insertions were identified from M. assamensis. We combined presence/absence analysis of 84 Alu elements with mitochondrial genomes as well as nuclear sequences (five autosomal genes, two Y chromosomal genes, and one X chromosomal fragment) to reconstruct a robust macaque phylogeny. Topologies generated from different inherited markers were similar supporting six well defined species groups and a close relationship of M. assamensis and M. thibetana, but differed in the placing of M. arctoides. Both Alu elements and nuclear genes supported that M. arctoides was close to the sinica group, whereas the mitochondrial data clustered it into the fascicularis/mulatta lineage. Our results reveal that a sex-biased hybridization most likely occurred in the evolutionary history of M. arctoides, and suggest an introgressive pattern of male-mediated gene flow from the ancestors of M. arctoides to the M. mulatta population followed by nuclear swamping. According to the estimation of divergence dates, the hybridization occurred around 0.88~1.77 mya (nuclear data) or 1.38~2.56 mya (mitochondrial data). In general, our study indicates that a combination of various molecular markers could help explain complicated evolutionary relationships. Our results have provided new insights into the evolutionary history of macaques and emphasize that hybridization might play an important role in macaque evolution. PMID:27135608

  2. Haplotype diversity generated by ancient recombination-like events in the MHC of Indian rhesus macaques.

    PubMed

    Doxiadis, Gaby G M; de Groot, Nanine; Otting, Nel; de Vos-Rouweler, Annemiek J M; Bolijn, Maria J; Heijmans, Corrine M C; de Groot, Natasja G; van der Wiel, Marit K H; Remarque, Edmond J; Vangenot, Christelle; Nunes, José M; Sanchez-Mazas, Alicia; Bontrop, Ronald E

    2013-08-01

    The Mamu-A, Mamu-B, and Mamu-DRB genes of the rhesus macaque show several levels of complexity such as allelic heterogeneity (polymorphism), copy number variation, differential segregation of genes/alleles present on a haplotype (diversity) and transcription level differences. A combination of techniques was implemented to screen a large panel of pedigreed Indian rhesus macaques (1,384 individuals representing the offspring of 137 founding animals) for haplotype diversity in an efficient and inexpensive manner. This approach allowed the definition of 140 haplotypes that display a relatively low degree of region variation as reflected by the presence of only 17 A, 18 B and 22 DRB types, respectively, exhibiting a global linkage disequilibrium comparable to that in humans. This finding contrasts with the situation observed in rhesus macaques from other geographic origins and in cynomolgus monkeys from Indonesia. In these latter populations, nearly every haplotype appears to be characterised by a unique A, B and DRB region. In the Indian population, however, a reshuffling of existing segments generated "new" haplotypes. Since the recombination frequency within the core MHC of the Indian rhesus macaques is relatively low, the various haplotypes were most probably produced by recombination events that accumulated over a long evolutionary time span. This idea is in accord with the notion that Indian rhesus macaques experienced a severe reduction in population during the Pleistocene due to a bottleneck caused by geographic changes. Thus, recombination-like processes appear to be a way to expand a diminished genetic repertoire in an isolated and relatively small founder population. PMID:23715823

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

    PubMed Central

    2011-01-01

    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, providing new opportunities to

  4. Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

    PubMed

    Itoh, Kosuke; Nejime, Masafumi; Konoike, Naho; Nakada, Tsutomu; Nakamura, Katsuki

    2015-09-01

    Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge. PMID:26031378

  5. Mitochondrial Genome and Nuclear Markers Provide New Insight into the Evolutionary History of Macaques

    PubMed Central

    Jiang, Juan; Yu, Jianqiu; Li, Jing; Li, Peng; Fan, Zhenxin; Niu, Lili; Deng, Jiabo; Yue, Bisong; Li, Jing

    2016-01-01

    The evolutionary history of macaques, genus Macaca, has been under debate due to the short times of divergence. In this study, maternal, paternal, and biparental genetic systems were applied to infer phylogenetic relationships among macaques and to trace ancient hybridization events in their evolutionary history. Using a PCR display method, 17 newly phylogenetically informative Alu insertions were identified from M. assamensis. We combined presence/absence analysis of 84 Alu elements with mitochondrial genomes as well as nuclear sequences (five autosomal genes, two Y chromosomal genes, and one X chromosomal fragment) to reconstruct a robust macaque phylogeny. Topologies generated from different inherited markers were similar supporting six well defined species groups and a close relationship of M. assamensis and M. thibetana, but differed in the placing of M. arctoides. Both Alu elements and nuclear genes supported that M. arctoides was close to the sinica group, whereas the mitochondrial data clustered it into the fascicularis/mulatta lineage. Our results reveal that a sex-biased hybridization most likely occurred in the evolutionary history of M. arctoides, and suggest an introgressive pattern of male-mediated gene flow from the ancestors of M. arctoides to the M. mulatta population followed by nuclear swamping. According to the estimation of divergence dates, the hybridization occurred around 0.88~1.77 mya (nuclear data) or 1.38~2.56 mya (mitochondrial data). In general, our study indicates that a combination of various molecular markers could help explain complicated evolutionary relationships. Our results have provided new insights into the evolutionary history of macaques and emphasize that hybridization might play an important role in macaque evolution. PMID:27135608

  6. Macaques at the margins: the biogeography and extinction of Macaca sylvanus in Europe

    NASA Astrophysics Data System (ADS)

    Elton, Sarah; O'Regan, Hannah J.

    2014-07-01

    The genus Macaca (Primates: Cercopithecidae) originated in Africa, dispersed into Europe in the Late Miocene and resided there until the Late Pleistocene. In this contribution, we provide an overview of the evolutionary history of Macaca in Europe, putting it into context with the wider late Miocene, Pliocene and Pleistocene European monkey fossil record (also comprising Mesopithecus, Paradolichopithecus, Dolichopithecus and Theropithecus). The Pliocene and Pleistocene European Macaca fossil material is largely regarded as Macaca sylvanus, the same species as the extant Barbary macaque in North Africa. The M. sylvanus specimens found at West Runton in Norfolk (53°N) during the Middle Pleistocene are among the most northerly euprimates ever discovered. Our simple time-budget model indicates that short winter day lengths would have imposed a significant constraint on activity at such relatively high latitudes, so macaque populations in Britain may have been at the limit of their ecological tolerance. Two basic models using climatic and topographic data for the Last Interglacial and the Last Glacial Maximum alongside Middle and Late Pleistocene fossil distributions indicate that much of Europe may have been suitable habitat for macaques. The models also indicate that areas of southern Europe in the present day have a climate that could support macaque populations. However, M. sylvanus became locally extinct in the Late Pleistocene, possibly at a similar time as the straight-tusked elephant, Palaeoloxodon antiquus, and narrow-nosed rhinoceros, Stephanorhinus hemitoechus. Its extinction may be related to vegetation change or increased predation from Homo, although other factors (such as stochastic factors occurring as a result of small population sizes) cannot be ruled out. Notwithstanding the cause of extinction, the European macaque may thus be a previously overlooked member of the Late Pleistocene faunal turnover.

  7. Pharmacokinetics of Ceftiofur Crystalline Free Acid in Male Rhesus Macaques (Macaca mulatta) after Subcutaneous Administration

    PubMed Central

    Salyards, Gregory W; Knych, Heather K; Hill, Ashley E; Kelly, Kristi R; Christe, Kari L

    2015-01-01

    Trauma is a common sequela to agonistic social encounters in rhesus macaques (Macaca mulatta), and veterinarians often prescribe antibiotics as part of a balanced treatment plan. Long-acting, single-dose, injectable antibiotics for use in rhesus macaques are unavailable currently. Ceftiofur crystalline free acid (CCFA) is a long-acting, single-dose, injectable third-generation cephalosporin that provides at least 7 d of ceftiofur therapeutic plasma concentrations in swine (Sus scrofa domesticus). We hypothesized that CCFA would achieve similar therapeutic concentrations (≥0.2 μg/mL) in rhesus macaques. We describe the pharmacokinetic profile of CCFA in healthy, adult male rhesus macaques (n = 6) in this 2-period, 2-treatment crossover study of 5 and 20 mg/kg SC administered once. Plasma ceftiofur metabolite concentrations were determined prior to and for a maximum of 21 d after administration. Noncompartmental pharmacokinetic analysis was performed. The 5-mg dose achieved a maximal plasma concentration of 2.24 ± 0.525 μg/mL at 2.59 ± 1.63 h, an AUC of 46.9 ± 17.6 h/μg/mL, and a terminal elimination half-life of 56.5 ± 21.7 h; for the 20-mg/kg dose, these parameters were 9.18 ± 4.90 μg/mL at 1.82 ± 1.30 h, 331 ± 84.4 h/μg/mL, and 69.7 ± 8.86 h, respectively. No adverse effects were noted after either dose. Macaques maintained plasma ceftiofur concentrations of 0.2 μg/mL or greater for at least 2 d after 5 mg/kg SC and at least 7 d after 20 mg/kg SC. PMID:26424255

  8. Adaptation of Subtype A Human Immunodeficiency Virus Type 1 Envelope to Pig-Tailed Macaque Cells▿

    PubMed Central

    Humes, Daryl; Overbaugh, Julie

    2011-01-01

    The relevance of simian/human immunodeficiency virus (SHIV) infection of macaques to HIV-1 infection in humans depends on how closely SHIVs mimic HIV-1 transmission, pathogenesis, and diversity. Circulating HIV-1 strains are predominantly subtypes C and A and overwhelmingly require CCR5 for entry, yet most SHIVs incorporate CXCR4-using subtype B envelopes (Envs). While pathogenic subtype C-based SHIVs have been constructed, the subtype A-based SHIVs (SHIV-As) constructed to date have been unable to replicate in macaque cells. To understand the barriers to SHIV-A replication in macaque cells, HIVAQ23/SIVvif was constructed by engineering a CCR5-tropic subtype A provirus to express SIV vif, which counters the macaque APOBEC3G restriction. HIVAQ23/SIVvif replicated poorly in pig-tailed macaque (Ptm) lymphocytes, but viruses were adapted to Ptm lymphocytes. Two independent mutations in gp120, G312V (V3 loop) and A204E (C2 region), were identified that increased peak virus levels by >100-fold. Introduction of G312V and A204E to multiple subtype A Envs and substitution of G312 and A204 with other residues increased entry into Ptm cells by 10- to 100-fold. G312V and A204E Env variants continued to require CCR5 for entry but were up to 50- and 200-fold more sensitive to neutralization by IgG1b12 and soluble CD4 and had a 5- to 50-fold increase in their ability to utilize Ptm CD4 compared to their wild-type counterparts. These findings identify the inefficient use of Ptm CD4 as an unappreciated restriction to subtype A HIV-1 replication in Ptm cells and reveal amino acid changes to gp120 that can overcome this barrier. PMID:21325401

  9. Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

    SciTech Connect

    Foley, Brian T; Korber, Bette T

    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.

  10. Inter-annual variation in characteristics of endozoochory by wild Japanese macaques.

    PubMed

    Tsuji, Yamato

    2014-01-01

    Endozoochory is important to the dynamics and regeneration of forest ecosystems. Despite the universality of inter-annual variation in fruit production, few studies have addressed the sign (seed predation versus seed dispersal) and strength (frequency and quantity) of fruit-frugivore interaction and the effectiveness of endozoochory in response to the long-term temporal context. In this study I evaluated the characteristics of endozoochorous dispersal by wild Japanese macaques Macaca fuscata inhabiting deciduous forest in northern Japan for five different years. I collected 378 fecal samples from the macaques in fall (September to November) and quantified the proportion of feces containing seeds, number of seeds per fecal sample, ratio of intact seeds, and seed diversity. The proportion of feces containing seeds of any species (five-year mean: 85.9%, range: 78-97%) did not show significant inter-annual variation, while species-level proportions did. The intact ratio of seeds (mean: 83%, range: 61-98%) varied significantly both between years and between months, and this varied among dominant plant species. The number of seeds per fecal sample (mean: 78, range: 32-102) varied monthly but did not between years, and the seed diversity (mean: 0.66, range: 0.57-0.81) did not show significant inter-annual variation, both of which were attributed to longer duration of macaques' gastro-intestinal passage time of seeds exceed their feeding bouts. This study demonstrated that frequency and success of seed dispersal over seed predation of macaque endozoochory showed inter-annual variation, indicating low specificity across the seed-macaque network. The temporal variability in the quality of seed dispersal may provide evidence of high resilience in response to fluctuating environmental conditions in the temperate forests. PMID:25272286

  11. Ranging and site fidelity in northern pigtailed macaques (Macaca leonina) over different temporal scales.

    PubMed

    José-Domínguez, Juan Manuel; Savini, Tommaso; Asensio, Norberto

    2015-08-01

    Space-use patterns are crucial to understanding the ecology, evolution, and conservation of primates, but detailed ranging data are scarce for many species, especially those in Southeast Asia. Researchers studying site fidelity to either home ranges or core areas have focused mainly on territorial species, whereas less information is available for non-territorial species. We analyzed the ranging patterns and site fidelity of one wild troop of northern pigtailed macaques over 16 months at different temporal scales. We used characteristic hull polygons in combination with spatial statistics to estimate home ranges and core areas. The total home range and core areas were 449 ha and 190 ha, respectively. Average daily path length was 2,246 m. The macaques showed a high defendabili--ty index according to the expected ranging of a non-territorial species in which movement does not theoretically permit the defense of a large territory. Overall, the study troop ranged more extensively than conspecific groups and closely related species studied elsewhere. These differences may reflect variable troop size, degree of terrestriality and habitat characteristics, but could also reflect methodological differences. The location, size and shape of home ranges and core areas, and extent of daily path lengths changed on a monthly basis resulting in low site fidelity between months. The macaques also showed clear shifts in the location of daily home ranges with low site fidelity scores between consecutive days. Daily home range and daily path length were related to seasonality, with greater values during the fruit-abundant period. Low site fidelity associated with lack of territoriality is consistent with macaques structuring their movement based on available food sources. However, ranging patterns and site fidelity can also be explained by macaques feeding on the move, a foraging strategy that hinders frequent and long visits to the same location. PMID:25864438

  12. Nonpathogenic CCR2-tropic SIVrcm after serial passage and its effect on SIVmac infection of Indian rhesus macaques

    PubMed Central

    Ling, Binhua; Veazey, Ronald S.; Marx, Preston A.

    2015-01-01

    The natural host of SIVrcm is the red-capped mangabey (Cercocebus torquatus torquatus). Although this virus infects macaques and human PBMCs, its pathogenic potential is unknown. We serially passaged SIVrcm through 9 rhesus macaques to assess its potential for virulence. SIVrcm infected all macaques with peak viremia 2 weeks postinfection yet viral loads decreased to undetectable levels about one month after inoculation. Remarkably, SIVrcm replication and virulence did not increase following 7 serial passages. While CD4+ T cells in the gut were decreased in early infection, proportions of memory CD4+CCR5+ T cells were not affected. Three SIVrcm-infected macaques were subsequently challenged with SIVmac251 to assess the potential for superinfection. Interestingly, animals previously infected with SIVrcm had 100 fold lower levels of SIVmac251 in plasma compared to naive animals inoculated with SIVmac251. These results suggest that SIVrcm is nonpathogenic and may be useful for examining effective immune responses in SIV infection. PMID:18662820

  13. Viral seroprevalence in northern pig-tailed macaques (Macaca leonina) derived from Ho Chi Minh City, Vietnam.

    PubMed

    Zhang, Ming-Xu; Zheng, Hong-Yi; Jiang, Jin; Pang, Wei; Zhang, Gao-Hong; Zheng, Yong-Tang

    2016-07-01

    Non-human primates are natural virus reservoirs, whether wild or domestic. In this study, we determined the seroprevalence of common viruses by ELISA in a northern pig-tailed macaque (Macaca leonina) colony derived from Ho Chi Minh City, Vietnam. A total of 20 types of virus which are commonly selected as target microorganisms for specific-pathogen-free colonies, or which have zoonotic potential were included in this study. The results showed only 2 in 90 northern pig-tailed macaques were seronegative for all the detected viruses, and at least 16 out of the total 20 types of virus tested were prevalent in this colony, so these macaques were commonly infected by various viruses. These macaques should be carefully assessed for viral seroprevalence in order to prevent zoonotic diseases from being transferred to human beings. PMID:26993123

  14. Comparison of Noncontact Infrared Thermometry and 3 Commercial Subcutaneous Temperature Transponding Microchips with Rectal Thermometry in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Brunell, Marla K

    2012-01-01

    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. PMID:23043815

  15. Comparison of pathogenicities of H7 avian influenza viruses via intranasal and conjunctival inoculation in cynomolgus macaques.

    PubMed

    Shichinohe, Shintaro; Itoh, Yasushi; Nakayama, Misako; Ozaki, Hiroichi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-06-01

    The outbreak of H7N9 low pathogenic avian influenza viruses in China has attracted attention to H7 influenza virus infection in humans. Since we have shown that the pathogenicity of H1N1 and H5N1 influenza viruses in macaques was almost the same as that in humans, we compared the pathogenicities of H7 avian influenza viruses in cynomolgus macaques via intranasal and conjunctival inoculation, which mimics natural infection in humans. H7N9 virus, as well as H7N7 highly pathogenic avian influenza virus, showed more efficient replication and higher pathogenicity in macaques than did H7N1 and H7N3 highly pathogenic avian influenza viruses. These results are different from pathogenicity in chickens as reported previously. Therefore, our results obtained in macaques help to estimate the pathogenicity of H7 avian influenza viruses in humans. PMID:26994587

  16. Problems associated with the seed-trap method when measuring seed dispersal in forests inhabited by Japanese macaques.

    PubMed

    Tsujino, Riyou; Yumoto, Takakazu

    2014-04-01

    Despite the widespread use of seed/litter traps in seed dispersal ecology, several problems have arisen when using this method in forests inhabited by semi-terrestrial monkeys. The first issue is the height of the trap relative to the location where macaques spit seeds and/or defecate. For Japanese macaques in the lowland forests of Yakushima Island, southern Japan, 30-50% of the seeds emitted from cheek pouches and faeces will not be caught by seed traps, leading to underestimation of seed fall. The second issue is the attractiveness of seed traps. Macaques sometimes play with the traps, potentially affecting the results of the seed-trap method in complex ways, including both negative and positive effects. To obtain reasonable estimates of total seed dispersal, we recommend that researchers conduct the seed-trap method concurrently with monkey observations, and that they should affix traps more securely to prevent macaques from destroying the traps. PMID:24378823

  17. Specific pathogen free macaque colonies: a review of principles and recent advances for viral testing and colony management.

    PubMed

    Yee, JoAnn L; Vanderford, Thomas H; Didier, Elizabeth S; Gray, Stanton; Lewis, Anne; Roberts, Jeffrey; Taylor, Kerry; Bohm, Rudolf P

    2016-04-01

    Specific pathogen free (SPF) macaques provide valuable animal models for biomedical research. In 1989, the National Center for Research Resources [now Office of Research Infrastructure Programs (ORIP)] of the National Institutes of Health initiated experimental research contracts to establish and maintain SPF colonies. The derivation and maintenance of SPF macaque colonies is a complex undertaking requiring knowledge of the biology of the agents for exclusion and normal physiology and behavior of macaques, application of the latest diagnostic technology, facilitiy management, and animal husbandry. This review provides information on the biology of the four viral agents targeted for exclusion in ORIP SPF macaque colonies, describes current state-of-the-art viral diagnostic algorithms, presents data from proficiency testing of diagnostic assays between laboratories at institutions participating in the ORIP SPF program, and outlines management strategies for maintaining the integrity of SPF colonies using results of diagnostic testing as a guide to decision making. PMID:26932456

  18. Macaque Monoclonal Antibodies Targeting Novel Conserved Epitopes within Filovirus Glycoprotein

    PubMed Central

    Keck, Zhen-Yong; Enterlein, Sven G.; Howell, Katie A.; Vu, Hong; Shulenin, Sergey; Warfield, Kelly L.; Froude, Jeffrey W.; Araghi, Nazli; Douglas, Robin; Biggins, Julia; Lear-Rooney, Calli M.; Wirchnianski, Ariel S.; Lau, Patrick; Wang, Yong; Herbert, Andrew S.; Dye, John M.; Glass, Pamela J.; Holtsberg, Frederick W.; Foung, Steven K. H.

    2015-01-01

    ABSTRACT Filoviruses cause highly lethal viral hemorrhagic fever in humans and nonhuman primates. Current immunotherapeutic options for filoviruses are mostly specific to Ebola virus (EBOV), although other members of Filoviridae such as Sudan virus (SUDV), Bundibugyo virus (BDBV), and Marburg virus (MARV) have also caused sizeable human outbreaks. Here we report a set of pan-ebolavirus and pan-filovirus monoclonal antibodies (MAbs) derived from cynomolgus macaques immunized repeatedly with a mixture of engineered glycoproteins (GPs) and virus-like particles (VLPs) for three different filovirus species. The antibodies recognize novel neutralizing and nonneutralizing epitopes on the filovirus glycoprotein, including conserved conformational epitopes within the core regions of the GP1 subunit and a novel linear epitope within the glycan cap. We further report the first filovirus antibody binding to a highly conserved epitope within the fusion loop of ebolavirus and marburgvirus species. One of the antibodies binding to the core GP1 region of all ebolavirus species and with lower affinity to MARV GP cross neutralized both SUDV and EBOV, the most divergent ebolavirus species. In a mouse model of EBOV infection, this antibody provided 100% protection when administered in two doses and partial, but significant, protection when given once at the peak of viremia 3 days postinfection. Furthermore, we describe novel cocktails of antibodies with enhanced protective efficacy compared to individual MAbs. In summary, the present work describes multiple novel, cross-reactive filovirus epitopes and innovative combination concepts that challenge the current therapeutic models. IMPORTANCE Filoviruses are among the most deadly human pathogens. The 2014-2015 outbreak of Ebola virus disease (EVD) led to more than 27,000 cases and 11,000 fatalities. While there are five species of Ebolavirus and several strains of marburgvirus, the current immunotherapeutics primarily target Ebola virus

  19. A population-genetic study of crab-eating macaques (Macaca fascicularis) on the island of Angaur, Palau, Micronesia.

    PubMed

    Kawamoto, Y; Nozawa, K; Matsubayashi, K; Gotoh, S

    1988-01-01

    Blood protein polymorphisms of an introduced population of the crab-eating macaques on Angaur Island, Palau, Micronesia, were examined electrophoretically to assess genetic variability. Results showed a high degree of genetic heterozygosity and some distinctive features in the genetic constitution of this island population. Negative evidence is presented regarding ancestry from a single pair of macaques. Their origin is discussed in relation to the genetic structure of the present population. PMID:3256533

  20. Social Tolerance in Wild Female Crested Macaques (Macaca nigra) in Tangkoko-Batuangus Nature Reserve, Sulawesi, Indonesia

    PubMed Central

    Duboscq, Julie; Micheletta, Jérôme; Agil, Muhammad; Hodges, Keith; Thierry, Bernard; Engelhardt, Antje

    2013-01-01

    In primates, females typically drive the evolution of the social system and present a wide diversity of social structures. To understand this diversity, it is necessary to document the consistency and/or flexibility of female social structures across and within species, contexts, and environments. Macaques (Macaca sp.) are an ideal taxon for such comparative study, showing both consistency and variation in their social relations. Their social styles, constituting robust sets of social traits, can be classified in four grades, from despotic to tolerant. However, tolerant species are still understudied, especially in the wild. To foster our understanding of tolerant societies and to assess the validity of the concept of social style, we studied female crested macaques, Macaca nigra, under entirely natural conditions. We assessed their degree of social tolerance by analyzing the frequency, intensity, and distribution of agonistic and affiliative behaviors, their dominance gradient, their bared-teeth display, and their level of conciliatory tendency. We also analyzed previously undocumented behavioral patterns in grade 4 macaques: reaction upon approach and distribution of affiliative behavior across partners. We compared the observed patterns to data from other populations of grade 4 macaques and from species of other grades. Overall, female crested macaques expressed a tolerant social style, with low intensity, frequently bidirectional, and reconciled conflicts. Dominance asymmetry was moderate, associated with an affiliative bared-teeth display. Females greatly tolerated one another in close proximity. The observed patterns matched the profile of other tolerant macaques and were outside the range of patterns of more despotic species. This study is the first comprehensive analysis of females’ social behavior in a tolerant macaque species under natural conditions and as such, contributes to a better understanding of macaque societies. It also highlights the

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

    PubMed

    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

  2. Sustained release of the CCR5 inhibitors CMPD167 and maraviroc from vaginal rings in rhesus macaques.

    PubMed

    Malcolm, R Karl; Veazey, Ronald S; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M; Murphy, Diarmaid J; Boyd, Peter; Major, Ian; Shattock, Robin J; Klasse, Per Johan; Doyle, Lara A; Rasmussen, Kelsi K; Goldman, Laurie; Ketas, Thomas J; Moore, John P

    2012-05-01

    Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ~10(6)-fold greater than the 50% inhibitory concentrations (IC(50)s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle. PMID:22330914

  3. Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

    PubMed Central

    Veazey, Ronald S.; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M.; Murphy, Diarmaid J.; Boyd, Peter; Major, Ian; Shattock, Robin J.; Klasse, Per Johan; Doyle, Lara A.; Rasmussen, Kelsi K.; Goldman, Laurie; Ketas, Thomas J.; Moore, John P.

    2012-01-01

    Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ∼106-fold greater than the 50% inhibitory concentrations (IC50s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle. PMID:22330914

  4. Self-Injurious Behavior Secondary to Cytomegalovirus-Induced Neuropathy in an SIV-Infected Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Clemmons, Elizabeth A; Gumber, Sanjeev; Strobert, Elizabeth; Bloomsmith, Mollie A; Jean, Sherrie M

    2015-01-01

    A 3.5-y-old, female rhesus macaque (Macaca mulatta) inoculated with SIVmac239 presented 8 mo later for inappetence and facial bruising. Physical examination revealed a superficial skin abrasion below the left eye, bruising below the left brow, and epistaxis of the left nostril. There were no significant findings on CBC, serum chemistry, urinalysis, or radiographs. Differential diagnoses included infectious etiologies, self-injurious behavior, immune-mediated dermatitis, and neoplasia. Lack of response to antibiotic and analgesic therapy and observations of the macaque made it apparent that the skin lesions were self-inflicted. The excoriations rapidly progressed to extend over the nose, and the left palpebrae became edematous. Euthanasia was elected because the macaque appeared to be experiencing continued discomfort despite analgesic therapy. Histopathologic examination revealed systemic cytomegalovirus (CMV) infection involving the facial nerves, periocular nerves, meninges, and perimesenteric lymph nodes. CMV is a common infection in macaques, with adult seroprevalence close to 100% in most colonies. Infection in immunocompetent animals is usually asymptomatic but can cause significant clinical disease in immunodeficient hosts. CMV is associated with a painful peripheral neuropathy in human AIDS patients, and analgesic treatment is often unsatisfactory. Peripheral neuropathy secondary to CMV should be considered as an underlying cause of self-injurious behavior in SIV-infected macaques. Macaques affected by other diseases and disorders may also be at risk for development of painful peripheral neuropathies. PMID:26141451

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

    PubMed

    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

  6. Evaluation of a Multivalent Vaccine against Lymphatic Filariasis in Rhesus macaque Model

    PubMed Central

    Dakshinamoorthy, Gajalakshmi; von Gegerfelt, Agneta; Andersen, Hanne; Lewis, Mark; Kalyanasundaram, Ramaswamy

    2014-01-01

    Lymphatic filariasis affects 120 million people worldwide and another 1.2 billion people are at risk of acquiring the infection. Chemotherapy with mass drug administration is substantially reducing the incidence of the infection. Nevertheless, an effective vaccine is needed to prevent the infection and eradicate the disease. Previously we reported that a multivalent fusion protein vaccine (rBmHAT) composed of small heat shock proteins 12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and large extracellular domain of tetraspanin (TSP LEL) could confer >95% protection against the challenge infection with Brugia malayi infective larvae (L3) in mouse and gerbil models. In this study we evaluated the immunogenicity and efficacy of rBmHAT fusion protein vaccine in a rhesus macaque model. Our results show that rBmHAT is highly immunogenic in rhesus macaques. All the vaccinated monkeys developed significant titers of antigen-specific IgG antibodies against each of the component antigens (16,000 for rBmHSP12.6), (24,000 for rBmALT-2) and (16,000 for rBmTSP-LEL). An in vitro antibody dependent cellular cytotoxicity (ADCC) assay performed using the sera samples from vaccinated monkeys showed that the anti-rBmHAT antibodies are functional with 35% killing of B. malayi L3s. Vaccinated monkeys also had antigen responding cells in the peripheral blood. Vaccine-induced protection was determined after challenging the monkeys with 500 B. malayi L3. Following challenge infection, 3 out of 5 vaccinated macaques failed to develop the infection. These three protected macaques had high titers of IgG1 antibodies and their PBMC secreted significantly high levels of IFN-γ in response to the vaccine antigens. The two vaccinated macaques that picked the infection had slightly low titers of antibodies and their PBMC secreted high levels of IL-10. Based on these findings we conclude that the rBmHAT vaccine is highly immunogenic and safe and can confer significant protection against

  7. The Organization of Collective Group Movements in Wild Barbary Macaques (Macaca sylvanus): Social Structure Drives Processes of Group Coordination in Macaques.

    PubMed

    Seltmann, Anne; Majolo, Bonaventura; Schülke, Oliver; Ostner, Julia

    2013-01-01

    Social animals have to coordinate activities and collective movements to benefit from the advantages of group living. Animals in large groups maintain cohesion by self-organization processes whereas in smaller groups consensus decisions can be reached. Where consensus decisions are relevant leadership may emerge. Variation in the organization of collective movements has been linked to variation in female social tolerance among macaque species ranging from despotic to egalitarian. Here we investigated the processes underlying group movements in a wild macaque species characterized by a degree of social tolerance intermediate to previously studied congeneric species. We focused on processes before, during and after the departure of the first individual. To this end, we observed one group of wild Barbary macaques (Macaca sylvanus) in the Middle Atlas, Morocco using all-occurrence behaviour sampling of 199 collective movements. We found that initiators of a collective movement usually chose the direction in which more individuals displayed pre-departure behavior. Dominant individuals contributed to group movements more than subordinates, especially juveniles, measured as frequencies of successful initiations and pre-departure behaviour. Joining was determined by affiliative relationships and the number of individuals that already joined the movement (mimetism). Thus, in our study group partially shared consensus decisions mediated by selective mimetism seemed to be prevalent, overall supporting the suggestion that a species' social style affects the organization of group movements. As only the most tolerant species show equally shared consensus decisions whereas in others the decision is partially shared with a bias to dominant individuals the type of consensus decisions seems to follow a stepwise relation. Joining order may also follow a stepwise, however opposite, relationship, because dominance only determined joining in highly despotic, but not in intermediate and

  8. Intergroup interactions in Tibetan macaques at Mt. Emei, China.

    PubMed

    Zhao, Q K

    1997-12-01

    Data on intergroup-interactions (I-I) were collected in 5 seasonally provisioned groups (A, B, D, D1, and E) of Tibetan macaques (Macaca thibetana) at Mt. Emei in three 70-day periods between 1991 April-June (P1), September-November (P2), December-1992 February (P3). The I-I were categorized as forewarning made by high-ranking males (including Branch Shaking and/or Loud Calls), long-distance interactions in space (specified by changes in their foraging movements), and close encounters (with Affinitive Behavior, Male's Herding Female, Sexual Interaction, Severe Conflict, Adult Male-male Conflict, Opportunistic Advance and Retreat, etc. performed by different age-sex classes). From periods P1 to P3, the I-I rate decreased with reduction in population density as a positive correlate of food clumpedness or the number of potential feeders along a pedestrian trail. On the other hand, from the birth season (BS, represented by P1 and P3) to the mating season (MS, represented by P2) the dominance relation between groups, which produced a winner and a loser in the encounters, became obscure; the proportion of close encounters in the I-I increased; the asymmetry (local groups over intruders) of forewarning signals disappeared; the rate of branch shaking decreased; and sometimes intergroup cohesion appeared. Considering that sexual interactions also occurred between the encountering groups, above changes in intergroup behaviors may be explained with a model of the way in which the competition for food (exclusion) and the sexual attractiveness between opposite sexes were in a dynamic equilibrium among the groups, with the former outweighing the latter in the BS, and conversely in the MS. Females made 93% of severe conflicts, which occurred in 18% of close encounters. Groups fissioned in the recent past shared the same home range, and showed the highest hostility to each other by females. In conspicuous contrast with females' great interest in intergroup food/range competition

  9. An Intravaginal Ring That Releases the NNRTI MIV-150 Reduces SHIV Transmission in Macaques

    PubMed Central

    Rodriguez, Aixa; Kizima, Larisa; Menon, Radhika; Goldman, Daniel; Kenney, Jessica; Aravantinou, Meropi; Seidor, Samantha; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Fernández-Romero, José A.; Robbiani, Melissa; Zydowsky, Thomas M.

    2015-01-01

    Microbicides may prevent HIV and sexually transmitted infections (STIs) in women; however, determining the optimal means of delivery of active pharmaceutical ingredients remains a major challenge. We previously demonstrated that a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150 partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase) infection, and the addition of zinc acetate rendered the gel significantly protective. We test the activity of MIV-150 without the addition of zinc acetate when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal rings (IVRs). MIV-150 was successfully delivered, because it was detected in vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies. Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our results demonstrate that MIV-150–containing IVRs have the potential to prevent HIV infection and highlight the possible use of IVRs for delivering drugs that block HIV and other STIs. PMID:22956201

  10. Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

    PubMed Central

    Li, Chun-Xia; Patel, Sudeep; Wang, Danny JJ; Zhang, Xiaodong

    2014-01-01

    The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of isoflurane resulted in significant increase in the mean CBF of the global, cortical, subcortical regions and the regional CBF in all subcortical structures and most cortical structures (such as motor cortex, anterior cingulate cortex, but not media prefrontal cortex). In addition, the changes of regional CBF in the affected regions correlated linearly with increasing isoflurane concentrations. The study demonstrates region specific CBF abnormal increase in adult macaque monkeys under high dose (2%) isoflurane and suggests the brain functionality in corresponding structures may be affected and need to be taken consideration in either human or non-human primate neuroimaging studies. PMID:24890304

  11. Seroprevalence of Japanese encephalitis virus infection in captive Japanese macaques (Macaca fuscata).

    PubMed

    Shimoda, Hiroshi; Saito, Akatsuki; Noguchi, Keita; Terada, Yutaka; Kuwata, Ryusei; Akari, Hirofumi; Takasaki, Tomohiko; Maeda, Ken

    2014-07-01

    Japanese encephalitis virus (JEV), which is transmitted by mosquitoes, infects many animal species and causes serious acute encephalitis in humans and horses. In this study, a serosurvey of JEV in Japanese macaques (Macaca fuscata) reared in Aichi Prefecture was conducted using purified JEV as an antigen for ELISA. The results revealed that 146 of 332 monkeys (44 %) were seropositive for JEV. In addition, 35 of 131 monkeys (27 %) born in the facility were seropositive, and the annual infection rate in the facility was estimated as 13 %. Our results provide evidence of the frequent exposure of many Japanese macaques to JEV, suggesting that there is a risk of JEV transmission to humans by mosquitoes. PMID:24748049

  12. Macaque Cardiac Physiology Is Sensitive to the Valence of Passively Viewed Sensory Stimuli

    PubMed Central

    Bliss-Moreau, Eliza; Machado, Christopher J.; Amaral, David G.

    2013-01-01

    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. PMID:23940712

  13. Hiding and perspective taking in long-tailed macaques (Macaca fascicularis).

    PubMed

    Kummer, H; Anzenberger, G; Hemelrijk, C K

    1996-03-01

    Seven long-tailed macaques (Macaca fascicularis) were trained by threats not to drink from a juice nipple as long as an experimenter was facing them. However, they were allowed to drink when the experimenter was standing with his or her back turned. During transfer tests, the monkeys had a choice between 2 juice nipples, one uncovered and the other hidden from the experimenter by a wooden screen, while the experimenter was facing them. We tested whether the monkeys would then prefer to drink behind the screen, thus demonstrating that they transferred knowledge acquired during training. Results did not yield a significant outcome, suggesting that the macaques did not transfer the observable "experimenter's visible open eyes" and that they did not take the experimenter's perspective. PMID:8851557

  14. Vaginal transmission of chimeric simian/human immunodeficiency viruses in rhesus macaques.

    PubMed Central

    Lu, Y; Brosio, P; Lafaile, M; Li, J; Collman, R G; Sodroski, J; Miller, C J

    1996-01-01

    Chimeric simian/human immunodeficiency viruses (SHIVs) that express the env genes derived from distinct HIV type 1 (HIV-1) isolates were tested for the ability to infect rhesus macaques following intravaginal inoculation. SHIVs containing either the HIV-1 HXBc2 or the HIV-1 89.6 envelope glycoproteins were capable of replicating in intravenously inoculated rhesus macaques. However, intravaginal inoculation of animals with these two SHIVs resulted in infection only with the SHIV containing the HIV-1 89.6 glycoprotein. Thus, properties conferred by the envelope glycoproteins in the chimeric virus affect the ability of particular SHIVs to initiate a systemic infection following vaginal inoculation. These results provide indirect support for the hypothesis that the selection of specific viral variants occurs in the genital tracts of individuals exposed to HIV by sexual contact. PMID:8627782

  15. Biogeography of the Intestinal Mucosal and Lumenal Microbiome in the Rhesus Macaque

    PubMed Central

    Yasuda, Koji; Oh, Keunyoung; Ren, Boyu; Tickle, Timothy L.; Franzosa, Eric A.; Wachtman, Lynn M.; Miller, Andrew D.; Westmoreland, Susan V.; Mansfield, Keith G.; Vallender, Eric J.; Miller, Gregory M.; Rowlett, James K.; Gevers, Dirk; Huttenhower, Curtis

    2015-01-01

    Summary The gut microbiome is widely studied by fecal sampling, but the extent to which stool reflects the commensal composition at intestinal sites is poorly understood. We investigated this relationship in rhesus macaques by 16S sequencing feces and paired lumenal and mucosal samples from 10 sites distal to the jejunum. Stool composition correlated highly with the colonic lumen and mucosa, and moderately with the distal small intestine. The mucosal microbiota varied most based on location and was enriched in oxygen-tolerant taxa (e.g. Helicobacter, Treponema), while the lumenal microbiota showed inter-individual variation and obligate anaerobe enrichment (e.g. Firmicutes). This mucosal and lumenal community variability corresponded to functional differences, such as nutrient availability. Additionally, Helicobacter, Faecalibacterium, and Lactobacillus levels in stool were highly predictive of their abundance at most other gut sites. These results quantify the composition and biogeographic relationships between gut microbial communities in macaques and support fecal sampling for translational studies. PMID:25732063

  16. Protection of rhesus macaques against inhalational anthrax with a Bacillus anthracis capsule conjugate vaccine.

    PubMed

    Chabot, Donald J; Ribot, Wilson J; Joyce, Joseph; Cook, James; Hepler, Robert; Nahas, Debbie; Chua, Jennifer; Friedlander, Arthur M

    2016-07-25

    The efficacy of currently licensed anthrax vaccines is largely attributable to a single Bacillus anthracis immunogen, protective antigen. To broaden protection against possible strains resistant to protective antigen-based vaccines, we previously developed a vaccine in which the anthrax polyglutamic acid capsule was covalently conjugated to the outer membrane protein complex of Neisseria meningitidis serotype B and demonstrated that two doses of 2.5μg of this vaccine conferred partial protection of rhesus macaques against inhalational anthrax . Here, we demonstrate complete protection of rhesus macaques against inhalational anthrax with a higher 50μg dose of the same capsule conjugate vaccine. These results indicate that B. anthracis capsule is a highly effective vaccine component that should be considered for incorporation in future generation anthrax vaccines. PMID:27329184

  17. Rhesus Macaques (Macaca mulatta) as Living Fossils of Hominoid Personality and Subjective Well-being

    PubMed Central

    Weiss, Alexander; Adams, Mark James; Widdig, Anja; Gerald, Melissa S.

    2014-01-01

    Personality dimensions capturing individual differences in behavior, cognition, and affect have been described in several species, including humans, chimpanzees, and orangutans. However, comparisons between species are limited by the use of different questionnaires. We asked raters to assess free-ranging rhesus macaques at two time points on personality and subjective well-being questionnaires used earlier to rate chimpanzees and orangutans. Principal-components analysis yielded domains we labeled Confidence, Friendliness, Dominance, Anxiety, Openness, and Activity. The presence of Openness in rhesus macaques suggests it is an ancestral characteristic. The absence of Conscientiousness suggests it is a derived characteristic in African apes. Higher Confidence and Friendliness, and lower Anxiety were prospectively related to subjective well-being, indicating that the connection between personality and subjective well-being in humans, chimpanzees, and orangutans is ancestral in catarrhine primates. As demonstrated here, each additional species studied adds another fold to the rich, historical story of primate personality evolution. PMID:21341912

  18. Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus

    PubMed Central

    Andrews, Chasity D.; Spreen, William R.; Mohri, Hiroshi; Moss, Lee; Ford, Susan; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Bohm, Rudolf P.; Cheng-Mayer, Cecilia; Hong, Zhi; Markowitz, Martin; Ho, David D.

    2015-01-01

    GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP). PMID:24594934

  19. Cleaving DNA with DNA

    NASA Astrophysics Data System (ADS)

    Carmi, Nir; Balkhi, Shameelah R.; Breaker, Ronald R.

    1998-03-01

    A DNA structure is described that can cleave single-stranded DNA oligonucleotides in the presence of ionic copper. This ``deoxyribozyme'' can self-cleave or can operate as a bimolecular complex that simultaneously makes use of duplex and triplex interactions to bind and cleave separate DNA substrates. Bimolecular deoxyribozyme-mediated strand scission proceeds with a kobs of 0.2 min-1, whereas the corresponding uncatalyzed reaction could not be detected. The duplex and triplex recognition domains can be altered, making possible the targeted cleavage of single-stranded DNAs with different nucleotide sequences. Several small synthetic DNAs were made to function as simple ``restriction enzymes'' for the site-specific cleavage of single-stranded DNA.

  20. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia

    NASA Astrophysics Data System (ADS)

    Shingai, Masashi; Nishimura, Yoshiaki; Klein, Florian; Mouquet, Hugo; Donau, Olivia K.; Plishka, Ronald; Buckler-White, Alicia; Seaman, Michael; Piatak, Michael; Lifson, Jeffrey D.; Dimitrov, Dimiter; Nussenzweig, Michel C.; Martin, Malcolm A.

    2013-11-01

    Neutralizing antibodies can confer immunity to primate lentiviruses by blocking infection in macaque models of AIDS. However, earlier studies of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies administered to infected individuals or humanized mice reported poor control of virus replication and the rapid emergence of resistant variants. A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals. These neutralizing antibodies target different regions of the HIV-1 envelope glycoprotein including the CD4-binding site, glycans located in the V1/V2, V3 and V4 regions, and the membrane proximal external region of gp41 (refs 9, 10, 11, 12, 13, 14). Here we have examined two of the new antibodies, directed to the CD4-binding site and the V3 region (3BNC117 and 10-1074, respectively), for their ability to block infection and suppress viraemia in macaques infected with the R5 tropic simian-human immunodeficiency virus (SHIV)-AD8, which emulates many of the pathogenic and immunogenic properties of HIV-1 during infections of rhesus macaques. Either antibody alone can potently block virus acquisition. When administered individually to recently infected macaques, the 10-1074 antibody caused a rapid decline in virus load to undetectable levels for 4-7days, followed by virus rebound during which neutralization-resistant variants became detectable. When administered together, a single treatment rapidly suppressed plasma viraemia for 3-5weeks in some long-term chronically SHIV-infected animals with low CD4+ T-cell levels. A second cycle of anti-HIV-1 monoclonal antibody therapy, administered to two previously treated animals, successfully controlled virus rebound. These results indicate that immunotherapy or a combination of immunotherapy plus conventional antiretroviral drugs might be useful as a treatment for chronically HIV-1-infected

  1. Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges

    PubMed Central

    Smith, James M.; Rastogi, Rachna; Teller, Ryan S.; Srinivasan, Priya; Mesquita, Pedro M. M.; Nagaraja, Umadevi; McNicholl, Janet M.; Hendry, R. Michael; Dinh, Chuong T.; Martin, Amy; Herold, Betsy C.; Kiser, Patrick F.

    2013-01-01

    Topical preexposure prophylaxis interrupts HIV transmission at the site of mucosal exposure. Intermittently dosed vaginal gels containing the HIV-1 reverse transcriptase inhibitor tenofovir protected pigtailed macaques depending on the timing of viral challenge relative to gel application. However, modest or no protection was observed in clinical trials. Intravaginal rings (IVRs) may improve efficacy by providing long-term sustained drug delivery leading to constant mucosal antiretroviral concentrations and enhancing adherence. Although a few IVRs have entered the clinical pipeline, 100% efficacy in a repeated macaque vaginal challenge model has not been achieved. Here we describe a reservoir IVR technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate (TDF) continuously over 28 d. With four monthly ring changes in this repeated challenge model, TDF IVRs generated reproducible and protective drug levels. All TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of four exposures assuming an eclipse of 7 d from infection to virus RNA detection. Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 × 105 ng/mL (range 1.1 × 104 to 6.6 × 105 ng/mL)] and ex vivo antiviral activity of cervicovaginal lavage samples. These observations support further advancement of TDF IVRs as well as the concept that extended duration drug delivery devices delivering topical antiretrovirals could be effective tools in preventing the sexual transmission of HIV in humans. PMID:24043812

  2. Dysregulation of Myelopoiesis by Chronic Alcohol Administration during Early SIV Infection of Rhesus Macaques

    PubMed Central

    Siggins, Robert W.; Molina, Patricia; Zhang, Ping; Bagby, Gregory J.; Nelson, Steve; Dufour, Jason; LeCapitaine, Nicole J.; Walsh, Cullen; Welsh, David A.

    2014-01-01

    Background Chronic alcohol intoxication suppresses immune function and increases osteoporosis risk suggesting bone tissue cytotoxicity. Human immunodeficiency virus (HIV) infection leads to similar impairments. This study investigated the effects of chronic alcohol administration during the early stage of simian immunodeficiency virus (SIV) infection on hematopoietic stem and progenitor cells and their differentiated progeny in the bone marrow and peripheral blood of rhesus macaques. Methods Rhesus macaques were administered alcohol or sucrose daily for a period of 3 months prior to intrarectal inoculation with 250 TCID50 of SIVmac251. Bone marrow aspirates and blood samples were taken prior to and 2 weeks after SIV infection. Bone marrow cells (BMCs) were assessed using flow cytometric phenotyping for upstream hematopoietic stem and progenitor cells (HSPCs) and for differentiated cells of the monocyte-granulocyte lineages. Likewise, cells were quantitated in peripheral blood. Results Of the bone marrow HSPCs, only the common lymphoid progenitor (CLP) was altered by alcohol administration pre-SIV (38±9.4 / 106 BMCs v 226±64.1 / 106 BMCs, sucrose v alcohol). Post-SIV, the frequency of CLPs in the bone marrow of alcohol-administered macaques decreased compared to the sucrose-administered macaques (107±47.6 / 106 BMCs v 43±16.3 / 106 BMCs). However, marrow mature cells of the monocyte lineage, specifically macrophages and osteoclast progenitors, were increased by both chronic alcohol administration and SIV infection (287% and 662%, respectively). As expected, mature cells such as granulocytes (polymorphonuclear cells (PMN)), B cells, and CD4+ T cells in the peripheral blood were decreased by SIV infection (37-62% decline from pre-infection), but not affected after three months of chronic alcohol administration. Conclusions Chronic alcohol administration disrupts myelomonocytic development in the bone marrow during the early period of SIV infection promoting

  3. Effect of Bacterial Pneumonia on Lung SIV Replication in Alcohol Consuming SIV Infected Rhesus Macaques

    PubMed Central

    Nelson, Steve; Happel, Kyle I.; Zhang, Ping; Myers, Leann; Dufour, Jason P.; Bagby, Gregory J.

    2013-01-01

    Background Opportunistic infections in HIV-infected persons have been shown to increase the rate of HIV replication. In populations where prophylaxis against Pneumocystis pneumonia is utilized, bacterial pneumonia is now the leading cause of lower respiratory tract infection in HIV+ patients. Our prior studies have shown that chronic alcohol consumption in simian demarcated immunodeficiency virus (SIV) infected rhesus macaques increases plasma viral load set point and accelerates progression to end-stage AIDS. While chronic alcohol abuse is well-known to increase the incidence and severity of bacterial pneumonia, the impact of alcohol consumption on local and systemic SIV/HIV burden during lung infection is unknown. Therefore, we utilized the macaque SIV infection model to examine the effect of chronic ethanol feeding on SIV burden during the course of pulmonary infection with Streptococcus pneumoniae, the most commonly identified etiology of bacterial pneumonia in HIV+ and HIV- persons in developed countries. Methods Alcohol was administered starting 3 months before SIVMac251 inoculation to the end of the study via an indwelling intragastric catheter to achieve a plasma alcohol concentration of 50–60 mM. Control animals received isocaloric sucrose. Four months after SIV infection, the right lung was inoculated with 2 × 106 CFU S. pneumoniae. Results Leukocyte recruitment into the lung, pulmonary bacterial clearance, and clinical course were similar between ethanol and control groups. While plasma SIV viral load was similar between groups post-pneumonia, chronic ethanol-fed macaques showed a prolonged increase in SIV RNA in bronchoalveolar lavage (BAL) fluid. Alveolar macrophages isolated from ethanol-fed macaques one day post-pneumonia showed greater nuclear factor kappa beta (NF-kB) activation. Conclusions This study indicates that chronic ethanol feeding results in enhanced local, but not systemic, SIV replication following pneumococcal pneumonia. Increased

  4. Minimally Invasive Lumbar Port System for the Collection of Cerebrospinal Fluid from Rhesus Macaques (Macaca mulatta).

    PubMed

    MacAllister, Rhonda Pung; Lester McCully, Cynthia M; Bacher, John; Thomas Iii, Marvin L; Cruz, Rafael; Wangari, Solomon; Warren, Katherine E

    2016-01-01

    Biomedical translational research frequently incorporates collection of CSF from NHP, because CSF drug levels are used as a surrogate for CNS tissue penetration in pharmacokinetic and dynamic studies. Surgical placement of a CNS ventricular catheter reservoir for CSF collection is an intensive model to create and maintain and thus may not be feasible or practical for short-term studies. Furthermore, previous NHP lumbar port models require laminectomy for catheter placement. The new model uses a minimally invasive technique for percutaneous placement of a lumbar catheter to create a closed, subcutaneous system for effective, repeated CSF sample collection. None of the rhesus macaques (Macaca mulatta; n = 10) implanted with our minimally invasive lumbar port (MILP) system experienced neurologic deficits, postoperative infection of the surgical site, or skin erosion around the port throughout the 21.7-mo study. Functional MILP systems were maintained in 70% of the macaques, with multiple, high-quality, 0.5- to 1.0-mL samples of CSF collected for an average of 3 mo by using aspiration or gravitational flow. Among these macaques, 57% had continuous functionality for a mean of 19.2 mo; 50% of the cohort required surgical repair for port repositioning and replacement during the study. The MILP was unsuccessful in 2 macaques, at an average of 9.5 d after surgery. Nonpatency in these animals was attributed to the position of the lumbar catheter. The MILP system is an appropriate replacement for temporary catheterization and previous models requiring laminectomy and is a short-term alternative for ventricular CSF collection systems in NHP. PMID:27538866

  5. Inter-Annual Variation in Characteristics of Endozoochory by Wild Japanese Macaques

    PubMed Central

    Tsuji, Yamato

    2014-01-01

    Endozoochory is important to the dynamics and regeneration of forest ecosystems. Despite the universality of inter-annual variation in fruit production, few studies have addressed the sign (seed predation versus seed dispersal) and strength (frequency and quantity) of fruit-frugivore interaction and the effectiveness of endozoochory in response to the long-term temporal context. In this study I evaluated the characteristics of endozoochorous dispersal by wild Japanese macaques Macaca fuscata inhabiting deciduous forest in northern Japan for five different years. I collected 378 fecal samples from the macaques in fall (September to November) and quantified the proportion of feces containing seeds, number of seeds per fecal sample, ratio of intact seeds, and seed diversity. The proportion of feces containing seeds of any species (five-year mean: 85.9%, range: 78–97%) did not show significant inter-annual variation, while species-level proportions did. The intact ratio of seeds (mean: 83%, range: 61–98%) varied significantly both between years and between months, and this varied among dominant plant species. The number of seeds per fecal sample (mean: 78, range: 32–102) varied monthly but did not between years, and the seed diversity (mean: 0.66, range: 0.57–0.81) did not show significant inter-annual variation, both of which were attributed to longer duration of macaques’ gastro-intestinal passage time of seeds exceed their feeding bouts. This study demonstrated that frequency and success of seed dispersal over seed predation of macaque endozoochory showed inter-annual variation, indicating low specificity across the seed–macaque network. The temporal variability in the quality of seed dispersal may provide evidence of high resilience in response to fluctuating environmental conditions in the temperate forests. PMID:25272286

  6. Estimates of heritability for reproductive traits in captive rhesus macaque females

    PubMed Central

    Gagliardi, Christine; Falkenstein, Kathrine P.; Franke, Donald E.; Kubisch, H. Michael

    2010-01-01

    Records from a colony of captive Indian rhesus macaques (Macaca mulatta) were used to estimate heritability for a number of reproductive traits. Records were based on a total of 7,816 births by 1,901 females from 1979 to 2007. Heritability was estimated with a linear animal model using a multiple trait derivative free REML set of programs. Because no male parents were identified, the numerator relationship matrix contained female kinships established over six generations. Reproductive traits included female age at the birth of the first, second and last infant, age at death, inter-birth intervals, number of infants born per female and infant survival. Heritability for each trait was estimated as the ratio of the additive genetic variance to phenotypic variance adjusted for significant fixed effects. Estimates of heritability for early reproduction ranged from 0.000 ± 0.072 for birth interval following the first reproduction to 0.171 ± 0.062 for age of female at the first infant. Higher estimates of heritability were found for female longevity [0.325 ± 0.143] and for productivity of deceased females born before 1991 [0.221 ± 0.138]. Heritability for infant survival ranged from 0.061 ± 0.018 for survival from 30d to 1yr to 0.290 ± 0.050 for survival from birth to 30d when adjusted to an underlying normal distribution. Eight of the 13 estimates of heritability for reproductive traits in this study were different from zero [P < 0.05]. Generally, heritability estimates reported here for reproductive traits of captive rhesus macaque females are similar to those reported in the literature for free ranging rhesus macaque females and for similar reproductive traits of other species. These estimates of heritability for reproductive traits appear to be among the first for a relatively large colony of captive rhesus macaque females. PMID:20653007

  7. Transgenerational effects of variable foraging demand stress in female bonnet macaques.

    PubMed

    Kinnally, Erin L; Feinberg, Caroline; Kim, David; Ferguson, Kerel; Coplan, Jeremy D; Mann, J John

    2013-05-01

    Stress coping is an important part of mammalian life, influencing somatic and mental health, social integration, and reproductive success. The experience of early psychological stress helps shape lifelong stress coping strategies. Recent studies have shown that the effects of early stress may not be restricted to the affected generation, but may also be transmitted to offspring. Understanding whether early stress influences development in subsequent generations may help us understand somewhat why many stress-related traits and diseases, for which little genetic basis has been discovered, run in families. Experimental early life "variable foraging demand" (VFD) stress has been associated with behavioral hypo-responsiveness to stress in infant and adolescent bonnet macaques. The present study examined the behavioral effects of experimental early VFD stress in adult bonnet macaques, and further investigated whether non-exposed adolescent offspring of VFD macaques were also affected. Thirty female bonnet macaques from four rearing histories were observed for behavioral response during stress: adults which had been VFD reared as infants (n = 11), adults which had been Control reared as infants (n = 9), and foraging demand naïve adolescents whose mothers were VFD (n = 4) or Control reared (n = 6). Subjects were observed for behavioral response during two experimental stressor conditions, including: (1) relocation to a novel environment; and (2) relocation with exposure to a "human intruder" making eye contact. Factor analysis yielded five factors that described categories of behavior across stress conditions. While adult VFD and Control reared females unexpectedly did not differ significantly, non-exposed adolescent offspring of VFD reared mothers displayed significant hypo-responsiveness in all behavioral categories compared with non-exposed adolescent offspring of Control females. We suggest that stress hypo-responsiveness previously observed in adolescent VFD reared

  8. Large-scale polymorphism discovery in macaque G-protein coupled receptors

    PubMed Central

    2013-01-01

    Background G-protein coupled receptors (GPCRs) play an inordinately large role in human health. Variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. GPCRs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms. Recently, non-human primate models have been developed focusing on naturally-occurring, functionally-parallel polymorphisms in candidate genes. This work aims to extend those studies broadly across the roughly 377 non-olfactory GPCRs. Initial efforts include resequencing 44 Indian-origin rhesus macaques (Macaca mulatta), 20 Chinese-origin rhesus macaques, and 32 cynomolgus macaques (M. fascicularis). Results Using the Agilent target enrichment system, capture baits were designed for GPCRs off the human and rhesus exonic sequence. Using next generation sequencing technologies, nearly 25,000 SNPs were identified in coding sequences including over 14,000 non-synonymous and more than 9,500 synonymous protein-coding SNPs. As expected, regions showing the least evolutionary constraint show greater rates of polymorphism and greater numbers of higher frequency polymorphisms. While the vast majority of these SNPs are singletons, roughly 1,750 non-synonymous and 2,900 synonymous SNPs were found in multiple individuals. Conclusions In all three populations, polymorphism and divergence is highly concentrated in N-terminal and C-terminal domains and the third intracellular loop region of GPCRs, regions critical to ligand-binding and signaling. SNP frequencies in macaques follow a similar pattern of divergence from humans and new polymorphisms in primates have been identified that may parallel those seen in humans, helping to establish better non-human primate models of disease. PMID:24119066

  9. Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques.

    PubMed

    Phuah, Jiayao; Wong, Eileen A; Gideon, Hannah P; Maiello, Pauline; Coleman, M Teresa; Hendricks, Matthew R; Ruden, Rachel; Cirrincione, Lauren R; Chan, John; Lin, Philana Ling; Flynn, JoAnne L

    2016-05-01

    Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses against Mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model of M. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells in M. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response in M. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined. PMID:26883591

  10. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis

    PubMed Central

    Lin, Philana Ling; Maiello, Pauline; Gideon, Hannah P.; Cadena, Anthony M.; Rodgers, Mark A.; Gregg, Robert; O’Malley, Melanie; Fillmore, Daniel; Frye, L. James; Rutledge, Tara; DiFazio, Robert M.; Janssen, Christopher; Klein, Edwin; Andersen, Peter L.; Fortune, Sarah M.; Flynn, JoAnne L.

    2016-01-01

    Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT) of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF) neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26) before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25). Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection. PMID:27379816

  11. Divergent Simian Arteriviruses Cause Simian Hemorrhagic Fever of Differing Severities in Macaques

    PubMed Central

    Moncla, Louise H.; Weiler, Andrea M.; Charlier, Olivia; Rojas, Oscar; Byrum, Russell; Ragland, Dan R.; Cohen, Melanie; Sanford, Hannah B.; Qin, Jing

    2016-01-01

    ABSTRACT Simian hemorrhagic fever (SHF) is a highly lethal disease in captive macaques. Three distinct arteriviruses are known etiological agents of past SHF epizootics, but only one, simian hemorrhagic fever virus (SHFV), has been isolated in cell culture. The natural reservoir(s) of the three viruses have yet to be identified, but African nonhuman primates are suspected. Eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy African cercopithecid monkeys. Here, we report the successful isolation in MARC-145 cell culture of one of these viruses, Kibale red colobus virus 1 (KRCV-1), from serum of a naturally infected red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) sampled in Kibale National Park, Uganda. Intramuscular (i.m.) injection of KRCV-1 into four cynomolgus macaques (Macaca fascicularis) resulted in a self-limiting nonlethal disease characterized by depressive behavioral changes, disturbance in coagulation parameters, and liver enzyme elevations. In contrast, i.m. injection of SHFV resulted in typical lethal SHF characterized by mild fever, lethargy, lymphoid depletion, lymphoid and hepatocellular necrosis, low platelet counts, increased liver enzyme concentrations, coagulation abnormalities, and increasing viral loads. As hypothesized based on the genetic and presumed antigenic distance between KRCV-1 and SHFV, all four macaques that had survived KRCV-1 injection died of SHF after subsequent SHFV injection, indicating a lack of protective heterotypic immunity. Our data indicate that SHF is a disease of macaques that in all likelihood can be caused by a number of distinct simian arteriviruses, although with different severity depending on the specific arterivirus involved. Consequently, we recommend that current screening procedures for SHFV in primate-holding facilities be modified to detect all known simian arteriviruses. PMID:26908578

  12. Paternal early experiences influence infant development through non-social mechanisms in Rhesus Macaques

    PubMed Central

    2015-01-01

    Background Early experiences influence the developing organism, with lifelong and potentially adaptive consequences. It has recently become clear that the effects of early experiences are not limited to the exposed generation, but can influence physiological and behavioral traits in the next generation. Mechanisms of transgenerational effects of parental early experiences on offspring development are often attributed to prenatal or postnatal parental influence, but recent data suggest that germ-line plasticity may also play a role in the transgenerational effects of early experiences. These non-genetic transgenerational effects are a potentially important developmental and evolutionary force, but the effects of parental experiences on behavior and physiology are not well understood in socially complex primates. In the non-human primate, the rhesus macaque, nursery rearing (NR) is an early life manipulation used for colony management purposes, and involves separating infants from parents early in life. We examined the effects of maternal and paternal early NR on infant rhesus macaque immunity, physiology, and behavior. Results We theorized that differences in behavior or physiology in the absence of parent-offspring social contact would point to biological and perhaps germ-line, rather than social, mechanisms of effect. Thus, all subjects were themselves NR. Male and female infant rhesus macaques (N= 206) were separated from parents and social groups in the first four days of life to undergo NR. These infants differed only in their degree of NR ancestry – whether their dams or sires were themselves NR. At 3-4 months of age, infants underwent a standardized biobehavioral assessment. Factors describing immunity, plasma cortisol, and emotion regulation were generated from these data using factor analysis. Paternal, but not maternal, NR was associated with greater emotionality and higher plasma cortisol, compared with infants born to CONTROL reared fathers

  13. Park Rangers’ Behaviors and Their Effects on Tourists and Tibetan Macaques (Macaca thibetana) at Mt. Huangshan, China

    PubMed Central

    Usui, Rie; Sheeran, Lori K.; Li, Jin-hua; Sun, Lixing; Wang, Xi; Pritchard, Alexander J.; DuVall-Lash, Alexander S.; Wagner, R. Steve

    2014-01-01

    Simple Summary Conflict between macaques and humans is a commonly reported problem in Asian tourism. However, without understanding how macaques are managed, the establishment of an effective management design is impracticable. This study explored how monkeys were managed and tourists were regulated at the Valley of the Wild Monkeys in Mt. Huangshan, Anhui Province, China, through a field observation. Two teams of park rangers alternated monthly and managed a group of macaques. The results suggested that undesired tourists’ interactions with monkeys were not regularly intervened by park rangers, and park rangers established dominance over the monkeys by using physical threats to manage them. Abstract Previous studies have reported the negative impacts of tourism on nonhuman primates (NHPs) and tourists and advocated the improvement of tourism management, yet what constitutes good quality management remains unclear. We explored whether rates of macaque aggression and self-directed behaviors (SDBs) differed under the supervision of two park ranger teams at the Valley of the Wild Monkeys (VWM) in Mt. Huangshan, Anhui Province, China. The two ranger teams provisioned and managed a group of macaques on an alternating monthly basis. Monkey, tourist and ranger behaviors were collected from August 16–September 30, 2012. Macaque aggression and SDB rates did not differ significantly under the management of the two teams. Overall, there was little intervention in tourist-macaque interactions by park rangers, and even when rangers discouraged tourists’ undesirable behaviors, tourist interactions with monkeys persisted. Furthermore, only one or sometimes two park rangers managed monkeys and tourists, and rangers established dominance over the monkeys to control them. In order to effectively manage tourists and monkeys by a single park ranger, we recommend that rangers: (1) prohibit tourists from feeding; (2) move around the viewing platform more frequently; and (3) limit

  14. Flow cytometric characterizations of leukocyte subpopulations in the peripheral blood of northern pig-tailed macaques (Macaca leonina)

    PubMed Central

    ZHENG, Hong-Yi; ZHANG, Ming-Xu; ZHANG, Lin-Tao; ZHANG, Xiao-Liang; PANG, Wei; LYU, Long-Bao; ZHENG, Yong-Tang

    2014-01-01

    Pig-tailed macaques (Macaca nemistrina group) have been extensively used as non-human primate animal models for various human diseases in recent years, notably for AIDS research due to their sensitivity to HIV-1. Northern pig-tailed macaques (M. leonina) are distributed in China and other surrounding Southeast Asia countries. Although northern pig-tailed macaques have been bred on a large scale as experimental animals since 2012, the reference value of normal levels of leukocytes is not available. To obtain such information, 62 blood samples from male and female healthy northern pig-tailed macaques at different ages were collected. The normal range of major leukocyte subpopulations, such as T lymphocytes, B lymphocytes, natural killer (NK) cells, monocytes, and the expression levels of activation or differentiation related molecules (CD38, HLA-DR, CCR5, CD21, IgD, CD80 and CD86) on lymphocytes were analyzed by flow cytometry. The counts of B cells decreased with age, but those of CD8+ T cells and NK cells and the frequency of CD38+HLA-DR+CD4+ T cells were positively correlated with age. The counts of leukocyte subpopulations were higher in males than those in females except for CD4+ T cells. Males also showed higher expression levels of IgD and CD21 within B cells. This study provides basic data about the leukocyte subpopulations of northern pig-tailed macaques and compares this species with commonly used Chinese rhesus macaques (M. mulatta), which is meaningful for the biomedical application of northern pig-tailed macaques. PMID:25465082

  15. Dry bedding provides cost-effective enrichment for group-housed rhesus macaques (Macaca mulatta).

    PubMed

    Doane, Cynthia J; Andrews, Kirk; Schaefer, Laura Jane; Morelli, Nathan; McAllister, Shannon; Coleman, Kristine

    2013-01-01

    Dry bedding has been shown to be an effective enrichment strategy for small groups of captive nonhuman primates housed in cages or in small enclosures with concrete flooring. However, dry bedding is used infrequently for large groups because of the perception that its use is time- and resource-intensive. We investigated the cost-effectiveness of this enrichment strategy in large groups (30 to 50 subjects) of rhesus macaques. Macaques were housed under 3 comparison conditions for 4 wk: pine shavings (n = 4), aspen and pine shaving mixture (n = 4), and nonbedded control (n = 4). As measures of resource consumption, husbandry tasks were documented by using time-in-motion methodology, and water usage was determined. In addition, groups underwent behavioral observations to assess the effect of dry bedding. The time required to care for units did not differ between bedded and nonbedded units. However, significantly less water was used for sanitization of bedded compared with nonbedded units. Monkeys housed in bedded units showed more foraging (13.8% ± 1.6% of time in bedded compared with 4.0% ± 0.3% of time in nonbedded units) and less aggression and self-grooming. Dry bedding benefited the macaques, reduced water usage and costs, and did not affect human resources. PMID:23849406

  16. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge.

    PubMed

    Radzio, Jessica; Spreen, William; Yueh, Yun Lan; Mitchell, James; Jenkins, Leecresia; García-Lerma, J Gerardo; Heneine, Walid

    2015-01-14

    Daily preexposure prophylaxis (PrEP) with Truvada is a proven HIV prevention strategy; however, its effectiveness is limited by low adherence. Antiretroviral drug formulations that require infrequent dosing may increase adherence and thus PrEP effectiveness. We investigated whether monthly injections of a long-acting formulation of the HIV integrase inhibitor GSK1265744 (GSK744 LA) prevented simian/human immunodeficiency virus (SHIV) infection by vaginal challenge in macaques. Female pigtail macaques (n = 12) were exposed to intravaginal inoculations of SHIV twice a week for up to 11 weeks. Half of the animals received a GSK744 LA injection every 4 weeks, and half received placebo. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all six macaques from infection. Placebo controls were all infected after a median of 4 (range, 2 to 20) vaginal challenges with SHIV. Efficacy was related to high and sustained vaginal and plasma drug concentrations that remained above the protein-adjusted 90% inhibitory concentration during the dosing cycles. These data support advancement of GSK744 LA as a potential PrEP candidate for women. PMID:25589631

  17. Seeing two faces together: preference formation in humans and rhesus macaques.

    PubMed

    Méary, David; Li, Zhihan; Li, Wu; Guo, Kun; Pascalis, Olivier

    2014-09-01

    Humans, great apes and old world monkeys show selective attention to faces depending on conspecificity, familiarity, and social status supporting the view that primates share similar face processing mechanisms. Although many studies have been done on face scanning strategy in monkeys and humans, the mechanisms influencing viewing preference have received little attention. To determine how face categories influence viewing preference in humans and rhesus macaques (Macaca mulatta), we performed two eye-tracking experiments using a visual preference task whereby pairs of faces from different species were presented simultaneously. The results indicated that viewing time was significantly influenced by the pairing of the face categories. Humans showed a strong bias towards an own-race face in an Asian-Caucasian condition. Rhesus macaques directed more attention towards non-human primate faces when they were paired with human faces, regardless of the species. When rhesus faces were paired with faces from Barbary macaques (Macaca sylvanus) or chimpanzees (Pan troglodytes), the novel species' faces attracted more attention. These results indicate that monkeys' viewing preferences, as assessed by a visual preference task, are modulated by several factors, species and dominance being the most influential. PMID:24638876

  18. Surface-based atlases of cerebellar cortex in the human, macaque, and mouse

    NASA Technical Reports Server (NTRS)

    Van Essen, David C.

    2002-01-01

    This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

  19. Fading perceptual resemblance: a path for rhesus macaques (Macaca mulatta) to conceptual matching?

    PubMed

    David Smith, J; Flemming, Timothy M; Boomer, Joseph; Beran, Michael J; Church, Barbara A

    2013-12-01

    Cognitive, comparative, and developmental psychologists have long been intrigued by humans' and animals' capacity to respond to abstract relations like sameness and difference, because this capacity may underlie crucial aspects of cognition like analogical reasoning. Recently, this capacity has been explored in higher-order, relational matching-to-sample (RMTS) tasks in which humans and animals try to complete analogies of sameness and difference between disparate groups of items. The authors introduced a new paradigm to this area, by yoking the relational-matching cue to a perceptual-matching cue. Then, using established algorithms for shape distortion, the perceptual cue was weakened and eliminated. Humans' RMTS performance easily transcended the elimination of perceptual support. In contrast, RMTS performance by six macaques faltered as they were weaned from perceptual support. No macaque showed evidence of mature RMTS performance, even given more than 260,000 training trials during which we tried to coax a relational-matching performance from them. It is an important species difference that macaques show so hesitant a response to conceptual relations when humans respond to them so effortlessly. It raises theoretical questions about the emergence of this crucial capacity during humans' cognitive evolution and during humans' cognitive development. PMID:24076537

  20. Enhanced visual exploration for real objects compared to pictures during free viewing in the macaque monkey.

    PubMed

    Mustafar, Faiz; De Luna, Paolo; Rainer, Gregor

    2015-09-01

    The question of whether animals perceive pictures as representation of real objects remains still unsolved. Object-picture perception is generally studied requiring animals to learn some information about real objects and transfer that knowledge to the pictorial domain, or vice versa. Here, we tackle the issue of object-picture perception from a different perspective, examining visual exploration behavior of two naïve macaque monkeys during free-viewing of objects and pictures of these objects on a computer monitor. Our main finding is that monkeys looked spontaneously longer at object rather than picture stimuli. However, we find striking similarities in temporal dynamics of gaze allocation within the time course of a single stimulus presentation, as well as in habituation rates within and across behavioral sessions. We also highlight differences between stimulus types in terms of spatial gaze patterns and looking strategies. Stimulus features that attract overt attention during spontaneous visual exploration are thus better predicted for object stimuli by a visual saliency model. Moreover, we provide evidence for a consistency in stimulus preference for objects and pictures, suggesting a correspondence of in how macaques perceive objects and their pictorial stimuli. Taken together, our data suggest that macaque monkeys exhibit evidence for correspondence between objects and pictures. This validates spontaneous visual exploration as a method for studying object-picture correspondence without a need for extensive behavioral training. We discuss the potential advantages of using object over picture stimuli in the context of studies on visual cognition. PMID:26003135

  1. Serological survey for two simian retroviruses in macaques and African green monkeys.

    PubMed

    Krugner-Higby, L; Kucera, L; Lerche, N; Sever, J; Fucillo, W; Allan, J; Benveniste, R

    1990-01-01

    Colonies of nonhuman primates at the Bowman Gray School of Medicine (BGSM) were tested for antibodies to two retroviruses associated with immunodeficiency by indirect immunofluorescence (IFA) and western blot. A total of 471 cynomolgus macaques (Macaca fascicularis), 144 rhesus monkeys (M. mulatta) and 67 stumptail monkey M. arctoides) were tested for SRV-1, and 152 African green monkeys (Cercopithecus aethiops) were tested for SIV. Of the macaques tested, 170 (36%) cynomolgus, 5 (3%) rhesus and 8 (12%) stumptails were positive for SRV-1 antibodies by IFA. Of the African green monkeys, 54 (36%) were IFA positive for SIV antibodies. A total of 143 African green monkeys tested by IFA also were tested by western blot. In the African green monkeys, the IFA had a positive predictive value of 98% and a negative predictive value of 96%. Of 176 IFA positive macaque sera tested by western blot, 49 (28%) were positive, 55 (31%) were considered equivocal (only one band, usually to p27 core protein), and 72 (41%) were negative. PMID:2153854

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

    PubMed

    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. PMID:25488714

  3. Repetition suppression for visual actions in the macaque superior temporal sulcus.

    PubMed

    Kuravi, Pradeep; Caggiano, Vittorio; Giese, Martin; Vogels, Rufin

    2016-03-01

    In many brain areas, repetition of a stimulus usually weakens the neural response. This "adaptation" or repetition suppression effect has been observed with mass potential measures such as event-related potentials (ERPs), in fMRI BOLD responses, and locally with local field potentials (LFPs) and spiking activity. Recently, it has been reported that macaque F5 mirror neurons do not show repetition suppression of their spiking activity for single repetitions of hand actions, which disagrees with human fMRI adaptation studies. This finding also contrasts with numerous studies showing repetition suppression in macaque inferior temporal cortex, including the rostral superior temporal sulcus (STS). Since the latter studies employed static stimuli, we assessed here whether the use of dynamic action stimuli abolishes repetition suppression in the awake macaque STS. To assess adaptation effects in the STS, we employed the same hand action movies as used when examining adaptation in F5. The upper bank STS neurons showed repetition suppression during the approaching phase of the hand action, which corresponded to the phase of the action for which these neurons responded overall the strongest. The repetition suppression was present for the spiking activity measured in independent single-unit and multiunit recordings as well as for the LFP power at frequencies > 50 Hz. Together with previous data in F5, these findings suggest that adaptation effects differ between F5 mirror neurons and the STS neurons. PMID:26745246

  4. Renal pigmentation due to chronic bismuth administration in a rhesus macaque (Macaca mulatta).

    PubMed

    Johnson, A L; Blaine, E T; Lewis, A D

    2015-05-01

    Renal pigmentation due to the administration of exogenous compounds is an uncommon finding in most species. This report describes renal pigmentation and intranuclear inclusions of the proximal convoluted tubules due to chronic bismuth administration in a rhesus macaque. An 11-year-old Indian-origin rhesus macaque with a medical history of chronic intermittent vomiting had been treated with bismuth subsalicylate, famotidine, and omeprazole singly or in combination over the course of 8 years. At necropsy, the renal cortices were diffusely dark green to black. Light and electron microscopy revealed intranuclear inclusions within the majority of renal proximal tubular epithelial cells. These inclusions appeared magenta to brown when stained with hematoxylin and eosin and were negative by the Ziehl-Neelsen acid-fast stain. Elemental analysis performed on frozen kidney measured bismuth levels to be markedly elevated at 110.6 ppm, approximately 500 to 1000 times acceptable limits. To our knowledge, this is the first report of renal bismuth deposition in a rhesus macaque resulting in renal pigmentation and intranuclear inclusions. PMID:24990482

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

    PubMed Central

    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

  6. Role of vocal tract characteristics in individual discrimination by Japanese macaques (Macaca fuscata).

    PubMed

    Furuyama, Takafumi; Kobayasi, Kohta I; Riquimaroux, Hiroshi

    2016-01-01

    The Japanese macaque (Macaca fuscata) exhibits a species-specific communication sound called the "coo call" to locate group members and maintain within-group contact. Monkeys have been demonstrated to be capable of discriminating between individuals based only on their voices, but there is still debate regarding how the fundamental frequencies (F0) and filter properties of the vocal tract characteristics (VTC) contribute to individual discrimination in nonhuman primates. This study was performed to investigate the acoustic keys used by Japanese macaques in individual discrimination. Two animals were trained with standard Go/NoGo operant conditioning to distinguish the coo calls of two unfamiliar monkeys. The subjects were required to continue depressing a lever until the stimulus changed from one monkey to the other. The test stimuli were synthesized by combining the F0s and VTC from each individual. Both subjects released the lever when the VTC changed, whereas they did not when the F0 changed. The reaction times to the test stimuli were not significantly different from that to the training stimuli that shared the same VTC. Our data suggest that vocal tract characteristics are important for the identification of individuals by Japanese macaques. PMID:27550840

  7. Intentional gestural communication and discrimination of human attentional states in rhesus macaques (Macaca mulatta).

    PubMed

    Canteloup, Charlotte; Bovet, Dalila; Meunier, Hélène

    2015-07-01

    The present study tested intentionality of a learned begging gesture and attention-reading abilities in rhesus macaques (Macaca mulatta). Subjects were trained to produce a begging gesture towards a hidden food reward that could be delivered by a human experimenter. More specifically, we investigated which attentional cues--body, face and/or eyes orientation of a human partner--were taken into account by the macaques in order to communicate with her. Our results provide strong evidence of intentional communication: the monkeys adjusted their behaviour to that of the partner. The latter's attentional state influenced the monkeys' likelihood of performing begging gestures and showing gaze alternation between the partner and the hidden food. By contrast, we found no evidence of attention-getting behaviours, persistence or elaboration of new communicative behaviours. Our results also showed that rhesus macaques discriminated gross cues including the presence, body and face orientation of the human experimenter but not her eyes. However, the monkeys emitted more gaze alternation and monitored the human's attentional state more closely when she also displayed gaze alternation, suggesting an important role of joint attention in gestural communication. PMID:25749401

  8. Pharmacokinetics of buprenorphine following intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta)

    PubMed Central

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

    2014-01-01

    This study reports the pharmacokinetics of buprenorphine in conscious rhesus macaques (Macaca mulatta) after intravenous (IV) and intramuscular (IM) administration. Four healthy, opioid-naïve, socially-housed, adult male macaques were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions. Blood samples were collected prior to, and up to 24 h, post-administration. Serum buprenorphine concentrations were analyzed with liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed with commercially available software. Mean residence time in the IV study as compared to the IM study was 177 (159–189) minutes vs. 185 (174–214) minutes, respectively [median (range)]. In the IV study, concentration back extrapolated to time zero was found to be 33.0 (16.8–57.0) ng/mL [median (range)]. On the other hand, the maximum serum concentration found in the IM study was 11.8 (6.30–14.8) ng/mL [median (range)]. Rhesus macaques maintained concentrations greater than 0.10 ng/mL for over 24 h in the IV study and over 12 h in the IM study. Bioavailability was found to be 68.1 (59.3–71.2)% [median (range)]. No significant adverse effects were observed in the monkeys at the 0.03 mg/kg dose of buprenorphine during either study. PMID:24666428

  9. Serologic Evaluation of Clinical and Subclinical Secondary Hepatic Amyloidosis in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    MacGuire, Jamus G; Christe, Kari L; Yee, JoAnn L; Kalman-Bowlus, Alexis L; Lerche, Nicholas W

    2009-01-01

    Secondary hepatic amyloidosis in nonhuman primates carries a grave prognosis once animals become clinically ill. The purpose of this study was to establish serologic parameters that potentially could be used to identify rhesus macaques undergoing subclinical development of secondary hepatic amyloidosis. A retrospective analysis was completed by using serum biochemical profiles from 26 histologically diagnosed amyloidotic macaques evaluated at 2 stages of disease, clinical and subclinical (3 to 32 mo prior to clinical signs of disease). Standard serum biochemistry values for cases were compared with institutional age- and gender-specific references ranges by construction of 95% confidence intervals for the difference between means. In addition, 19 histologically diagnosed amyloidotic macaques and 19 age-matched controls were assayed for changes in various parameters by using routinely banked, frozen (–80 °C) sera available from clinical and subclinical time points. Clinically amyloidotic animals displayed increased levels of alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyltranspeptidase, and macrophage colony-stimulating factor and significantly decreased quantities of albumin and total cholesterol. Subclinical amyloidotic animals displayed increased levels of alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, and serum amyloid A and decreased concentrations of albumin and total cholesterol. The serologic parameters studied indicate a temporal relationship of these factors not previously described, show a clear pattern of disease progression, and could be useful in subclinical disease detection. PMID:19389309

  10. Protan-like spectral sensitivity of foveal Y ganglion cells of the retina of macaque monkeys.

    PubMed Central

    de Monasterio, F M; Schein, S J

    1980-01-01

    1. The spectral sensitivity of two varieties of macaque Y ganglion cells with a centre-surround organization, type III (non-colour opponent) and type IV (broad-band colour opponent), was examined with test stimuli of different size, shape and wave-length. 2. The spectral sensitivity of type III cells to large stimuli decreased at the long wave-lengths with decreasing retinal eccentricity; this change was due to a lower sensitivity of green-sensitive than of red-sensitive cone input to the surround of foveal cells, which resulted in stronger surround antagonism at the long than at the short wave-lengths leading to a rudimentary form of colour opponency. 3. The spectral properties of foveal type III cells were intermediate between those of perifoveal type III cells, whose surrounds receive a rather similar input from both cone types, and of the predominantly foveal type IV cells, whose surrounds appeared to lack input from green-sensitive cones. 4. The results indicate that both cell types represent varieties within a continuum of a single macaque Y-cell system which has a reduced long-wave-length sensitivity in the foveal region. The fact that a similar reduction of long-wave-length sensitivity can be observed in (foveal) macaque photopic luminosity functions measured with different techniques by different authors suggest that both types of Y cell have an important role in the processing of luminance information. PMID:6770078

  11. Role of vocal tract characteristics in individual discrimination by Japanese macaques (Macaca fuscata)

    PubMed Central

    Furuyama, Takafumi; Kobayasi, Kohta I.; Riquimaroux, Hiroshi

    2016-01-01

    The Japanese macaque (Macaca fuscata) exhibits a species-specific communication sound called the “coo call” to locate group members and maintain within-group contact. Monkeys have been demonstrated to be capable of discriminating between individuals based only on their voices, but there is still debate regarding how the fundamental frequencies (F0) and filter properties of the vocal tract characteristics (VTC) contribute to individual discrimination in nonhuman primates. This study was performed to investigate the acoustic keys used by Japanese macaques in individual discrimination. Two animals were trained with standard Go/NoGo operant conditioning to distinguish the coo calls of two unfamiliar monkeys. The subjects were required to continue depressing a lever until the stimulus changed from one monkey to the other. The test stimuli were synthesized by combining the F0s and VTC from each individual. Both subjects released the lever when the VTC changed, whereas they did not when the F0 changed. The reaction times to the test stimuli were not significantly different from that to the training stimuli that shared the same VTC. Our data suggest that vocal tract characteristics are important for the identification of individuals by Japanese macaques. PMID:27550840

  12. Personality Structure in Brown Capuchin Monkeys: Comparisons with Chimpanzees, Orangutans, and Rhesus Macaques

    PubMed Central

    Morton, F. Blake; Lee, Phyllis C.; Buchanan-Smith, Hannah M.; Brosnan, Sarah F.; Thierry, Bernard; Paukner, Annika; de Waal, Frans B. M.; Widness, Jane; Essler, Jennifer L.; Weiss, Alexander

    2013-01-01

    Species comparisons of personality structure (i.e. how many personality dimensions and the characteristics of those dimensions) can facilitate questions about the adaptive function of personality in nonhuman primates. Here we investigate personality structure in the brown capuchin monkey (Sapajus apella), a New World primate species, and compare this structure to those of chimpanzees (Pan troglodytes), orangutans (Pongo spp.), and rhesus macaques (Macaca mulatta). Brown capuchins evolved behavioral and cognitive traits that are qualitatively similar to those of great apes, and individual differences in behavior and cognition are closely associated with differences in personality. Thus, we hypothesized that brown capuchin personality structure would overlap more with great apes than with rhesus macaques. We obtained personality ratings from seven sites on 127 brown capuchin monkeys. Principal-components analysis identified five personality dimensions (Assertiveness, Openness, Neuroticism, Sociability, and Attentiveness), which were reliable across raters and, in a subset of subjects, significantly correlated with relevant behaviors up to a year later. Comparisons between species revealed that brown capuchins and great apes overlapped in personality structure, particularly chimpanzees in the case of Neuroticism. However, in some respects (i.e. capuchin Sociability and Openness) the similarities between capuchins and great apes were not significantly greater than those between capuchins and rhesus macaques. We discuss the relevance of our results to brown capuchin behavior, and the evolution of personality structure in primates. PMID:23668695

  13. Winter ecology of the Arunachal macaque Macaca munzala in Pangchen Valley, western Arunachal Pradesh, northeastern India.

    PubMed

    Mendiratta, Uttara; Kumar, Ajith; Mishra, Charudutt; Sinha, Anindya

    2009-11-01

    The newly described Arunachal macaque Macaca munzala occurs largely in sub-tropical to temperate environments at elevations of c. 1,800-3,000 m in Arunachal Pradesh, northeastern India. We studied its over-wintering strategy by comparing the diet, ranging, and behavior of a troop of 24 individuals during winter and spring (December 2005 to May 2006) through instantaneous scan sampling (3,002 records, 448 scans, 112 hr of observation). We also monitored the phenology of food plants. The macaques spent more time (41-66%) feeding in the winter than in spring (33-51%), whereas time spent moving and resting was greater in spring. The diet composed largely of plants, with animal matter being eaten rarely. The number of plant species in the diet increased from 18 to 25 whereas food types rose from 18 to 36 from winter to spring, respectively. Although only two species formed 75% of the winter diet, seven species comprised this proportion in spring. Availability of fruits and young leaves increased in spring; the troop moved more and utilized a larger part of its range during this time. Seasonal changes in behavior could be explained by the scarcity of food and the costs of thermoregulation in winter. Our study suggests that the Arunachal macaque inhabits a highly seasonal environment and has an over-wintering strategy that includes subsisting on a high-fiber diet by increasing the time spent feeding, and minimizing energy expenditure by reducing the time spent moving. PMID:19655365

  14. Use-Wear Patterns on Wild Macaque Stone Tools Reveal Their Behavioural History

    PubMed Central

    Haslam, Michael; Gumert, Michael D.; Biro, Dora; Carvalho, Susana; Malaivijitnond, Suchinda

    2013-01-01

    Burmese long-tailed macaques (Macaca fascicularis aurea) are one of a limited number of wild animal species to use stone tools, with their tool use focused on pounding shelled marine invertebrates foraged from intertidal habitats. These monkeys exhibit two main styles of tool use: axe hammering of oysters, and pound hammering of unattached encased foods. In this study, we examined macroscopic use-wear patterns on a sample of 60 wild macaque stone tools from Piak Nam Yai Island, Thailand, that had been collected following behavioural observation, in order to (i) quantify the wear patterns in terms of the types and distribution of use-damage on the stones, and (ii) develop a Use-Action Index (UAI) to differentiate axe hammers from pound hammers by wear patterns alone. We used the intensity of crushing damage on differing surface zones of the stones, as well as stone weight, to produce a UAI that had 92% concordance when compared to how the stones had been used by macaques, as observed independently prior to collection. Our study is the first to demonstrate that quantitative archaeological use-wear techniques can accurately reconstruct the behavioural histories of non-human primate stone tools. PMID:23977365

  15. Use of enclosure space by captive lion-tailed macaques (Macaca silenus) housed in Indian zoos.

    PubMed

    Mallapur, Avanti; Waran, Natalie; Sinha, Anindya

    2005-01-01

    Captive nonhuman animals use enclosure space differentially. Enclosure features strongly influence this. This study recorded both the enclosure space used by 47 captive lion-tailed macaques housed in 13 zoos across India and the behavior of the macaques. The exhibition of abnormal behaviors, food-related behaviors, and social interactions correlated significantly with the use of the edge zone (the part of the enclosure closest to the visitor area). Animals housed in barren enclosures used the edge zone to a significantly greater percentage than did those housed in complex exhibits. Percentages of autogrooming, social interactions, and food-related behaviors significantly correlated with the use of the enrich zone. Space use studies assist in recognizing areas within the enclosure, which captive animals actively use. Conversely, the studies can identify areas infrequently used and show how to make maximum use of these enclosure areas. Further studies targeting both the increase in percentages of natural behaviors exhibited and use of the enrich zone used the current study on captive lion-tailed macaques for their design. PMID:16468946

  16. Evaluation of Functional NK Cell Responses in Vaccinated and SIV-Infected Rhesus Macaques

    PubMed Central

    Vargas-Inchaustegui, Diego A.; Ying, Olivia; Demberg, Thorsten; Robert-Guroff, Marjorie

    2016-01-01

    NK cells are crucial components of the innate immune system due to their capacity to exert rapid cytotoxic and immunomodulatory function in the absence of prior sensitization. NK cells can become activated by exposure to target cells and/or by cytokines produced by antigen-presenting cells. In this study, we examined the effects of a simian immunodeficiency virus (SIV) vaccine regimen and subsequent SIV infection on the cytotoxic and immunomodulatory functions of circulatory NK cells. While vaccination did not significantly impact the capacity of NK cells to kill MHC-devoid 721.221 target cells, SIV-infection led to a significant decrease in target cell killing. NK cells from uninfected macaques were responsive to a low dose (5 ng/ml) of IL-15 pre-activation, leading to significant increases in their cytotoxic potential, however, NK cells from SIV-infected macaques required a higher dose (50 ng/ml) of IL-15 pre-activation in order to significantly increase their cytotoxic potential. By contrast, no differences were observed in the capacity of NK cells from vaccinated and SIV-infected macaques to respond to IL-12 and IL-18. Similarly, NK cells both before and after infection exhibited equivalent responses to Fc-mediated activation. Collectively, our results show that early SIV-infection impairs the natural cytotoxic capacity of circulatory NK cells without affecting Fc-mediated or cytokine-producing function.

  17. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.

    PubMed

    Hessell, Ann J; Jaworski, J Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F; Hammond, Katherine B; Cheever, Tracy A; Barnette, Philip T; Legasse, Alfred W; Planer, Shannon; Stanton, Jeffrey J; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S; Axthelm, Michael K; Lewis, Anne; Hirsch, Vanessa M; Graham, Barney S; Mascola, John R; Sacha, Jonah B; Haigwood, Nancy L

    2016-04-01

    Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8(+) T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

  18. Fading Perceptual Resemblance: A Path for Rhesus Macaques (Macaca mulatta) to Conceptual Matching?

    PubMed Central

    Smith, J. David; Flemming, Timothy M.; Boomer, Joseph; Beran, Michael J.; Church, Barbara A.

    2013-01-01

    Cognitive, comparative, and developmental psychologists have long been intrigued by humans’ and animals’ capacity to respond to abstract relations like sameness and difference, because this capacity may underlie crucial aspects of cognition like analogical reasoning. Recently, this capacity has been explored in higher-order, relational matching-to-sample (RMTS) tasks in which humans and animals try to complete analogies of sameness and difference between disparate groups of items. The authors introduced a new paradigm to this area, by yoking the relational-matching cue to a perceptual-matching cue. Then, using established algorithms for shape distortion, the perceptual cue was weakened and eliminated. Humans’ RMTS performance easily transcended the elimination of perceptual support. In contrast, RMTS performance by six macaques faltered as they were weaned from perceptual support. No macaque showed evidence of mature RMTS performance, even given more than 260,000 training trials during which we tried to coax a relational-matching performance from them. It is an important species difference that macaques show so hesitant a response to conceptual relations when humans respond to them so effortlessly. It raises theoretical questions about the emergence of this crucial capacity during humans’ cognitive evolution and during humans’ cognitive development. PMID:24076537

  19. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever.

    PubMed

    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. PMID:21820469

  20. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever

    PubMed Central

    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

  1. Long-tailed macaques select mass of stone tools according to food type

    PubMed Central

    Gumert, Michael D.; Malaivijitnond, Suchinda

    2013-01-01

    Tool selection can affect the success of a tool-based feeding task, and thus tool-using animals should select appropriate tools when processing foods. We performed a field experiment on Piak Nam Yai Island in Laem Son National Park, Thailand, to test whether Burmese long-tailed macaques (Macaca fascicularis aurea) selected stone tools according to food type. We baited the island's shores with stone sets (‘tool tests’) in an effort to attract macaques to use stones presented in a quasi-experimental design. Tool tests were placed at 344 locations for 126 days over a 2 year period, with each set containing four stones of different mass (categories: X, 40–60 g; S, 90–100 g; M, 150–200 g; and L, 400–1000 g). Tool tests were checked when we could access them. The number of times each tool test was checked varied (1–32), for a total of 1950 checks. We also studied 375 non-experimental stone tools that were found at naturally occurring tool-use sites. Our data were not collected by direct observation, but by inspecting stones after use. We found an association between stone mass and food type. In the tool tests, we found S-stones were chosen most often for attached oysters, and L-stones were chosen most often for unattached foods. L-stones were almost always chosen for larger unattached foods (greater than 3 cm length), while for smaller unattached foods (less than or equal to 3 cm length) selection was less skewed to L-stones and more evenly distributed between the M- and L-stone categories. In the non-experimental study, we found that mass varied significantly across five food categories (range: 16–5166 g). We reveal more detail on macaque stone tool mass than previous studies, showing that macaques select differing stone masses across a variety of tool-processed foods. Our study is the first step in investigating the behavioural and cognitive mechanisms that macaques are using during tool selection. PMID:24101623

  2. DNA repair

    SciTech Connect

    Friedberg, E.C.; Hanawalt, P.C. )

    1988-01-01

    Topics covered in this book included: Eukaryote model systems for DNA repair study; Sensitive detection of DNA lesions and their repair; and Defined DNA sequence probes for analysis of mutagenesis and repair.

  3. Fatal Baylisascaris larva migrans in a colony of Japanese macaques kept by a safari-style zoo in Japan.

    PubMed

    Sato, Hiroshi; Une, Yumi; Kawakami, Shigehisa; Saito, Eriko; Kamiya, Haruo; Akao, Nobuaki; Furuoka, Hidefumi

    2005-06-01

    A colony of Japanese macaques (Macaca fuscata fuscata) kept by a safari-style zoo in Japan experienced 9 sporadic cases of fatal neurological diseases, such as epilepsy and posterior paralysis, during the 12 yr from 1989 to 2001. This macaque colony consisted of approximately 30 animals, on average, during this period, and the macaques shared their living space with II American black bears (Ursus americanus) harboring zoonotic roundworms (Baylisascaris transfuga). Close to this enclosure, a cote for 2-3 raccoons (Procyon lotor) was placed, and raw sewage from this cote ran into a shallow drain in the area for macaques and bears. However, fecal examinations in recent years did not detect the infection of raccoons with zoonotic roundworms (Baylisascaris procyonis). Postmortem histological examination of the latest 2 ill macaques detected multifocal malacia in the brain; 2 ascarid larvae of 60 microm maximum width were encapsulated in the cerebrum and lungs of 1 of the animals. To determine the causative ascarid species of the fatal larva migrans, we analyzed 2 additional encapsulated Baylisascaris larvae collected from formalin-fixed lungs by morphological and molecular approaches. This sporadic outbreak is the second record of Baylisascaris larva migrans in animals in Japan. PMID:16108577

  4. Postnatal development of the hippocampus in the Rhesus macaque (Macaca mulatta): a longitudinal magnetic resonance imaging study.

    PubMed

    Hunsaker, Michael R; Scott, Julia A; Bauman, Melissa D; Schumann, Cynthia M; Amaral, David G

    2014-07-01

    Nonhuman primates are widely used models to investigate the neural substrates of human behavior, including the development of higher cognitive and affective function. Due to their neuroanatomical and behavioral homologies with humans, the rhesus macaque monkey (Macaca mulatta) provides an excellent animal model in which to characterize the maturation of brain structures from birth through adulthood and into senescence. To evaluate hippocampal development in rhesus macaques, structural magnetic resonance imaging scans were obtained longitudinally at 9 time points between 1 week and 260 weeks (5 years) of age on 24 rhesus macaque monkeys (12 males, 12 females). In our sample, the hippocampus reaches 50% of its adult volume by 13 weeks of age and reaches an adult volume by 52 weeks in both males and females. The hippocampus appears to be slightly larger at 3 years than at 5 years of age. Male rhesus macaques have larger hippocampi than females from 8 weeks onward by approximately 5%. Interestingly, there was increased variability in hemispheric asymmetry for hippocampus volumes at younger ages than at later ages. These data provide a comprehensive evaluation of the longitudinal development of male and female rhesus macaque hippocampus across development from 1 week to 5 years of age. PMID:24648155

  5. Postnatal Development of the Hippocampus in the Rhesus Macaque (Macaca mulatta): A Longitudinal Magnetic Resonance Imaging Study

    PubMed Central

    Hunsaker, Michael R.; Scott, Julia A.; Bauman, Melissa D.; Schumann, Cynthia M.; Amaral, David G.

    2014-01-01

    Nonhuman primates are widely used models to investigate the neural substrates of human behavior, including the development of higher cognitive and affective function. Due to their neuroanatomical and behavioral homologies with humans, the rhesus macaque monkey (Macaca mulatta) provides an excellent animal model in which to characterize the maturation of brain structures from birth through adulthood and into senescence. To evaluate hippocampal development in rhesus macaques, structural magnetic resonance imaging scans were obtained longitudinally at 9 time points between 1 week and 260 weeks (5 years) of age on 24 rhesus macaque monkeys (12 male, 12 female). In our sample, the hippocampus reaches 50% of its adult volume by 13 weeks of age and reaches an adult volume by 52 weeks in both males and females. The hippocampus appears to be slightly larger at 3 years than at 5 years of age. Male rhesus macaques have larger hippocampi than females from 8 weeks onward by approximately 5%. Interestingly, there was increased variability in hemispheric asymmetry for hippocampus volumes at younger ages than at later ages. These data provide a comprehensive evaluation of the longitudinal development of male and female rhesus macaque hippocampus across development from 1 week to 5 years of age. PMID:24648155

  6. Social rank versus affiliation: Which is more closely related to leadership of group movements in Tibetan macaques (Macaca thibetana)?

    PubMed

    Wang, Xi; Sun, Lixing; Sheeran, Lori K; Sun, Bing-Hua; Zhang, Qi-Xin; Zhang, Dao; Xia, Dong-Po; Li, Jin-Hua

    2016-08-01

    Research on leadership is a critical step for understanding collective decision making. However, only 4 of the 22 extant macaque species have been examined for the impact of social rank and affiliation on the initiation of collective movement. It is far from clear whether such impact exists and, if so, how it works among other macaques. To answer these questions, we investigated free-ranging, Tibetan macaques' (Macaca thibetana) group departures from a provisioning area and tested two alternative hypotheses: personal versus distributed leadership. Personal leadership predicts that a single, highest ranking individual initiates the most group movements, whereas distributed leadership predicts that different members lead the group on different occasions and affiliative individuals have more initiations. We recorded how often and how successfully adults initiated group movements from a provisioning area into the forest, and related these variables to the duration of interindividual proximity and grooming time in the forest. All adults initiated group movements, but did so variably. Social rank was related neither to the number of successful initiations nor to the success ratio of initiations. By contrast, eigenvector centrality based on proximity relations was positively correlated with the number and ratio of successful initiations. Moreover, successful initiations were positively correlated with social grooming. Overall, Tibetan macaques showed a pattern of distributed leadership. Our study demonstrated the relationship between social affiliation and individual leadership in a macaque society. Am. J. Primatol. 78:816-824, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990010

  7. Variation in hair δ13C and δ15N values in long-tailed macaques (Macaca fascicularis) from Singapore

    USGS Publications Warehouse

    Schillaci, Michael A.; Castellini, J. Margaret; Stricker, Craig A.; Jones-Engel, Lisa; Lee, Benjamin P.Y.-H.

    2014-01-01

    Much of the primatology literature on stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) has focused on African and New World species, with comparatively little research published on Asian primates. Here we present hair δ13C and δ15N isotope values for a sample of 33 long-tailed macaques from Singapore. We evaluate the suggestion by a previous researcher that forest degradation and biodiversity loss in Singapore have led to a decline in macaque trophic level. The results of our analysis indicated significant spatial variability in δ13C but not δ15N. The range of variation in δ13C was consistent with a diet based on C3 resources, with one group exhibiting low values consistent with a closed canopy environment. Relative to other macaque species from Europe and Asia, the macaques from Singapore exhibited a low mean δ13C value but mid-range mean δ15N value. Previous research suggesting a decline in macaque trophic level is not supported by the results of our study.

  8. Suprazero Cooling Rate, Rather Than Freezing Rate, Determines Post Thaw Quality Of Rhesus Macaque Sperm

    PubMed Central

    Martorana, Kelly; Klooster, Katie; Meyers, Stuart

    2013-01-01

    Sperm become most sensitive to cold shock when cooled from 37ºC to 5ºC at rates that are too fast or too slow; cold shock increases the susceptibility to oxidative damage due to its influence on reactive oxygen species (ROS) production ([1]. ROS are significant stress factors that are generated during cooling and low temperature storage, and may be a main cause of decreased motility and fertility upon warming. ROS have been shown to change cellular function through the disruption of the sperm plasma membrane and through damage to proteins and DNA. The objective of this study was to determine which cryopreservation rates result in the lowest degree of oxidative damage and greatest sperm quality. In the rhesus model it has not been determined whether suprazero cooling or subzero freezing rates causes a significant amount of ROS damage to sperm. Semen samples were collected from male rhesus macaques, washed, and resuspended in TEST-yolk cryopreservation buffer to 100 x 106 sperm/mL. Sperm were frozen in 0.5mL straws at four different combinations of suprazero and subzero rates. Three different suprazero rates were used between 22ºC and 0ºC: 0.5ºC/min (Slow), 45ºC/min (Medium), and 93ºC/min (Fast). These suprazero rates were used in combination with two different subzero rates for temperatures 0ºC to −110ºC: 42ºC/min (Medium) and 87ºC/min (Fast). The different freezing groups were as follows: Slow-Med (SM), Slow-Fast (SF), Med-Med (MM), and Fast-Fast (FF). Flow cytometry was used to detect lipid peroxidation (LPO), a result of ROS generation. Motility was evaluated using a computer assisted sperm motion analyzer. The MM and FF treated sperm had less viable (P < 0.0001) and motile sperm (P < 0.001) than the SM, SF, or fresh sperm. Sperm exposed to MM and FF treatments demonstrated significantly higher oxidative damage than SM, SF, or fresh sperm (P < 0.05). The SM and SF treated sperm showed decreased motility, membrane integrity, and LPO compared to fresh

  9. Elucidating population histories using genomic DNA sequences.

    PubMed

    Vigilant, Linda

    2009-04-01

    In 1993, Cliff Jolly suggested that rather than debating species definitions and classifications, energy would be better spent investigating multidimensional patterns of variation and gene flow among populations. Until now, however, genetic studies of wild primate populations have been limited to very small portions of the genome. Access to complete genome sequences of humans, chimpanzees, macaques, and other primates makes it possible to design studies surveying substantial amounts of DNA sequence variation at multiple genetic loci in representatives of closely related but distinct wild primate populations. Such data can be analyzed with new approaches that estimate not only when populations diverged but also the relative amounts and directions of subsequent gene flow. These analyses will reemphasize the difficulty of achieving consistent species and subspecies definitions by revealing the extent of variation in the amount and duration of gene flow accompanying population divergences. PMID:19817223

  10. 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.

    PubMed

    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. PMID:20156101

  11. 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

    PubMed Central

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

    2010-01-01

    Abstract 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. PMID:20156101

  12. Food resources, distribution and seasonal variations in ranging in lion-tailed macaques, Macaca silenus in the Western Ghats, India.

    PubMed

    Erinjery, Joseph J; Kavana, T S; Singh, Mewa

    2015-01-01

    The distribution and availability of food was examined to see how it influenced ranging patterns and sleeping site selection in a group of lion-tailed macaques. The home range and core area were 130.48 ha (95% kernel) and 26.68 ha (50% kernel) respectively. The lion-tailed macaques had a longer day range, had a greater number of sleeping sites and used more core areas in the summer as compared to the monsoon and the post-monsoon seasons. The ranging patterns and sleeping site use were influenced by the major food resources used in a particular season. The ranging was mainly influenced by Artocarpus heterophyllus in monsoon, Cullenia exarillata and Toona ciliata in post- monsoon, and Artocarpus heterophyllus and Ficus amplissima in summer. The distribution of these four plant species is, therefore, critical to ranging, and thus to conservation of the lion-tailed macaque. PMID:25217980

  13. Use of Femoral Head and Neck Ostectomy and Physical Therapy to Manage Osteoarthritis in a Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Uchihashi, Mayu; Hampel, Joseph A; Nemzek, Jean A; Saccone, Phillip A; Eaton, Kathryn A; Nowland, Megan H

    2015-01-01

    Osteoarthritis is associated with pain and immobility in both humans and animals. However, available resources for osteoarthritis management in captive NHP are limited. This case report describes a novel management strategy for a 10-y-old male macaque with unilateral hindlimb lameness, prominent muscle wasting, and severely limited range of motion. Radiographs of the affected limb showed lytic lesions of the femoral head. To relieve pain and improve mobility, femoral head and neck ostectomy (FHO) was performed, and multiple pharmacotherapies were initiated. The macaque also received a unique method of physical therapy that required no sedation, acted as enrichment, and was implemented by using a conventional caging system. The response to therapy was monitored by measuring thigh circumference in the operated and nonoperated limbs, which demonstrated improvement in both legs. The unique physical therapy in conjunction with surgery and pharmacotherapy benefited the macaque with osteoarthritis by reducing discomfort and improving mobility. PMID:26141450

  14. Seasonal variations in the activity budget of Japanese macaques in the coniferous forest of Yakushima: effects of food and temperature.

    PubMed

    Hanya, Goro

    2004-07-01

    Seasonal variations in the activity budget of Japanese macaques in the coniferous forest of Yakushima were studied over the course of 1 year. On an annual basis, they spent 38% of the daytime feeding, 16% traveling, 14% in social interactions, and 32% engaged in resting. The effects of temperature and food-related factors (i.e., food distribution, feeding speed, and food abundance) on the seasonal variations of activity budget were examined by stepwise multiple regression analysis. When the temperature was low, the macaques decreased traveling and feeding time, in accordance with the prediction that endothermal animals save energy under severe thermoregulatory cost. When the feeding speed of available foods was slow, they spent more time feeding. When high-quality foods were abundant, they decreased feeding time. These macaques did not respond to fluctuations in food distribution. The present results indicate the importance of temperature, in addition to food-related factors, as a determinant of activity budgets. PMID:15258960

  15. Evaluation of pigtail macaques as a model for the effects of copper intrauterine devices (IUDs) on HIV infection

    PubMed Central

    Engel, Robyn M.; Morris, Monica; Henning, Tara; Ritter, Jana M.; Jones, Tara L.; Dietz, Sharon; Ayers, Jessica; Vishwanathan, Sundaram A.; Jenkins, Leecresia; Zaki, Sherif; Wildemeersch, Dirk; Garber, David; Powell, Nathaniel; Hendry, R. Michael; McNicholl, Janet; Kersh, Ellen N.

    2014-01-01

    Background Long-acting, hormonal contraception may increase HIV risk. Copper intrauterine devices (IUDs) could serve as non-hormonal alternatives. We pilot a pigtail macaque model for evaluating HIV susceptibility factors during copper IUD use. Methods Frameless and flexible GyneFix® copper IUDs were surgically implanted into three SHIVSF162p3-positive macaques via hysterotomy and monitored for up to four months. Four macaques served as no-IUD controls. Results All animals retained the devices without complications. No consistent change in vaginal viral RNA or inflammatory cytokines was seen. Two animals had altered menstrual cycles and experienced marked thinning of vaginal epithelium after IUD insertion. Histological examination of uterine tissue at necropsy revealed endometrial ulceration and lymphocytic inflammation with glandular loss at sites of direct IUD contact. Conclusions Although the need for insertion surgery could limit its usefulness, this model will allow studies on copper IUDs and SHIV shedding, disease progression, and HIV susceptibility factors. PMID:24372425

  16. Capture and Transfer of Simian Immunodeficiency Virus by Macaque Dendritic Cells Is Enhanced by DC-SIGN

    PubMed Central

    Yu Kimata, Monica T.; Cella, Marina; Biggins, Julia E.; Rorex, Colin; White, Robert; Hicks, Sarah; Wilson, Joelle M.; Patel, Parul G.; Allan, Jonathan S.; Colonna, Marco; Kimata, Jason T.

    2002-01-01

    Dendritic cells (DCs) are among the first cells encountered by human and simian immunodeficiency virus (HIV and SIV) following mucosal infection. Because these cells efficiently capture and transmit virus to T cells, they may play a major role in mediating HIV and SIV infection. Recently, a C-type lectin protein present on DCs, DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), was shown to efficiently bind and present HIV and SIV to CD4+, coreceptor-positive cells in trans. However, the significance of DC-SIGN for virus transmission and pathogenesis in vivo remains unclear. Because SIV infection of macaques may represent the best model to study the importance of DC-SIGN in HIV infection, we cloned and characterized pig-tailed macaque DC-SIGN and generated monoclonal antibodies (MAbs) against it. We demonstrate that, like human DC-SIGN, pig-tailed macaque DC-SIGN (ptDC-SIGN) is expressed on DCs and macrophages but not on monocytes, T cells, or B cells. Moderate levels of ptDC-SIGN expression were detected on the surface of DCs, and low-level expression was found on macrophages. Additionally, we show that ptDC-SIGN efficiently binds and transmits replication-competent SIVmne variants to CD4+, coreceptor-positive cells. Moreover, transmission of virus between pig-tailed macaque DCs and CD4+ T cells is largely ptDC-SIGN dependent. Interestingly, MAbs directed against ptDC-SIGN vary in the capacity to block transmission of different SIVmne variants. These data demonstrate that ptDC-SIGN plays a central role in transmitting virus from macaque DCs to T cells, and they suggest that SIVmne variants may differ in their interactions with ptDC-SIGN. Thus, SIVmne infection of pig-tailed macaques may provide an opportunity to investigate the significance of DC-SIGN in primate lentiviral infections. PMID:12414925

  17. Facial musculature in the rhesus macaque (Macaca mulatta): evolutionary and functional contexts with comparisons to chimpanzees and humans

    PubMed Central

    Burrows, Anne M; Waller, Bridget M; Parr, Lisa A

    2009-01-01

    Facial expression is a common mode of visual communication in mammals but especially so in primates. Rhesus macaques (Macaca mulatta) have a well-documented facial expression repertoire that is controlled by the facial/mimetic musculature as in all mammals. However, little is known about the musculature itself and how it compares with those of other primates. Here we present a detailed description of the facial musculature in rhesus macaques in behavioral, evolutionary and comparative contexts. Formalin-fixed faces from six adult male specimens were dissected using a novel technique. The morphology, attachments, three-dimensional relationships and variability of muscles were noted and compared with chimpanzees (Pan troglodytes) and with humans. The results showed that there was a greater number of facial muscles in rhesus macaques than previously described (24 muscles), including variably present (and previously unmentioned) zygomaticus minor, levator labii superioris alaeque nasi, depressor septi, anterior auricularis, inferior auricularis and depressor supercilii muscles. The facial muscles of the rhesus macaque were very similar to those in chimpanzees and humans but M. mulatta did not possess a risorius muscle. These results support previous studies that describe a highly graded and intricate facial expression repertoire in rhesus macaques. Furthermore, these results indicate that phylogenetic position is not the primary factor governing the structure of primate facial musculature and that other factors such as social behavior are probably more important. The results from the present study may provide valuable input to both biomedical studies that use rhesus macaques as a model for human disease and disorder that includes assessment of facial movement and studies into the evolution of primate societies and communication. PMID:19563473

  18. Distribution of Vesicular Glutamate Transporter 2 (VGluT2) in the Primary Visual Cortex of the Macaque and Human

    PubMed Central

    Garcia-Marin, Virginia; Ahmed, Tunazzina H.; Afzal, Yasmeen C.; Hawken, Michael J.

    2014-01-01

    The majority of thalamic terminals in V1 arise from lateral geniculate nucleus (LGN) afferents. Thalamic afferent terminals are preferentially labeled by an isoform of the vesicular glutamate transporter, VGluT2. The goal of our study was to determine the distribution of VGluT2-ir puncta in macaque and human visual cortex. First, we investigated the distribution of VGluT2-ir puncta in all layers of macaque monkey primary visual cortex (V1), and found a very close correspondence between the known distribution of LGN afferents from previous studies and the distribution of VGluT2-immunoreactive (-ir) puncta. There was also a close correspondence between cytochrome oxidase density and VGluT2-ir puncta distribution. After validating the correspondence in macaque, we made a comparative study in human V1. In many aspects, the distribution of VGluT2-ir puncta in human was qualitatively similar to that of the macaque: high densities in layer 4C, patches of VGluT2-ir puncta in the supragranular layer (2/3), lower but clear distribution in layers 1 and 6, and very few puncta in layers 5 and 4B. However, there were also important differences between macaques and humans. In layer 4A of human, there was a sparse distribution of VGluT2-ir puncta, whereas in macaque, there was a dense distribution with the characteristic honeycomb organization. The results suggest important changes in the pattern of cortical VGluT2 immunostaining that may be related to evolutionary differences in the cortical organization of LGN afferents between Old World monkeys and humans. PMID:22684983

  19. PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS

    PubMed Central

    Venneti, Sriram; Lopresti, Brian J.; Wang, Guoji; Bissel, Stephanie J.; Mathis, Chester A.; Meltzer, Carolyn C.; Boada, Fernando; Capuano, Saverio; Kress, Geraldine J.; Davis, Denise K.; Ruszkiewicz, James; Reynolds, Ian J.; Murphey-Corb, Michael; Trichel, Anita M.; Wisniewski, Stephen R.; Wiley, Clayton A.

    2004-01-01

    HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques result in encephalitis in approximately one-quarter of infected individuals and is characterized by infiltration of the brain with infected and activated macrophages. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (PK11195) is a ligand specific for the peripheral benzodiazepine receptor abundant on macrophages and is expressed in low levels in the noninfected brain. We hypothesized that positron-emission tomography (PET) with the carbon-11–labeled, R-enantiomer form of PK11195 ([11C](R)-PK11195) could image brain macrophages and hence the development of encephalitis in vivo. [11C](R)-PK11195 binding was assessed in the brain using PET in 11 SIV infected macaques, six of which showed increased binding in vivo. Postmortem examination of the brain in these six macaques demonstrated encephalitis, while macaques that did not show an increase in [11C](R)-PK11195 binding did not develop SIV encephalitis. Brain tissue from SIV encephalitic macaques also showed increased [3H](R)-PK11195 binding compared with binding in nonencephalitic macaques. Increased PK11195 binding in vivo and in postmortem brain tissue correlated with abundance of macrophages but not astrocytes. Our results suggest that PET [11C](R)-PK11195 imaging can detect the presence of macrophages in SIV encephalitis in vivo and may be useful to predict the development of HIV encephalitis and in studies of the pathogenesis and treatment of HIV dementia. PMID:15057304

  20. Niche partitioning between sympatric rhesus macaques and Yunnan snub-nosed monkeys at Baimaxueshan Nature Reserve, China.

    PubMed

    Grueter, Cyril C; Li, Da-Yong; Feng, Shun-Kai; Ren, Bao-Ping

    2010-10-01

    Here we provide a preliminary assessment of dietary and habitat requirements of two sympatric primate taxa, a "simple-stomached" and "complex-stomached" species (Rhinopithecus bieti Colobinae vs. Macaca mulatta Cercopithecinae), as a basis for illuminating how the two coexist. Of ca. 22 plant food species consumed by the macaques, at least 16 were also eaten by the snub-nosed monkeys. Both species showed a preference for fruits. While the snub-nosed monkeys did not utilize any resources associated with human communities, rhesus macaques did occasionally raid agricultural crops. The mean elevation of the snub-nosed monkey group was 3,218 m, while the mean elevation of the macaque group was 2,995 m. Macaques were also spotted on meadows whereas snub-nosed monkeys evidently avoided these. For both species, mixed deciduous broadleaf/conifer forest was the most frequently used ecotype, but whereas evergreen broadleaf forest (Cyclobalanopsis community) accounted for only 3% of the location records of the snub-nosed monkeys, it accounted for 36% of the location records of the macaques. Groups of the two species usually kept a considerable spatial distance from one another (mean 2.4 km). One close encounter and confrontation between groups of the two species resulted in the macaque group moving away. Our findings suggest that the coexistence of the two taxa is facilitated via differential macrohabitat use and spatial avoidance. Although divergent habitat-use strategies may reflect interspecific competition, they may also merely reflect different physiological or ecological requirements. PMID:20979254

  1. SHIV-162P3 Infection of Rhesus Macaques Given Maraviroc Gel Vaginally Does Not Involve Resistant Viruses

    PubMed Central

    Tsibris, Athe M. N.; Pal, Urboshi; Schure, Allison L.; Veazey, Ronald S.; Kunstman, Kevin J.; Henrich, Timothy J.; Klasse, P. J.; Wolinsky, Steven M.; Kuritzkes, Daniel R.; Moore, John P.

    2011-01-01

    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 [IC50] 1.87 nM) and virus isolated from the three MVC-treated macaques (MVC IC50 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. PMID:22164225

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

    PubMed

    Tsibris, Athe M N; Pal, Urboshi; Schure, Allison L; Veazey, Ronald S; Kunstman, Kevin J; Henrich, Timothy J; Klasse, P J; Wolinsky, Steven M; Kuritzkes, Daniel R; Moore, John P

    2011-01-01

    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. PMID:22164225

  3. Muscarinic acetylcholine receptors are expressed by most parvalbumin-immunoreactive neurons in area MT of the macaque

    PubMed Central

    Disney, Anita A; Alasady, Hussein A; Reynolds, John H

    2014-01-01

    Background In the mammalian neocortex, cells that express parvalbumin (PV neurons) comprise a dominant class of inhibitory neuron that substantially overlaps with the fast/narrow-spiking physiological phenotype. Attention has pronounced effects on narrow-spiking neurons in the extrastriate cortex of macaques, and more consistently so than on their broad-spiking neighbors. Cortical neuromodulation by acetylcholine (ACh) is a candidate mechanism for aspects of attention and in the primary visual cortex (V1) of the macaque, receptors for ACh (AChRs) are strongly expressed by inhibitory neurons. In particular, most PV neurons in macaque V1 express m1 muscarinic AChRs and exogenously applied ACh can cause the release of γ-aminobutyric acid. In contrast, few PV neurons in rat V1 express m1 AChRs. While this could be a species difference, it has also been argued that macaque V1 is anatomically unique when compared with other cortical areas in macaques. Aims The aim of this study was to better understand the extent to which V1 offers a suitable model circuit for cholinergic anatomy in the macaque occipital lobe, and to explore cholinergic modulation as a biological basis for the changes in circuit behavior seen with attention. Materials and methods We compared expression of m1 AChRs by PV neurons between area V1 and the middle temporal visual area (MT) in macaque monkeys using dual-immunofluorescence confocal microscopy. Results and conclusion We find that, as in V1, most PV neurons in MT express m1 AChRs but, unlike in V1, it appears that so do most excitatory neurons. This provides support for V1 as a model of cholinergic modulation of inhibition in macaque visual cortex, but not of cholinergic modulation of visual cortical circuits in general. We also propose that ACh acting via m1 AChRs is a candidate underlying mechanism for the strong effects of attention on narrow-spiking neurons observed in behaving animals. PMID:24944872

  4. A Newly-Identified Polymorphism in Rhesus Macaque Complement Factor H Modulates Binding Affinity for Meningococcal FHbp

    PubMed Central

    Konar, Monica; Beernink, Peter T.; Granoff, Dan M.

    2015-01-01

    Background Two meningococcal serogroup B vaccines contain Factor H binding protein (FHbp). Binding of Factor H (FH) to FHbp was thought to be specific for human or chimpanzee FH. However, in a previous study an amino acid polymorphism in rhesus macaque FH domain 6, tyrosine at position 352 (Y352) was associated with high binding to FHbp, whereas histidine at position 352 (H352) was associated with low binding. Methods and Results Here we report that a second FH polymorphism at position 360 also affects macaque FH binding. Of 43 macaques, 11 had high FH binding and 32 had low binding. As in our previous study, all 11 animals with high binding had Y352, and 24 with low binding had H352. However the remaining eight with low FH binding had Y352, which was predicted to yield high binding. All eight had S360 instead of P360. Thus, three allelic variants at positions 352 and 360 affect macaque FH binding to FHbp: HP (low), YS (low), and YP (high). We measured binding affinity of each FH sequence type to FHbp by surface plasmon resonance. Two animals with high binding types (YS/YP and HP/YP) had dissociation constants (KD) of 10.4 and 18.2 nM, respectively, which were similar to human FH (19.8 nM). Two macaques with low binding (HP/HP and HP/YS) had KD values approximately five-fold higher (100.3 and 99.5 nM, respectively). A third macaque with low binding (YS/YS) had a KD value too high to be measured. Conclusions Macaques have at least three allelic variants encoding FH with different affinities for FHbp (five genotypic combinations of these variants). Since in previous studies binding of FH to FHbp vaccines decreased protective antibody responses, our data will aid in selection of macaques with FH binding that is similar to humans for further investigation of FHbp vaccine immunogenicity. PMID:26285122

  5. Reduced representation genome sequencing suggests low diversity on the sex chromosomes of tonkean macaque monkeys.

    PubMed

    Evans, Ben J; Zeng, Kai; Esselstyn, Jacob A; Charlesworth, Brian; Melnick, Don J

    2014-09-01

    In species with separate sexes, social systems can differ in the relative variances of male versus female reproductive success. Papionin monkeys (macaques, mangabeys, mandrills, drills, baboons, and geladas) exhibit hallmarks of a high variance in male reproductive success, including a female-biased adult sex ratio and prominent sexual dimorphism. To explore the potential genomic consequences of such sex differences, we used a reduced representation genome sequencing approach to quantifying polymorphism at sites on autosomes and sex chromosomes of the tonkean macaque (Macaca tonkeana), a species endemic to the Indonesian island of Sulawesi. The ratio of nucleotide diversity of the X chromosome to that of the autosomes was less than the value (0.75) expected with a 1:1 sex ratio and no sex differences in the variance in reproductive success. However, the significance of this difference was dependent on which outgroup was used to standardize diversity levels. Using a new model that includes the effects of varying population size, sex differences in mutation rate between the autosomes and X chromosome, and GC-biased gene conversion (gBGC) or selection on GC content, we found that the maximum-likelihood estimate of the ratio of effective population size of the X chromosome to that of the autosomes was 0.68, which did not differ significantly from 0.75. We also found evidence for 1) a higher level of purifying selection on genic than nongenic regions, 2) gBGC or natural selection favoring increased GC content, 3) a dynamic demography characterized by population growth and contraction, 4) a higher mutation rate in males than females, and 5) a very low polymorphism level on the Y chromosome. These findings shed light on the population genomic consequences of sex differences in the variance in reproductive success, which appear to be modest in the tonkean macaque; they also suggest the occurrence of hitchhiking on the Y chromosome. PMID:24987106

  6. Double Virus Vector Infection to the Prefrontal Network of the Macaque Brain

    PubMed Central

    Tanaka, Shingo; Koizumi, Masashi; Kikusui, Takefumi; Ichihara, Nobutsune; Kato, Shigeki; Kobayashi, Kazuto; Sakagami, Masamichi

    2015-01-01

    To precisely understand how higher cognitive functions are implemented in the prefrontal network of the brain, optogenetic and pharmacogenetic methods to manipulate the signal transmission of a specific neural pathway are required. The application of these methods, however, has been mostly restricted to animals other than the primate, which is the best animal model to investigate higher cognitive functions. In this study, we used a double viral vector infection method in the prefrontal network of the macaque brain. This enabled us to express specific constructs into specific neurons that constitute a target pathway without use of germline genetic manipulation. The double-infection technique utilizes two different virus vectors in two monosynaptically connected areas. One is a vector which can locally infect cell bodies of projection neurons (local vector) and the other can retrogradely infect from axon terminals of the same projection neurons (retrograde vector). The retrograde vector incorporates the sequence which encodes Cre recombinase and the local vector incorporates the “Cre-On” FLEX double-floxed sequence in which a reporter protein (mCherry) was encoded. mCherry thus came to be expressed only in doubly infected projection neurons with these vectors. We applied this method to two macaque monkeys and targeted two different pathways in the prefrontal network: The pathway from the lateral prefrontal cortex to the caudate nucleus and the pathway from the lateral prefrontal cortex to the frontal eye field. As a result, mCherry-positive cells were observed in the lateral prefrontal cortex in all of the four injected hemispheres, indicating that the double virus vector transfection is workable in the prefrontal network of the macaque brain. PMID:26193102

  7. Whole-scalp EEG mapping of somatosensory evoked potentials in macaque monkeys.

    PubMed

    Gindrat, Anne-Dominique; Quairiaux, Charles; Britz, Juliane; Brunet, Denis; Lanz, Florian; Michel, Christoph M; Rouiller, Eric M

    2015-07-01

    High-density scalp EEG recordings are widely used to study whole-brain neuronal networks in humans non-invasively. Here, we validate EEG mapping of somatosensory evoked potentials (SSEPs) in macaque monkeys (Macaca fascicularis) for the long-term investigation of large-scale neuronal networks and their reorganisation after lesions requiring a craniotomy. SSEPs were acquired from 33 scalp electrodes in five adult anaesthetized animals after electrical median or tibial nerve stimulation. SSEP scalp potential maps were identified by cluster analysis and identified in individual recordings. A distributed, linear inverse solution was used to estimate the intracortical sources of the scalp potentials. SSEPs were characterised by a sequence of components with unique scalp topographies. Source analysis confirmed that median nerve SSEP component maps were in accordance with the somatotopic organisation of the sensorimotor cortex. Most importantly, SSEP recordings were stable both intra- and interindividually. We aim to apply this method to the study of recovery and reorganisation of large-scale neuronal networks following a focal cortical lesion requiring a craniotomy. As a prerequisite, the present study demonstrated that a 300-mm(2) unilateral craniotomy over the sensorimotor cortex necessary to induce a cortical lesion, followed by bone flap repositioning, suture and gap plugging with calcium phosphate cement, did not induce major distortions of the SSEPs. In conclusion, SSEPs can be successfully and reproducibly recorded from high-density EEG caps in macaque monkeys before and after a craniotomy, opening new possibilities for the long-term follow-up of the cortical reorganisation of large-scale networks in macaque monkeys after a cortical lesion. PMID:24791748

  8. Tenofovir diphosphate concentrations and prophylactic effect in a macaque model of rectal simian HIV transmission

    PubMed Central

    Anderson, Peter L.; Glidden, David V.; Bushman, Lane R.; Heneine, Walid; García-Lerma, J. Gerardo

    2014-01-01

    Objectives This study evaluated the relationship between intracellular tenofovir diphosphate concentrations in peripheral blood mononuclear cells and prophylactic efficacy in a macaque model for HIV pre-exposure prophylaxis (PrEP). Methods Macaques were challenged with simian HIV (SHIV) via rectal inoculation once weekly for up to 14 weeks. A control group (n = 34) received no drug, a second group (n = 6) received oral tenofovir disoproxil fumarate/emtricitabine 3 days before each virus challenge and a third group (n = 6) received the same dosing plus another dose 2 h after virus challenge. PBMCs were collected just before each weekly virus challenge. The relationship between tenofovir diphosphate in PBMCs and prophylactic efficacy was assessed with a Cox proportional hazards model. Results The percentages of animals infected in the control, one-dose and two-dose groups were 97, 83 and 17, respectively. The mean (SD) steady-state tenofovir diphosphate concentration (fmol/106 cells) was 15.8 (7.6) in the one-dose group and 30.7 (10.1) in the two-dose group. Each 5 fmol tenofovir diphosphate/106 cells was associated with a 40% (95% CI 17%–56%) reduction in risk of SHIV acquisition, P = 0.002. The tenofovir diphosphate concentration associated with a 90% reduction in risk (EC90) was 22.6 fmol/106 cells (95% CI 13.8–60.8). Conclusions The prophylactic EC90 for tenofovir diphosphate identified in macaques exposed rectally compares well with the EC90 previously identified in men who have sex with men (MSM; 16 fmol/106 cells, 95% CI 3–28). These results highlight the relevance of this model to inform human PrEP studies of oral tenofovir disoproxil fumarate/emtricitabine for MSM. PMID:24862094

  9. Abdominal Lipomatosis with Secondary Self-Strangulation of Masses in an Adult Rhesus Macaque (Macaca mulatta)

    PubMed Central

    Chum, Helen H; Long, C Tyler; McKeon, Gabriel P; Chang, Angela G; Luong, Richard H; Albertelli, Megan A

    2014-01-01

    An 10-y-old, intact male rhesus macaque (Macaca mulatta) presented for bilateral scrotal swelling and a distended abdomen. A soft mass in the left upper quadrant of the abdomen was palpated. A barium study did not reveal any gastrointestinal abnormalities. Exploratory laparotomy revealed a large (1.25 kg, 15.0 × 13.0 × 9.5 cm), red and tan, soft, circumscribed, spherical mass within the greater omentum and 10 to 20 smaller (diameter, 1 to 4 cm), soft to firm masses in the mesentery and greater omentum. The resected mass was a self-strangulating abdominal lipoma, a pedunculated neoplasm composed of white adipocytes arising from peritoneal adipose tissue undergoing secondary coagulation necrosis after strangulation of the blood supply due to twisting of the mass around the peduncle. The smaller masses were histologically consistent with simple or self-strangulating pedunculated abdominal lipomas. The macaque presented again 9 mo later with a firm, 5.0-cm mass in the midabdomen, with intestinal displacement visible on radiographs. Given this animal's medical history and questionable prognosis, euthanasia was elected. Necropsy revealed numerous, multifocal to coalescing, 1.0- to 15.0-cm, pale tan to yellow, circumscribed, soft to firm, spherical to ellipsoid, pedunculated masses that were scattered throughout the mesentery, greater omentum, lesser omentum, and serosal surfaces of the gastrointestinal tract. All of the masses were pedunculated abdominal lipomas, and most demonstrated coagulation necrosis due to self-strangulation of the blood supply. To our knowledge, this report is the first to describe abdominal lipomatosis with secondary self-strangulation of masses in a rhesus macaque. PMID:25402181

  10. Abdominal lipomatosis with secondary self-strangulation of masses in an adult rhesus macaque (Macaca mulatta).

    PubMed

    Chum, Helen H; Long, C Tyler; McKeon, Gabriel P; Chang, Angela G; Luong, Richard H; Albertelli, Megan A

    2014-10-01

    An 10-y-old, intact male rhesus macaque (Macaca mulatta) presented for bilateral scrotal swelling and a distended abdomen. A soft mass in the left upper quadrant of the abdomen was palpated. A barium study did not reveal any gastrointestinal abnormalities. Exploratory laparotomy revealed a large (1.25 kg, 15.0 × 13.0 × 9.5 cm), red and tan, soft, circumscribed, spherical mass within the greater omentum and 10 to 20 smaller (diameter, 1 to 4 cm), soft to firm masses in the mesentery and greater omentum. The resected mass was a self-strangulating abdominal lipoma, a pedunculated neoplasm composed of white adipocytes arising from peritoneal adipose tissue undergoing secondary coagulation necrosis after strangulation of the blood supply due to twisting of the mass around the peduncle. The smaller masses were histologically consistent with simple or self-strangulating pedunculated abdominal lipomas. The macaque presented again 9 mo later with a firm, 5.0-cm mass in the midabdomen, with intestinal displacement visible on radiographs. Given this animal's medical history and questionable prognosis, euthanasia was elected. Necropsy revealed numerous, multifocal to coalescing, 1.0- to 15.0-cm, pale tan to yellow, circumscribed, soft to firm, spherical to ellipsoid, pedunculated masses that were scattered throughout the mesentery, greater omentum, lesser omentum, and serosal surfaces of the gastrointestinal tract. All of the masses were pedunculated abdominal lipomas, and most demonstrated coagulation necrosis due to self-strangulation of the blood supply. To our knowledge, this report is the first to describe abdominal lipomatosis with secondary self-strangulation of masses in a rhesus macaque. PMID:25402181

  11. Effects of Age and Estradiol on Gene Expression in the Rhesus Macaque Hypothalamus

    PubMed Central

    Eghlidi, Dominique H.; Urbanski, Henryk F.

    2015-01-01

    Background The hypothalamus plays a key role in mediating the effects of estrogen on many physiological functions, including reproduction, metabolism, and thermoregulation. We have previously observed marked estrogen-dependent gene expression changes within the hypothalamus of rhesus macaques during aging, especially in the KNDy neurons of the arcuate-median eminence (ARC-ME) that produce kisspeptin, neurokinin B, and dynorphin A. Little is known, however, about the mechanisms involved in mediating the feedback from estrogen onto these neurons. Methods We used real-time PCR to profile age and estrogen-dependent gene expression changes in the rhesus macaque hypothalamus. Our focus was on genes that encode steroid receptors (ESR1, ESR2, PGR, and AR), and on enzymes that contribute to the local synthesis of 17β-estradiol (E2) (STS, HSD3B1/2, HSD17B5, and CYP19A). In addition, we used RT2 Profiler™ PCR Arrays to profile a larger set of genes that are integral to hypothalamic function. Results KISS1, KISS1R, TAC3, NPY2R mRNA levels increased in surgically menopausal (ovariectomized) old females, relative to age-matched ovariectomized animals that received E2 hormone therapy. In contrast, PGR, HSD17B, GNRH2, SLC6A3, KISS-1, TAC3, and NPY2R mRNA levels increased after E2 supplementation. Conclusion The rhesus macaque ARC-ME expresses many genes that are responsive to changes in circulating estrogen levels, even during old age, and these may contribute to the cause of normal and pathophysiological changes that occur during menopause. PMID:25765287

  12. Lack of Prophylactic Efficacy of Oral Maraviroc in Macaques despite High Drug Concentrations in Rectal Tissues

    PubMed Central

    Massud, Ivana; Aung, Wutyi; Martin, Amy; Bachman, Shanon; Mitchell, James; Aubert, Rachael; Solomon Tsegaye, Theodros; Kersh, Ellen; Pau, Chou-Pong; Heneine, Walid

    2013-01-01

    Maraviroc (MVC) is a potent CCR5 coreceptor antagonist that is in clinical testing for daily oral pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model consisting of weekly SHIV162p3 exposures to evaluate the efficacy of oral MVC in preventing rectal SHIV transmission. MVC dosing was informed by the pharmacokinetic profile seen in blood and rectal tissues and consisted of a human-equivalent dose given 24 h before virus exposure, followed by a booster postexposure dose. In rectal secretions, MVC peaked at 24 h (10,242 ng/ml) with concentrations at 48 h that were about 40 times those required to block SHIV infection of peripheral blood mononuclear cells (PBMCs) in vitro. Median MVC concentrations in rectal tissues at 24 h (1,404 ng/g) were 30 and 10 times those achieved in vaginal or lymphoid tissues, respectively. MVC significantly reduced macrophage inflammatory protein 1β-induced CCR5 internalization in rectal mononuclear cells, an indication of efficient binding to CCR5 in rectal lymphocytes. The half-life of CCR5-bound MVC in PBMCs was 2.6 days. Despite this favorable profile, 5/6 treated macaques were infected during five rectal SHIV exposures as were 3/4 controls. MVC treatment was associated with a significant increase in the percentage of CD3+/CCR5+ cells in blood. We show that high and durable MVC concentrations in rectal tissues are not sufficient to prevent SHIV infection in macaques. The increases in CD3+/CCR5+ cells seen during MVC treatment point to unique immunological effects of CCR5 inhibition by MVC. The implications of these immunological effects on PrEP with MVC require further evaluation. PMID:23740994

  13. No-scalpel vasectomy by electrocauterization in free range rhesus macaques (Macaca mulatta)

    PubMed Central

    Kumar, V.; Raj, A.

    2012-01-01

    The objective of the study was to standardize a new method of vasectomy in male rhesus macaques (Macaca mulatta). A total of 208 free range male rhesus macaques captured from different locations in Shivalik Hills in a population control programme of the rhesus macaques in India. General anaesthesia was achieved by using a combination of ketamine hydrochloride at 8 mg/kg body weight and xylazine hydrochloride at 2mg/kg body weight intramuscularly in squeeze cage. Surgical procedure of vasectomy was carried out by single-hole no-scalpel technique using a single pre-scrotal skin incision above the median raphae. Spermatic cord was grasped with ringed forceps and was pulled out through the single-hole incision. Vas deferens was separated from the artery-vein complexus and about 3-4 cm portion of vas deferens was resected. Cauterization of both ends of the vas deferens was achieved with electrocautery. The induction time for anaesthesia was 1.40±0.18 min while surgical time for vasectomy was found to be 5.09±0.22 min. Recovery from general anaesthesia was without side-effects after a mean duration of 36.07±1.22 min, whereas the duration of anaesthesia was observed to be 82.27±4.96 min. There were no major complications following the surgery and recovery of animals was smooth. Animals were kept in postoperative care for five days and released at the same capturing site. PMID:26623283

  14. Characterisation of macaque testicular leucocyte populations and T-lymphocyte immunity.

    PubMed

    De Rose, Robert; Fernandez, Caroline S; Hedger, Mark P; Kent, Stephen J; Winnall, Wendy R

    2013-12-01

    The rodent testis is well established as a site of immune privilege where both innate and acquired immune responses are suppressed. Immune cells and responses within human or non-human primate testes, by contrast, are poorly characterised. This study used multi-colour flow cytometry to characterise the leukocytes in testicular cells isolated from 12 young adult pigtail macaques (Macaca nemestrina) by collagenase dispersal, and to measure the cytokine responses of macaque testicular T-lymphocytes to mitogens. B-lymphocytes and granulocytes were present in very low numbers (0.24% and 3.3% of leukocytes respectively), indicating minimal blood contamination. A median of 30.8% of the recovered testicular leukocytes were CD3+ lymphocytes, with CD4 and CD8 T-lymphocyte proportions similar to those in the blood. The proportion of naïve T-lymphocytes in the testis was low, with significantly higher frequencies of central memory cells, compared with the blood. A median of 42.7% of the testicular leukocytes were CD163+ macrophages, while 4.5% were CD14+CD163- monocyte-like macrophages. Small populations of myeloid and plasmacytoid dendritic cells, NK cells and NKT cells were also detected. Following mitogen stimulation, 19.7% of blood T-lymphocytes produced IFNγ and/or TNF, whereas significantly fewer (4.4%) of the testicular T-lymphocytes responded to stimulation. Our results characterise the immune cells within the adult macaque testis and identify a suppression of T-lymphocyte responses. This study provides a baseline to examine the immunology of the primate testis and suggests that testicular immune privilege could also be present in primates. PMID:24139314

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

    PubMed

    Solyst, James A; Buffalo, Elizabeth A

    2014-01-01

    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. PMID:25414633

  16. Comparison of diffusion tractography and tract-tracing measures of connectivity strength in rhesus macaque connectome.

    PubMed

    van den Heuvel, Martijn P; de Reus, Marcel A; Feldman Barrett, Lisa; Scholtens, Lianne H; Coopmans, Fraukje M T; Schmidt, Ruben; Preuss, Todd M; Rilling, James K; Li, Longchuan

    2015-08-01

    With the mapping of macroscale connectomes by means of in vivo diffusion-weighted MR Imaging (DWI) rapidly gaining in popularity, one of the necessary steps is the examination of metrics of connectivity strength derived from these reconstructions. In the field of human macroconnectomics the number of reconstructed fiber streamlines (NOS) is more and more used as a metric of cortico-cortical interareal connectivity strength, but the link between DWI NOS and in vivo animal tract-tracing measurements of anatomical connectivity strength remains poorly understood. In this technical report, we communicate on a comparison between DWI derived metrics and tract-tracing metrics of projection strength. Tract-tracing information on projection strength of interareal pathways was extracted from two commonly used macaque connectome datasets, including (1) the CoCoMac database of collated tract-tracing experiments of the macaque brain and (2) the high-resolution tract-tracing dataset of Markov and Kennedy and coworkers. NOS and density of reconstructed fiber pathways derived from DWI data acquired across 10 rhesus macaques was found to positively correlate to tract-tracing based measurements of connectivity strength across both the CoCoMac and Markov dataset (both P < 0.001), suggesting DWI NOS to form a valid method of assessment of the projection strength of white matter pathways. Our findings provide confidence of in vivo DWI connectome reconstructions to represent fairly realistic estimates of the wiring strength of white matter projections. Our cross-modal comparison supports the notion of in vivo DWI to be a valid methodology for robust description and interpretation of brain wiring. PMID:26058702

  17. Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques

    PubMed Central

    Ng, Cherie T.; Jaworski, J. Pablo; Jayaraman, Pushpa; Sutton, William F.; Delio, Patrick; Kuller, LaRene; Anderson, David; Landucci, Gary; Richardson, Barbra A.; Burton, Dennis R.; Forthal, Donald N.; Haigwood, Nancy L.

    2010-01-01

    Maternal HIV-1-specific antibodies are efficiently transferred to newborns; their role in disease control is unknown. We administered non-sterilizing levels of neutralizing IgG, including the human neutralizing monoclonal IgG1b12, to six newborn macaques before oral challenge with SHIVSF612P3. All rapidly developed neutralizing antibodies and had significantly reduced plasma viremia for 6 months. These studies support the use of neutralizing antibodies in enhancing B cell responses and viral control in perinatal settings. PMID:20890292

  18. Immune responses to HTLV-I(ACH) during acute infection of pig-tailed macaques.

    PubMed

    McGinn, Therese M; Wei, Qing; Stallworth, Jackie; Fultz, Patricia N

    2004-04-01

    Human T cell lymphotropic virus type 1 (HTLV-I) is causally linked to adult T cell leukemia/lymphoma (ATL) and a chronic progressive neurological disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A nonhuman primate model that reproduces disease symptoms seen in HTLV-I-infected humans might facilitate identification of initial immune responses to the virus and an understanding of pathogenic mechanisms in HTLV-I-related disease. Previously, we showed that infection of pig-tailed macaques with HTLV-I(ACH) is associated with multiple signs of disease characteristic of both HAM/TSP and ATL. We report here that within the first few weeks after HTLV-I(ACH) infection of pig-tailed macaques, serum concentrations of interferon (IFN)-alpha increased and interleukin-12 decreased transiently, levels of nitric oxide were elevated, and activation of CD4(+) and CD8(+) lymphocytes and CD16(+) natural killer cells in peripheral blood were observed. HTLV-I(ACH) infection elicited virus-specific antibodies in all four animals within 4 to 6 weeks; however, Tax-specific lymphoproliferative responses were not detected until 25-29 weeks after infection in all four macaques. IFN-gamma production by peripheral blood cells stimulated with a Tax or Gag peptide was detected to varying degrees in all four animals by ELISPOT assay. Peripheral blood lymphocytes from one animal that developed only a marginal antigen-specific cellular response were unresponsive to mitogen stimulation during the last few weeks preceding its death from a rapidly progressive disease syndrome associated with HTLV-I(ACH) infection of pig-tailed macaques. The results show that during the first few months after HTLV-I(ACH) infection, activation of both innate and adaptive immunity, limited virus-specific cellular responses, sustained immune system activation, and, in some cases, immunodeficiency were evident. Thus, this animal model might be valuable for understanding early stages of infection

  19. Effect of chronic morphine administration on circulating dendritic cells in SIV-infected rhesus macaques.

    PubMed

    Cornwell, William D; Wagner, Wendeline; Lewis, Mark G; Fan, Xiaoxuan; Rappaport, Jay; Rogers, Thomas J

    2016-06-15

    We studied the effect of chronic morphine administration on the circulating dendritic cell population dynamics associated with SIV infection using rhesus macaques. Animals were either first infected with SIV and then given chronic morphine, or visa versa. SIV infection increased the numbers of myeloid DCs (mDCs), but morphine treatment attenuated this mDC expansion. In contrast, morphine increased the numbers of plasmacytoid DCs (pDCs) in SIV-infected animals. Finally, chronic morphine administration (no SIV) transiently increased the numbers of circulating pDCs. These results show that chronic morphine induces a significant alteration in the available circulating levels of critical antigen-presenting cells. PMID:27235346

  20. Analysis of simian immunodeficiency virus sequence variation in tissues of rhesus macaques with simian AIDS.

    PubMed Central

    Kodama, T; Mori, K; Kawahara, T; Ringler, D J; Desrosiers, R C

    1993-01-01

    One rhesus macaque displayed severe encephalomyelitis and another displayed severe enterocolitis following infection with molecularly cloned simian immunodeficiency virus (SIV) strain SIVmac239. Little or no free anti-SIV antibody developed in these two macaques, and they died relatively quickly (4 to 6 months) after infection. Manifestation of the tissue-specific disease in these macaques was associated with the emergence of variants with high replicative capacity for macrophages and primary infection of tissue macrophages. The nature of sequence variation in the central region (vif, vpr, and vpx), the env gene, and the nef long terminal repeat (LTR) region in brain, colon, and other tissues was examined to see whether specific genetic changes were associated with SIV replication in brain or gut. Sequence analysis revealed strong conservation of the intergenic central region, nef, and the LTR. However, analysis of env sequences in these two macaques and one other revealed significant, interesting patterns of sequence variation. (i) Changes in env that were found previously to contribute to the replicative ability of SIVmac for macrophages in culture were present in the tissues of these animals. (ii) The greatest variability was located in the regions between V1 and V2 and from "V3" through C3 in gp120, which are different in location from the variable regions observed previously in animals with strong antibody responses and long-term persistent infection. (iii) The predominant sequence change of D-->N at position 385 in C3 is most surprising, since this change in both SIV and human immunodeficiency virus type 1 has been associated with dramatically diminished affinity for CD4 and replication in vitro. (iv) The nature of sequence changes at some positions (146, 178, 345, 385, and "V3") suggests that viral replication in brain and gut may be facilitated by specific sequence changes in env in addition to those that impart a general ability to replicate well in

  1. Environmental enrichment for rhesus macaques: a cost-effective exercise cage.

    PubMed

    Storey, P L; Turner, P V; Tremblay, J L

    2000-01-01

    Providing suitable and varied environmental enrichment opportunities for nonhuman primates is both challenging and expensive, requiring institutions to be innovative when planning an enrichment program. Equipment must be durable, nontoxic, easily sanitized and disinfected, and readily assembled or prepared by animal care personnel. We developed a portable exercise cage for singly housed macaques from pre-existing but outdated caging; our cage met the described requirements and was used in animal-holding rooms. Modifying existing caging for this purpose led to substantial cost savings. These cages have proved to be popular with animals and their affiliated research teams. PMID:11178309

  2. Geographic distribution and habitat diversity of the Barbary Macaque sylvanus L.

    PubMed

    Taub, D M

    1977-01-01

    During a 15-month behavioral study in Morocco and a 3-month survey in Morocco and Algeria, the present distribution of the Barbary macaque was determined. In Algeria, monkeys are found in seven constricted and disjunct localities in the Grande and Petite Kabylie mountain ranges. These localities are severely restricted in space and are located in remote or inaccessible areas which support only small populations. Their habitats include mixed cedar and holm oak forests, humid Portuguese and cork oak mixes and gorges dominated by scrub vegetation. In only two regions (Guerrouch and Agfadou) can population of reasonable size be found; even there they do not approach the abundance found in the central Middle Atlas zone of Morocco. Distribution was more extensive earlier in this century and some areas have become unoccupied within the past 15 years. Today, their absolute numbers and population densities are low in all but two locations. Algeria contains approximately 23% (5,500 maximum) of the total number of surviving Barbary macaques in North Africa. About 77% of the total number of Barbary macaques occur in Morocco. Moroccan habitats include high cedar forests, cedar/holm-oak mixtures and pure holm oak forests. Macaque distribution in the High Atlas is restricted to the Ourika valley where only a small relict population survives. There are between five and eight small, disjunct forest pockets in the Rif which support small groups of monkeys. In the Middle Atlas, monkeys are found in high numbers and in relatively wide stretches of distribution, although there are constricted areas of low densities in this region also. 65% (14,000 maximum) of the animals and their highest densities occur in the high mixed cedar forests of the Central zone, and mixed cedar forest appears to be the preferred habitat for the species. With the exception of the Central zone, their remaining distribution is typically disjunct and constricted, and population densities aer low. As in Algeria

  3. Behavioral measurement of temporal contrast sensitivity development in macaque monkeys (Macaca nemestrina)

    PubMed Central

    Stavros, Kara A.; Kiorpes, Lynne

    2009-01-01

    We measured the developmental time course for temporal contrast sensitivity in macaque monkeys. The animals, aged 5 wks to 4 yrs, detected an unpatterned field of light sinusoidally modulated over time at frequencies ranging from 1 to 40 Hz. Young infants showed reduced sensitivity for all frequencies, and a reduced range of detectable frequencies. Sensitivity to high and low frequencies developed at different rates, but the shape of the temporal contrast sensitivity function did not change significantly with age. Temporal contrast sensitivity matures earlier than spatial contrast sensitivity. The development of high, but not low, frequency sensitivity may be limited by maturation of the magnocellular pathway. PMID:18406441

  4. Putative rhesus macaque germline predecessors of human broadly HIV-neutralizing antibodies: differences from the human counterparts and implications for HIV-1 vaccine development

    PubMed Central

    Yuan, Tingting; Li, Jingjing; Zhang, Yu; Wang, Yanping; Streaker, Emily; Dimitrov, Dimiter S.; Zhang, Mei-Yun

    2011-01-01

    Broadly neutralizing antibodies (bnAbs) are likely to be a key component of protective immunity conferred by an effective HIV-1 vaccine. We and others have reported that putative human germline predecessors of known human bnAbs lack measurable binding to HIV-1 envelope glycoproteins (Env), which could be a new challenge for eliciting human bnAbs. Rhesus macaques have been used as nonhuman primate models for testing vaccine candidates, but little is known about their germline Abs. Here we show the similarities and differences between putative rhesus macaque and human germline predecessors and possible intermediate antibodies of one of the best characterized bnAbs, b12. Similar to the human counterpart, a putative rhesus macaque b12 germline antibody lacks measurable binding to HIV-1 Envs, suggesting that initiation of somatic maturation of rhesus macaque germline b12 predecessor may also be a challenge. However, differences in sequence characteristics and binding properties between macaque and human b12 germline and intermediate antibodies suggest that the two germline predecessors may undergo different maturation pathways in rhesus macaques and in humans. These results indicate that immunogens that could initiate the immune responses and drive somatic mutations leading to elicitation of b12 or b12-like bnAbs in rhesus macaques and in humans are likely to be different. This has important implications for HIV-1 vaccine development. PMID:21807049

  5. Immunohistochemical Characterization of Slow and Fast Myosin Heavy Chain Composition of Muscle Fibres in the Styloglossus Muscle of the Human and Macaque (M. rhesus)

    PubMed Central

    Sokoloff, Alan J.; Yang, Betty; Li, Haiyan; Burkholder, Thomas J.

    2007-01-01

    Objective Muscle fibre contractile diversity is thought to be increased by the hybridization of multiple myosin heavy chain (MHC) isoforms in single muscle fibres. Reports of hybrid fibres composed of MHCI and MHCII isoforms in human, but not macaque, tongue muscles, suggest a human adaptation for increased tongue muscle contractile diversity. Here we test whether hybrid fibres composed of MHCI and MHCII are unique to human tongue muscles or are present as well in the macaque. Methods MHC composition of the macaque and human styloglossus was characterized with antibodies that allowed identification of three muscle fibre phenotypes, a slow phenotype composed of MHCI, a fast phenotype composed of MHCII and a hybrid phenotype composed of MHCI and MHCII. Results The fast phenotype constitutes 68.5% of fibres in the macaque and 43.4% of fibres in the human (P<0001). The slow phenotype constitutes 20.2% of fibres in the macaque and 39.3% of fibres in the human (P<0001). The hybrid phenotype constitutes 11.2% of fibres in the macaque and 17.3% of fibres in the human (P=0002). Macaques and humans do not differ in fiber size (cross-sectional area, diameter). However, measures of fibre size differ by phenotype such that fast > hybrid > slow (P<0.05). Conclusion These data demonstrate differences in the relative percent of muscle fibre phenotypes in the macaque and human styloglossus but also demonstrate that all three phenotypes are present in both species. These data suggest a similar range of mechanical properties in styloglossus muscle fibres of the macaque and human. PMID:17210117

  6. CD8+ cell depletion of SHIV89.6P-infected macaques induces CD4+ T cell proliferation that contributes to increased viral loads

    PubMed Central

    Mueller, Yvonne M.; Do, Duc H.; Boyer, Jean D.; Kader, Muhamuda; Mattapallil, Joseph J.; Lewis, Mark G.; Weiner, David B.; Katsikis, Peter D.

    2009-01-01

    Previous studies have shown that depletion of CD8+ cells during acute and chronic simian immunodeficiency virus (SIV) infection leads to increased viral replication, morbidity and mortality which have been attributed to loss of CD8+ T cell-mediated control of SIV virus. However, these studies did not exclude that CD8+ cell depletion increased homeostatic proliferation of CD4+ T cells, resulting in increased viral targets and therefore viral rebound. Chronically SHIV89.6P-infected cynomolgus macaques were CD8+ cell-depleted and frequencies, cell numbers and phenotype of CD4+ T cells and viral infection were examined using flow cytometry and quantitative real-time PCR. Frequencies and numbers of Ki-67-expressing CD4+ T cells were increased with CD8+ cell depletion. This proliferation of CD4+ T cells occurred even in animals with no rebound of viral loads. Most of the proliferating cells were effector memory CD4+ T cells. Plasma SHIV RNA copies positively correlated with proliferating CD4+ T cells and SHIV DNA copies in Ki-67+ CD4+ T cells. Although this study does not exclude an important role for virus-specific CD8+ T cells in SIV and SHIV infection, our data suggest that homeostatic proliferation is an important contributor to increases in plasma viremia that follow CD8+ cell depletion. PMID:19786539

  7. Evaluation of protection induced by a dengue virus serotype 2 envelope domain III protein scaffold/DNA vaccine in non-human primates.

    PubMed

    McBurney, Sean P; Sunshine, Justine E; Gabriel, Sarah; Huynh, Jeremy P; Sutton, William F; Fuller, Deborah H; Haigwood, Nancy L; Messer, William B

    2016-06-24

    We describe the preclinical development of a dengue virus vaccine targeting the dengue virus serotype 2 (DENV2) envelope domain III (EDIII). This study provides proof-of-principle that a dengue EDIII protein scaffold/DNA vaccine can protect against dengue challenge. The dengue vaccine (EDIII-E2) is composed of both a protein particle and a DNA expression plasmid delivered simultaneously via intramuscular injection (protein) and gene gun (DNA) into rhesus macaques. The protein component can contain a maximum of 60 copies of EDIII presented on a multimeric scaffold of Geobacillus stearothermophilus E2 proteins. The DNA component is composed of the EDIII portion of the envelope gene cloned into an expression plasmid. The EDIII-E2 vaccine elicited robust antibody responses to DENV2, with neutralizing antibody responses detectable following the first boost and reaching titers of greater than 1:100,000 following the second and final boost. Vaccinated and naïve groups of macaques were challenged with DENV2. All vaccinated macaques were protected from detectable viremia by infectious assay, while naïve animals had detectable viremia for 2-7 days post-challenge. All naïve macaques had detectable viral RNA from day 2-10 post-challenge. In the EDIII-E2 group, three macaques were negative for viral RNA and three were found to have detectable viral RNA post challenge. Viremia onset was delayed and the duration was shortened relative to naïve controls. The presence of viral RNA post-challenge corresponded to a 10-30-fold boost in neutralization titers 28 days post challenge, whereas no boost was observed in the fully protected animals. Based on these results, we determine that pre-challenge 50% neutralization titers of >1:6000 correlated with sterilizing protection against DENV2 challenge in EDIII-E2 vaccinated macaques. Identification of the critical correlate of protection for the EDIII-E2 platform in the robust non-human primate model lays the groundwork for further

  8. Differential induction of type I interferons in macaques by wild-type measles virus alone or with the hemagglutinin protein of the Edmonston vaccine strain.

    PubMed

    Van Nguyen, Nguyen; Kato, Sei-Ich; Nagata, Kyosuke; Takeuchi, Kaoru

    2016-07-01

    Measles vaccines are highly effective and safe; however, the mechanism(s) underlying their attenuation has not been well understood. In this study, type I IFNs (IFN-α and IFN-β) induction in macaques infected with measles virus (MV) strains was examined. Type I IFNs were not induced in macaques infected with wild-type MV. However, IFN-α was sharply induced in most macaques infected with recombinant wild-type MV bearing the hemagglutinin (H) protein of the Edmonston vaccine strain. These results indicate that the H protein of MV vaccine strains may have a role in MV attenuation. PMID:27278100

  9. Effects of Maternal and Infant Characteristics on Birth Weight and Gestation Length in a Colony of Rhesus Macaques (Macaca mulatta)

    PubMed Central

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

    2008-01-01

    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. PMID:19149417

  10. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy

    PubMed Central

    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. PMID:26125617

  11. Park Rangers' Behaviors and Their Effects on Tourists and Tibetan Macaques (Macaca thibetana) at Mt. Huangshan, China.

    PubMed

    Usui, Rie; Sheeran, Lori K; Li, Jin-Hua; Sun, Lixing; Wang, Xi; Pritchard, Alexander J; DuVall-Lash, Alexander S; Wagner, R Steve

    2014-01-01

    Previous studies have reported the negative impacts of tourism on nonhuman primates (NHPs) and tourists and advocated the improvement of tourism management, yet what constitutes good quality management remains unclear. We explored whether rates of macaque aggression and self-directed behaviors (SDBs) differed under the supervision of two park ranger teams at the Valley of the Wild Monkeys (VWM) in Mt. Huangshan, Anhui Province, China. The two ranger teams provisioned and managed a group of macaques on an alternating monthly basis. Monkey, tourist and ranger behaviors were collected from August 16-September 30, 2012. Macaque aggression and SDB rates did not differ significantly under the management of the two teams. Overall, there was little intervention in tourist-macaque interactions by park rangers, and even when rangers discouraged tourists' undesirable behaviors, tourist interactions with monkeys persisted. Furthermore, only one or sometimes two park rangers managed monkeys and tourists, and rangers established dominance over the monkeys to control them. In order to effectively manage tourists and monkeys by a single park ranger, we recommend that rangers: (1) prohibit tourists from feeding; (2) move around the viewing platform more frequently; and (3) limit the number of tourists each visiting session. PMID:26480324

  12. Gut-Resident Lactobacillus Abundance Associates with IDO1 Inhibition and Th17 Dynamics in SIV-Infected Macaques.

    PubMed

    Vujkovic-Cvijin, Ivan; Swainson, Louise A; Chu, Simon N; Ortiz, Alexandra M; Santee, Clark A; Petriello, Annalise; Dunham, Richard M; Fadrosh, Douglas W; Lin, Din L; Faruqi, Ali A; Huang, Yong; Apetrei, Cristian; Pandrea, Ivona; Hecht, Frederick M; Pilcher, Christopher D; Klatt, Nichole R; Brenchley, Jason M; Lynch, Susan V; McCune, Joseph M

    2015-11-24

    Gut microbes can profoundly modulate mucosal barrier-promoting Th17 cells in mammals. A salient feature of HIV/simian immunodeficiency virus (SIV) immunopathogenesis is the loss of Th17 cells, which has been linked to increased activity of the immunomodulatory enzyme, indoleamine 2,3-dioxygenase 1 (IDO 1). The role of gut microbes in this system remains unknown, and the SIV-infected rhesus macaque provides a well-described model for HIV-associated Th17 loss and mucosal immune disruption. We observed a specific depletion of gut-resident Lactobacillus during acute and chronic SIV infection of rhesus macaques, which was also seen in early HIV-infected humans. This depletion in rhesus macaques correlated with increased IDO1 activity and Th17 loss. Macaques supplemented with a Lactobacillus-containing probiotic exhibited decreased IDO1 activity during chronic SIV infection. We propose that Lactobacillus species inhibit mammalian IDO1 and thus may help to preserve Th17 cells during pathogenic SIV infection, providing support for Lactobacillus species as modulators of mucosal immune homeostasis. PMID:26586432

  13. Repertoire comparison of the B-cell receptor encoding loci in humans and rhesus macaques by next generation sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rhesus macaques are a widely used model system for the study of vaccines, infectious diseases, and microbial pathogenesis. Their value as a model lies in their close evolutionary relationship to humans, which, in theory, allows them to serve as a close approximation of the human immune system. Howev...

  14. Topical Delivery of Tenofovir Disoproxil Fumarate and Emtricitabine from Pod-Intravaginal Rings Protects Macaques from Multiple SHIV Exposures

    PubMed Central

    Gunawardana, Manjula; Churchman, Scott A.; Yang, Flora; Dinh, Chuong T.; Mitchell, James M.; Zhang, Jining; Fanter, Rob; Miller, Christine S.; Butkyavichene, Irina; McNicholl, Janet M.; Smith, Thomas J.; Baum, Marc M.; Smith, James M.

    2016-01-01

    Topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure. Controlled, sustained release of antiretroviral (ARV) drugs may help overcome these low adherence rates if the product is protective for extended periods of time. The oral combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is currently the only FDA-approved ARV drug for HIV PrEP. A novel pod-intravaginal ring (IVR) delivering TDF and FTC at independently controlled rates was evaluated for efficacy at preventing SHIV162p3 infection in a rigorous, repeat low-dose vaginal exposure model using normally cycling female pigtailed macaques. Six macaques received pod-IVRs containing TDF (65 mg) and FTC (68 mg) every two weeks, and weekly vaginal exposures to 50 TCID50 of SHIV162p3 began one week after the first pod-IVR insertion. All pod-IVR-treated macaques were fully protected throughout the study (P = 0.0002, Log-rank test), whereas all control animals became infected with a median of 4 exposures to infection. The topical, sustained release of TDF and FTC from the pod-IVR maintained protective drug levels in macaques over four months of virus exposures. This novel and versatile delivery system has the capacity to deliver and maintain protective levels of multiple drugs and the protection observed here warrants clinical evaluation of this pod-IVR design. PMID:27275923

  15. Time resolved optical detection for white matter lesion detection: preclinical tests on macaque brains and MRI co-registration

    NASA Astrophysics Data System (ADS)

    Planat-Chrétien, A.; Berger, M.; Hervé, L.; Watroba, L.; Demilly, J.; Flament, J.; Stimmer, L.; Aubourg, P.; Dinten, J.-M.

    2015-07-01

    We conducted a preclinical assessment on young macaques aimed at detecting white matter lesions. We present the protocol we implemented to achieve the lesions detection using a bedside non-invasive optical-based Time-Resolved instrumentation we have optimized for this purpose. We validated the reconstructed 3D absorption map with co-registration of MRI data.

  16. Mitochondrial DNA.

    ERIC Educational Resources Information Center

    Wright, Russell G.; Bottino, Paul J.

    1986-01-01

    Provides background information for teachers on mitochondrial DNA, pointing out that it may have once been a free-living organism. Includes a ready-to-duplicate exercise titled "Using Microchondrial DNA to Measure Evolutionary Distance." (JN)

  17. A combined oral contraceptive affects mucosal SHIV susceptibility factors in a pigtail macaque model

    PubMed Central

    Ostergaard, Sharon Dietz; Butler, Katherine; Ritter, Jana M.; Johnson, Ryan; Sanders, Jeanine; Powell, Nathaniel; Lathrop, George; Zaki, Sherif R.; McNicholl, Janet M.; Kersh, Ellen N.

    2015-01-01

    Background Injectable hormonal contraception may increase women’s risk of HIV acquisition, and can affect biological risk factors in animal models of HIV. We established, for the first time, a model to investigate whether combined oral contraceptives (COC) alter SHIV susceptibility in macaques. Methods Seven pigtail macaques were administered a monophasic levonorgestrel (LNG)/ethinyl estradiol (EE) COC at 33% or 66% of the human dose for 60 days. Menstrual cycling, vaginal epithelial thickness and other SHIV susceptibility factors were monitored for a mean of 18 weeks. Results Mean vaginal epithelial thicknesses was 290.8 μm at baseline and 186.2 μm during COC (p=0.0141, Mann Whitney test). Vaginal pH decreased from 8.5 during to 6.5 post- treatment (0.0176 two-tailed t-test). Measured microflora was unchanged. Conclusions COC caused thinning of the vaginal epithelium and vaginal pH changes, which may increase SHIV susceptibility. 0.033 mg LNG + 0.0066 mg EE appeared effective in suppressing ovulation. PMID:25536296

  18. Implicit and Explicit Category Learning by Macaques (Macaca mulatta) and Humans (Homo sapiens)

    PubMed Central

    Smith, J. David; Beran, Michael J.; Crossley, Matthew J.; Boomer, Joseph. T.; Ashby, F. Gregory

    2010-01-01

    An influential theoretical perspective differentiates in humans an explicit, rule-based system of category learning from an implicit system that slowly associates different regions of perceptual space with different response outputs. This perspective was extended for the first time to the category learning of nonhuman primates. Humans and macaques learned categories composed of sine-wave gratings that varied across trials in bar width and bar orientation. The categories had either a single-dimensional, rule-based solution or a two-dimensional, information-integration solution. Humans strongly dimensionalized the stimuli and learned the rule-based task far more quickly. Six macaques showed the same performance advantage in the rule-based task. In humans, rule-based category learning is linked to explicit cognition, consciousness, and to declarative reports about the contents of cognition. The present results demonstrate an empirical continuity between human and nonhuman primate cognition, suggesting that nonhuman primates may have some structural components of humans’ capacity for explicit cognition. PMID:20141317

  19. Imaging endocervical mucus anatomy and dynamics in macaque female reproductive track using optical coherence tomography

    PubMed Central

    Chen, Siyu; Yi, Ji; Dong, Biqin; Sun, Cheng; Kiser, Patrick F.; Hope, Thomas J.

    2015-01-01

    Background Endocervical mucus acts as an important barrier to block human immunodeficiency virus (HIV) infection and other sexually transmitted diseases (STDs). Disruption of the mucus layer increases the risk of infection for females. An effective method to image the mucus properties can serve as a pre-screening step to risk-stratify the susceptible population. Methods We proposed to use optical coherence tomography (OCT) to quantitatively measure the thickness of endocervical mucus. We used a home-built bench-top OCT system to monitor the dynamic change in mucus thickness of a cultivated sample. We also fabricated a prototype endoscopic OCT probe to demonstrate potential in situ applications. Results We observed a 200% increase in the endocervical mucus thickness after cultivating in 37 °C phosphate buffered saline solution for 30 minutes. During mucus hydrolysis, we found that mucus layer thickness decreased to about 60% of its original value after applying neuraminidase. Three dimensional volumetric image of intact macaque inner vaginal wall was also acquired. Conclusions We demonstrated that OCT can quantitatively measure the endocervical mucus thickness and its dynamics in ex vivo experiments. Endoscopic OCT has the potential to resolve fine structures inside macaque female reproductive track (FRT) for in vivo applications. PMID:25694952

  20. Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

    NASA Technical Reports Server (NTRS)

    Gazzaley, A. H.; Thakker, M. M.; Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.

  1. Parameter comparison of white matter diffusion tensor imaging (DTI) in rhesus macaques (Macaca mulatta).

    PubMed

    Mo, Yin; Chao, Fang; Song, Ming; Liu, Ci-Rong; Liu, Hui-Lang; Qian, Xi-Ying; Zhao, Xu-Dong

    2014-05-01

    In this study, we analyzed diffusion tensor imaging (DTI) results of brain white matter in rhesus macaques (Macaca mulatta) with four different parameter settings and found that the sequence A (b=1 000 s/mm(2), spatial resolution=1.25 mm×1.25 mm× 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm(2), spatial resolution=1.25 mm×1.25 mm×1.25 mm, numbers of direction=33, NSA=3) could accurately track coarse fibers. The fractional anisotropy (FA) derived from sequence C (b=1 000s/mm(2), spatial resolution=0.55 mm×0.55 mm×2.5 mm, direction number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By comparison, the high resolution and the FA with high contrast of gray matter and white matter derived from sequence D (b=800 s/mm(2), spatial resolution=1.0 mm×1.0 mm ×1.0 mm, numbers of direction=33, NSA=3) qualified in its application in tracking both thick and thin fibers, making it an optimal DTI setting for rhesus macaques. PMID:24866488

  2. Assessment of Multiplate platelet aggregometry using citrate, heparin or hirudin in Rhesus macaques.

    PubMed

    Dugan, Greg; O'Donnell, Lisa; Hanbury, David B; Cline, J Mark; Caudell, David L

    2015-01-01

    Electrical impedance aggregometry (EIA) has gained popularity in clinical and research applications. Nonhuman primates are used to study disease and drug-related mechanisms that affect hemostasis, therefore establishing normal EIA parameters are necessary. The anticoagulants sodium heparin, hirudin and sodium citrate and three agonists, ADP, ASPI, and collagen were evaluated. Whole blood from 12 adult male rhesus macaques was collected to evaluate anticoagulants, sodium heparin, hirudin and sodium citrate using three agonists (ADP, ASPI and collagen), on the Multiplate® 5.0 Analyzer. Platelet function was reported for three parameters: Area under the curve (AUC), aggregation, and aggregation velocity. There was a significant difference in mean AUC between citrate and heparin samples, and citrate and hirudin samples regardless of the agonist used. There was no difference in AUC between heparin and hirudin. ADP-activated samples showed an increase in impedance with hirudin samples compared to citrate. Furthermore, heparin and hirudin out-perform citrate as the anticoagulant for EIA in the macaque. Finally, this study demonstrates the utility of the Multiplate® system in this model and provides important insight into anticoagulant choice when using EIA. PMID:25549285

  3. PARAQUAT IS EXCLUDED BY THE BLOOD BRAIN BARRIER IN RHESUS MACAQUE: AN IN VIVO PET STUDY

    PubMed Central

    Bartlett, Rachel M.; Holden, James E.; Nickles, R. Jerome; Murali, Dhanabalan; Barbee, David L.; Barnhart, Todd E.; Christian, Bradley C.; DeJesus, Onofre T.

    2009-01-01

    Environmental factors have long been thought to have a role in the etiology of idiopathic Parkinson’s Disease (PD). Since the discovery of the selective neurotoxicity of MPTP to dopamine cells, suspicion has focused on paraquat, a common herbicide with chemical structure similar to 1-methyl-4-phenylpyridinium (MPP+), the MPTP metabolite responsible for its neurotoxicity. Although in vitro evidence for paraquat neurotoxicity to dopamine cells is well established, its in vivo effects have been ambiguous because paraquat is di-cationic in plasma, which raises questions about its ability to cross the blood brain barrier. This study assessed the brain uptake of [11C]-paraquat in adult male rhesus macaques using quantitative PET imaging. Results showed minimal uptake of [11C]-paraquat in the macaque brain. The highest concentrations of paraquat was seen in the pineal gland and the lateral ventricles. Global brain concentrations including those in known dopamine areas were consistent with the blood volume in those structures. This acute exposure study found that paraquat is excluded from the brain by the blood brain barrier and thus does not readily support the causative role of paraquat exposure in idiopathic Parkinson’s Disease. PMID:19135428

  4. Electroretinogram analysis of relative spectral sensitivity in genetically identified dichromatic macaques

    PubMed Central

    Hanazawa, Akitoshi; Mikami, Akichika; Angelika, Puti Sulistyo; Takenaka, Osamu; Goto, Shunji; Onishi, Akishi; Koike, Satoshi; Yamamori, Tetsuo; Kato, Keichiro; Kondo, Aya; Suryobroto, Bambang; Farajallah, Achmad; Komatsu, Hidehiko

    2001-01-01

    The retinas of macaque monkeys usually contain three types of photopigment, providing them with trichromatic color vision homologous to that of humans. However, we recently used molecular genetic analysis to identify several macaques with a dichromatic genotype. The affected X chromosome of these animals contains a hybrid gene of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) photopigments instead of separate genes encoding L and M photopigments. The product of the hybrid gene exhibits a spectral sensitivity close to that of M photopigment; consequently, male monkeys carrying the hybrid gene are genetic protanopes, effectively lacking L photopigment. In the present study, we assessed retinal expression of L photopigment in monkeys carrying the hybrid gene. The relative sensitivities to middle-wavelength (green) and long-wavelength (red) light were measured by electroretinogram flicker photometry. We found the sensitivity to red light to be extremely low in protanopic male monkeys compared with monkeys with the normal genotype. In female heterozygotes, sensitivity to red light was intermediate between the genetic protanopes and normal monkeys. Decreased sensitivity to long wavelengths was thus consistent with genetic loss of L photopigment. PMID:11427736

  5. Receptive-field Properties of V1 and V2 Neurons in Mice and Macaque monkeys

    PubMed Central

    Van den Bergh, Gert; Zhang, Bin; Arckens, Lutgarde; Chino, Yuzo M.

    2010-01-01

    We report the results of extracellular single-unit recording experiments where we quantitatively analyzed the receptive-field (RF) properties of neurons in V1 and an adjacent extrastriate visual area (V2L) of anesthetized mice with emphasis on the RF center-surround organization. We compared the results with the RF center-surround organization of V1 and V2 neurons in macaque monkeys. If species differences in spatial scale are taken into consideration, mouse V1 and V2L neurons had remarkably fine stimulus selectivity, and the majority of response properties in V2L were not different from those in V1. The RF center-surround organization of mouse V1 neurons was qualitatively similar to that for macaque monkeys (i.e., the RF center is surrounded by extended suppressive regions). However, unlike in monkey V2, a significant proportion of cortical neurons, largely complex cells in V2L, did not exhibit quantifiable RF surround suppression. Simple cells had smaller RF centers than complex cells, and the prevalence and strength of surround suppression were greater in simple cells than in complex cells. These findings, particularly on the RF center-surround organization of visual cortical neurons, give new insights into the principles governing cortical circuits in the mouse visual cortex and should provide further impetus for the use of mice in studies on the genetic and molecular basis of RF development and synaptic plasticity. PMID:20394058

  6. Dietary Omega-3 Fatty Acids Modulate Large-Scale Systems Organization in the Rhesus Macaque Brain

    PubMed Central

    Kroenke, Christopher D.; Neuringer, Martha; Fair, Damien A.

    2014-01-01

    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. PMID:24501348

  7. The first observation of seasonal affective disorder symptoms in Rhesus macaque.

    PubMed

    Qin, Dongdong; Chu, Xunxun; Feng, Xiaoli; Li, Zhifei; Yang, Shangchuan; Lü, Longbao; Yang, Qing; Pan, Lei; Yin, Yong; Li, Jiali; Xu, Lin; Chen, Lin; Hu, Xintian

    2015-10-01

    Diurnal animals are a better model for seasonal affective disorder (SAD) than nocturnal ones. Previous work with diurnal rodents demonstrated that short photoperiod conditions brought about depression-like behavior. However, rodents are at a large phylogenetic distance from humans. In contrast, nonhuman primates are closely similar to humans, making them an excellent candidate for SAD model. This study made the first attempt to develop SAD in rhesus macaque (Macaca mulatta) and it was found that short photoperiod conditions could lead monkeys to display depressive-like huddling behavior, less spontaneous locomotion, as well as less reactive locomotion. In addition to these depression-related behavioral changes, the physiological abnormalities that occur in patients with SAD, such as weight loss, anhedonia and hypercortisolism, were also observed in those SAD monkeys. Moreover, antidepressant treatment could reverse all of the depression-related symptoms, including depressive-like huddling behavior, less spontaneous locomotion, less reactive locomotion, weight loss, anhedonia and hypercortisolism. For the first time, this study observed the SAD symptoms in rhesus macaque, which would provide an important platform for the understanding of the etiology of SAD as well as developing novel therapeutic interventions in the future. PMID:26164484

  8. Unraveling the Pathogenesis of HIV Peripheral Neuropathy: Insights from a Simian Immunodeficiency Virus Macaque Model

    PubMed Central

    Mangus, Lisa M.; Dorsey, Jamie L.; Laast, Victoria A.; Ringkamp, Matthias; Ebenezer, Gigi J.; Hauer, Peter; Mankowski, Joseph L.

    2014-01-01

    Peripheral neuropathy (PN) is the most frequent neurologic complication in individuals infected with human immunodeficiency virus (HIV). It affects over one third of infected patients, including those receiving effective combination antiretroviral therapy. The pathogenesis of HIV-associated peripheral neuropathy (HIV-PN) remains poorly understood. Clinical studies are complicated because both HIV and antiretroviral treatment cause damage to the peripheral nervous system. To study HIV-induced peripheral nervous system (PNS) damage, a unique simian immunodeficiency virus (SIV)/pigtailed macaque model of HIV-PN that enabled detailed morphologic and functional evaluation of the somatosensory pathway throughout disease progression was developed. Studies in this model have demonstrated that SIV induces key pathologic features that closely resemble HIV-induced alterations, including inflammation and damage to the neuronal cell bodies in somatosensory ganglia and decreased epidermal nerve fiber density. Insights generated in the model include: finding that SIV alters the conduction properties of small, unmyelinated peripheral nerves; and that SIV impairs peripheral nerve regeneration. This review will highlight the major findings in the SIV-infected pigtailed macaque model of HIV-PN, and will illustrate the great value of a reliable large animal model to show the pathogenesis of this complex, HIV-induced disorder of the PNS. PMID:24615443

  9. Efficient transduction of pigtailed macaque hematopoietic repopulating cells with HIV-based lentiviral vectors

    PubMed Central

    Trobridge, Grant D.; Beard, Brian C.; Gooch, Christina; Wohlfahrt, Martin; Olsen, Philip; Fletcher, James; Malik, Punam

    2008-01-01

    Lentiviral vectors are attractive for hematopoietic stem cell (HSC) gene therapy because they do not require mitosis for nuclear entry, they efficiently transduce hematopoietic repopulating cells, and self-inactivating (SIN) designs can be produced at high titer. Experiments to evaluate HIV-derived lentiviral vectors in nonhuman primates prior to clinical trials have been hampered by low transduction frequencies due in part to host restriction by TRIM5α. We have established conditions for efficient transduction of pigtailed macaque (Macaca nemestrina) long-term repopulating cells using VSV-G–pseudotyped HIV-based lentiviral vectors. Stable, long-term, high-level gene marking was observed in 3 macaques using relatively low MOIs (5-10) in a 48-hour ex vivo transduction protocol. All animals studied had rapid neutrophil engraftment with a median of 10.3 days to a count greater than 0.5 × 109/L (500/μL). Expression was detected in all lineages, with long-term marking levels in granulocytes at approximately 20% to 30%, and in lymphocytes at approximately 12% to 23%. All animals had polyclonal engraftment as determined by analysis of vector integration sites. These data suggest that lentiviral vectors should be highly effective for HSC gene therapy, particularly for diseases in which maintaining the engraftment potential of stem cells using short-term ex vivo transduction protocols is critical. PMID:18388180

  10. Assessing the Effects of Tourist Provisioning on the Health of Wild Barbary Macaques in Morocco

    PubMed Central

    Maréchal, Laëtitia; Semple, Stuart; Majolo, Bonaventura; MacLarnon, Ann

    2016-01-01

    Feeding wildlife is a very popular tourist activity, largely because it facilitates the close observation of animals in their natural habitat. Such provisioning may benefit animals by improving their survival and reproductive success, especially during periods of natural food shortage. However, provisioning by tourists may also have negative impacts on the health of the animals involved; to date such impacts are poorly understood. Here, we investigated the effects of tourist provisioning on the health of wild adult Barbary macaques, Macaca sylvanus, in Morocco. We compared health measures between a heavily provisioned group and a group that received negligible food from tourists and, in the former group, we also assessed health measures in relation to the intensity of provisioning. We used a broad range of non-invasive health measures relating to birth rate and survival, disease and injury risk, body size and condition, and physiological stress. Our findings indicate that feeding by tourists may overall have negative impacts on the health of Barbary macaques, being linked in particular to larger body size, elevated stress levels and more alopecia. Finally, we propose a framework to help consider the potential costs and benefits of provisioning, which may facilitate future research and management decisions on whether—and how much—provisioning is acceptable. PMID:27203861

  11. Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin

    PubMed Central

    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

  12. [Comparisons of aggressive behavior for Tibetan Macaques (Macaca thibetana) to tourists from Mt. Huangshan, China].

    PubMed

    Ji, Huan; Li, Jin-Hua; Sun, Bing-Hua; Zhu, Yong

    2010-08-01

    To investigate the relationship between monkey-human aggressive behaviors and age/sex classes of monkey (initiator) and human (recipient), by using all-occurrence sampling and continuous recording, we evaluated the monkey-human aggressive behaviors between macaques (Macaca thibetana) and tourists at Mt. Huangshan in two periods (Nov.-Dec.2008 and Apr.-May 2009). After we divide the aggression into three types according to the dangerous level to tourists, some significant patterns were observed.Our observations indicate that Tibetan macaques respond differently to human according to the age/sex classes involved. On one hand, We found that the adult male monkeys tend to be more aggressive than expected (P<0.01), while the adult female monkeys and immature monkeys participated in AGIII behaviors (threat) less than expected (P<0.01); On the other hand, The adult male human received more aggressive behaviors than expected (P<0.01), while the adult female human and child received less aggressive in AGIII behaviors (threat) (P<0.01). Our results provide not only a scientific basis for the management advice that adult male monkeys and adult male human should be given special attention, but also a good management model of Huangshan for other primate tourist exploring places. PMID:20740706

  13. A rhesus macaque model of Asian-lineage Zika virus infection

    PubMed Central

    Dudley, Dawn M.; Aliota, Matthew T.; Mohr, Emma L.; Weiler, Andrea M.; Lehrer-Brey, Gabrielle; Weisgrau, Kim L.; Mohns, Mariel S.; Breitbach, Meghan E.; Rasheed, Mustafa N.; Newman, Christina M.; Gellerup, Dane D.; Moncla, Louise H.; Post, Jennifer; Schultz-Darken, Nancy; Schotzko, Michele L.; Hayes, Jennifer M.; Eudailey, Josh A.; Moody, M. Anthony; Permar, Sallie R.; O'Connor, Shelby L.; Rakasz, Eva G.; Simmons, Heather A.; Capuano, Saverio; Golos, Thaddeus G.; Osorio, Jorge E.; Friedrich, Thomas C.; O'Connor, David H.

    2016-01-01

    Infection with Asian-lineage Zika virus (ZIKV) has been associated with Guillain–Barré syndrome and fetal abnormalities, but the underlying mechanisms remain poorly understood. Animal models of infection are thus urgently needed. Here we show that rhesus macaques are susceptible to infection by an Asian-lineage ZIKV closely related to strains currently circulating in the Americas. Following subcutaneous inoculation, ZIKV RNA is detected in plasma 1 day post infection (d.p.i.) in all animals (N=8, including 2 pregnant animals), and is also present in saliva, urine and cerebrospinal fluid. Non-pregnant and pregnant animals remain viremic for 21 days and for up to at least 57 days, respectively. Neutralizing antibodies are detected by 21 d.p.i. Rechallenge 10 weeks after the initial challenge results in no detectable virus replication, indicating protective immunity against homologous strains. Therefore, Asian-lineage ZIKV infection of rhesus macaques provides a relevant animal model for studying pathogenesis and evaluating potential interventions against human infection, including during pregnancy. PMID:27352279

  14. Large granular lymphocytes are universally increased in human, macaque, and feline lentiviral infection.

    PubMed

    Sprague, Wendy S; Apetrei, Cristian; Avery, Anne C; Peskind, Robert L; Vandewoude, Sue

    2015-10-15

    Large granular lymphocytes (LGLs) have only been anecdotally reported in HIV infection. We previously reported an LGL lymphocytosis in FIV-infected cats associated with a rise in FIV proviral loads and a marked neutropenia that persisted during chronic infection. Extensive immunophenotyping of peripheral blood mononuclear cells in cats chronically infected with FIV were identified LGLs as CD8lo(+)FAS(+); this cell population expanded commensurate with viral load. CD8lo(+)FAS(+) cells expressed similar levels of interferon-γ compared to CD8lo(+)FAS(+) cells from FIV-naive control animals, yet CD3ɛ expression, which was increased on total CD8(+) T cells in FIV-infected cats, was decreased on CD8lo(+)FAS(+) cells. Down-modulation of CD3 expression was reversed after culturing PBMC for 3 days in culture with ConA/IL-2. We identified CD8lo(+)FAS(+) LGLs to be polyclonal T cells lacking CD56 expression. Blood smears from HIV-infected individuals and SIVmac239-infected rhesus macaques revealed increased LGLs compared to HIV/SIV negative counterparts. In humans, there was no correlation with viral load or treatment and in macaques the LGLs arose in acute SIV infection with increases in viremia. This is the first report describing and partially characterizing LGL lymphocytosis in association with lentiviral infections in three different species. PMID:26292765

  15. Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

    PubMed Central

    Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

    2013-01-01

    Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

  16. Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

    PubMed

    Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

    2013-01-01

    Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. PMID:23098805

  17. Retrograde ejaculation associated spontaneous sperm cystolithiasis in four rhesus macaques (Macaca mulatta).

    PubMed

    Gumber, Sanjeev; Courtney, Cynthia L; Strait, Karen R; Sharma, Prachi; Freebersyser, Julie E; Crane, Maria M

    2013-11-01

    Retrograde ejaculation (RE) has been reported in humans and animals but RE with subsequent sperm calculi has rarely been reported. This report documents clinical and pathological findings of spontaneous sperm cystolithiasis in four rhesus macaques. While this condition has been associated with repeated electroejaculation, spontaneous sperm cystolithiasis is highly unusual. The animals presented with either stranguria, dysuria, hematuria, distended abdomen or lethargy. Ultrasound examination revealed several hyperechoic masses within the lumen of the urinary bladder. The animals were euthanized due to poor prognosis or study end points. Postmortem examination revealed multiple angular, amorphous, soft to firm, pale yellow to greenish-brown and variably sized calculi in the lumen of the urinary bladder or prostatic/penile urethra. Histologically, the calculi were composed of numerous sperm embedded in abundant brightly eosinophilic matrix. Based on gross and histologic findings, RE associated sperm cystolithiasis was diagnosed, with ulcerative urethritis as the major primary apparent etiology. To the authors' knowledge, this is the first report of four spontaneous cases of sperm cystolithiasis in rhesus macaques. PMID:23735542

  18. Retrograde ejaculation associated spontaneous sperm cystolithiasis in four Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Gumber, Sanjeev; Courtney, Cynthia L; Strait, Karen R; Sharma, Prachi; Freebersyser, Julie E; Crane, Maria M

    2015-01-01

    Retrograde ejaculation (RE) has been reported in humans and animals but RE with subsequent sperm calculi has rarely been reported. This report documents clinical and pathological findings of spontaneous sperm cystolithiasis in four rhesus macaques. While this condition has been associated with repeated electroejaculation, spontaneous sperm cystolithiasis is highly unusual. The animals presented with either stranguria, dysuria, hematuria, distended abdomen or lethargy. Ultrasound examination revealed several hyperechoic masses within the lumen of the urinary bladder. The animals were euthanized due to poor prognosis or study end points. Postmortem examination revealed multiple angular, amorphous, soft to firm, pale yellow to greenish-brown and variably sized calculi in the lumen of the urinary bladder or prostatic/penile urethra. Histologically, the calculi were composed of numerous sperm embedded in abundant brightly eosinophilic matrix. Based on gross and histologic findings, RE associated sperm cystolithiasis was diagnosed, with ulcerative urethritis as the major primary apparent etiology. To the authors’ knowledge, this is the first report of four spontaneous cases of sperm cystolithiasis in rhesus macaques. PMID:23735542

  19. Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin.

    PubMed

    Pincus, Seth H; Bhaskaran, Manoj; Brey, Robert N; Didier, Peter J; Doyle-Meyers, Lara A; Roy, Chad J

    2015-06-01

    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

  20. Cortical chemoarchitecture shapes macroscale effective functional connectivity patterns in macaque cerebral cortex.

    PubMed

    Turk, Elise; Scholtens, Lianne H; van den Heuvel, Martijn P

    2016-05-01

    The mammalian cortex is a complex system of-at the microscale level-interconnected neurons and-at the macroscale level-interconnected areas, forming the infrastructure for local and global neural processing and information integration. While the effects of regional chemoarchitecture on local cortical activity are well known, the effect of local neurotransmitter receptor organization on the emergence of large scale region-to-region functional interactions remains poorly understood. Here, we examined reports of effective functional connectivity-as measured by the action of strychnine administration acting on the chemical balance of cortical areas-in relation to underlying regional variation in microscale neurotransmitter receptor density levels in the macaque cortex. Linking cortical variation in microscale receptor density levels to collated information on macroscale functional connectivity of the macaque cortex, we show macroscale patterns of effective corticocortical functional interactions-and in particular, the strength of connectivity of efferent macroscale pathways-to be related to the ratio of excitatory and inhibitory neurotransmitter receptor densities of cortical areas. Our findings provide evidence for the microscale chemoarchitecture of cortical areas to have a direct stimulating influence on the emergence of macroscale functional connectivity patterns in the mammalian brain. Hum Brain Mapp 37:1856-1865, 2016. © 2016 Wiley Periodicals, Inc. PMID:26970255

  1. Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

    PubMed

    Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

    2015-09-01

    In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. PMID:25902927

  2. Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation.

    PubMed

    Ueno, Masataka; Nakamichi, Masayuki

    2016-08-01

    It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation. PMID:27262980

  3. Muscarinic Acetylcholine Receptors in Macaque V1 Are Most Frequently Expressed by Parvalbumin-Immunoreactive Neurons

    PubMed Central

    Disney, Anita A.; Aoki, Chiye

    2010-01-01

    Acetylcholine (ACh) is believed to underlie mechanisms of arousal and attention in mammals. ACh also has a demonstrated functional effect in visual cortex that is both diverse and profound. We have reported previously that cholinergic modulation in V1 of the macaque monkey is strongly targeted toward GABAergic interneurons. Here we examine the localization of m1 and m2 muscarinic receptor subtypes across subpopulations of GABAergic interneurons—identified by their expression of the calcium-binding proteins parvalbumin, calbindin, and calretinin—using dual-immunofluorescence confocal microscopy in V1 of the macaque monkey. In doing so, we find that the vast majority (87%) of parvalbumin-immunoreactive neurons express m1-type muscarinic ACh receptors. m1 receptors are also expressed by 60% of calbindin-immunoreactive neurons and 40% of calretinin-immunoreactive neurons. m2 AChRs, on the other hand, are expressed by only 31% of parvalbumin neurons, 23% of calbindin neurons, and 25% of calretinin neurons. Parvalbumin-immunoreactive cells comprise ≈75% of the inhibitory neuronal population in V1 and included in this large subpopulation are neurons known to veto and regulate the synchrony of principal cell spiking. Through the expression of m1 ACh receptors on nearly all of these PV cells, the cholinergic system avails itself of powerful control of information flow through and processing within the network of principal cells in the cortical circuit. PMID:18265004

  4. Adaptation to speed in macaque middle temporal and medial superior temporal areas.

    PubMed

    Price, Nicholas S C; Born, Richard T

    2013-03-01

    The response of a sensory neuron to an unchanging stimulus typically adapts, showing decreases in response gain that are accompanied by changes in the shape of tuning curves. It remains unclear whether these changes arise purely due to spike rate adaptation within single neurons or whether they are dependent on network interactions between neurons. Further, it is unclear how the timescales of neural and perceptual adaptation are related. To examine this issue, we compared speed tuning of middle temporal (MT) and medial superior temporal neurons in macaque visual cortex after adaptation to two different reference speeds. For 75% of speed-tuned units, adaptation caused significant changes in tuning that could be explained equally well as lateral shifts, vertical gain changes, or both. These tuning changes occurred rapidly, as both neuronal firing rate and Fano factor showed no evidence of changing beyond the first 500 ms after motion onset, and the magnitude of tuning curve changes showed no difference between trials with adaptation durations shorter or longer than 1 s. Importantly, the magnitude of tuning shifts was correlated with the transient-sustained index, which measures a well characterized form of rapid response adaptation in MT, and is likely associated with changes at the level of neuronal networks. Tuning curves changed in a manner that increased neuronal sensitivity around the adapting speed, consistent with improvements in human and macaque psychophysical performance that we observed over the first several hundred ms of adaptation. PMID:23467352

  5. Assessing the Effects of Tourist Provisioning on the Health of Wild Barbary Macaques in Morocco.

    PubMed

    Maréchal, Laëtitia; Semple, Stuart; Majolo, Bonaventura; MacLarnon, Ann

    2016-01-01

    Feeding wildlife is a very popular tourist activity, largely because it facilitates the close observation of animals in their natural habitat. Such provisioning may benefit animals by improving their survival and reproductive success, especially during periods of natural food shortage. However, provisioning by tourists may also have negative impacts on the health of the animals involved; to date such impacts are poorly understood. Here, we investigated the effects of tourist provisioning on the health of wild adult Barbary macaques, Macaca sylvanus, in Morocco. We compared health measures between a heavily provisioned group and a group that received negligible food from tourists and, in the former group, we also assessed health measures in relation to the intensity of provisioning. We used a broad range of non-invasive health measures relating to birth rate and survival, disease and injury risk, body size and condition, and physiological stress. Our findings indicate that feeding by tourists may overall have negative impacts on the health of Barbary macaques, being linked in particular to larger body size, elevated stress levels and more alopecia. Finally, we propose a framework to help consider the potential costs and benefits of provisioning, which may facilitate future research and management decisions on whether-and how much-provisioning is acceptable. PMID:27203861

  6. Use of an Aquarium as a Novel Enrichment Item for Singly Housed Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Meade, Theresa M; Hutchinson, Eric; Krall, Caroline; Watson, Julie

    2014-01-01

    Lo