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Sample records for macaque cd8aa homodimer

  1. GHR/PRLR Heteromultimer Is Composed of GHR Homodimers and PRLR Homodimers.

    PubMed

    Liu, Ying; Zhang, Yue; Jiang, Jing; Lobie, Peter E; Paulmurugan, Ramasamy; Langenheim, John F; Chen, Wen Y; Zinn, Kurt R; Frank, Stuart J

    2016-05-01

    GH receptor (GHR) and prolactin (PRL) receptor (PRLR) are homologous transmembrane cytokine receptors. Each prehomodimerizes and ligand binding activates Janus Kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) signaling pathways by inducing conformational changes within receptor homodimers. In humans, GHR is activated by GH, whereas PRLR is activated by both GH and PRL. We previously devised a split luciferase complementation assay, in which 1 receptor is fused to an N-terminal luciferase (Nluc) fragment, and the other receptor is fused to a C-terminal luciferase (Cluc) fragment. When receptors approximate, luciferase activity (complementation) results. Using this assay, we reported ligand-independent GHR-GHR complementation and GH-induced complementation changes characterized by acute augmentation above basal signal, consistent with induction of conformational changes that bring GHR cytoplasmic tails closer. We also demonstrated association between GHR and PRLR in T47D human breast cancer cells by coimmunoprecipitation, suggesting that, in addition to forming homodimers, these receptors form hetero-assemblages with functional consequences. We now extend these analyses to examine basal and ligand-induced complementation of coexpressed PRLR-Nluc and PRLR-Cluc chimeras and coexpressed GHR-Nluc and PRLR-Cluc chimeras. We find that PRLR-PRLR and GHR-PRLR form specifically interacting ligand-independent assemblages and that either GH or PRL augments PRLR-PRLR complementation, much like the GH-induced changes in GHR-GHR dimers. However, in contrast to the complementation patterns for GHR-GHR or PRLR-PRLR homomers, both GH and PRL caused decline in luciferase activity for GHR-PRLR heteromers. These and other data suggest that GHR and PRLR associate in complexes comprised of GHR-GHR/PRLR-PRLR heteromers consisting of GHR homodimers and PRLR homodimers, rather than GHR-PRLR heterodimers. PMID:27003442

  2. Observation of an E2 (Ubc9)-homodimer by crystallography.

    PubMed

    Alontaga, Aileen Y; Ambaye, Nigus D; Li, Yi-Jia; Vega, Ramir; Chen, Chih-Hong; Bzymek, Krzysztof P; Williams, John C; Hu, Weidong; Chen, Yuan

    2016-06-01

    Post-translational modifications by the small ubiquitin-like modifiers (SUMO), in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009) [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2) for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A). This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1), SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015) [2], [3], [4], [5], [6], [7], [8], [9], [10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999) [10], [11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C). The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The

  3. Observation of an E2 (Ubc9)-homodimer by crystallography.

    PubMed

    Alontaga, Aileen Y; Ambaye, Nigus D; Li, Yi-Jia; Vega, Ramir; Chen, Chih-Hong; Bzymek, Krzysztof P; Williams, John C; Hu, Weidong; Chen, Yuan

    2016-06-01

    Post-translational modifications by the small ubiquitin-like modifiers (SUMO), in particular the formation of poly-SUMO-2 and -3 chains, regulates essential cellular functions and its aberration leads to life-threatening diseases (Geoffroy and Hay, 2009) [1]. It was shown previously that the non-covalent interaction between SUMO and the conjugating enzyme (E2) for SUMO, known as Ubc9, is required for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. However, the structure of SUMO-Ubc9 non-covalent complex, by itself, could not explain how the poly-SUMO-2/3 chain forms and consequently a Ubc9 homodimer, although never been observed, was proposed for poly-SUMO-2/3 chain formation (Knipscheer et al., 2007) [2]. Here, we solved the crystal structure of a heterotrimer containing a homodimer of Ubc9 and the RWD domain from RWDD3. The asymmetric Ubc9 homodimer is mediated by the N-terminal region of one Ubc9 molecule and a surface near the catalytic Cys of the second Ubc9 molecule (Fig. 1A). This N-terminal surface of Ubc9 that is involved in the homodimer formation also interacts with the RWD domain, the ubiquitin-fold domain of the SUMO activating enzyme (E1), SUMO, and the E3 ligase, RanBP2 (Knipscheer et al., 2007; Tong et al.. 1997; Tatham et al., 2005; Reverter and Lima, 2005; Capili and Lima, 2007; Wang et al., 2009, 2010; Wang and Chen, 2010; Alontaga et al., 2015) [2], [3], [4], [5], [6], [7], [8], [9], [10]. The existence of the Ubc9 homodimer in solution is supported by previously published solution NMR studies of rotational correlation time and chemical shift perturbation (Alontaga et al., 2015; Yuan et al., 1999) [10], [11]. Site-directed mutagenesis and biochemical analysis suggests that this dimeric arrangement of Ubc9 is likely important for poly-SUMO chain formation (Fig. 1B and C). The asymmetric Ubc9 homodimer described for the first time in this work could provide the critical missing link in the poly-SUMO chain formation mechanism. The

  4. [Interface domain of hepatitis E virus capsid protein homodimer].

    PubMed

    Li, Shao-Wei; He, Zhi-Qiang; Wang, Ying-Bin; Chen, Yi-Xin; Liu, Ru-Shi; Lin, Jian; Gu, Ying; Zhang, Jun; Xia, Ning-Shao

    2004-01-01

    Hepatitis E is a main cause of acute viral hepatitis in developing countries where it occurs as sporadic cases and in epidemics form. The causative agent, hepatitis E virus, is transmitted primarily by the fecal-oral route. The approximately 7.5 kb positive-sense single-strand RNA genome includes three open reading frames (ORFs), one of which (ORF2) is postulated to encode the major viral capsid protein (pORF2) of 660 amino acid residues. We earlier showed that a bacterially expressed peptide, designated as NE2, located from amino acid residues 394 to 606 of ORF2, was found to aggregate into homodimer to at least hexamer. To understand the interface domains within this peptide vital for dimerization and formation of major neutralizing epitopes, NE2 protein underwent terminal-truncated and site-directed mutation. The hydrophobic region, ORF2 aa597-aa602 (AVAVLA), played a key role in oligomerization. Any amino acid residue of this region replaced with glutamic acid residue, the peptide can not refold as homodimer and/or oligomer. The immunoreactivities of these mutant peptides, blotted with anti-HEV neutralizing monoclonal antibody (8C11) and convalescent human sera, show associated to the formation of homodimer. The intermolecular contact region on homodimer was investigated by chemical cross-linking of two site-directed cysteines. When the alanine on aa597 site mutated with cysteine, two different homodimers were found in SDS-PAGE analysis. One (42kD) can be disassociated with 8mol/L urea, which is postulated to form by virtue of hydrophobic interaction, and the other (60kD) falls apart with the reductant DTT present. The exact conformation, generating the cross-linking reaction of cysteines, was further investigated by induced-oxidation on monomer and hydrophobic homodimer of A597C protein with GSH/GSSG. And the results revealed, it is the conformation of hydrophobic homodimer that induces the disulfide bond come into being, instead of the one of monomer. So the

  5. A covalent homodimer probing early oligomers along amyloid aggregation

    PubMed Central

    Halabelian, Levon; Relini, Annalisa; Barbiroli, Alberto; Penco, Amanda; Bolognesi, Martino; Ricagno, Stefano

    2015-01-01

    Early oligomers are crucial in amyloid aggregation; however, due to their transient nature they are among the least structurally characterized species. We focused on the amyloidogenic protein beta2-microglobulin (β2m) whose early oligomers are still a matter of debate. An intermolecular interaction between D strands of facing β2m molecules was repeatedly observed, suggesting that such interface may be relevant for β2m dimerization. In this study, by mutating Ser33 to Cys, and assembling the disulphide-stabilized β2m homodimer (DimC33), such DD strand interface was locked. Although the isolated DimC33 display a stability similar to wt β2m under native conditions, it shows enhanced amyloid aggregation propensity. Three distinct crystal structures of DimC33 suggest that dimerization through the DD interface is instrumental for enhancing DimC33 aggregation propensity. Furthermore, the crystal structure of DimC33 in complex with the amyloid-specific dye Thioflavin-T pinpoints a second interface, which likely participates in the first steps of β2m aggregation. The present data provide new insight into β2m early steps of amyloid aggregation. PMID:26420657

  6. Vector description of electric and hydrophobic interactions in protein homodimers.

    PubMed

    Mozo-Villarías, Angel; Cedano, Juan; Querol, Enrique

    2016-05-01

    This article describes the formation of homodimers from their constituting monomers, based on the rules set by a simple model of electric and hydrophobic interactions. These interactions are described in terms of the electric dipole moment (D) and hydrophobic moment vectors (H) of proteins. The distribution of angles formed by the two dipole moments of monomers constituting dimers were analysed, as well as the distribution of angles formed by the two hydrophobic moments. When these distributions were fitted to Gaussian curves, it was found that for biological dimers, the D vectors tend mostly to adopt a perpendicular arrangement with respect to each other, in which the constituting dipoles have the least interaction. A minor population tends towards an antiparallel arrangement implying maximum electric attraction. Also in biological dimers, the H vectors of most monomers tend to interact in such a way that the total hydrophobic moment of the dimer increases with respect to those of the monomers. This shows that hydrophobic moments have a tendency to align. In dimers originating in the crystallisation process, the distribution of angles formed by both hydrophobic and electric dipole moments appeared rather featureless, probably because of unspecific interactions in the crystallisation processes. The model does not describe direct interactions between H and D vectors although the distribution of angles formed by both vectors in dimers was analysed. It was found that in most cases these angles tended to be either small (both moments aligned parallel to each other) or large (antiparallel disposition). PMID:26658743

  7. IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis.

    PubMed

    Lee, Seon-Yeong; Jung, Young Ok; Kim, Doo-Jin; Kang, Chang-Min; Moon, Young-Mee; Heo, Yu-Jung; Oh, Hye-Jwa; Park, Seong-Jeong; Yang, Se-Hwan; Kwok, Seung Ki; Ju, Ji-Hyeon; Park, Sung-Hwan; Sung, Young Chul; Kim, Ho-Youn; Cho, Mi-La

    2015-10-01

    IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)2 subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist-knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)2 on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)2 model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)2 inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4(+)CD25(+)Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor-related organ receptor γt and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)2 suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling. PMID:26324771

  8. IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis

    PubMed Central

    Lee, Seon-Yeong; Jung, Young Ok; Kim, Doo-Jin; Kang, Chang-Min; Moon, Young-Mee; Heo, Yu-Jung; Oh, Hye-Jwa; Park, Seong-Jeong; Yang, Se-Hwan; Kwok, Seung Ki; Ju, Ji-Hyeon; Park, Sung-Hwan; Sung, Young Chul

    2015-01-01

    IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)2 subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist–knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)2 on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)2 model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)2 inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4+CD25+Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor–related organ receptor γt and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)2 suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling. PMID:26324771

  9. Japanese macaques as laboratory animals.

    PubMed

    Isa, Tadashi; Yamane, Itaru; Hamai, Miya; Inagaki, Haruhisa

    2009-10-01

    The Japanese macaque (Macaca fuscata), along with rhesus and long-tailed macaques, is one of the macaca species. In Japan, it has been preferred for use as a laboratory animal, particularly in the field of neuroscience, because of its high level of intelligence and its gentle nature. In addition, the species has a relatively homogeneous genetic background and field researchers have accumulated abundant information on the social behavior of wild Japanese macaques. As future neuroscience research will undoubtedly be more focused on the higher cognitive functions of the brain, including social behavior among multiple individuals, the Japanese macaque can be expected to become even more valuable as a laboratory animal in the near future. The Ministry of Education, Culture, Sports, Science and Technology has launched a National BioResource Project (NBRP) to establish a stable breeding and supply system for Japanese macaques for laboratory use. The project is in progress and should lead to the establishment of a National Primate Center in Japan, which will support the supply of monkeys as well as social outreach and handling of animal welfare issues.

  10. The basic helix-loop-helix transcription factor Hand1 regulates mouse development as a homodimer.

    PubMed

    Hu, Dong; Scott, Ian C; Snider, Fran; Geary-Joo, Colleen; Zhao, Xiang; Simmons, David G; Cross, James C

    2013-10-15

    Hand1 is a basic helix-loop-helix transcription factor that is essential for development of the placenta, yolk sac and heart during mouse development. While Hand1 is essential for trophoblast giant cell (TGC) differentiation, its potential heterodimer partners are not co-expressed in TGCs. To test the hypothesis that Hand1 functions as homodimer, we generated knock-in mice in which the Hand1 gene was altered to encode a tethered homodimer (TH). Some Hand1(TH/-) conceptuses in which the only form of Hand1 is Hand1(TH) are viable and fertile, indicating that homodimer Hand1 is sufficient for mouse survival. ~2/3 of Hand1(TH/-) and all Hand1(TH/TH) mice died in utero and displayed severe placental defects and variable cardial and cranial-facial abnormalities, indicating a dosage-dependent effect of Hand1(TH). Meanwhile, expression of the Hand1(TH) protein did not have negative effects on viability or fertility in all Hand1(TH/+) mice. These data imply that Hand1 homodimer plays a dominant role during development and its expression dosage is critical for survival, whereas Hand1 heterodimers can be either dispensable or play a regulatory role to modulate the activity of Hand1 homodimer in vivo.

  11. Nicotinamidase/pyrazinamidase of Mycobacterium tuberculosis forms homo-dimers stabilized by disulfide bonds.

    PubMed

    Rueda, Daniel; Sheen, Patricia; Gilman, Robert H; Bueno, Carlos; Santos, Marco; Pando-Robles, Victoria; Batista, Cesar V; Zimic, Mirko

    2014-12-01

    Recombinant wild-pyrazinamidase from H37Rv Mycobacterium tuberculosis was analyzed by gel electrophoresis under differential reducing conditions to evaluate its quaternary structure. PZAse was fractionated by size exclusion chromatography under non-reducing conditions. PZAse activity was measured and mass spectrometry analysis was performed to determine the identity of proteins by de novo sequencing and to determine the presence of disulfide bonds. This study confirmed that M. tuberculosis wild type PZAse was able to form homo-dimers in vitro. Homo-dimers showed a slightly lower specific PZAse activity compared to monomeric PZAse. PZAse dimers were dissociated into monomers in response to reducing conditions. Mass spectrometry analysis confirmed the existence of disulfide bonds (C72-C138 and C138-C138) stabilizing the quaternary structure of the PZAse homo-dimer.

  12. 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

  13. Structures of the Yeast Ribonucleotide Reductase Rnr2 and Rnr4 Homodimers

    SciTech Connect

    Sommerhalter, M.; Voegtli, W.C.; Perlstein, D.L.; Ge, J.; Stubbe, J.; Rosenzweig, A.C.

    2010-03-08

    Class I ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides. Eukaryotic RNRs comprise two subunits, the R1 subunit, which contains substrate and allosteric effector binding sites, and the R2 subunit, which houses a catalytically essential diiron-tyrosyl radical cofactor. In Saccharomyces cerevisiae, there are two variants of the R2 subunit, called Rnr2 and Rnr4. Rnr4 is unique in that it lacks three iron-binding residues conserved in all other R2s. Nevertheless, Rnr4 is required to activate Rnr2, and the functional species in vivo is believed to be a heterodimeric complex between the two proteins. The crystal structures of the Rnr2 and Rnr4 homodimers have been determined and are compared to that of the heterodimer. The homodimers are very similar to the heterodimer and to mouse R2 in overall fold, but there are several key differences. In the Rnr2 homodimer, one of the iron-binding helices, helix {alpha}B, is not well-ordered. In the heterodimer, interactions with a loop region connecting Rnr4 helices {alpha}A and {alpha}3 stabilize this Rnr2 helix, which donates iron ligand Asp 145. Sequence differences between Rnr2 and Rnr4 prevent the same interactions from occurring in the Rnr2 homodimer. These findings provide a structural rationale for why the heterodimer is the preferred complex in vivo. The active-site region in the Rnr4 homodimer reveals interactions not apparent in the heterodimer, supporting previous conclusions that this subunit does not bind iron. When taken together, these results support a model in which Rnr4 stabilizes Rnr2 for cofactor assembly and activity.

  14. Encapsulation and Characterization of Proton-Bound Amine Homodimers in a Water Soluble, Self-Assembled Supramolecular Host

    SciTech Connect

    Pluth, Michael; Fiedler, Dorothea; Mugridge, Jeffrey; Bergman, Robert; Raymond, Kenneth

    2008-10-01

    Cyclic amines can be encapsulated in a water-soluble self-assembled supramolecular host upon protonation. The hydrogen bonding ability of the cyclic amines, as well as the reduced degrees of rotational freedom, allows for the formation of proton-bound homodimers inside of the assembly which are otherwise not observable in aqueous solution. The generality of homodimer formation was explored with small N-alkyl aziridines, azetidines, pyrrolidines and piperidines. Proton-bound homodimer formation is observed for N-alkylaziridines (R = methyl, isopropyl, tert-butyl), N-alkylazetidines (R = isopropyl, tertbutyl), and N-methylpyrrolidine. At high concentration, formation of a proton-bound homotrimer is observed in the case of N-methylaziridine. The homodimers stay intact inside the assembly over a large concentration range, thereby suggesting cooperative encapsulation. Both G3(MP2)B3 and G3B3 calculations of the proton-bound homodimers were used to investigate the enthalpy of the hydrogen bond in the proton-bound homodimers and suggest that the enthalpic gain upon formation of the proton-bound homodimers may drive guest encapsulation.

  15. Assembly of Bak homodimers into higher order homooligomers in the mitochondrial apoptotic pore

    PubMed Central

    Mandal, Tirtha; Shin, Seungjin; Aluvila, Sreevidya; Chen, Hui-Chen; Grieve, Carter; Choe, Jun-Yong; Cheng, Emily H.; Hustedt, Eric J.; Oh, Kyoung Joon

    2016-01-01

    In mitochondrial apoptosis, Bak is activated by death signals to form pores of unknown structure on the mitochondrial outer membrane via homooligomerization. Cytochrome c and other apoptotic factors are released from the intermembrane space through these pores, initiating downstream apoptosis events. Using chemical crosslinking and double electron electron resonance (DEER)-derived distance measurements between specific structural elements in Bak, here we clarify how the Bak pore is assembled. We propose that previously described BH3-in-groove homodimers (BGH) are juxtaposed via the ‘α3/α5’ interface, in which the C-termini of helices α3 and α5 are in close proximity between two neighboring Bak homodimers. This interface is observed concomitantly with the well-known ‘α6:α6’ interface. We also mapped the contacts between Bak homodimers and the lipid bilayer based on EPR spectroscopy topology studies. Our results suggest a model for the lipidic Bak pore, whereby the mitochondrial targeting C-terminal helix does not change topology to accommodate the lining of the pore lumen by BGH. PMID:27488021

  16. Assembly of Bak homodimers into higher order homooligomers in the mitochondrial apoptotic pore.

    PubMed

    Mandal, Tirtha; Shin, Seungjin; Aluvila, Sreevidya; Chen, Hui-Chen; Grieve, Carter; Choe, Jun-Yong; Cheng, Emily H; Hustedt, Eric J; Oh, Kyoung Joon

    2016-01-01

    In mitochondrial apoptosis, Bak is activated by death signals to form pores of unknown structure on the mitochondrial outer membrane via homooligomerization. Cytochrome c and other apoptotic factors are released from the intermembrane space through these pores, initiating downstream apoptosis events. Using chemical crosslinking and double electron electron resonance (DEER)-derived distance measurements between specific structural elements in Bak, here we clarify how the Bak pore is assembled. We propose that previously described BH3-in-groove homodimers (BGH) are juxtaposed via the 'α3/α5' interface, in which the C-termini of helices α3 and α5 are in close proximity between two neighboring Bak homodimers. This interface is observed concomitantly with the well-known 'α6:α6' interface. We also mapped the contacts between Bak homodimers and the lipid bilayer based on EPR spectroscopy topology studies. Our results suggest a model for the lipidic Bak pore, whereby the mitochondrial targeting C-terminal helix does not change topology to accommodate the lining of the pore lumen by BGH. PMID:27488021

  17. Nuclear receptor coactivators facilitate vitamin D receptor homodimer action on direct repeat hormone response elements.

    PubMed

    Takeshita, A; Ozawa, Y; Chin, W W

    2000-03-01

    Vitamin D receptor (VDR) is a ligand-dependent transcription factor that regulates target gene expression. Although VDR forms stable heterodimer complex with retinoid X receptors (RXRs) on vitamin D-response elements (VDREs), it is still not clear whether VDR/RXR heterodimers are the only VDR complexes responsible for vitamin D-mediated gene transcription. In this report, we analyzed the effect of nuclear receptor coactivators (SRC-1 and TRAM-1) on VDR homodimer and VDR/RXR heterodimer formation by electrophoretic mobility shift assay. We found that VDR forms stable homodimers after interaction with the coactivators on a VDRE (DR+3). Of particular note, DR+4 and DR+5 hormone-response elements (HREs) may also support such interactions. Cotransfection experiments revealed further that the coactivators enhance ligand-induced VDR transcription on these elements. Our studies suggest the important role of VDR homodimers, in addition to VDR/RXR heterodimers, in vitamin D-induced transactivation. Thus, specific coactivator-VDR interactions on HREs may determine target gene transactivation.

  18. Organization of the mitochondrial apoptotic BAK pore: oligomerization of the BAK homodimers.

    PubMed

    Aluvila, Sreevidya; Mandal, Tirtha; Hustedt, Eric; Fajer, Peter; Choe, Jun Yong; Oh, Kyoung Joon

    2014-01-31

    The multidomain pro-apoptotic Bcl-2 family proteins BAK and BAX are believed to form large oligomeric pores in the mitochondrial outer membrane during apoptosis. Formation of these pores results in the release of apoptotic factors including cytochrome c from the intermembrane space into the cytoplasm, where they initiate the cascade of events that lead to cell death. Using the site-directed spin labeling method of electron paramagnetic resonance (EPR) spectroscopy, we have determined the conformational changes that occur in BAK when the protein targets to the membrane and forms pores. The data showed that helices α1 and α6 disengage from the rest of the domain, leaving helices α2-α5 as a folded unit. Helices α2-α5 were shown to form a dimeric structure, which is structurally homologous to the recently reported BAX "BH3-in-groove homodimer." Furthermore, the EPR data and a chemical cross-linking study demonstrated the existence of a hitherto unknown interface between BAK BH3-in-groove homodimers in the oligomeric BAK. This novel interface involves the C termini of α3 and α5 helices. The results provide further insights into the organization of the BAK oligomeric pores by the BAK homodimers during mitochondrial apoptosis, enabling the proposal of a BAK-induced lipidic pore with the topography of a "worm hole."

  19. Muscle dimensions in the Japanese macaque hand.

    PubMed

    Ogihara, Naomichi; Oishi, Motoharu

    2012-10-01

    Macaques have been used as an important paradigm for understanding the neural control mechanisms of human precision grip capabilities. Therefore, we dissected the forearms and hands of two male Japanese macaques to systematically record the muscle mass, fascicle length and physiological cross-sectional area (PCSA). Comparisons of the mass fractions and PCSA fractions of the hand musculature among the Japanese macaque, chimpanzee, and human demonstrated that the sizes of the thenar and hypothenar eminence muscle groups are more balanced in the macaque and chimpanzee, but those of the thenar eminence group are much larger in the human, indicating that the capacity to generate force at the tip of the thumb is more restricted in macaques, despite their high manual dexterity. In the macaque, however, the extrinsic flexor muscles are much larger, possibly to facilitate weight bearing by the forelimbs in pronograde quadrupedal locomotion and forceful grasping of arboreal supports in gap-crossing movements such as leaping. Taking such anatomical differences imposed on the hand musculoskeletal system into consideration seems to be an important method of clarifying the mechanisms of precision grip in macaques.

  20. 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

  1. 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

  2. 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

  3. Evaluation of a technetium-99m labeled bombesin homodimer for GRPR imaging in prostate cancer.

    PubMed

    Yu, Zilin; Carlucci, Giuseppe; Ananias, Hildo J K; Dierckx, Rudi A J O; Liu, Shuang; Helfrich, Wijnand; Wang, Fan; de Jong, Igle J; Elsinga, Philip H

    2013-02-01

    Multimerization of peptides can improve the binding characteristics of the tracer by increasing local ligand concentration and decreasing dissociation kinetics. In this study, a new bombesin homodimer was developed based on an ε-aminocaproic acid-bombesin(7-14) (Aca-bombesin(7-14)) fragment, which has been studied for targeting the gastrin-releasing peptide receptor (GRPR) in prostate cancer. The bombesin homodimer was conjugated to 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and labeled with (99m)Tc for SPECT imaging. The in vitro binding affinity to GRPR, cell uptake, internalization and efflux kinetics of the radiolabeled bombesin dimer were investigated in the GRPR-expressing human prostate cancer cell line PC-3. Biodistribution and the GRPR-targeting potential were evaluated in PC-3 tumor-bearing athymic nude mice. When compared with the bombesin monomer, the binding affinity of the bombesin dimer is about ten times lower. However, the (99m)Tc labeled bombesin dimer showed a three times higher cellular uptake at 4 h after incubation, but similar internalization and efflux characters in vitro. Tumor uptake and in vivo pharmacokinetics in PC-3 tumor-bearing mice were comparable. The tumor was visible on the dynamic images in the first hour and could be clearly distinguished from non-targeted tissues on the static images after 4 h. The GRPR-targeting ability of the (99m)Tc labeled bombesin dimer was proven in vitro and in vivo. This bombesin homodimer provides a good starting point for further studies on enhancing the tumor targeting activity of bombesin multimers.

  4. Differences in binding behavior of (-)-epigallocatechin gallate to β-lactoglobulin heterodimers (AB) compared to homodimers (A) and (B).

    PubMed

    Keppler, Julia K; Martin, Dierk; Garamus, Vasil M; Schwarz, Karin

    2015-11-01

    The lipocalin β-lactoglobulin (β-LG) exists in different natural genetic variants--of which β-LG A and B are predominant in bovine milk. At physiological conditions the protein dimerizes--building homodimers of β-LG A and β-LG B and heterodimers of β-LG AB. Although β-LG is one of the most intensely characterized lipocalins, the interaction behavior of ligands with hetero- and homodimers of β-LG is largely unknown. The present findings revealed significant differences for hetero- and homodimers regarding ligand binding capacity as tested with a model ligand (i.e. surface binding (-)-epigallocatechin gallate (EGCG)). These findings were confirmed using FT-IR, where the addition of EGCG influenced the β-sheet backbone of homodimer A and B with significantly higher intensity compared to heterodimer AB. Further, shape analysis by SAXS revealed oligomerization of both types of dimers upon addition of EGCG; however, homodimer A and B produced significantly larger aggregates compared to the heterodimer AB. In summary, the present study revealed that EGCG showed significantly different interaction reactivity (binding sites, aggregation size and conformational changes) to the hetero and homodimers of β-LG in the order β-LG A > B > AB. The results suggest that conformational differences between homodimers and heterodimers strongly influence the EGCG binding ability. This may also occur with other polyphenols and ligands of β-LG and gives not only important information for β-LG binding studies, but may also apply for polymorphisms of other self-aggregating lipocalins. PMID:26038095

  5. Differences in binding behavior of (-)-epigallocatechin gallate to β-lactoglobulin heterodimers (AB) compared to homodimers (A) and (B).

    PubMed

    Keppler, Julia K; Martin, Dierk; Garamus, Vasil M; Schwarz, Karin

    2015-11-01

    The lipocalin β-lactoglobulin (β-LG) exists in different natural genetic variants--of which β-LG A and B are predominant in bovine milk. At physiological conditions the protein dimerizes--building homodimers of β-LG A and β-LG B and heterodimers of β-LG AB. Although β-LG is one of the most intensely characterized lipocalins, the interaction behavior of ligands with hetero- and homodimers of β-LG is largely unknown. The present findings revealed significant differences for hetero- and homodimers regarding ligand binding capacity as tested with a model ligand (i.e. surface binding (-)-epigallocatechin gallate (EGCG)). These findings were confirmed using FT-IR, where the addition of EGCG influenced the β-sheet backbone of homodimer A and B with significantly higher intensity compared to heterodimer AB. Further, shape analysis by SAXS revealed oligomerization of both types of dimers upon addition of EGCG; however, homodimer A and B produced significantly larger aggregates compared to the heterodimer AB. In summary, the present study revealed that EGCG showed significantly different interaction reactivity (binding sites, aggregation size and conformational changes) to the hetero and homodimers of β-LG in the order β-LG A > B > AB. The results suggest that conformational differences between homodimers and heterodimers strongly influence the EGCG binding ability. This may also occur with other polyphenols and ligands of β-LG and gives not only important information for β-LG binding studies, but may also apply for polymorphisms of other self-aggregating lipocalins.

  6. Photoelectron spectroscopy and density functional theory studies on the uridine homodimer radical anions

    NASA Astrophysics Data System (ADS)

    Jae Ko, Yeon; Storoniak, Piotr; Wang, Haopeng; Bowen, Kit H.; Rak, Janusz

    2012-11-01

    We report the photoelectron spectrum (PES) of the homogeneous dimer anion radical of uridine, (rU)2•-. It features a broad band consisting of an onset of ˜1.2 eV and a maximum at the electron binding energy (EBE) ranging from 2.0 to 2.5 eV. Calculations performed at the B3LYP/6-31++G** level of theory suggest that the PES is dominated by dimeric radical anions in which one uridine nucleoside, hosting the excess charge on the base moiety, forms hydrogen bonds via its O8 atom with hydroxyl of the other neutral nucleoside's ribose. The calculated adiabatic electron affinities (AEAGs) and vertical detachment energies (VDEs) of the most stable homodimers show an excellent agreement with the experimental values. The anionic complexes consisting of two intermolecular uracil-uracil hydrogen bonds appeared to be substantially less stable than the uracil-ribose dimers. Despite the fact that uracil-uracil anionic homodimers are additionally stabilized by barrier-free electron-induced proton transfer, their relative thermodynamic stabilities and the calculated VDEs suggest that they do not contribute to the experimental PES spectrum of (rU)2•-.

  7. The HhH domain of the human DNA repair protein XPF forms stable homodimers.

    PubMed

    Das, Devashish; Tripsianes, Konstantinos; Jaspers, Nicolaas G J; Hoeijmakers, Jan H J; Kaptein, Robert; Boelens, Rolf; Folkers, Gert E

    2008-03-01

    The human XPF-ERCC1 protein complex plays an essential role in nucleotide excision repair by catalysing positioned nicking of a DNA strand at the 5' side of the damage. We have recently solved the structure of the heterodimeric complex of the C-terminal domains of XPF and ERCC1 (Tripsianes et al., Structure 2005;13:1849-1858). We found that this complex comprises a pseudo twofold symmetry axis and that the helix-hairpin-helix motif of ERCC1 is required for DNA binding, whereas the corresponding domain of XPF is functioning as a scaffold for complex formation with ERCC1. Despite the functional importance of heterodimerization, the C-terminal domain of XPF can also form homodimers in vitro. We here compare the stabilities of homodimeric and heterodimeric complexes of the C-terminal domains of XPF and ERCC1. The higher stability of the XPF HhH complexes under various experimental conditions, determined using CD and NMR spectroscopy and mass spectrometry, is well explained by the structural differences that exist between the HhH domains of the two complexes. The XPF HhH homodimer has a larger interaction interface, aromatic stacking interactions, and additional hydrogen bond contacts as compared to the XPF/ERCC1 HhH complex, which accounts for its higher stability. PMID:17912758

  8. Daughterless homodimer synergizes with Eyeless to induce Atonal expression and retinal neuron differentiation

    PubMed Central

    Tanaka-Matakatsu, Miho; Miller, John; Borger, Daniel; Tang, Wei-Jen; Du, Wei

    2014-01-01

    Class I Basic Helix-Loop-Helix (bHLH) transcription factors form homodimers or heterodimers with class II bHLH proteins. While bHLH heterodimers are known to have diverse roles, little is known about the role of class I homodimers. In this manuscript, we show that linked a dimer of Daughterless (Da), the only Drosophila class I bHLH protein, activates Atonal (Ato) expression and retinal neuron differentiation synergistically with the retinal determination factor Eyeless (Ey). The HLH protein Extramacrocheate (Emc), which forms heterodimer with Da, antagonizes the synergistic activation from Da but not the Da-Da linked dimer with Ey. We show that Da directly interacts with Ey and promotes Ey binding to the Ey binding site in the Ato 3′ enhancer. Interestingly, the Ey binding site in the Ato 3′ enhancer contains an embedded E-box that is also required for the synergistic activation by Ey and Da. Finally we show that mammalian homologs of Ey and Da can functionally replace their Drosophila counterparts to synergistically activate the Ato enhancer, suggesting that the observed function is evolutionary conserved. PMID:24886829

  9. Synthesis and activity of novel homodimers of Morita-Baylis-Hillman adducts against Leishmania donovani: A twin drug approach.

    PubMed

    da Silva, Wagner A V; Rodrigues, Daniele C; de Oliveira, Ramon G; Mendes, Rhuan K S; Olegário, Tayná R; Rocha, Juliana C; Keesen, Tatjana S L; Lima-Junior, Claudio G; Vasconcellos, Mário L A A

    2016-09-15

    It is reported here the synthesis of novel Homodimers 12-19 of Morita-Baylis-Hillman adducts (MBHA) from one-pot Morita-Baylis-Hillman Reaction (MBHR) between aromatic aldehydes as eletrophiles and ethylene glycol diacrylate as Michael acceptor (35-94% yields) using cheap and green conditions. The bioactivities were evaluated against promastigote form of Leishmania donovani. All homodimers showed to be more potent than corresponding monomers. It is worth highlighting that the halogenated homodimers 17 and 18 (0.50μM) is almost 400 times more active than the corresponding monomer 10 and 1.24 times more potent than the second-line drug amphotericin B (0.62μM). Moreover, the selectivity index to 18 is very high (SIrb>400) far better than amphotericin B (SIrb=18.73). This is the first report of twin drugs strategy applied on Morita-Baylis-Hillman adducts. PMID:27520941

  10. 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.

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

    PubMed Central

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

    2015-01-01

    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

  12. A Novel Styryldehydropyridocolinium Homodimer: Synthesis and Fluorescence Properties Upon Interaction with DNA.

    PubMed

    Yao, Huirong; Chang, Lifang; Liu, Chang; Jiao, Xiaojie; He, Song; Liu, Haijun; Zeng, Xianshun

    2015-11-01

    A novel homodimer of the styryldehydropyridocolinium dye (TPTP) has been synthesized and characterized. Free TPTP exhibited low fluorescence quantum yield and large Stokes shift (over 160 nm) in water. However, it showed a significant fluorescence turn-on effect upon intercalation into DNA base pairs. Meanwhile, the fluorescence intensity of the intercalated structures formed by TPTP and DNA decreased quickly upon addition of deoxyribonuclease I, indicating that the dye can be used to monitor deoxyribonuclease I activity and DNA hydrolysis. Electrophoresis analysis revealed that the dye had intercalative binding to DNA and can potentially be used for DNA staining in electrophoresis. Thus, the innate nature of large Stokes shift and excellent fluorescence turn on effect upon interaction with DNA endue the dye with a wide range of applications.

  13. A Novel Styryldehydropyridocolinium Homodimer: Synthesis and Fluorescence Properties Upon Interaction with DNA.

    PubMed

    Yao, Huirong; Chang, Lifang; Liu, Chang; Jiao, Xiaojie; He, Song; Liu, Haijun; Zeng, Xianshun

    2015-11-01

    A novel homodimer of the styryldehydropyridocolinium dye (TPTP) has been synthesized and characterized. Free TPTP exhibited low fluorescence quantum yield and large Stokes shift (over 160 nm) in water. However, it showed a significant fluorescence turn-on effect upon intercalation into DNA base pairs. Meanwhile, the fluorescence intensity of the intercalated structures formed by TPTP and DNA decreased quickly upon addition of deoxyribonuclease I, indicating that the dye can be used to monitor deoxyribonuclease I activity and DNA hydrolysis. Electrophoresis analysis revealed that the dye had intercalative binding to DNA and can potentially be used for DNA staining in electrophoresis. Thus, the innate nature of large Stokes shift and excellent fluorescence turn on effect upon interaction with DNA endue the dye with a wide range of applications. PMID:26384336

  14. The PRiMA-linked Cholinesterase Tetramers Are Assembled from Homodimers

    PubMed Central

    Chen, Vicky P.; Xie, Heidi Q.; Chan, Wallace K. B.; Leung, K. Wing; Chan, Gallant K. L.; Choi, Roy C. Y.; Bon, Suzanne; Massoulié, Jean; Tsim, Karl W. K.

    2010-01-01

    Acetylcholinesterase (AChE) is anchored onto cell membranes by the transmembrane protein PRiMA (proline-rich membrane anchor) as a tetrameric globular form that is prominently expressed in vertebrate brain. In parallel, the PRiMA-linked tetrameric butyrylcholinesterase (BChE) is also found in the brain. A single type of AChE-BChE hybrid tetramer was formed in cell cultures by co-transfection of cDNAs encoding AChET and BChET with proline-rich attachment domain-containing proteins, PRiMA I, PRiMA II, or a fragment of ColQ having a C-terminal GPI addition signal (QN-GPI). Using AChE and BChE mutants, we showed that AChE-BChE hybrids linked with PRiMA or QN-GPI always consist of AChET and BChET homodimers. The dimer formation of AChET and BChET depends on the catalytic domains, and the assembly of tetramers with a proline-rich attachment domain-containing protein requires the presence of C-terminal “t-peptides” in cholinesterase subunits. Our results indicate that PRiMA- or ColQ-linked cholinesterase tetramers are assembled from AChET or BChET homodimers. Moreover, the PRiMA-linked AChE-BChE hybrids occur naturally in chicken brain, and their expression increases during development, suggesting that they might play a role in cholinergic neurotransmission. PMID:20566626

  15. Macaque monkeys experience visual crowding.

    PubMed

    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.

  16. Macaque models of enhanced susceptibility to HIV.

    PubMed

    Henning, Tara R; McNicholl, Janet M; Vishwanathan, Sundaram A; Kersh, Ellen N

    2015-01-01

    There are few nonhuman primate models of enhanced HIV susceptibility. Such models can improve comprehension of HIV acquisition risk factors and provide rigorous testing platforms for preclinical prevention strategies. This paper reviews past, current, and proposed research on macaque HIV acquisition risk models and identifies areas where modeling is significantly lacking. We compare different experimental approaches and provide practical considerations for designing macaque susceptibility studies. Modifiable (mucosal and systemic coinfections, hormonal contraception, and rectal lubricants) and non-modifiable (hormonal fluctuations) risk factors are highlighted. Risk acquisition models via vaginal, rectal, and penile challenge routes are discussed. There is no consensus on the best statistical model for evaluating increased susceptibility, and additional research is required. The use of enhanced susceptibility macaque models would benefit multiple facets of the HIV research field, including basic acquisition and pathogenesis studies as well as the vaccine and other biomedical preventions pipeline.

  17. Radiation and phylogeography in the Japanese macaque, Macaca fuscata.

    PubMed

    Marmi, Josep; Bertranpetit, Jaume; Terradas, Jaume; Takenaka, Osamu; Domingo-Roura, Xavier

    2004-03-01

    The Japanese macaque (Macaca fuscata) presumably differentiated from eastern rhesus macaque (Macaca mulatta) populations during the Pleistocene and the two species are closely related. In order to analyse speciation and subspeciation events in the Japanese macaque and to describe historical and current relationships among their populations, we sequenced and analysed a fragment of 392bp of mitochondrial DNA (mtDNA) control region in 50 individuals belonging to six populations of Japanese macaque and compared these sequences with 89 eastern rhesus macaque control region sequences from GenBank/EMBL database. There were high genetic similarities between both species and only two positions were fixed within each species, which supports the inclusion of the Japanese macaque in a single species with eastern populations of rhesus macaques. Japanese macaque ancestors colonised Japan after the separation of the two species, estimated at between 0.31 and 0.88 million years ago (Mya). The star-like phylogeny, multimodal mismatch distribution, and lack of correlation between geographic and genetic distances are in accordance with a rapid dispersion of macaques throughout the archipelago after the arrival into Japan. The species shows low genetic variation within populations and high levels of genetic differentiation among populations with no mtDNA haplotype shared across populations. Genetic distances between Yakushima macaques (Macaca fuscata yakui) and any other population of Macaca fuscata fuscata subspecies are comparable to the distances between populations of Honshu, Awajishima, and Kyushu, not supporting the classification of Yakushima macaques as a different subspecies.

  18. NFATc2 recruits cJun homodimers to an NFAT site to synergistically activate interleukin-2 transcription.

    PubMed

    Walters, Ryan D; Drullinger, Linda F; Kugel, Jennifer F; Goodrich, James A

    2013-11-01

    Transcription of interleukin-2 (IL-2), a pivotal cytokine in the mammalian immune response, is induced by NFAT and AP-1 transcriptional activators in stimulated T cells. NFATc2 and cJun drive high levels of synergistic human IL-2 transcription, which requires a unique interaction between the C-terminal activation domain of NFATc2 and cJun homodimers. Here we studied the mechanism by which this interaction contributes to synergistic activation of IL-2 transcription. We found that NFATc2 can recruit cJun homodimers to the -45 NFAT element, which lacks a neighboring AP-1 site. The bZip domain of cJun is sufficient to interact with the C-terminal activation domain of NFATc2 in the absence of DNA and this interaction is inhibited by AP-1 DNA. When the -45 NFAT site was replaced by either an NFAT/AP-1 composite site or a single AP-1 site the specificity for cJun homodimers in synergistically activating IL-2 transcription was lost, and cJun/cFos heterodimers strongly activated transcription. These studies support a model in which IL-2 transcriptional synergy is mediated by the unique recruitment of a cJun homodimer to the -45 NFAT site by NFATc2, where it acts as a co-activator for IL-2 transcription.

  19. Crystal structure of schistatin, a disintegrin homodimer from saw-scaled viper (Echis carinatus) at 2.5 A resolution.

    PubMed

    Bilgrami, Sameeta; Tomar, Shailly; Yadav, Savita; Kaur, Punit; Kumar, Janesh; Jabeen, Talat; Sharma, Sujata; Singh, Tej P

    2004-08-13

    This is the first structure of a biological homodimer of disintegrin. Disintegrins are a class of small (4-14 kDa) proteins that bind to transmembrane integrins selectively. The present molecule is the first homodimer that has been isolated from the venom of Echis carinatus. The monomeric chain contains 64 amino acid residues. The three-dimensional structure of schistatin has been determined by the multiple isomorphous replacement method. It has been refined to an R-factor of 0.190 using all the data to 2.5 A resolution. The two subunits of the disintegrin homodimer are related by a 2-fold crystallographic symmetry. Thus, the crystallographic asymmetric unit contains a monomer of disintegrin. The monomer folds into an up-down topology with three sets of antiparallel beta-strands. The structure is well ordered with four intramolecular disulfide bonds. the two monomers are firmly linked to each other through two intermolecular disulfide bridges at their N termini together with several other interactions. This structure has corrected the error in the disulfide bond pattern of the two intermolecular disulfide bridges that was reported earlier using chemical methods. Unique sequence and structural features of the schistatin monomers suggest that they have the ability to bind well with both alphaIIb beta3 and alphav beta3 integrins. The N termini anchored two chains of the dimer diverge away at their C termini exposing the Arg-Gly-Asp motif into opposite directions thus enhancing their binding efficiency to integrins. This is one of the unique features of the present disintegrin homodimer and seems to be responsible for the clustering of integrin molecules. The homodimer binds to integrins apparently with a higher affinity than the monomers and also plays a role in the signaling pathway. PMID:15317139

  20. 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

  1. Personality structure and social style in macaques.

    PubMed

    Adams, Mark James; Majolo, Bonaventura; Ostner, Julia; Schülke, Oliver; De Marco, Arianna; Thierry, Bernard; Engelhardt, Antje; Widdig, Anja; Gerald, Melissa S; Weiss, Alexander

    2015-08-01

    Why regularities in personality can be described with particular dimensions is a basic question in differential psychology. Nonhuman primates can also be characterized in terms of personality structure. Comparative approaches can help reveal phylogenetic constraints and social and ecological patterns associated with the presence or absence of specific personality dimensions. We sought to determine how different personality structures are related to interspecific variation in social style. Specifically, we examined this question in 6 different species of macaques, because macaque social style is well characterized and can be categorized on a spectrum of despotic (Grade 1) versus tolerant (Grade 4) social styles. We derived personality structures from adjectival ratings of Japanese (Macaca fuscata; Grade 1), Assamese (M. assamensis; Grade 2), Barbary (M. sylvanus; Grade 3), Tonkean (M. tonkeana; Grade 4), and crested (M. nigra; Grade 4) macaques and compared these species with rhesus macaques (M. mulatta; Grade 1) whose personality was previously characterized. Using a nonparametric method, fuzzy set analysis, to identify commonalities in personality dimensions across species, we found that all but 1 species exhibited consistently defined Friendliness and Openness dimensions, but that similarities in personality dimensions capturing aggression and social competence reflect similarities in social styles. These findings suggest that social and phylogenetic relationships contribute to the origin, maintenance, and diversification of personality.

  2. Positional behavior of free-ranging Japanese macaques (Macaca fuscata).

    PubMed

    Chatani, Kaoru

    2003-01-01

    Positional behavior was quantitatively studied in identified free-ranging Japanese macaques (Macaca fuscata). Five male and 11 female adults were observed in a forested mountain habitat. Data were analyzed for proportion of bout distance, number and time of each locomotion and postural type. Japanese macaques are semiterrestrial, and mainly walk and run quadrupedally. This supports the notion that Macaca are generally quadrupeds. Sex differences in positional behavior were found in the preference of substrate and types of positional behavior. Males and females tend to be terrestrial and arboreal, respectively. Males leap more frequently and longer in distance than do females when they are feeding in trees. These sex differences are considered to be related to differences in morphology, food choice, social activity, and the nursing of infants. Frequencies of leaping and the distance covered by leaping in Japanese macaques are more than those of long-tailed macaques which are arboreal quadrupeds. However, Japanese macaques leap shorter distances at a time than do long-tailed macaques, which indicates that body size may be related to leaping distance more than the frequency of leaping and the distance covered by leaping. Japanese macaques are not as specialized for terrestrial locomotion as pig-tailed macaques. They use both terrestrial and arboreal supports, and are considered to be semi-terrestrial quadrupeds, somewhere between the arboreal long-tailed macaque and the terrestrial pig-tailed macaque.

  3. Contrasting infection susceptibility of the Japanese macaques and cynomolgus macaques to closely related malaria parasites, Plasmodium vivax and Plasmodium cynomolgi.

    PubMed

    Tachibana, Shin-Ichiro; Kawai, Satoru; Katakai, Yuko; Takahashi, Hideo; Nakade, Toru; Yasutomi, Yasuhiro; Horii, Toshihiro; Tanabe, Kazuyuki

    2015-06-01

    Although the human malaria parasite Plasmodium vivax is closely related to Asian Old World monkey malaria parasites, there are no reports of P. vivax infections in macaques. In this study, we compared the infectivity of P. vivax and Plasmodium cynomolgi in Japanese macaques (Macaca fuscata) and in cynomolgus macaques (Macaca fascicularis). The Japanese macaques were highly susceptible to P. cynomolgi but not to P. vivax, whereas cynomolgus macaques showed mild/limited P. cynomolgi infection and were, also, not susceptible to P. vivax. Serotyping and amino acid sequence comparison of erythrocyte surface Duffy antigen/receptor for chemokines (DARC) indicate that the Japanese macaque DARC sequence is nearly identical to that of rhesus (Macaca mulatta) and cynomolgus macaques. This suggests that the macaques share a common mechanism for preventing P. vivax infection. Comparison of amino acid sequences of the Duffy-binding-like (DBL) domain from several different Plasmodium species suggests that P. vivax DBLs will not bind to macaque DARCs, which can explain the lack of P. vivax infectivity. The DBL sequence analyses also suggest that P. cynomolgi DBLs may target Japanese macaque erythrocytes through a DARC-independent interaction.

  4. Metal-Mediated Affinity and Orientation Specificity in a Computationally Designed Protein Homodimer

    SciTech Connect

    Der, Bryan S.; Machius, Mischa; Miley, Michael J.; Mills, Jeffrey L.; Szyperski, Thomas; Kuhlman, Brian

    2015-10-15

    Computationally designing protein-protein interactions with high affinity and desired orientation is a challenging task. Incorporating metal-binding sites at the target interface may be one approach for increasing affinity and specifying the binding mode, thereby improving robustness of designed interactions for use as tools in basic research as well as in applications from biotechnology to medicine. Here we describe a Rosetta-based approach for the rational design of a protein monomer to form a zinc-mediated, symmetric homodimer. Our metal interface design, named MID1 (NESG target ID OR37), forms a tight dimer in the presence of zinc (MID1-zinc) with a dissociation constant <30 nM. Without zinc the dissociation constant is 4 {micro}M. The crystal structure of MID1-zinc shows good overall agreement with the computational model, but only three out of four designed histidines coordinate zinc. However, a histidine-to-glutamate point mutation resulted in four-coordination of zinc, and the resulting metal binding site and dimer orientation closely matches the computational model (C{alpha} rmsd = 1.4 {angstrom}).

  5. Periaxin and AHNAK Nucleoprotein 2 Form Intertwined Homodimers through Domain Swapping*

    PubMed Central

    Han, Huijong; Kursula, Petri

    2014-01-01

    Periaxin (PRX) is an abundant protein in the peripheral nervous system, with an important role in myelination. PRX participates in large molecular complexes, most likely through the interactions of its N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain. We present the crystal structures of the PDZ-like domains from PRX and its homologue AHNAK nucleoprotein 2 (AHNAK2). The unique intertwined, domain-swapped dimers provide a structural basis for the homodimerization of both proteins. The core of the homodimer is formed by a 6-stranded antiparallel β sheet, with every other strand from a different chain. The AHNAK2 PDZ domain structure contains a bound class III ligand peptide. The binding pocket is preformed, and the peptide-PDZ interactions have unique aspects, including two salt bridges and weak recognition of the peptide C terminus. Tight homodimerization may be central to the scaffolding functions of PRX and AHNAK2 in molecular complexes linking the extracellular matrix to the cytoskeletal network. PMID:24675079

  6. Regulation of the PI3K pathway through a p85α monomer–homodimer equilibrium

    PubMed Central

    Cheung, Lydia WT; Walkiewicz, Katarzyna W; Besong, Tabot MD; Guo, Huifang; Hawke, David H; Arold, Stefan T; Mills, Gordon B

    2015-01-01

    The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p110α-free p85α homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN. As a consequence, homodimeric but not monomeric p85α suppresses the PI3K pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation. Further, the p85α homodimer enhances the lipid phosphatase activity and membrane association of PTEN. Strikingly, we identified cancer patient-derived oncogenic p85α mutations that target the homodimerization or PTEN interaction surface. Collectively, our data suggest the equilibrium of p85α monomer–dimers regulates the PI3K pathway and disrupting this equilibrium could lead to disease development. DOI: http://dx.doi.org/10.7554/eLife.06866.001 PMID:26222500

  7. Interaction of an annexin V homodimer (Diannexin) with phosphatidylserine on cell surfaces and consequent antithrombotic activity.

    PubMed

    Kuypers, Frans A; Larkin, Sandra K; Emeis, Jef J; Allison, Anthony C

    2007-03-01

    Annexin V (AV), a protein with anticoagulant activity, exerts antithrombotic activity by binding to phosphatidylserine (PS), inhibiting activation of serine proteases important in blood coagulation. The potential use of this protein as an anticoagulant is limited as it rapidly passes from the blood into the kidneys due to its relatively small size (36 kDa). We used recombinant DNA technology to produce a homodimer of human AV (DAV, 73 kDa), which exceeds the renal filtration threshold, and has a 6.5-hour half-life in the rat circulation. Human red blood cells with externalized PS were used to show that DAV had a higher affinity for PS-exposing cells than AV. DAV labeling sensitively identifies PS-exposing cells, was found to be a potent inhibitor of the activity of the prothombinase complexes and inhibits the ability of secretory phospholipaseA(2) to hydrolyze phospholipids of PS-exposing cells, reducing the formation of mediators of blood coagulation and reperfusion injury. DAV exerts dose-dependent antithrombotic activity in rat veins. This combination of activities suggests that DAV is a valuable probe to measure PS exposure and may be efficacious as a novel drug in a wide range of clinical situations.

  8. Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping.

    PubMed

    Han, Huijong; Kursula, Petri

    2014-05-16

    Periaxin (PRX) is an abundant protein in the peripheral nervous system, with an important role in myelination. PRX participates in large molecular complexes, most likely through the interactions of its N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain. We present the crystal structures of the PDZ-like domains from PRX and its homologue AHNAK nucleoprotein 2 (AHNAK2). The unique intertwined, domain-swapped dimers provide a structural basis for the homodimerization of both proteins. The core of the homodimer is formed by a 6-stranded antiparallel β sheet, with every other strand from a different chain. The AHNAK2 PDZ domain structure contains a bound class III ligand peptide. The binding pocket is preformed, and the peptide-PDZ interactions have unique aspects, including two salt bridges and weak recognition of the peptide C terminus. Tight homodimerization may be central to the scaffolding functions of PRX and AHNAK2 in molecular complexes linking the extracellular matrix to the cytoskeletal network. PMID:24675079

  9. The infrared band intensities and other properties of the homodimers of the methyl and silyl halides: An ab initio study

    NASA Astrophysics Data System (ADS)

    Ford, Thomas A.

    2012-02-01

    The properties of the homodimers of methyl and silyl fluoride, chloride and bromide have been determined by means of ab initio molecular orbital calculations. The interaction energies, molecular structures, vibrational spectra and molecular orbital properties have been investigated, and some common features within each family have been observed. A number of systematic differences in the properties of the dimers have also been noted and rationalized. Typically, discussion of the results of such calculations has focused on the vibrational wavenumber shifts occurring on complexation, and the accompanying changes in the infrared band intensities have received relatively little attention. This paper aims to reposition infrared intensities as valid and useful parameters with which to interpret the formation of the homodimers of polar molecules.

  10. Native Serotonin 5-HT2C Receptors Are Expressed as Homodimers on the Apical Surface of Choroid Plexus Epithelial Cells

    PubMed Central

    Grinde, Ellinor; Lindsley, Tara; Teitler, Milt; Mancia, Filippo; Cowan, Ann; Mazurkiewicz, Joseph E.

    2015-01-01

    G protein–coupled receptors (GPCRs) are a prominent class of plasma membrane proteins that regulate physiologic responses to a wide variety of stimuli and therapeutic agents. Although GPCR oligomerization has been studied extensively in recombinant cells, it remains uncertain whether native receptors expressed in their natural cellular environment are monomers, dimers, or oligomers. The goal of this study was to determine the monomer/oligomer status of a native GPCR endogenously expressed in its natural cellular environment. Native 5-HT2C receptors in choroid plexus epithelial cells were evaluated using fluorescence correlation spectroscopy (FCS) with photon counting histogram (PCH). An anti–5-HT2C fragment antigen binding protein was used to label native 5-HT2C receptors. A known monomeric receptor (CD-86) served as a control for decoding the oligomer status of native 5-HT2C receptors by molecular brightness analysis. FCS with PCH revealed molecular brightness values for native 5-HT2C receptors equivalent to the molecular brightness of a homodimer. 5-HT2C receptors displayed a diffusion coefficient of 5 × 10−9 cm2/s and were expressed at 32 receptors/μm2 on the apical surface of choroid plexus epithelial cells. The functional significance and signaling capabilities of the homodimer were investigated in human embryonic kidney 293 cells using agonists that bind in a wash-resistant manner to one or both protomers of the homodimer. Whereas agonist binding to one protomer resulted in G protein activation, maximal stimulation required occupancy of both protomers. This study is the first to demonstrate the homodimeric structure of 5-HT2C receptors endogenously expressed in their native cellular environment, and identifies the homodimer as a functional signaling unit. PMID:25609374

  11. Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by the cofactor FHL2.

    PubMed

    Hill, Alison A; Riley, Paul R

    2004-11-01

    The basic helix-loop-helix (bHLH) factor Hand1 plays an essential role in cardiac morphogenesis, and yet its precise function remains unknown. Protein-protein interactions involving Hand1 provide a means of determining how Hand1-induced gene expression in the developing heart might be regulated. Hand1 is known to form either heterodimers with near-ubiquitous E-factors and other lineage-restricted class B bHLH proteins or homodimers with itself in vitro. To date, there have been no reported Hand1 protein interactions involving non-bHLH proteins. Heterodimer-versus-homodimer choice is mediated by the phosphorylation status of Hand1; however, little is known about the in vivo function of these dimers or, importantly, how they are regulated. In an effort to understand how Hand1 activity in the heart might be regulated postdimerization, we have investigated tertiary Hand1-protein interactions with non-bHLH factors. We describe a novel interaction of Hand1 with the LIM domain protein FHL2, a known transcriptional coactivator and corepressor expressed in the developing cardiovascular system. FHL2 interacts with Hand1 via the bHLH domain and is able to repress Hand1/E12 heterodimer-induced transcription but has no effect on Hand1/Hand1 homodimer activity. This effect of FHL2 is not mediated either at the level of dimerization or via an effect of Hand1/E12 DNA binding. In summary, our data describe a novel differential regulation of Hand1 heterodimers versus homodimers by association of the cofactor FHL2 and provide insight into the potential for a tertiary level of control of Hand1 activity in the developing heart.

  12. Structure of a Thyroid Hormone Receptor DNA-Binding Domain Homodimer Bound to an Inverted Palindrome DNA Response Element

    SciTech Connect

    Chen, Yi; Young, Matthew A.

    2010-10-22

    Thyroid hormone receptor (TR), as a member of the nuclear hormone receptor family, can recognize and bind different classes of DNA response element targets as either a monomer, a homooligomer, or a heterooligomer. We report here the first crystal structure of a homodimer TR DNA-binding domain (DBD) in complex with an inverted repeat class of thyroid response element (TRE). The structure shows a nearly symmetric structure of the TR DBD assembled on the F2 TRE where the base recognition contacts in the homodimer DNA complex are conserved relative to the previously published structure of a TR-9-cis-retinoic acid receptor heterodimer DNA complex. The new structure also reveals that the T-box region of the DBD can function as a structural hinge that enables a large degree of flexibility in the position of the C-terminal extension helix that connects the DBD to the ligand-binding domain. Although the isolated TR DBDs exist as monomers in solution, we have measured highly cooperative binding of the two TR DBD subunits onto the inverted repeat DNA sequence. This suggests that elements of the DBD can influence the specific TR oligomerization at target genes, and it is not just interactions between the ligand-binding domains that are responsible for TR oligomerization at target genes. Mutational analysis shows that intersubunit contacts at the DBD C terminus account for some, but not all, of the cooperative homodimer TR binding to the inverted repeat class TRE.

  13. Pre-existent asymmetry in the human cyclooxygenase-2 sequence homodimer.

    PubMed

    Dong, Liang; Sharma, Narayan P; Jurban, Brice J; Smith, William L

    2013-10-01

    Prostaglandin endoperoxide H synthase-2 (PGHS-2), also known as cyclooxygenase-2 (COX-2), is a sequence homodimer. However, the enzyme exhibits half-site heme and inhibitor binding and functions as a conformational heterodimer having a catalytic subunit (Ecat) with heme bound and an allosteric subunit (Eallo) lacking heme. Some recombinant heterodimers composed of a COX-deficient mutant subunit and a native subunit (i.e. Mutant/Native PGHS-2) have COX activities similar to native PGHS-2. This suggests that the presence of heme plus substrate leads to the subunits becoming lodged in a semi-stable Eallo-mutant/Ecat-Native∼heme form during catalysis. We examined this concept using human PGHS-2 dimers composed of combinations of Y385F, R120Q, R120A, and S530A mutant or native subunits. With some heterodimers (e.g. Y385F/Native PGHS-2), heme binds with significantly higher affinity to the native subunit. This correlates with near native COX activity for the heterodimer. With other heterodimers (e.g. S530A/Native PGHS-2), heme binds with similar affinities to both subunits, and the COX activity approximates that expected for an enzyme in which each monomer contributes equally to the net COX activity. With or without heme, aspirin acetylates one-half of the subunits of the native PGHS-2 dimer, the Ecat subunits. Subunits having an S530A mutation are refractory to acetylation. Curiously, aspirin acetylates only one-quarter of the monomers of S530A/Native PGHS-2 with or without heme. This implies that there are comparable amounts of two noninterchangeable species of apoenzymes, Eallo-S530A/Ecat-Native and Eallo-Native/Ecat-S530A. These results suggest that native PGHS-2 assumes a reasonably stable, asymmetric Eallo/Ecat form during its folding and processing. PMID:23955344

  14. Human cyclooxygenase-2 is a sequence homodimer that functions as a conformational heterodimer.

    PubMed

    Dong, Liang; Vecchio, Alex J; Sharma, Narayan P; Jurban, Brice J; Malkowski, Michael G; Smith, William L

    2011-05-27

    Prostaglandin endoperoxide H synthases 1 and 2, also known as cyclooxygenases (COXs) 1 and 2, convert arachidonic acid (AA) to prostaglandin endoperoxide H(2). Prostaglandin endoperoxide H synthases are targets of nonspecific nonsteroidal anti-inflammatory drugs and COX-2-specific inhibitors called coxibs. PGHS-2 is a sequence homodimer. Each monomer has a peroxidase and a COX active site. We find that human PGHS-2 functions as a conformational heterodimer having a catalytic monomer (E(cat)) and an allosteric monomer (E(allo)). Heme binds tightly only to the peroxidase site of E(cat), whereas substrates, as well as certain inhibitors (e.g. celecoxib), bind the COX site of E(cat). E(cat) is regulated by E(allo) in a manner dependent on what ligand is bound to E(allo). Substrate and nonsubstrate fatty acids (FAs) and some COX inhibitors (e.g. naproxen) preferentially bind to the COX site of E(allo). AA can bind to E(cat) and E(allo), but the affinity of AA for E(allo) is 25 times that for E(cat). Palmitic acid, an efficacious stimulator of human PGHS-2, binds only E(allo) in palmitic acid/murine PGHS-2 co-crystals. Nonsubstrate FAs can potentiate or attenuate actions of COX inhibitors depending on the FA and whether the inhibitor binds E(cat) or E(allo). Our studies suggest that the concentration and composition of the free FA pool in the environment in which PGHS-2 functions in cells, the FA tone, is a key factor regulating PGHS-2 activity and its responses to COX inhibitors. We suggest that differences in FA tone occurring with different diets will likely affect both base-line prostanoid synthesis and responses to COX inhibitors. PMID:21467029

  15. Mapping the Homodimer Interface of an Optimized, Artificial, Transmembrane Protein Activator of the Human Erythropoietin Receptor

    PubMed Central

    Bears, Zachary; Barrera, Francisco N.; Alonso, Miriam; Engelman, Donald M.; DiMaio, Daniel

    2014-01-01

    Transmembrane proteins constitute a large fraction of cellular proteins, and specific interactions involving membrane-spanning protein segments play an important role in protein oligomerization, folding, and function. We previously isolated an artificial, dimeric, 44-amino acid transmembrane protein that activates the human erythropoietin receptor (hEPOR) in trans. This artificial protein supports limited erythroid differentiation of primary human hematopoietic progenitor cells in vitro, even though it does not resemble erythropoietin, the natural ligand of this receptor. Here, we used a directed-evolution approach to explore the structural basis for the ability of transmembrane proteins to activate the hEPOR. A library that expresses thousands of mutants of the transmembrane activator was screened for variants that were more active than the original isolate at inducing growth factor independence in mouse cells expressing the hEPOR. The most active mutant, EBC5-16, supports erythroid differentiation in human cells with activity approaching that of EPO, as assessed by cell-surface expression of glycophorin A, a late-stage marker of erythroid differentiation. EBC5-16 contains a single isoleucine to serine substitution at position 25, which increases its ability to form dimers. Genetic studies confirmed the importance of dimerization for activity and identified the residues constituting the homodimer interface of EBC5-16. The interface requires a GxxxG dimer packing motif and a small amino acid at position 25 for maximal activity, implying that tight packing of the EBC5-16 dimer is a crucial determinant of activity. These experiments identified an artificial protein that causes robust activation of its target in a natural host cell, demonstrated the importance of dimerization of this protein for engagement of the hEPOR, and provided the framework for future structure-function studies of this novel mechanism of receptor activation. PMID:24788775

  16. The ToxR protein of Vibrio cholerae forms homodimers and heterodimers.

    PubMed Central

    Ottemann, K M; Mekalanos, J J

    1996-01-01

    The ToxR protein of Vibrio cholerae regulates the expression of several virulence factors that play important roles in the pathogenesis of cholera. Previous experiments with ToxR-alkaline phosphatase (ToxR-PhoA) fusion proteins suggested a model for gene regulation in which the inactive form of ToxR was a monomer and the active form of ToxR was a dimer (V. L. Miller, R. K. Taylor, and J. J. Mekalanos, Cell 48:271-279, 1987). In order to examine whether ToxR exists in a dimeric form in vivo, biochemical cross-linking analyses were carried out. Different dimeric cross-linked species were detected depending on the expression level of ToxR: when overexpressed, ToxR+ToxR homodimers and ToxR+ToxS heterodimers were detected, and when ToxR was expressed at normal levels, exclusively ToxR+ToxS heterodimers were detected. The amount of overexpression was quantitated by using ToxR-PhoA fusion proteins and was found to correspond to 2.7-fold the normal level of ToxR. The formation of both homodimeric ToxR species and heterodimeric ToxR+ToxS species is consistent with previously reported genetic data that suggested that both types of ToxR oligomeric interactions occur. However, variation in the amount of either the homodimeric or heterodimeric form detectable by this cross-linking analysis was not observed to correlate with laboratory culture conditions known to modulate ToxR activity. Thus, genetic and biochemical data indicate that ToxR is able to interact with both itself and ToxS but that these interactions may not explain mechanistically the observed changes in ToxR activity that occur in response to environmental conditions. PMID:8550410

  17. Characterization of Corynebacterium species in macaques

    PubMed Central

    Venezia, Jaime; Cassiday, Pamela K.; Marini, Robert P.; Shen, Zeli; Buckley, Ellen M.; Peters, Yaicha; Taylor, Nancy; Dewhirst, Floyd E.; Tondella, Maria L.

    2012-01-01

    Bacteria of the genus Corynebacterium are important primary and opportunistic pathogens. Many are zoonotic agents. In this report, phenotypic (API Coryne analysis), genetic (rpoB and 16S rRNA gene sequencing), and physical methods (MS) were used to distinguish the closely related diphtheroid species Corynebacterium ulcerans and Corynebacterium pseudotuberculosis, and to definitively diagnose Corynebacterium renale from cephalic implants of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques used in cognitive neuroscience research. Throat and cephalic implant cultures yielded 85 isolates from 43 macaques. Identification by API Coryne yielded C. ulcerans (n = 74), Corynebacterium pseudotuberculosis (n = 2), C. renale or most closely related to C. renale (n = 3), and commensals and opportunists (n = 6). The two isolates identified as C. pseudotuberculosis by API Coryne required genetic and MS analysis for accurate characterization as C. ulcerans. Of three isolates identified as C. renale by 16S rRNA gene sequencing, only one could be confirmed as such by API Coryne, rpoB gene sequencing and MS. This study emphasizes the importance of adjunct methods in identification of coryneforms and is the first isolation of C. renale from cephalic implants in macaques. PMID:22723254

  18. 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

  19. Comparative analysis of three-dimensional structures of homodimers of uridine phosphorylase from Salmonella typhimurium in the unligated state and in a complex with potassium ion

    SciTech Connect

    Lashkov, A. A.; Zhukhlistova, N. E.; Gabdulkhakov, A. G.; Mikhailov, A. M.

    2009-03-15

    The spatial organization of the homodimer of unligated uridine phosphorylase from Salmonella typhimurium (St UPh) was determined with high accuracy. The structure was refined at 1.80 A resolution to R{sub work} = 16.1% and R{sub free} = 20.0%. The rms deviations for the bond lengths, bond angles, and chiral angles are 0.006 A, 1.042{sup o}, and 0.071{sup o}, respectively. The coordinate error estimated by the Luzzati plot is 0.166 A. The coordinate error based on the maximum likelihood is 0.199 A. A comparative analysis of the spatial organization of the homodimer in two independently refined structures and the structure of the homodimer St UPh in the complex with a K{sup +} ion was performed. The substrate-binding sites in the homodimers StUPhs in the unligated state were found to act asynchronously. In the presence of a potassium ion, the three-dimensional structures of the subunits in the homodimer are virtually identical, which is apparently of importance for the synchronous action of both substrate-binding sites. The atomic coordinates of the refined structure of the homodimer and structure factors have been deposited in the Protein Data Bank (PDB ID code 3DPS).

  20. 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

  1. 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

  2. Effects of tourists on Barbary macaques at Gibraltar.

    PubMed

    O'Leary, H; Fa, J E

    1993-01-01

    Interactions between tourists and Barbary macaques (Macaca sylvanus) at Queen's Gate, Gibraltar, are described. Interaction rates are high, with 99.6 interactions/h at peak times. Macaques spend 13.2% of their day interacting with tourists and 41.9% inactive. An overall ratio of 3.2:1 between human-initiated and macaque-initiated interactions was found. Of interactions involving humans, 85% concerned tourists. Diurnal activity patterns of the macaques were adapted to tourist visitation patterns. Old animals initiated more food-related interactions than younger ones. Infants/juveniles were the commonest class in contacts with humans and vehicles. Interactions involving more than one macaque were rare. High interaction rates were recorded for mothers and babies.

  3. 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

  4. Cooperative Signaling between Homodimers of Metabotropic Glutamate Receptors 1 and 5

    PubMed Central

    Sevastyanova, Tatyana N.

    2014-01-01

    Metabotropic glutamate receptors (mGluRs) function as dimers. Recent work suggests that mGluR1 and mGluR5 may physically interact, but the nature and functional consequences of this relationship have not been addressed. In this study, the functional and pharmacological consequences of this interaction were investigated. Using heterologous expression of mGluR cDNA in rat sympathetic neurons from the superior cervical ganglion and inhibition of the native calcium currents as an assay for receptor activation, a functional interdependence between mGluR1 and mGluR5 was demonstrated. In neurons coexpressing these receptors, combining a selective mGluR1 competitive antagonist with either an mGluR1- or mGluR5-selective negative allosteric modulator (NAM) BAY36-7620 [(3aS,6aS)-hexahydro-5-methylene-6a-(2-naphthalenylmethyl)-1H-cyclopenta[c]furan-1-one] or MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride], respectively, strongly occluded signaling by both receptors to an approximately equal degree. By contrast, in cells coexpressing mGluR1 and mGluR2, combining the same mGluR1 competitive inhibitor with an mGluR1 or mGluR2 NAM yielded partial and full inhibition of the response, respectively, as expected for independently acting receptors. In neurons expressing mGluR1 and mGluR5, the selective NAMs each strongly inhibited the response to glutamate, suggesting that these receptors do not interact as heterodimers, which would not be inhibited by selective NAMs. Finally, evidence for a similar mGluR1/mGluR5 functional dependence is shown in medium spiny striatal neurons. Together, these data demonstrate cooperative signaling between mGluR1 and mGluR5 in a manner inconsistent with heterodimerization, and thus suggest an interaction between homodimers. PMID:25113912

  5. 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.

  6. 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

  7. 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.

  8. Spectrocolourimetry visualized differences in sexual skin colouration in macaques.

    PubMed

    Ono, Eiri; Suzuki, Juri; Ishida, Takafumi

    2015-01-01

    The females of some catarrhines develop conspicuous sexual skin transformations in their hind limbs. Among macaques (one of the radiated and adapted catarrhine groups with diversified sexual skin transformations), differences in sexual skin colouration between the Japanese macaque Macaca fuscata and the rhesus macaque M. mulatta have not been quantitatively analysed. In this study, the sexual skin colouration of these macaques was spectrocolourimetrically measured in the non-mating season (NMS) and the mating season (MS) and represented in a CIELAB space with the variables L*, a* and b*. The variables L*, a* and b* represent positions on the light-dark, red/magenta-green, and yellow-blue axes, respectively. In the Japanese macaques the average ± SD of L*, a* and b* was 53.61 ± 3.31, 11.51 ± 4.57 and 6.66 ± 2.25 in the NMS and 46.60 ± 2.78, 19.97 ± 2.99 and 8.80 ± 1.34 in the MS, respectively, while in the rhesus macaques the average ± SD of L*, a* and b* was 60.09 ± 3.96, 5.99 ± 4.59 and 5.83 ± 2.37 in the NMS and 52.70 ± 6.54, 13.62 ± 6.86 and 8.07 ± 1.43 in the MS, respectively. The sexual skin of the Japanese macaques was consistently much redder (larger a*) and darker (smaller L*) than that of the rhesus macaques. The smaller L* suggested a greater dermal melanin content in the Japanese macaques. These closely related macaque species have similar but distinct sexual skin colourations. Spectrocolourimetry is thus useful to suggest the histophysiological background of the colouration.

  9. The C-terminal domain of the MutL homolog from Neisseria gonorrhoeae forms an inverted homodimer.

    PubMed

    Namadurai, Sivakumar; Jain, Deepti; Kulkarni, Dhananjay S; Tabib, Chaitanya R; Friedhoff, Peter; Rao, Desirazu N; Nair, Deepak T

    2010-01-01

    The mismatch repair (MMR) pathway serves to maintain the integrity of the genome by removing mispaired bases from the newly synthesized strand. In E. coli, MutS, MutL and MutH coordinate to discriminate the daughter strand through a mechanism involving lack of methylation on the new strand. This facilitates the creation of a nick by MutH in the daughter strand to initiate mismatch repair. Many bacteria and eukaryotes, including humans, do not possess a homolog of MutH. Although the exact strategy for strand discrimination in these organisms is yet to be ascertained, the required nicking endonuclease activity is resident in the C-terminal domain of MutL. This activity is dependent on the integrity of a conserved metal binding motif. Unlike their eukaryotic counterparts, MutL in bacteria like Neisseria exist in the form of a homodimer. Even though this homodimer would possess two active sites, it still acts a nicking endonuclease. Here, we present the crystal structure of the C-terminal domain (CTD) of the MutL homolog of Neisseria gonorrhoeae (NgoL) determined to a resolution of 2.4 Å. The structure shows that the metal binding motif exists in a helical configuration and that four of the six conserved motifs in the MutL family, including the metal binding site, localize together to form a composite active site. NgoL-CTD exists in the form of an elongated inverted homodimer stabilized by a hydrophobic interface rich in leucines. The inverted arrangement places the two composite active sites in each subunit on opposite lateral sides of the homodimer. Such an arrangement raises the possibility that one of the active sites is occluded due to interaction of NgoL with other protein factors involved in MMR. The presentation of only one active site to substrate DNA will ensure that nicking of only one strand occurs to prevent inadvertent and deleterious double stranded cleavage. PMID:21060849

  10. ThWRKY4 from Tamarix hispida Can Form Homodimers and Heterodimers and Is Involved in Abiotic Stress Responses

    PubMed Central

    Wang, Liuqiang; Zheng, Lei; Zhang, Chunrui; Wang, Yucheng; Lu, Mengzhu; Gao, Caiqiu

    2015-01-01

    WRKY proteins are a large family of transcription factors that are involved in diverse developmental processes and abiotic stress responses in plants. However, our knowledge of the regulatory mechanisms of WRKYs participation in protein–protein interactions is still fragmentary, and such protein–protein interactions are fundamental in understanding biological networks and the functions of proteins. In this study, we report that a WRKY protein from Tamarix hispida, ThWRKY4, can form both homodimers and heterodimers with ThWRKY2 and ThWRKY3. In addition, ThWRKY2 and ThWRKY3 can both bind to W-box motif with binding affinities similar to that of ThWRKY4. Further, the expression patterns of ThWRKY2 and ThWRKY3 are similar to that of ThWRKY4 when plants are exposed to abscisic acid (ABA). Subcellular localization shows that these three ThWRKY proteins are nuclear proteins. Taken together, these results demonstrate that ThWRKY4 is a dimeric protein that can form functional homodimers or heterodimers that are involved in abiotic stress responses. PMID:26580593

  11. Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4.

    PubMed

    Nicoludis, John M; Vogt, Bennett E; Green, Anna G; Schärfe, Charlotta Pi; Marks, Debora S; Gaudet, Rachelle

    2016-01-01

    Protocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop and maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of the antiparallel EC1-4 homodimer of human PcdhγB3, a member of the γ subfamily of clustered Pcdhs. Structure and sequence comparisons of α, β, and γ clustered Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification of loop region structure and composition in EC2 and EC3, which contains isoform-specific conservation of primarily polar residues. In contrast, the EC1/EC4 interface comprises hydrophobic interactions that provide non-selective dimerization affinity. Using sequence coevolution analysis, we found evidence for a similar antiparallel EC1-4 interaction in non-clustered Pcdh families. We thus deduce that the EC1-4 antiparallel homodimer is a general interaction strategy that evolved before the divergence of these distinct protocadherin families. PMID:27472898

  12. Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4

    PubMed Central

    Nicoludis, John M; Vogt, Bennett E; Green, Anna G; Schärfe, Charlotta PI; Marks, Debora S; Gaudet, Rachelle

    2016-01-01

    Protocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop and maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of the antiparallel EC1-4 homodimer of human PcdhγB3, a member of the γ subfamily of clustered Pcdhs. Structure and sequence comparisons of α, β, and γ clustered Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification of loop region structure and composition in EC2 and EC3, which contains isoform-specific conservation of primarily polar residues. In contrast, the EC1/EC4 interface comprises hydrophobic interactions that provide non-selective dimerization affinity. Using sequence coevolution analysis, we found evidence for a similar antiparallel EC1-4 interaction in non-clustered Pcdh families. We thus deduce that the EC1-4 antiparallel homodimer is a general interaction strategy that evolved before the divergence of these distinct protocadherin families. DOI: http://dx.doi.org/10.7554/eLife.18449.001 PMID:27472898

  13. Intracranial meningioma with ophthalmoplegia in a rhesus macaque (Macaca mulatta).

    PubMed

    Tanaka, Takayuki; Canfield, Don R

    2012-10-01

    A 21-y-old female rhesus macaque presented with signs of internal and external ophthamoplegia, including anisocoria and ptosis. Ophthalmoplegia is the paralysis or weakness of one or more intraocular or extraocular muscles that control the movement of eye; this condition can be caused by neurologic or muscle disorders. The macaque was euthanized due to progression of clinical symptoms, and postmortem gross examination revealed a mass at the base of the brain attached to the meninges. Histopathologic examination led to the diagnosis of intracranial meningioma. Here we describe a case of intracranial meningioma with internal and external ophthalmoplegia in a rhesus macaque (Macaca mulatta).

  14. 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

  15. 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.

  16. The Rhesus macaque (Macaca mulatta) sperm proteome.

    PubMed

    Skerget, Sheri; Rosenow, Matthew; Polpitiya, Ashoka; Petritis, Konstantinos; Dorus, Steve; Karr, Timothy L

    2013-11-01

    Mass spectrometry based proteomics has facilitated sperm composition studies in several mammalian species but no studies have been undertaken in non-human primate species. Here we report the analysis of the 1247 proteins that comprise the Rhesus macaque (Macaca mulatta) sperm proteome (termed the MacSP). Comparative analysis with previously characterized mouse and human sperm proteomes reveals substantial levels of orthology (47% and 40% respectively) and widespread overlap of functional categories based on Gene Ontology analyses. Approximately 10% of macaque sperm genes (113/1247) are significantly under-expressed in the testis as compared with other tissues, which may reflect proteins specifically acquired during epididymal maturation. Phylogenetic and genomic analyses of three MacSP ADAMs (A-Disintegrin and Metalloprotease proteins), ADAM18-, 20- and 21-like, provides empirical support for sperm genes functioning in non-human primate taxa which have been subsequently lost in the lineages leading to humans. The MacSP contains proteasome proteins of the 20S core subunit, the 19S proteasome activator complex and an alternate proteasome activator PA200, raising the possibility that proteasome activity is present in mature sperm. Robust empirical characterization of the Rhesus sperm proteome should greatly expand the possibility for targeted molecular studies of spermatogenesis and fertilization in a commonly used model species for human infertility.

  17. 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

  18. The Rhesus Macaque (Macaca mulatta) Sperm Proteome*

    PubMed Central

    Skerget, Sheri; Rosenow, Matthew; Polpitiya, Ashoka; Petritis, Konstantinos; Dorus, Steve; Karr, Timothy L.

    2013-01-01

    Mass spectrometry based proteomics has facilitated sperm composition studies in several mammalian species but no studies have been undertaken in non-human primate species. Here we report the analysis of the 1247 proteins that comprise the Rhesus macaque (Macaca mulatta) sperm proteome (termed the MacSP). Comparative analysis with previously characterized mouse and human sperm proteomes reveals substantial levels of orthology (47% and 40% respectively) and widespread overlap of functional categories based on Gene Ontology analyses. Approximately 10% of macaque sperm genes (113/1247) are significantly under-expressed in the testis as compared with other tissues, which may reflect proteins specifically acquired during epididymal maturation. Phylogenetic and genomic analyses of three MacSP ADAMs (A-Disintegrin and Metalloprotease proteins), ADAM18-, 20- and 21-like, provides empirical support for sperm genes functioning in non-human primate taxa which have been subsequently lost in the lineages leading to humans. The MacSP contains proteasome proteins of the 20S core subunit, the 19S proteasome activator complex and an alternate proteasome activator PA200, raising the possibility that proteasome activity is present in mature sperm. Robust empirical characterization of the Rhesus sperm proteome should greatly expand the possibility for targeted molecular studies of spermatogenesis and fertilization in a commonly used model species for human infertility. PMID:23816990

  19. Grooming reciprocity in male Tibetan macaques.

    PubMed

    Xia, Dong-Po; Li, Jin-Hua; Garber, Paul A; Matheson, Megan D; Sun, Bing-Hua; Zhu, Yong

    2013-10-01

    In several primate species, adult males are reported to compete for access to reproductive partners as well as forming affiliative and cohesive social bonds based on the exchange of goods or services. We hypothesized that among a broad set of fitness-maximizing strategies, grooming can be used by individual adult males to enhance social relationships through reciprocity and/or through the interchange of grooming for a different but equivalent good or service. We used focal animal sampling and continuously recorded dyadic grooming and agonistic interactions to test a series of predictions regarding male social interactions in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China. During the non-mating season or between males of similar rank throughout the year, grooming effort given was matched by grooming effort received. However, lower ranking males groomed higher ranking males at a greater rate and/or for a longer duration during both the mating and non-mating periods. We found that higher ranking males directed less aggression towards males with whom they formed a frequent grooming partnership, indicating that grooming received was interchanged for increased social tolerance. These data suggest that individual male Tibetan macaques employ alternative social strategies associated with grooming reciprocity or interchange depending on dominance rank and rates of aggression, and highlight the importance of both biological markets and grooming reciprocity as behavioral mechanisms used by resident adult males to form and maintain affiliative social bonds.

  20. Development of Pattern Recognition in Infant Pigtailed Macaques (Macaca nemestrina).

    ERIC Educational Resources Information Center

    Gunderson, Virginia M.; Sackett, Gene P.

    1984-01-01

    Examined the development of pattern recognition in infant pigtailed macaques using the familiarization novelty technique. Results indicate that by at least 200 days postconception subjects show a consistently reliable visual response to novelty. (Author/RH)

  1. Disseminated Hemangiosarcoma in a Juvenile Rhesus Macaque (Macaca mulatta).

    PubMed

    Beck, Amanda P; Gray, Stanton B; Chaffee, Beth K

    2016-01-01

    Hemangiosarcoma is a malignant tumor of vascular endothelial origin that is sporadically reported in rhesus macaques. This report describes the clinicopathologic features of a 1-y-old rhesus macaque with spontaneous disseminated hemangiosarcoma that originally presented as a focal cutaneous mass. Histopathologic examination of multiple tumor foci revealed regions in which the neoplastic cells formed diffuse sheets, as well as the well-defined vascular channels typically associated with hemangiosarcoma. Multiple endothelial cell immunomarkers were used to confirm the diagnosis in this rhesus macaque. The tumor exhibited staining properties consistent with those seen in domestic animals and humans. In addition, to our knowledge, this animal represents the youngest case of any form of spontaneous hemangiosarcoma reported in the rhesus macaque to date.

  2. A radiation hybrid mapping panel for the rhesus macaque.

    PubMed

    Murphy, W J; Page, J E; Smith, C; Desrosiers, R C; O'Brien, S J

    2001-01-01

    The genomes of nonhuman primates have recently become highly visible candidates for full genome analysis, as they provide powerful models of human disease and a better understanding of the evolution of the human genome. We describe the creation of a 5000 rad radiation hybrid (RH) mapping panel for the rhesus macaque. Duplicate genotypes of 84 microsatellite and coding gene sequence tagged sites from six macaque chromosomes produced an estimated whole genome retention frequency of 0.33. To test the mapping ability of the panel, we constructed RH maps for macaque chromosomes 7 and 9 and compared them to orthologous locus orders in existing human and baboon maps derived from different methodologies. Concordant marker order between all three species maps suggests that the current panel represents a powerful mapping resource for generating high-density comparative maps of the rhesus macaque and other species genomes. PMID:11948222

  3. Theoretical Study on the UVR8 Photoreceptor: Sensing Ultraviolet-B by Tryptophan and Dissociation of Homodimer.

    PubMed

    Li, Xin; Chung, Lung Wa; Morokuma, Keiji; Li, Guohui

    2014-08-12

    By the irradiation of ultraviolet-B (UV-B) light, UVR8 photoreceptor can undergo dissociation of the protein homodimer and regulate gene expression in plants. We have carried out high-level quantum mechanics (QM) and ONIOM(QM:MM) calculations and molecular dynamics (MD) simulations to study spectra of key tryptophan residues in UVR8 homodimer and to clarify the key role of important charged residues and their salt bridges as well as the feasible dissociation mechanism. First, benchmark calculations on the absorption and emission of 3-methylindole in the gas phase have been performed by different QM methods (TD-DFT, CASSCF, MS-CASPT2, and SAC-CI). Twenty different DFT functionals, including double hybrid and Minnesota functionals, were tested, but all these functionals failed to give satisfactory description of two key transitions. In comparison, SAC-CI and CASPT2 methods can give reliable transition energies and a correct order of (1)La and (1)Lb excited states. Furthermore, the vertical absorption and emission energies of tryptophan in UVR8 have been investigated by the ONIOM method. The present results suggest that W285 is the major chromophore of UVR8, while W233 can also sense the UV-B light and may be responsible for exciton coupling. Geometrical effects as well as electrostatic and polarization interactions with the protein matrix were found to influence optical properties of these tryptophan residues in UVR8. At the homodimeric interface, R286-D107 and R338-D44 salt bridges are suggested to play a crucial role for the UVR8 monomerization. In addition, the UV-B induced dissociation mechanism of the UVR8 homodimer has been proposed. The electrostatic repulsion between the partially negatively charged benzene ring of W285 in the (1)La excited state and the negatively charged D44/D107, along with electron and/or proton transfers among W285, R286 (or R338), W233 and D129, was suggested to result in the breakage of the key salt bridges, and destabilization as well

  4. Intra- and interspecific variation in macaque molar enamel thickness.

    PubMed

    Kato, Akiko; Tang, Nancy; Borries, Carola; Papakyrikos, Amanda M; Hinde, Katie; Miller, Ellen; Kunimatsu, Yutaka; Hirasaki, Eishi; Shimizu, Daisuke; Smith, Tanya M

    2014-11-01

    Enamel thickness has played an important role in studies of primate taxonomy, phylogeny, and functional morphology, although its variation among hominins is poorly understood. Macaques parallel hominins in their widespread geographic distribution, relative range of body sizes, and radiation during the last five million years. To explore enamel thickness variation, we quantified average and relative enamel thickness (AET and RET) in Macaca arctoides, Macaca fascicularis, Macaca fuscata, Macaca mulatta, Macaca nemestrina, and Macaca sylvanus. Enamel area, dentine area, and enamel-dentine junction length were measured from mesial sections of 386 molars scanned with micro-computed tomography, yielding AET and RET indices. Intraspecific sex differences were not found in AET or RET. Macaca fuscata had the highest AET and RET, M. fascicularis showed the lowest AET, and M. arctoides had the lowest RET. The latitudinal distribution of macaque species was associated with AET for these six species. Temperate macaques had thicker molar enamel than did tropical macaques, suggesting that thick enamel may be adaptive in seasonal environments. Additional research is needed to determine if thick enamel in temperate macaques is a response to intensified hard-object feeding, increased abrasion, and/or a broader diet with a greater range of food material properties. The extreme ecological flexibility of macaques may prohibit identification of consistent trends between specific diets and enamel thickness conditions. Such complications of interpretation of ecological variability, dietary diversity, and enamel thickness may similarly apply for fossil Homo species.

  5. Color vision test for dichromatic and trichromatic macaque monkeys.

    PubMed

    Koida, Kowa; Yokoi, Isao; Okazawa, Gouki; Mikami, Akichika; Widayati, Kanthi Arum; Miyachi, Shigehiro; Komatsu, Hidehiko

    2013-01-01

    Dichromacy is a color vision defect in which one of the three cone photoreceptors is absent. Individuals with dichromacy are called dichromats (or sometimes "color-blind"), and their color discrimination performance has contributed significantly to our understanding of color vision. Macaque monkeys, which normally have trichromatic color vision that is nearly identical to humans, have been used extensively in neurophysiological studies of color vision. In the present study we employed two tests, a pseudoisochromatic color discrimination test and a monochromatic light detection test, to compare the color vision of genetically identified dichromatic macaques (Macaca fascicularis) with that of normal trichromatic macaques. In the color discrimination test, dichromats could not discriminate colors along the protanopic confusion line, though trichromats could. In the light detection test, the relative thresholds for longer wavelength light were higher in the dichromats than the trichromats, indicating dichromats to be less sensitive to longer wavelength light. Because the dichromatic macaque is very rare, the present study provides valuable new information on the color vision behavior of dichromatic macaques, which may be a useful animal model of human dichromacy. The behavioral tests used in the present study have been previously used to characterize the color behaviors of trichromatic as well as dichromatic new world monkeys. The present results show that comparative studies of color vision employing similar tests may be feasible to examine the difference in color behaviors between trichromatic and dichromatic individuals, although the genetic mechanisms of trichromacy/dichromacy is quite different between new world monkeys and macaques. PMID:24187056

  6. Color vision test for dichromatic and trichromatic macaque monkeys.

    PubMed

    Koida, Kowa; Yokoi, Isao; Okazawa, Gouki; Mikami, Akichika; Widayati, Kanthi Arum; Miyachi, Shigehiro; Komatsu, Hidehiko

    2013-11-01

    Dichromacy is a color vision defect in which one of the three cone photoreceptors is absent. Individuals with dichromacy are called dichromats (or sometimes "color-blind"), and their color discrimination performance has contributed significantly to our understanding of color vision. Macaque monkeys, which normally have trichromatic color vision that is nearly identical to humans, have been used extensively in neurophysiological studies of color vision. In the present study we employed two tests, a pseudoisochromatic color discrimination test and a monochromatic light detection test, to compare the color vision of genetically identified dichromatic macaques (Macaca fascicularis) with that of normal trichromatic macaques. In the color discrimination test, dichromats could not discriminate colors along the protanopic confusion line, though trichromats could. In the light detection test, the relative thresholds for longer wavelength light were higher in the dichromats than the trichromats, indicating dichromats to be less sensitive to longer wavelength light. Because the dichromatic macaque is very rare, the present study provides valuable new information on the color vision behavior of dichromatic macaques, which may be a useful animal model of human dichromacy. The behavioral tests used in the present study have been previously used to characterize the color behaviors of trichromatic as well as dichromatic new world monkeys. The present results show that comparative studies of color vision employing similar tests may be feasible to examine the difference in color behaviors between trichromatic and dichromatic individuals, although the genetic mechanisms of trichromacy/dichromacy is quite different between new world monkeys and macaques.

  7. Asbestosis in a Japanese Macaque (Macaca fuscata).

    PubMed

    Tsugo, Kosuke; Kashimura, Akane; Une, Yumi

    2015-10-01

    Asbestosis is a chronic lung disease caused by inhalation of asbestos, a fibrous mineral. It is one of the most severe diseases resulting from environmental contamination. We found asbestosis in a female Japanese macaque over 25 years of age that died from senility. Clear needle-like crystals were deposited throughout the lung lobes, particularly in the perivascular areas. Asbestos bodies were observed in some of these crystals. Fibrosis without inflammation was observed in the periarterial and peribronchiolar regions. The crystals were identified as tremolite, and a total of 16,633,968 asbestos bodies and 465,334,411 tremolite fibers were observed in 1 g of dry lung tissue. No tumors or pleural adhesions were seen. This is the first report of spontaneous asbestosis in a nonhuman animal.

  8. 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.

  9. Pooled genomic indexing of rhesus macaque

    PubMed Central

    Milosavljevic, Aleksandar; Harris, Ronald A.; Sodergren, Erica J.; Jackson, Andrew R.; Kalafus, Ken J.; Hodgson, Anne; Cree, Andrew; Dai, Weilie; Csuros, Miklos; Zhu, Baoli; de Jong, Pieter J.; Weinstock, George M.; Gibbs, Richard A.

    2005-01-01

    Pooled genomic indexing (PGI) is a method for mapping collections of bacterial artificial chromosome (BAC) clones between species by using a combination of clone pooling and DNA sequencing. PGI has been used to map a total of 3858 BAC clones covering ∼24% of the rhesus macaque (Macaca mulatta) genome onto 4178 homologous loci in the human genome. A number of intrachromosomal rearrangements were detected by mapping multiple segments within the individual rhesus BACs onto multiple disjoined loci in the human genome. Transversal pooling designs involving shuffled BAC arrays were employed for robust mapping even with modest DNA sequence read coverage. A further innovation, short-tag pooled genomic indexing (ST-PGI), was also introduced to further improve the economy of mapping by sequencing multiple, short, mapable tags within a single sequencing reaction. PMID:15687293

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

    PubMed

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

    2011-01-01

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

  11. Thermal and chemical unfolding pathways of PaSdsA1 sulfatase, a homo-dimer with topologically interlinked chains.

    PubMed

    Aguirre, César; Goto, Yuji; Costas, Miguel

    2016-01-01

    Understanding the mechanisms as to how interlinked proteins entangle and fold is a challenge. PaSdsA1 sulfatase is a homo-dimer containing two zinc atoms per monomer. The monomer chains are interlinked in a dimerization domain. To study the unfolding pathways denaturation experiments were performed. In the native protein three forms coexist in chemical equilibrium, each with a different number of zinc atoms. In the chemical unfolding of the holo-dimers the entanglement of the chains is preserved and acts as a 'folding seed', allowing the unfolding process to be reversible. Thermal irreversible unfolding of the holo-dimers favours dissociation, producing monomers that are SDS-stabilized. The thermal unfolding of these monomers is reversible. However, it is not possible to form dimers from unfolded monomers.

  12. A novel EID family member, EID-3, inhibits differentiation and forms a homodimer or heterodimer with EID-2

    SciTech Connect

    Sasajima, Yuka; Tanaka, Hiroyuki; Miyake, Satoshi; Yuasa, Yasuhito . E-mail: yuasa.monc@tmd.ac.jp

    2005-08-05

    The EID family members, i.e., E1A-like inhibitor of differentiation-1 (EID-1) and EID-1-like inhibitor of differentiation-2 (EID-2), were identified as negative regulators of cellular differentiation. EID-1 seems to inhibit differentiation by blocking histone acetyltransferase activity and EID-2 possibly inhibits differentiation through binding to class I histone deacetylases (HDACs). Here, we report a novel inhibitor of differentiation exhibiting homology with EID-2 termed EID-3 (EID-2-like inhibitor of differentiation-3). Like EID-2, EID-3 inhibited MyoD- and GR{alpha}-dependent transcription and blocked muscle differentiation in cultured cells by binding to class I HDACs. Unlike that of EID-2, the C-terminus, but not the N-terminus, of EID-3 was required for nuclear localization. EID-3 formed a homodimer or heterodimer with EID-2. These results suggest that EID-3 inhibits differentiation by blocking transcription as a complex in cells.

  13. DNA binding of Jun and Fos bZip domains: homodimers and heterodimers induce a DNA conformational change in solution.

    PubMed Central

    John, M; Leppik, R; Busch, S J; Granger-Schnarr, M; Schnarr, M

    1996-01-01

    We constructed plasmids encoding the sequences for the bZip modules of c-Jun and c-Fos which could then be expressed as soluble proteins in Escherichia coli. The purified bZip modules were tested for their binding capacities of synthetic oligonucleotides containing either TRE or CRE recognition sites in electrophoretic mobility shift assays and circular dichroism (CD). Electrophoretic mobility shift assays showed that bZip Jun homodimers and bZip Jun/Fos heterodimers bind a collagenase-like TRE (CTGACTCAT) with dissociation constants of respectively 1.4 x 10(-7) M and 5 x 10(-8) M. As reported earlier [Patel et al. (1990) Nature 347, 572-575], DNA binding induces a marked change of the protein structure. However, we found that the DNA also undergoes a conformational change. This is most clearly seen with small oligonucleotides of 13 or 14 bp harboring respectively a TRE (TGACTCA) or a CRE (TGACGTCA) sequence. In this case, the positive DNA CD signal at 280 nm increases almost two-fold with a concomitant blue-shift of 3-4 nm. Within experimental error the same spectral changes are observed for TRE and CRE containing DNA fragments. The spectral changes observed with a non-specific DNA fragment are weaker and the signal of free DNA is recovered upon addition of much smaller salt concentrations than required for a specific DNA fragment. Surprisingly the spectral changes induced by Jun/Jun homodimers are not identical to those induced by Jun/Fos heterodimers. However, in both cases the increase of the positive CD band and the concomitant blue shift would be compatible with a B to A-transition of part of the binding site or a DNA conformation intermediate between the canonical A and B structures. PMID:8948639

  14. 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

  15. Q-ball imaging of macaque white matter architecture.

    PubMed

    Tuch, David S; Wisco, Jonathan J; Khachaturian, Mark H; Ekstrom, Leeland B; Kötter, Rolf; Vanduffel, Wim

    2005-05-29

    Diffusion-weighted magnetic resonance imaging holds substantial promise as a technique for non-invasive imaging of white matter (WM) axonal projections. For diffusion imaging to be capable of providing new insight into the connectional neuroanatomy of the human brain, it will be necessary to histologically validate the technique against established tracer methods such as horseradish peroxidase and biocytin histochemistry. The macaque monkey provides an ideal model for histological validation of the diffusion imaging method due to the phylogenetic proximity between humans and macaques, the gyrencephalic structure of the macaque cortex, the large body of knowledge on the neuroanatomic connectivity of the macaque brain and the ability to use comparable magnetic resonance acquisition protocols in both species. Recently, it has been shown that high angular resolution diffusion imaging (HARDI) can resolve multiple axon orientations within an individual imaging voxel in human WM. This capability promises to boost the accuracy of tract reconstructions from diffusion imaging. If the macaque is to serve as a model for histological validation of the diffusion tractography method, it will be necessary to show that HARDI can also resolve intravoxel architecture in macaque WM. The present study therefore sought to test whether the technique can resolve intravoxel structure in macaque WM. Using a HARDI method called q-ball imaging (QBI) it was possible to resolve composite intravoxel architecture in a number of anatomic regions. QBI resolved intravoxel structure in, for example, the dorsolateral convexity, the pontine decussation, the pulvinar and temporal subcortical WM. The paper concludes by reviewing remaining challenges for the diffusion tractography project.

  16. 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.

  17. 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…

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

    PubMed Central

    Zumbrun, Elizabeth E.; Bloomfield, Holly A.; Dye, John M.; Hunter, Ty C.; Dabisch, Paul A.; Garza, Nicole L.; Bramel, Nicholas R.; Baker, Reese J.; Williams, Roger D.; Nichols, Donald K.; Nalca, Aysegul

    2012-01-01

    Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV) Boniface in non-human primates (NHP) belonging to three different species. Groups of cynomolgus macaques (cyno), rhesus macaques (rhesus), and African green monkeys (AGM) were challenged with target doses of 50 or 500 plaque-forming units (pfu) of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP. PMID:23202456

  19. An HLA-B27 Homodimer Specific Antibody Recognizes a Discontinuous Mixed-Disulfide Epitope as Identified by Affinity-Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Iuraşcu, Marius-Ionuţ; Marroquin Belaunzanar, Osiris; Cozma, Claudia; Petrausch, Ulf; Renner, Christoph; Przybylski, Michael

    2016-06-01

    HLA-B27 homodimer formation is believed to be a hallmark of HLA-B27 associated spondyloarthritides. Recently, we have generated a homodimer-specific monoclonal antibody (HD6) and have demonstrated that HLA-B27 homodimer complexes are present on monocytes of healthy HLA-B27 gene carriers at low levels, with significantly increased levels at active disease. The capability of the HD6 antibody to discriminate between correctly formed HLA-B27 heterotrimers and pathology-associated homodimers is striking and cannot be explained by the primary structure of HLA-B27. We hypothesized that HD6 accesses a unique epitope and used affinity-mass spectrometry for its identification. The HD6 antibody was immobilized on an activated sepharose affinity column, and HLA-B27 homodimer characterized for affinity. The epitope was identified by proteolytic epitope excision and MALDI mass spectrometry, and shown to comprise a discontinuous Cys-203- 257-Cys mixed-disulfide peptide structure that is not accessible in HLA-B27 heterotrimers due to protection by noncovalently linked β2-microglobulin. The epitope peptides were synthesized by solid phase peptide synthesis, and the two monomeric peptide components, HLA-B27(203-219) and HLA-B27(257-273), as well as the homo- and hetero-dimeric disulfide linked combinations prepared. The affinity binding constants KD towards the antibodies were determined using a surface acoustic wave (SAW) biosensor, and showed the highest affinity with a KD of approximately 40 nM to the HD6 antibody for the (203-219)-SS-(257-273) mixed disulfide epitope.

  20. 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

  1. Rotational Displacement Skills in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Hughes, Kelly D.; Santos, Laurie R.

    2016-01-01

    Rotational displacement tasks, in which participants must track an object at a hiding location within an array while the array rotates, exhibit a puzzling developmental pattern in humans. Human children take an unusually long time to master this task and tend to solve rotational problems through the use of nongeometric features or landmarks as opposed to other kinds of spatial cues. We investigated whether these developmental characteristics are unique to humans by testing rotational displacement skills in a monkey species, the rhesus macaque (Macaca mulatta), using a looking-time method. Monkeys first saw food hidden in two differently colored boxes within an array. The array was then rotated 180° and the boxes reopened to reveal the food in an expected or unexpected location. Our first two experiments explored the developmental time-course of performance on this rotational displacement task. We found that adult macaques looked longer at the unexpected event, but such performance was not mirrored in younger-aged macaques. In a third study, we systematically varied featural information and visible access to the array to investigate which strategies adult macaques used in solving rotational displacements. Our results show that adult macaques need both sets of information to solve the task. Taken together, these results suggest both similarities and differences in mechanisms by which human and nonhuman primates develop this spatial skill. PMID:22866770

  2. The genomic sequence of lymphocryptovirus from cynomolgus macaque.

    PubMed

    Kamperschroer, Cris; Gosink, Mark M; Kumpf, Steven W; O'Donnell, Lynn M; Tartaro, Karrie R

    2016-01-15

    Lymphocryptoviruses such as Epstein-Barr virus (EBV) cause persistent infections in human and non-human primates, and suppression of the immune system can increase the risk of lymphocryptovirus (LCV)-associated tumor development in both human and non-human primates. To enable LCV infection as a non-clinical model to study effects of therapeutics on EBV immunity, we determined the genomic DNA sequence of the LCV from cynomolgus macaque, a species commonly used for non-clinical testing. Comparison to rhesus macaque LCV and human EBV sequences indicates that LCV from the cynomolgus macaque has the same genomic arrangement and a high degree of similarity in most genes, especially with rhesus macaque LCV. Genes showing lower similarity were those encoding proteins involved in latency and/or tumor promotion or immune evasion. The genomic sequence of LCV from cynomolgus macaque should aid the development of non-clinical tools for identifying therapeutics that impact LCV immunity and carry potential lymphoma risk.

  3. 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.

  4. Hepatitis C Virus Infects Rhesus Macaque Hepatocytes and Simianized Mice

    PubMed Central

    Scull, Margaret A.; Shi, Chao; de Jong, Ype P.; Gerold, Gisa; Ries, Moritz; von Schaewen, Markus; Donovan, Bridget M.; Labitt, Rachael N.; Horwitz, Joshua A.; Gaska, Jenna M.; Hrebikova, Gabriela; Xiao, Jing W.; Flatley, Brenna; Fung, Canny; Chiriboga, Luis; Walker, Christopher M.; Evans, David T.; Rice, Charles M.; Ploss, Alexander

    2015-01-01

    At least 170 million people are chronically infected with hepatitis C virus (HCV). Due to the narrow host range of HCV and restricted use of chimpanzees, there is currently no suitable animal model for HCV pathogenesis studies or the development of a HCV vaccine. To identify cellular determinants of interspecies transmission and establish a novel immunocompetent model system, we examined the ability of HCV to infect hepatocytes from a small non-human primate, the rhesus macaque (Macaca mulatta). We show that the rhesus orthologs of critical HCV entry factors support viral glycoprotein-dependent virion uptake. Primary hepatocytes from rhesus macaques are also permissive for HCV RNA replication and particle production, which is enhanced when antiviral signaling is suppressed. We demonstrate that this may be due to the diminished capacity of HCV to antagonize MAVS-dependent innate cellular defenses. To test the ability of HCV to establish persistent replication in vivo, we engrafted primary rhesus macaque hepatocytes into immunocompromised xenorecipients. Inoculation of resulting simian liver chimeric mice with either HCV genotype 1a or 2a resulted in HCV serum viremia for up to 10 weeks. Conclusion: Together, these data indicate that rhesus macaques may be a viable model for HCV and implicate host immunity as a potential species-specific barrier to HCV infection. We conclude that suppression of host immunity or further viral adaptation may allow robust HCV infection in rhesus macaques and creation of a new animal model for studies of HCV pathogenesis, lentivirus coinfection and vaccine development. PMID:25820364

  5. 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

  6. 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

  7. 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

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

    PubMed

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

    2015-01-01

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

  9. 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.

  10. Haplessly hoping: macaque major histocompatibility complex made easy.

    PubMed

    Wiseman, Roger W; Karl, Julie A; Bohn, Patrick S; Nimityongskul, Francesca A; Starrett, Gabriel J; O'Connor, David H

    2013-01-01

    Major histocompatibility complex (MHC) gene products control the repertoire of T cell responses that an individual may create against pathogens and foreign tissues. This text will review the current understanding of MHC genetics in nonhuman primates, with a focus on Mauritian-origin cynomolgus macaques (Macaca fascicularis) and Indian-origin rhesus macaques (Macaca mulatta). These closely related macaque species provide important experimental models for studies of infectious disease pathogenesis, vaccine development, and transplantation research. Recent advances resulting from the application of several cost effective, high-throughput approaches, with deep sequencing technologies have revolutionized our ability to perform MHC genotyping of large macaque cohorts. Pyrosequencing of cDNA amplicons with a Roche/454 GS Junior instrument, provides excellent resolution of MHC class I allelic variants with semi-quantitative estimates of relative levels of transcript abundance. Introduction of the Illumina MiSeq platform significantly increased the sample throughput, since the sample loading workflow is considerably less labor intensive, and each instrument run yields approximately 100-fold more sequence data. Extension of these sequencing methods from cDNA to genomic DNA amplicons further streamlines the experimental workflow and opened opportunities for retrospective MHC genotyping of banked DNA samples. To facilitate the reporting of MHC genotypes, and comparisons between groups of macaques, this text also introduces an intuitive series of abbreviated rhesus MHC haplotype designations based on a major Mamu-A or Mamu-B transcript characteristic for ancestral allele combinations. The authors believe that the use of MHC-defined macaques promises to improve the reproducibility, and predictability of results from pre-clinical studies for translation to humans.

  11. 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.

  12. 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

  13. A case of pulmonary acariasis in lung of Japanese macaque.

    PubMed

    Hiraoka, E; Sato, T; Shirai, W; Kimura, J; Nogami, S; Itou, M; Shimizu, K

    2001-01-01

    A 20-year-old female Japanese macaque, weighing 8.7 kg, developed severe pulmonary acariasis. Numerous whitish nodules, 2-4 mm, were scattered throughout the lungs. Histologically multifocal granulomatous lesions consisting of a large number of eosinophils, epithelioid cells, foreign body type giant cells, and collagen fibers were aggregated around the mait bodies. Numerous mast cells were also detected in the lesions by toluidine blue staining, and tested positive for tryptase by immunohistochemistry. This may be the first reported case of severe pulmonary acariasis in a Japanese macaque.

  14. Immunopathology of Japanese macaque encephalomyelitis is similar to multiple sclerosis.

    PubMed

    Blair, Tiffany C; Manoharan, Minsha; Rawlings-Rhea, Stephanie D; Tagge, Ian; Kohama, Steven G; Hollister-Smith, Julie; Ferguson, Betsy; Woltjer, Randall L; Frederick, Meredith C; Pollaro, James; Rooney, William D; Sherman, Larry S; Bourdette, Dennis N; Wong, Scott W

    2016-02-15

    Japanese macaque encephalomyelitis (JME) is an inflammatory demyelinating disease that occurs spontaneously in a colony of Japanese macaques (JM) at the Oregon National Primate Research Center. Animals with JME display clinical signs resembling multiple sclerosis (MS), and magnetic resonance imaging reveals multiple T2-weighted hyperintensities and gadolinium-enhancing lesions in the central nervous system (CNS). Here we undertook studies to determine if JME possesses features of an immune-mediated disease in the CNS. Comparable to MS, the CNS of animals with JME contain active lesions positive for IL-17, CD4+ T cells with Th1 and Th17 phenotypes, CD8+ T cells, and positive CSF findings.

  15. Transmission of Naturally Occurring Lymphoma in Macaque Monkeys

    NASA Astrophysics Data System (ADS)

    Hunt, Ronald D.; Blake, Beverly J.; Chalifoux, Laura V.; Sehgal, Prabhat K.; King, Norval W.; Letvin, Norman L.

    1983-08-01

    Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and cryptosporidiosis. They also showed evidence of an abnormal circulating peripheral blood mononuclear cell. These findings, all characteristic of the acquired immune deficiency syndrome (AIDS) of macaques, suggest a link between these transmissible lymphomas and AIDS in macaque monkeys.

  16. A Rhesus Macaque Model of Pulmonary Nontuberculous Mycobacterial Disease.

    PubMed

    Winthrop, Kevin; Rivera, Andrea; Engelmann, Flora; Rose, Sasha; Lewis, Anne; Ku, Jennifer; Bermudez, Luiz; Messaoudi, Ilhem

    2016-02-01

    In this study, we sought to develop a nonhuman primate model of pulmonary Mycobacterium avium complex (MAC) disease. Blood and bronchoalveolar lavage fluid were collected from three female rhesus macaques infected intrabronchially with escalating doses of M. avium subsp. hominissuis. Immunity was determined by measuring cytokine levels, lymphocyte proliferation, and antigen-specific responses. Disease progression was monitored clinically and microbiologically with serial thoracic radiographs, computed tomography scans, and quantitative mycobacterial cultures. The animal subjected to the highest inoculum showed evidence of chronic pulmonary MAC disease. Therefore, rhesus macaques could provide a robust model in which to investigate host-pathogen interactions during MAC infection.

  17. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

    PubMed Central

    Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

    2016-01-01

    Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

  18. Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule

    PubMed Central

    Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A.; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

    2016-01-01

    Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity. PMID:27782157

  19. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo.

    PubMed

    Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

    2016-01-01

    Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

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

    PubMed

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

    2016-10-01

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

  1. 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.

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

    PubMed

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

    2016-10-01

    Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc. PMID:27343148

  3. Detection thresholds of macaque otolith afferents.

    PubMed

    Yu, Xiong-Jie; Dickman, J David; Angelaki, Dora E

    2012-06-13

    The vestibular system is our sixth sense and is important for spatial perception functions, yet the sensory detection and discrimination properties of vestibular neurons remain relatively unexplored. Here we have used signal detection theory to measure detection thresholds of otolith afferents using 1 Hz linear accelerations delivered along three cardinal axes. Direction detection thresholds were measured by comparing mean firing rates centered on response peak and trough (full-cycle thresholds) or by comparing peak/trough firing rates with spontaneous activity (half-cycle thresholds). Thresholds were similar for utricular and saccular afferents, as well as for lateral, fore/aft, and vertical motion directions. When computed along the preferred direction, full-cycle direction detection thresholds were 7.54 and 3.01 cm/s(2) for regular and irregular firing otolith afferents, respectively. Half-cycle thresholds were approximately double, with excitatory thresholds being half as large as inhibitory thresholds. The variability in threshold among afferents was directly related to neuronal gain and did not depend on spike count variance. The exact threshold values depended on both the time window used for spike count analysis and the filtering method used to calculate mean firing rate, although differences between regular and irregular afferent thresholds were independent of analysis parameters. The fact that minimum thresholds measured in macaque otolith afferents are of the same order of magnitude as human behavioral thresholds suggests that the vestibular periphery might determine the limit on our ability to detect or discriminate small differences in head movement, with little noise added during downstream processing.

  4. Amino acid 72 of mouse and human GDF9 mature domain is responsible for altered homodimer bioactivities but has subtle effects on GDF9:BMP15 heterodimer activities.

    PubMed

    Peng, Jia; Wigglesworth, Karen; Rangarajan, Adithya; Eppig, John J; Thompson, Thomas B; Matzuk, Martin M

    2014-12-01

    Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted paralogs of the transforming growth factor beta (TGFbeta) superfamily. In mammals, these two growth factors play critical roles in folliculogenesis. As previously reported, an arginine in the pre-helix loop of GDF5 defines the high binding specificity to its type 1 receptor. Interestingly, bioactive mouse GDF9 and human BMP15 share the conserved arginine in the pre-helix loop, but their low-activity counterparts (mouse BMP15 and human GDF9) have a glycine or a proline instead. To address the question of whether the arginine residue defines the different activities of GDF9 and BMP15 homodimers and their heterodimers in human and mouse, we used site-directed mutagenesis to change the species-specific residues in human and mouse proteins, and examined their activities in our in vitro assays. Although amino acid 72 of mature GDF9 is responsible for altered homodimer bioactivities, neither the corresponding BMP15 amino acid 62 nor the intact pre-helix loop is indispensable for BMP15 homodimer activity. However, amino acid 72 in GDF9 only has only subtle effects on GDF9:BMP15 heterodimer activity. Based on previous studies and our recent findings, we provide hypothetical models to understand the molecular mechanism to define activities of the homodimeric and heterodimeric ligands. The arginine residue in the pre-helix loop of GDF9 homodimer may prevent the inhibition from its pro-domain or directly alter receptor binding, but this residue in GDF9 does not significantly affect the heterodimer activity, because of suggested conformational changes during heterodimer formation.

  5. Assessing natural introgression in 2 biomedical model species, the rhesus macaque (Macaca mulatta) and the long-tailed macaque (Macaca fascicularis).

    PubMed

    Bonhomme, Maxime; Cuartero, Sergi; Blancher, Antoine; Crouau-Roy, Brigitte

    2009-01-01

    Rhesus macaque (Macaca mulatta) and long-tailed macaque (Macaca fascicularis) are the 2 most commonly used primate model species in biomedical sciences. Although morphological studies have revealed a weak hybridization at the interspecific contact zone, in the north of Indochina, a molecular study has suggested an ancient introgression from rhesus to long-tailed macaque into the Indo-Chinese peninsula. However, the gene flow between these 2 taxa has never been quantified using genetic data and theoretical models. In this study, we have examined genetic variation within and between the parapatric Chinese rhesus macaque and Indo-Chinese long-tailed macaque populations, using 13 autosomal, 5 sex-linked microsatellite loci and mitochondrial DNA sequence data. From these data, we assessed genetic structure and estimated gene flow using a Bayesian clustering approach and the "Isolation with Migration" model. Our results reveal a weak interspecific genetic differentiation at both autosomal and sex-linked loci, suggesting large population sizes and/or gene flow between populations. According to the Bayesian clustering, Chinese rhesus macaque is a highly homogeneous gene pool that contributes strongly to the current Indo-Chinese long-tailed macaque genetic makeup, whether or not current admixture is assumed. Coalescent simulations, which integrated the characteristics of the loci, pointed out 1) a higher effective population size in rhesus macaque, 2) no mitochondrial gene flow, and 3) unilateral and male-mediated nuclear gene flow of approximately 10 migrants per generation from rhesus to long-tailed macaque. These patterns of genetic structure and gene flow suggest extensive ancient introgression from Chinese rhesus macaque into the Indo-Chinese long-tailed macaque population.

  6. A conserved proline residue in the leucine zipper region of AtbZIP34 and AtbZIP61 in Arabidopsis thaliana interferes with the formation of homodimer

    SciTech Connect

    Shen Huaishun; Cao Kaiming; Wang Xiping

    2007-10-19

    Two putative Arabidopsis E group bZIP transcript factors, AtbZIP34 and AtbZIP61, are nuclear-localized and their transcriptional activation domain is in their N-terminal region. By searching GenBank, we found other eight plant homologues of AtbZIP34 and AtbZIP61. All of them have a proline residue in the third heptad of zipper region. Yeast two-hybrid assay and EMSA showed that AtbZIP34 and AtbZIP61 could not form homodimer while their mutant forms, AtbZIP34m and AtbZIP61m, which the proline residue was replaced by an alanine residue in the zipper region, could form homodimer and bind G-box element. These results suggest that the conserved proline residue interferes with the homodimer formation. However, both AtbZIP34 and AtbZIP61 could form heterodimers with members of I group and S group transcription factors in which some members involved in vascular development. So we speculate that AtbZIP34 and AtbZIP61 may participate in plant development via interacting with other group bZIP transcription factors.

  7. Structures of a minimal human CFTR first nucleotide-binding domain as a monomer, head-to-tail homodimer, and pathogenic mutant

    SciTech Connect

    Atwell, Shane; Brouillette, Christie G.; Conners, Kris; Emtage, Spencer; Gheyi, Tarun; Guggino, William B.; Hendle, Jorg; Hunt, John F.; Lewis, Hal A.; Lu, Frances; Protasevich, Irina I.; Rodgers, Logan A.; Romero, Rich; Wasserman, Stephen R.; Weber, Patricia C.; Wetmore, Diana; Zhang, Feiyu F.; Zhao, Xun

    2010-04-26

    Upon removal of the regulatory insert (RI), the first nucleotide binding domain (NBD1) of human cystic fibrosis transmembrane conductance regulator (CFTR) can be heterologously expressed and purified in a form that remains stable without solubilizing mutations, stabilizing agents or the regulatory extension (RE). This protein, NBD1 387-646({Delta}405-436), crystallizes as a homodimer with a head-to-tail association equivalent to the active conformation observed for NBDs from symmetric ATP transporters. The 1.7-{angstrom} resolution X-ray structure shows how ATP occupies the signature LSGGQ half-site in CFTR NBD1. The {Delta}F508 version of this protein also crystallizes as a homodimer and differs from the wild-type structure only in the vicinity of the disease-causing F508 deletion. A slightly longer construct crystallizes as a monomer. Comparisons of the homodimer structure with this and previously published monomeric structures show that the main effect of ATP binding at the signature site is to order the residues immediately preceding the signature sequence, residues 542-547, in a conformation compatible with nucleotide binding. These residues likely interact with a transmembrane domain intracellular loop in the full-length CFTR channel. The experiments described here show that removing the RI from NBD1 converts it into a well-behaved protein amenable to biophysical studies yielding deeper insights into CFTR function.

  8. Two new crystal forms of the choline-binding domain of the major pneumococcal autolysin: insights into the dynamics of the active homodimer.

    PubMed

    Fernández-Tornero, Carlos; García, Ernesto; López, Rubens; Giménez-Gallego, Guillermo; Romero, Antonio

    2002-08-01

    Very little is known about the in vivo regulation of the catalytic activity of the major pneumococcal autolysin (LytA), a surface-exposed enzyme that rules the self-destruction of pneumococcal cells through degradation of their peptidoglycan backbone. Two new crystal forms of the cell wall anchoring domain of LytA were obtained, and their structures were solved and refined to 2.4A and 2.8A resolution. The domain is a homodimer with a boomerang-like shape in which the tertiary structure of each monomer is comprised by six independent beta hairpins arranged in a superhelical fashion. Choline molecules at the hydrophobic interface of consecutive hairpins maintain this unique structure. The C-terminal hairpin (last 13 residues of LytA) in the solenoid is responsible for the formation of the catalytically active homodimer. Although the general fold in the structures derived from both crystal forms is essentially the same, two different conformations of the basic homodimer are observed. Biochemical approaches have demonstrated the fundamental role of the 11 C-terminal residues in the catalytic activity of LytA. The studies reported here reveal the importance of some amino acid residues at the C terminus in the determination of the relative distance of the active dimeric form of the autolysin, which appears to be essential for the catalytic activity of this enzyme.

  9. A conserved proline residue in the leucine zipper region of AtbZIP34 and AtbZIP61 in Arabidopsis thaliana interferes with the formation of homodimer.

    PubMed

    Shen, Huaishun; Cao, Kaiming; Wang, Xiping

    2007-10-19

    Two putative Arabidopsis E group bZIP transcript factors, AtbZIP34 and AtbZIP61, are nuclear-localized and their transcriptional activation domain is in their N-terminal region. By searching GenBank, we found other eight plant homologues of AtbZIP34 and AtbZIP61. All of them have a proline residue in the third heptad of zipper region. Yeast two-hybrid assay and EMSA showed that AtbZIP34 and AtbZIP61 could not form homodimer while their mutant forms, AtbZIP34m and AtbZIP61m, which the proline residue was replaced by an alanine residue in the zipper region, could form homodimer and bind G-box element. These results suggest that the conserved proline residue interferes with the homodimer formation. However, both AtbZIP34 and AtbZIP61 could form heterodimers with members of I group and S group transcription factors in which some members involved in vascular development. So we speculate that AtbZIP34 and AtbZIP61 may participate in plant development via interacting with other group bZIP transcription factors. PMID:17719007

  10. Courtship behaviour in Japanese macaques during heterosexual and homosexual consortships.

    PubMed

    Vasey, P L; Rains, D; VanderLaan, D P; Duckworth, N; Kovacovsky, S D

    2008-07-01

    Female Japanese macaques (Macaca fuscata) in the Arashiyama population near Kyoto, Japan, are unusual, in that they exhibit what many would consider to be male-typical sexual characteristics. Specifically, they mount other females within the context of temporary, but exclusive, sexual relationships (i.e., homosexual consortships) and they sometimes exhibit a preference for female sexual partners, even when given the choice of a sexually motivated male alternative. In this study, we examined whether female Japanese macaques also exhibited male-typical patterns of courtship behaviour during homosexual consortships. Data were collected on courtship behaviour during heterosexual and homosexual consortships in free-ranging Japanese macaques from the Arashiyama (Japan) population. We analyzed the occurrence of 12 different courtship behaviours during 3374 heterosexual inter-mount intervals and 1412 homosexual inter-mount intervals. Sex differences between heterosexually consorting males and females existed for only two of the 12 courtship behaviours we investigated: inclined-back presentations and sexual vocalizations. Dominant and subordinate homosexually consorting females were sex-typical in their expression of inclined-back presentations and sexual vocalizations. Consequently, facultative same-sex sexual partner preference, mounting and consortships do not co-occur with male-typical patterns of courtship behaviour in female Japanese macaques.

  11. Oral squamous cell carcinoma in a pigtailed macaque (Macaca nemestrina).

    PubMed

    Stockinger, Diane E; Fong, Derek L; Vogel, Keith W; Durning, W McIntyre; Torrence, Anne E; Rose, Timothy M; Staheli, Jeannette P; Baldessari, Audrey; Murnane, Robert D; Hukkannen, Renee R

    2014-06-01

    An adult, gravid, female pigtailed macaque (Macaca nemestrina) presented for facial swelling centered on the left mandible that was approximately 5 cm wide. Differential diagnoses included infectious, inflammatory, and neoplastic origins. Definitive antemortem diagnosis was not possible, and the macaque's condition worsened despite supportive care. Necropsy findings included a mandibular mass that was locally invasive and expansile, encompassing approximately 80% of the left mandibular bone. The mass replaced portions of the soft palate, hard palate, sinuses, ear canal, and the caudal-rostral calvarium and masseter muscle. Histologically, the mass was a neoplasm that was poorly circumscribed, unencapsulated, and infiltrative invading regional bone and soft tissue. The mass consisted of polygonal squamous epithelial cells with intercellular bridging that breached the epithelial basement membrane and formed invasive nests, cords, and trabeculae. The mitotic rate averaged 3 per 400× field of view, with occasional bizarre mitotic figures. Epithelial cells often exhibited dyskeratosis, and the nests often contained compact lamellated keratin (keratin pearls). The neoplasm was positive via immunohistochemistry for pancytokeratin, variably positive for S100, and negative for vimentin, smooth muscle actin, and desmin. The gross, histologic, and immunohistochemical findings were consistent with an aggressive oral squamous cell carcinoma. The neoplasm was negative via PCR for papilloma virus. In general, neoplasia in macaques is rare. Although squamous cell carcinomas are one of the most common oral neoplasia in many species, to our knowledge this case represents the first reported oral squamous cell carcinoma in a pigtailed macaque.

  12. 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

  13. Surgical technique for allogeneic uterus transplantation in macaques

    PubMed Central

    Obara, Hideaki; Kisu, Iori; Kato, Yojiro; Yamada, Yohei; Matsubara, Kentaro; Emoto, Katsura; Adachi, Masataka; Matoba, Yusuke; Umene, Kiyoko; Nogami, Yuya; Banno, Kouji; Tsuchiya, Hideaki; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Saiki, Yoko; Sato, Shin-ichi; Nakagawa, Kenshi; Shiina, Takashi; Aoki, Daisuke; Kitagawa, Yuko

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques. PMID:27786258

  14. 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…

  15. Ecosystem impacts of folivory and frugivory by Japanese macaques in two temperate forests in Yakushima.

    PubMed

    Hanya, Goro; Fuse, Mieko; Aiba, Shin-Ichiro; Takafumi, Hino; Tsujino, Riyou; Agetsuma, Naoki; Chapman, Colin A

    2014-06-01

    Comparing animal consumption to plant primary production provides a means of assessing an animal's impact on the ecosystem and an evaluation of resource limitation. Here, we compared annual fruit and leaf consumption by Japanese macaques (Macaca fuscata) relative to the annual production of these foods in the lowlands and highlands of Yakushima Island, Japan. We estimated consumption by macaques by the direct observation of macaque groups for 1 year in each habitat. We estimated leaf production as the sum of leaf litter fall (corrected for the effect of translocated organic and inorganic matter) and folivory by insects (assumed to be 10%) and by macaques. We estimated fruit production as the sum of fruit litter fall and consumption by birds (estimated by the seed fall) and macaques. The impact of macaque folivory at the community level was negligible relative to production (∼0.04%) compared with folivory by insects (assumed to be 10%); however, for some species, macaque folivory reached up to 10.1% of production. Tree species on which macaques fed did not decline in abundance over 13 years, suggesting that their folivory did not influence tree species dynamics. For the three major fleshy-fruited species in the highland site, macaques consumed a considerable portion of total fruit production (6-40%), rivaling the consumption by birds (32-75%). We conclude that at the community level, macaque folivory was negligible compared with the leaf production, but frugivory was not.

  16. 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

  17. 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

  18. Characterization of spontaneous malignant lymphomas in Japanese macaques (Macaca fuscata).

    PubMed

    Hirata, A; Hashimoto, K; Katoh, Y; Sakai, H; Bruce, A G; Rose, T M; Kaneko, A; Suzuki, J; Nikami, H; Yanai, T

    2015-05-01

    Lymphomas are common spontaneous tumors in nonhuman primates but remain poorly characterized in Japanese macaques (Macaca fuscata). This study examined 5 cases of spontaneous malignant lymphoma in Japanese macaques, focusing on the immunophenotypes and presence of simian lymphocryptoviruses, which are Epstein-Barr virus-related herpesviruses in nonhuman primates. The macaques with lymphoma were 5 to 28 years old, indicating that lymphomas develop over a wide age range. The common macroscopic findings were splenomegaly and enlargement of lymph nodes. Histologic and immunohistochemical analyses revealed that all cases were non-Hodgkin type and exhibited a T-cell phenotype, positive for CD3 but negative for CD20 and CD79α. The lymphomas exhibited diverse cellular morphologies and were subdivided into 3 types according to the World Health Organization classification. These included 3 cases of peripheral T-cell lymphoma, not otherwise specified; 1 case of T-cell prolymphocytic leukemia; and 1 case of an unclassifiable T-cell lymphoma. Positive signals were detected by in situ hybridization in 2 of the 4 examined cases using probes for the Epstein-Barr virus-encoded small RNA (EBER). Furthermore, the presence of M. fuscata lymphocryptovirus 2, a macaque homolog of Epstein-Barr virus, was demonstrated in EBER-positive cases by polymerase chain reaction amplification followed by direct sequencing. Immunohistochemistry using antibody to the Epstein-Barr virus-encoded nuclear antigen 2 was negative, even in the EBER-positive cases. The present study suggests that T-cell lymphoma is more common than B-cell lymphoma in Japanese macaques and that M. fuscata lymphocryptovirus 2 is present in some cases.

  19. 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

  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. 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

  2. Macaques in farms and folklore: exploring the human-nonhuman primate interface in Sulawesi, Indonesia.

    PubMed

    Riley, Erin P; Priston, Nancy E C

    2010-09-01

    The island of Sulawesi is an ecologically diverse and anthropogenically complex region in the Indonesian archipelago; it is home to multiple macaque species and a key locus of human-nonhuman primate interconnections. Here, we review the ethnoprimatology of Sulawesi by exploring two primary domains of the human-macaque interface: overlapping resource use and cultural perceptions of macaques. Crop raiding is the primary form of overlapping resource use. While the raiding of cacao plantations predominates in Central and South Sulawesi, subsistence crops (e.g., sweet potato and maize) are most vulnerable on Buton, Southeast Sulawesi. Despite this overlap levels of conflict are generally low, with farmers showing considerable tolerance. This tolerance can be explained by positive perceptions of the macaques despite their crop raiding behavior, and the finding that in some areas macaques figure prominently in local folklore, hence affording them protection. These findings provide some hope for the future management and conservation of these endemic macaques.

  3. 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

  4. Brain abscess in a rhesus macaque (Macaca mulatta) with a cephalic implant.

    PubMed

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

    2013-08-01

    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.

  5. 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

  6. 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.

  7. Free-field audiogram of the Japanese macaque (Macaca fuscata).

    PubMed

    Jackson, L L; Heffner, R S; Heffner, H E

    1999-11-01

    The audiograms of three Japanese macaques and seven humans were determined in a free-field environment using loudspeakers. The monkeys and humans were tested using tones ranging from 8 Hz to 40 kHz and 4 Hz to 22.4 kHz, respectively. At a level of 60 dB sound pressure level the monkeys were able to hear tones extending from 28 Hz to 37 kHz with their best sensitivity of 1 dB occurring at 4 kHz. The human 60-dB hearing range extended from 31 Hz to 17.6 kHz with a best sensitivity of -10 dB at 2 and 4 kHz. These results indicate that the Japanese macaque has low-frequency hearing equal to that of humans and better than that indicated by previous audiograms obtained using headphones.

  8. Retained fetal adrenal cortex in a cynomolgus macaque (Macaca fascicularis).

    PubMed

    Radi, Zaher; Evans, Mark

    2014-10-01

    An incidental, bilateral, retained fetal adrenal cortex was detected in a male cynomolgus macaque (age, approximately 2.4 y) used in a 4-week toxicology study. Microscopic examination of the adrenal gland cortex zone revealed the presence of additional solid sheets and columns of cells supported by vascular capillary bed and composed of large polyhedral cells with abundant eosinophilic, slightly finely vacuolated cytoplasm that surrounded the entire circumference of the medulla. Nuclei were vesicular, round to oval with prominent small nucleoli. There was no evidence for inflammation or cellular degeneration. Based on the microscopic examination, a diagnosis of retained fetal cortex of the adrenal gland was made. This morphologic change resembles fetal cortex in human infants. To our knowledge, this case description is the first report of a cynomolgus macaque with the rare entity of retained fetal cortex, which should not be misinterpreted as a test article-related change.

  9. 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.

  10. 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

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

    PubMed Central

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

    2013-01-01

    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. PMID:24701000

  12. Atypical OmpR/PhoB Subfamily Response Regulator GlnR of Actinomycetes Functions as a Homodimer, Stabilized by the Unphosphorylated Conserved Asp-focused Charge Interactions*

    PubMed Central

    Lin, Wei; Wang, Ying; Han, Xiaobiao; Zhang, Zilong; Wang, Chengyuan; Wang, Jin; Yang, Huaiyu; Lu, Yinhua; Jiang, Weihong; Zhao, Guo-Ping; Zhang, Peng

    2014-01-01

    The OmpR/PhoB subfamily protein GlnR of actinomycetes is an orphan response regulator that globally coordinates the expression of genes related to nitrogen metabolism. Biochemical and genetic analyses reveal that the functional GlnR from Amycolatopsis mediterranei is unphosphorylated at the potential phosphorylation Asp50 residue in the N-terminal receiver domain. The crystal structure of this receiver domain demonstrates that it forms a homodimer through the α4-β5-α5 dimer interface highly similar to the phosphorylated typical response regulator, whereas the so-called “phosphorylation pocket” is not conserved, with its space being occupied by an Arg52 from the β3-α3 loop. Both in vitro and in vivo experiments confirm that GlnR forms a functional homodimer via its receiver domain and suggest that the charge interactions of Asp50 with the highly conserved Arg52 and Thr9 in the receiver domain may be crucial in maintaining the proper conformation for homodimerization, as also supported by molecular dynamics simulations of the wild type GlnR versus the deficient mutant GlnR(D50A). This model is backed by the distinct phenotypes of the total deficient GlnR(R52A/T9A) double mutant versus the single mutants of GlnR (i.e. D50N, D50E, R52A and T9A), which have only minor effects upon both dimerization and physiological function of GlnR in vivo, albeit their DNA binding ability is weakened compared with that of the wild type. By integrating the supportive data of GlnRs from the model Streptomyces coelicolor and the pathogenic Mycobacterium tuberculosis, we conclude that the actinomycete GlnR is atypical with respect to its unphosphorylated conserved Asp residue being involved in the critical Arg/Asp/Thr charge interactions, which is essential for maintaining the biologically active homodimer conformation. PMID:24733389

  13. Selective deamidation of recombinant human stem cell factor during in vitro aging: isolation and characterization of the aspartyl and isoaspartyl homodimers and heterodimers.

    PubMed

    Hsu, Y R; Chang, W C; Mendiaz, E A; Hara, S; Chow, D T; Mann, M B; Langley, K E; Lu, H S

    1998-02-24

    During in vitro aging, deamidation of recombinant human stem cell factor produced in Escherichia. coli was detected by HPLC analysis and by the release of soluble ammonia. The deamidation rate is very slow in buffers at low pH or at low temperatures; however, the rate is significantly accelerated in alkaline buffers such as sodium bicarbonate in combination with elevated temperatures. HPLC isolation of various deamidated forms followed by peptide mapping and mass spectrometric analyses revealed that the deamidation involves Asn10 in the sequence -T9NNV- near the N-terminus of the protein. Following peptide mapping analysis, significant amounts of aspartyl and isoaspartyl peptides were identified, indicating the conversion of asparagine into both aspartate and isoaspartate residues. As a result of spontaneous association-dissociation of stem cell factor dimer, a total of five deamidated forms, including two homodimers and three heterodimers, were detected and isolated. Cell proliferation assays showed that two rhSCF heterodimeric species, derived from dimerization between isoaspartyl and other stem cell factor monomers, retain only approximately half of the biological activity. The homodimer with isoaspartic acid in place of Asn10 is 50-fold less potent, while the aspartyl homodimer, either isolated during deamidation experiments or recombinantly prepared by site-directed mutagenesis (e.g., N10D and N10D/N11D variants), exhibits higher activity than the standard molecule. In comparison, synthetic N10A and N10E variants, though missing the deamidation site, are significantly less active. All these variants lacking the Asn10 deamidation site are relatively more stable than those containing the asparagine residue. The results indicate that the biological function and chemical stability of stem cell factor are influenced by the nature of the residue at position 10. PMID:9485371

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

    PubMed

    Colagross-Schouten, Angela M; Canfield, Don R

    2015-12-01

    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.

  15. 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

  16. The human homologue of macaque area V6A.

    PubMed

    Pitzalis, S; Sereno, M I; Committeri, G; Fattori, P; Galati, G; Tosoni, A; Galletti, C

    2013-11-15

    In macaque monkeys, V6A is a visuomotor area located in the anterior bank of the POs, dorsal and anterior to retinotopically-organized extrastriate area V6 (Galletti et al., 1996). Unlike V6, V6A represents both contra- and ipsilateral visual fields and is broadly retinotopically organized (Galletti et al., 1999b). The contralateral lower visual field is over-represented in V6A. The central 20°-30° of the visual field is mainly represented dorsally (V6Ad) and the periphery ventrally (V6Av), at the border with V6. Both sectors of area V6A contain arm movement-related cells, active during spatially-directed reaching movements (Gamberini et al., 2011). In humans, we previously mapped the retinotopic organization of area V6 (Pitzalis et al., 2006). Here, using phase-encoded fMRI, cortical surface-based analysis and wide-field retinotopic mapping, we define a new cortical region that borders V6 anteriorly and shows a clear over-representation of the contralateral lower visual field and the periphery. As with macaque V6A, the eccentricity increases moving ventrally within the area. The new region contains a non-mirror-image representation of the visual field. Functional mapping reveals that, as in macaque V6A, the new region, but not the nearby area V6, responds during finger pointing and reaching movements. Based on similarity in position, retinotopic properties, functional organization and relationship with the neighboring extrastriate visual areas, we propose that the new cortical region is the human homologue of macaque area V6A.

  17. 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

  18. 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

  19. 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.

  20. Cryotolerance of Sperm from Transgenic Rhesus Macaques (Macaca mulatta).

    PubMed

    Moran, Sean P; Chi, Tim; Prucha, Melinda S; Agca, Yuksel; Chan, Anthony Ws

    2016-01-01

    Cryopreservation is an important tool routinely used in preserving sperm for assisted reproductive technologies and for genetic preservation of unique animal models. Here we investigated the viability of fresh and frozen sperm from rhesus macaques on the basis of motility, membrane integrity, and acrosome integrity. Sperm motility was determined by visual evaluation; membrane and acrosome integrity were assessed simultaneously through triple staining with Hoechst 33342, propidium iodide, and fluorescein isothiocyanate-peanut agglutinin. We compared thawed semen that had been cryopreserved by using 2 different media with fresh semen from wildtype (WT) macaques; fresh semen from a model of Huntington disease (HD) with fresh WT semen; and fresh HD with cryopreserved-thawed HD semen. Our new freezing media (TEST EQ) preserved the acrosome better, with less net damage, than did traditional TEST (egg yolk extender containing TES and Tris) media. In addition, the percentage of membrane-damaged cells was similar in fresh HD semen (38.6%±2.9%) and WT semen (35.5%±1.9%). Membrane and acrosomal damage were not different between HD and WT sperm after cryopreservation and subsequent thawing. Furthermore, cryopreservation had similar negative effects on the motility of HD and WT sperm. These data illustrate that semen from a rhesus macaque model of HD is similarly cryotoleratant to that from WT animals. PMID:27657705

  1. Metastatic hepatocellular carcinoma in a juvenile rhesus macaque (Macaca mulatta).

    PubMed

    Laing, Steven T; Lemoy, Marie J; Sammak, Rebecca L; Tarara, Ross P

    2013-10-01

    Neoplasia in juvenile (younger than 5 y) rhesus macaques has been estimated to represent only approximately 1.4% of all occurrences of spontaneous neoplasia. Here we report an unusual case of a 3.75-y-old primiparous female rhesus macaque that was euthanized due to poor prognosis associated with progressive anemia, marked hepatomegaly, and radiographic evidence of meta- static neoplasia. Postmortem examination revealed an invasive, hemorrhagic hepatic mass that effaced approximately 70% of the liver parenchyma and had evidence of metastatic spread to multiple abdominal organs, the lungs, and the pituitary gland. Neoplastic polygonal cells lined large necrohemorrhagic cavities and exhibited marked anisocytosis and anisokaryosis, with frequent multinucleate cells. There was no desmoplasia associated with the primary neoplasm or metastases. Immunohistochemical studies revealed the neoplastic cells to be diffusely reactive with pancytokeratin, cytokeratin 7, and cytokeratin 8/18 antibodies and rarely reactive with carcinoembryonic antigen antibodies. The cells did not react with vimentin, S100, CD31, or factor VIII antibodies. Tumor morphology and immunophenotype led to the diagnosis of anaplastic hepatocellular carcinoma. This report represents the first known case of metastatic liver neoplasia in a rhesus macaque. The young age of this animal and the aggressive nature of the neoplasm are highly unusual and reminiscent of adolescent onset hepatocellular carcinoma in humans.

  2. Auditory Artificial Grammar Learning in Macaque and Marmoset Monkeys

    PubMed Central

    Wilson, Benjamin; Slater, Heather; Kikuchi, Yukiko; Milne, Alice E.; Marslen-Wilson, William D.; Smith, Kenny

    2013-01-01

    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

  3. 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

  4. 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

  5. Enteric ganglionitis in rhesus macaques infected with simian immunodeficiency virus.

    PubMed

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

    2007-06-01

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

  6. Infectivity and pathogenesis of titered dosages of simian immunodeficiency virus experimentally inoculated into longtailed macaques (Macaca fascicularis).

    PubMed

    Tsai, C C; Follis, K E; Grant, R F; Nolte, R E; Wu, H; Benveniste, R E

    1993-10-01

    The 50% macaque infectious dose (MID50) and pathogenesis of uncloned simian immunodeficiency virus (isolated from a pigtailed macaque, SIVmne) was determined in longtailed macaques (Macaca fascicularis). Five pairs of macaques were inoculated with 10-fold dilutions of the virus stock, and one macaque was mock-infected. The virologic and clinical status of these macaques was monitored for up to 80 weeks. The MID50 of SIVmne was determined to be 10(2) cell culture infectious dose of the original virus stock. In order to test the infectivity and pathogenesis of an established viral dose, six additional macaques were inoculated with 10x MID50 (10(3) cell culture infectious dose) of the SIVmne. The virologic and clinical status of these macaques was monitored for 40 weeks. All of the macaques inoculated with 10x MID50 or greater became infected as evidenced by seroconversion and consistent virus isolation from peripheral blood mononuclear cells. Macaques infected with SIVmne had an initial sharp decrease in CD2, CD20, CD4, CD8, and CD4CD29 lymphocyte subsets, whereas the CD4:CD8 ratio increased. Viremic macaques developed persistent slight to moderate peripheral lymphadenopathy approximately 3 to 4 weeks after inoculation. Four macaques subsequently died of AIDS-like disease at 29, 33, 42, and 80 weeks after inoculation. Data obtained from the viral titration study and the acute infection model will aid in the development of animal trials to evaluate antiretroviral therapies and preventive vaccines against human immunodeficiency virus infection.

  7. Identification and phylogenetic analysis of Japanese Macaque Babesia-1 (JM-1) detected from a Japanese Macaque (Macaca fuscata fuscata).

    PubMed

    Hirata, Haruyuki; Kawai, Satoru; Maeda, Mari; Jinnai, Michio; Fujisawa, Kohei; Katakai, Yuko; Hikosaka, Kenji; Tanabe, Kazuyuki; Yasutomi, Yasuhiro; Ishihara, Chiaki

    2011-10-01

    We demonstrate here the identification and phylogenetic characterization of Babesia microti (B. microti)-like parasite detected from a splenectomized Japanese macaque (Macaca fuscata fuscata) at a facility for laboratory animal science. On Day 133 after splenectomy, intra-erythrocytic parasites were found on light microscopic examination, and the level of parasitemia reached 0.3% on blood smear. Molecular characterization of the parasite using nested-polymerization chain reactions targeting the 18S rRNA, β-tubulin, and subunit 7 (eta) of the chaperonin-containing t-complex polypeptide 1 (CCT7) genes were identified as a B. microti-like parasite, designated the Japanese Macaque Babesia-1 (JM-1).

  8. Correction of Refractive Errors in Rhesus Macaques (Macaca mulatta) Involved in Visual Research

    PubMed Central

    Mitchell, Jude F; Boisvert, Chantal J; Reuter, Jon D; Reynolds, John H; Leblanc, Mathias

    2014-01-01

    Macaques are the most common animal model for studies in vision research, and due to their high value as research subjects, often continue to participate in studies well into old age. As is true in humans, visual acuity in macaques is susceptible to refractive errors. Here we report a case study in which an aged macaque demonstrated clear impairment in visual acuity according to performance on a demanding behavioral task. Refraction demonstrated bilateral myopia that significantly affected behavioral and visual tasks. Using corrective lenses, we were able to restore visual acuity. After correction of myopia, the macaque's performance on behavioral tasks was comparable to that of a healthy control. We screened 20 other male macaques to assess the incidence of refractive errors and ocular pathologies in a larger population. Hyperopia was the most frequent ametropia but was mild in all cases. A second macaque had mild myopia and astigmatism in one eye. There were no other pathologies observed on ocular examination. We developed a simple behavioral task that visual research laboratories could use to test visual acuity in macaques. The test was reliable and easily learned by the animals in 1 d. This case study stresses the importance of screening macaques involved in visual science for refractive errors and ocular pathologies to ensure the quality of research; we also provide simple methodology for screening visual acuity in these animals. PMID:25427343

  9. 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

  10. Possible use of heterospecific food-associated calls of macaques by sika deer for foraging efficiency.

    PubMed

    Koda, Hiroki

    2012-09-01

    Heterospecific communication signals sometimes convey relevant information for animal survival. For example, animals use or eavesdrop on heterospecific alarm calls concerning common predators. Indeed, most observations have been reported regarding anti-predator strategies. Use of heterospecific signals has rarely been observed as part of a foraging strategy. Here, I report empirical evidence, collected using playback experiments, showing that Japanese sika deer, Cevus nippon, use heterospecific food calls of Japanese macaques, Macaca fuscata yakui, for foraging efficiency. The deer and macaques both inhabit the wild forest of Yakushima Island with high population densities and share many food items. Anecdotal observations suggest that deer often wait to browse fruit falls under the tree where a macaque group is foraging. Furthermore, macaques frequently produce food calls during their foraging. If deer effectively obtain fruit from the leftovers of macaques, browsing fruit fall would provide a potential benefit to the deer, and, further, deer are likely to associate macaque food calls with feeding activity. The results showed that playback of macaque food calls under trees gathered significantly more deer than silence control periods. These results suggest that deer can associate macaque food calls with foraging activities and use heterospecific calls for foraging efficiency.

  11. Infinium monkeys: Infinium 450K array for the Cynomolgus macaque (Macaca fascicularis).

    PubMed

    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

    2014-05-08

    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.

  12. 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…

  13. 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.

  14. Conformational Differences Among Solution Structures of the Type I[alpha], II[alpha], and II[beta] Protein Kinase A Regulatory Subunit Homodimers: Role of the Linker Regions

    SciTech Connect

    Vigil, D.; Blumenthal, D.K.; Heller, W.T.; Brown, S.; Canaves, J.M.; Taylor, S.S.; Trewhella, J.

    2010-11-16

    The regulatory (R) subunits of the cAMP-dependent protein kinase (protein kinase A or PKA) are multi-domain proteins responsible for conferring cAMP-dependence and localizing PKA to specific subcellular locations. There are four isoforms of the R subunit in mammals that are similar in molecular mass and domain organization, but clearly serve different biological functions. Although high-resolution structures are available for the cAMP-binding domains and dimerization/docking domains of two isoforms, there are no high-resolution structures of any of the intact R subunit homodimer isoforms. The results of small-angle X-ray scattering studies presented here indicate that the RI{alpha}, RII{alpha}, and RII{beta} homodimers differ markedly in overall shape, despite extensive sequence homology and similar molecular masses. The RII{alpha} and RII{beta} homodimers have very extended, rod-like shapes, whereas the RI{alpha} homodimer likely has a compact Y-shape. Based on a comparison of the R subunit sequences, we predict that the linker regions are the likely cause of these large differences in shape among the isoforms. In addition, we show that cAMP binding does not cause large conformational changes in type I{alpha} or II{alpha} R subunit homodimers, suggesting that the activation of PKA by cAMP involves only local conformational changes in the R subunits.

  15. [Measurement and analysis of hematology and blood chemistry parameters in northern pig-tailed macaques (Macaca leonina)].

    PubMed

    Pang, Wei; Lü, Long-Bao; Wang, Yun; Li, Gui; Huang, Dong-Ti; Lei, Ai-Hua; Zhang, Gao-Hong; Zheng, Yong-Tang

    2013-04-01

    The pig-tailed macaque is an important non-human primate experimental animal model that has been widely used in the research of AIDS and other diseases. Pig-tailed macaques include Mentawai macaques (Macaca pagensis), Sunda pig-tailed macaques (M. nemestrina) and northern pig-tailed macaques (M. leonina). Northern pig-tailed macaques inhabit China and surrounding Southeast Asia countries. To our knowledge, no reports have been published regarding the hematology and blood chemistry parameters of northern pig-tailed macaques, which are important for the objective evaluation of experimental results. We measured and analyzed 18 hematology parameters and 13 blood chemistry parameters in juvenile (aged 2-4 years) and adult (aged 5-10 years) northern pig-tailed macaques. We found that red blood cells, hemoglobin and alkaline phosphatase values were lower in female macaques than male macaques in both juvenile and adult groups. White blood cells, lymphocyte, monocytes, platelet distribution width, cholesterol, aspartate aminotransferase and alkaline phosphatase values were higher in juvenile macaques than adult macaques, while creatinine and triglycerides values were lower in juvenile macaques. Mean corpuscular hemoglobin and creatinine values were positively correlated with weight in juvenile groups. In adult groups, mean corpuscular hemoglobin, percentage of granulocyte, hemoglobin and creatinine were also positively correlated with weight, and lymphocyte, percentage of lymphocyte, red cell distribution width, aspartate aminotransferase and cholesterol values were negatively correlated with weight. The results suggest that age, gender and weight of northern pig-tailed macaques affected their hematology and blood chemistry parameters. This hematological and blood chemistry study has great significance in biomedical research and animal models using northern pig-tailed macaque as an experimental animal.

  16. Next Step toward Optimization of GRP Receptor Avidities: Determination of the Minimal Distance between BBN(7-14) Units in Peptide Homodimers.

    PubMed

    Fischer, G; Lindner, S; Litau, S; Schirrmacher, R; Wängler, B; Wängler, C

    2015-08-19

    As the gastrin releasing peptide receptor (GRPR) is overexpressed on several tumor types, it represents a promising target for the specific in vivo imaging of these tumors using positron emission tomography (PET). We were able to show that PESIN-based peptide multimers can result in substantially higher GRPR avidities, highly advantageous in vivo pharmacokinetics and tumor imaging properties compared to the respective monomers. However, the minimal distance between the peptidic binders, resulting in the lowest possible system entropy while enabling a concomitant GRPR binding and thus optimized receptor avidities, has not been determined so far. Thus, we aimed here to identify the minimal distance between two GRPR-binding peptides in order to provide the basis for the development of highly avid GRPR-specific PET imaging agents. We therefore synthesized dimers of the GRPR-binding bombesin analogue BBN(7-14) on a dendritic scaffold, exhibiting different distances between both peptide binders. The homodimers were further modified with the chelator NODAGA, radiolabeled with (68)Ga, and evaluated in vitro regarding their GRPR avidity. We found that the most potent of the newly developed radioligands exhibits GRPR avidity twice as high as the most potent reference compound known so far, and that a minimal distance of 62 bond lengths between both peptidic binders within the homodimer can result in concomitant peptide binding and optimal GRPR avidities. These findings answer the question as to what molecular design should be chosen when aiming at the development of highly avid homobivalent peptidic ligands addressing the GRPR.

  17. Localization of Persistent Enterocytozoon bieneusi Infection in Normal Rhesus Macaques (Macaca mulatta) to the Hepatobiliary Tree

    PubMed Central

    Mansfield, Keith G.; Carville, Angela; Hebert, Daniel; Chalifoux, Laura; Shvetz, Daniel; Lin, K. C.; Tzipori, S.; Lackner, Andrew A.

    1998-01-01

    Enterocytozoon bieneusi is the most common microsporidian parasite recognized in human patients with AIDS. Recently, we identified a virtually identical organism causing a spontaneous infection associated with hepatobiliary and intestinal disease in simian immunodeficiency virus (SIV)-infected macaques. To examine the natural history of the infection, we examined captive rhesus macaques for E. bieneusi by PCR, in situ hybridization, and cytochemical techniques. PCR performed on fecal DNA detected enterocytozoon infection in 22 (16.7%) of 131 normal rhesus macaques (Macaca mulatta), compared to 18 (33.8%) of 53 rhesus macaques experimentally inoculated with SIV. In normal rhesus macaques, persistence of infection was demonstrated for up to 262 days and was usually not associated with clinical signs. In six of seven normal rhesus animals, E. bieneusi was detected by PCR in bile obtained through percutaneous cholecystocentesis but not by in situ hybridization performed on endoscopic biopsies of duodenum and proximal jejunum. PMID:9666017

  18. Extraction and characterization of the rhesus macaque T cell receptor β-chain genes

    PubMed Central

    Greenaway, Hui Yee; Kurniawan, Monica; Price, David A; Douek, Daniel C; Davenport, Miles P; Venturi, Vanessa

    2009-01-01

    Rhesus macaque models have been instrumental for the development and testing of vaccines prior to human studies and have provided fundamental insights into the determinants of immune efficacy in a variety of infectious diseases. However, the characterization of antigen-specific T cell receptor (TCR) repertoires during adaptive immune responses in these models has previously relied on human TCR gene assignments. Here, we extracted and characterized TCR β-chain (TRB) genes from the recently sequenced rhesus macaque genome that are homologous to the human TRB genes. Comparison of the rhesus macaque TRB genes with the human TRB genes revealed an average best-match similarity of 92.9%. Furthermore, we confirmed the usage of most rhesus macaque TRB genes by expressed TCRβ sequences within epitope-specific TCR repertoires. This primary description of the rhesus macaque TRB genes will provide a standardized nomenclature and enable better characterization of TCR usage in studies that utilize this species. PMID:19506572

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

    PubMed

    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.

  20. 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

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

    PubMed

    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

  2. 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

  3. Control of Shigella flexneri in Celebes black macaques (Macaca nigra).

    PubMed

    Olson, L C; Bergquist, D Y; Fitzgerald, D L

    1986-06-01

    Stool specimens collected systematically from a group of Celebes black macaques (Macaca nigra) with a high incidence of diarrhea were examined microbiologically. Numerous isolates of Shigella flexneri, Campylobacter jejuni and pathogenic Escherichia coli were recovered. Previous parasitology reports had revealed that the majority of the animals had Balantidium coli. Subsequently, the group was treated with trimethoprim-sulfamethoxazole, erythromycin and tetracycline. After treatment, Shigella flexneri was not detected in the stool of any animal for 1 year, and the clinical condition of the group was improved. Reduced recovery rates were obtained with other enteric pathogens. PMID:3523037

  4. In-depth proteomic analysis of whole testis tissue from the adult rhesus macaque.

    PubMed

    Wang, Jing; Xia, Yankai; Wang, Gaigai; Zhou, Tao; Guo, Yueshuai; Zhang, Chao; An, Xia; Sun, Yujie; Guo, Xuejiang; Zhou, Zuomin; Sha, Jiahao

    2014-06-01

    The rhesus macaque is similar to humans both anatomically and physiologically as a primate, and has therefore been used extensively in medical and biological research, including reproductive physiology. Despite sequencing of the macaque genome, limited postgenomic studies have been performed to date. In studies aimed at characterizing spermatogenesis, we successfully identified 9078 macaque testis proteins corresponding to 8662 genes, using advanced MS and an optimized proteomics platform, indicative of complex protein compositions during macaque spermatogenesis. Immunohistochemistry analysis further revealed the presence of proteins from different types of testicular cells, including Sertoli cells, Leydig cells, and various stages of germ cells. Our data provide expression evidence at protein level of 3010 protein-coding genes in 8662 identified testis genes for the first time. We further identified 421 homologous genes from the proteome already known to be essential for male infertility in mouse. Comparative analysis of the proteome showed high similarity with the published human testis proteome, implying that macaque and human may use similar proteins to regulate spermatogenesis. Our in-depth analysis of macaque spermatogenesis provides a rich resource for further studies, and supports the utility of macaque as a suitable model for the study of human reproduction.

  5. Mycophagy among Japanese macaques in Yakushima: fungal species diversity and behavioral patterns.

    PubMed

    Sawada, Akiko; Sato, Hirotoshi; Inoue, Eiji; Otani, Yosuke; Hanya, Goro

    2014-04-01

    Mycophagy (fungus-feeding) by Japanese macaques (Macaca fuscata yakui) in Yakushima has been observed by many researchers, but no detailed information is available on this behavior, including which fungal species are consumed. To provide a general description of mycophagy and to understand how and whether macaques avoid poisonous fungi, we conducted behavioral observation of wild Japanese macaques in Yakushima and used molecular techniques to identify fungal species. The results indicate that the diet of the macaques contains a large variety of fungal species (67 possible species in 31 genera), although they compose a very small portion of the total diet (2.2% of annual feeding time). Fungi which were eaten by macaques immediately after they were picked up were less likely to be poisonous than those which were examined (sniffed, nibbled, carefully handled) by macaques. However, such examining behaviors did not appear to increase the macaques' abilities to detect poisonous fungi. Fungi that were only partially consumed included more poisonous species than those fully consumed with/without examining behavior, yet this was not significant. Taste, therefore, might also play an important role in discriminating poisonous from non-poisonous.

  6. 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.

  7. 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

  8. Characterization and allelic polymorphisms of rhesus macaque (Macaca mulatta) IgG Fc receptor genes.

    PubMed

    Nguyen, Doan C; Scinicariello, Franco; Attanasio, Roberta

    2011-06-01

    Macaque models are invaluable for AIDS research. Indeed, initial development of HIV-1 vaccines relies heavily on simian immunodeficiency virus-infected rhesus macaques. Neutralizing antibodies, a major component of anti-HIV protective responses, ultimately interact with Fc receptors on phagocytic and natural killer cells to eliminate the pathogen. Despite the major role that Fc receptors play in protective responses, there is very limited information available on these molecules in rhesus macaques. Therefore, in this study, rhesus macaque CD32 (FcγRII) and CD64 (FcγRI) homologues were genetically characterized. In addition, presence of CD16 (FcγRIII), CD32, and CD64 allelic polymorphisms were determined in a group of nine animals. Results from this study show that the predicted structures of macaque CD32 and CD64 are highly similar to their human counterparts. Macaque and human CD32 and CD64 extracellular domains are 88-90% and 94-95% homologous, respectively. Although all cysteines are conserved between the two species, macaque CD32 exhibits two additional N-linked glycosylation sites, whereas CD64 lacks three of them when compared to humans. Five CD32, three CD64, and three CD16 distinct allelic sequences were indentified in the nine animals examined, indicating a relatively high level of polymorphism in macaque Fcγ receptors. Together, these results validate rhesus macaques as models for vaccine development and antibody responses, while at the same time, underscoring the need to take into account the high degree of genetic heterogeneity present in this species when designing experimental protocols.

  9. Early hematologic changes in rhesus macaques (Macaca mulatta) infected with pathogenic and nonpathogenic isolates of SIVmac.

    PubMed

    Mandell, C P; Jain, N C; Miller, C J; Marthas, M; Dandekar, S

    1993-01-01

    Early hematologic changes were studied over a 14 day period in three groups of six rhesus macaques intravenously infected with pathogenic and nonpathogenic isolates of SIVmac. Abnormalities in blood included a mild blood loss anemia, sporadic lymphopenia, and variable CD4+ and CD8+ T lymphocyte numbers. Prominent bone marrow findings in macaques inoculated with pathogenic uncloned SIVmac and molecularly cloned pathogenic SIVmac-239 were hypercellularity, myeloid and megakaryocytic hyperplasia, and lymphoid aggregates. Infrequent mild morphologic abnormalities were present in macaques infected with a nonpathogenic molecular clone, SIVmac-1A11. PMID:8105092

  10. 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.

  11. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity

    PubMed Central

    Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier; Barman, Ishita; Strop, Pavel; Chin, Sherman Michael; Pham, Amber; Bolton, Gary; McDonough, Dan; Lindquist, Kevin; Pons, Jaume; Rajpal, Arvind

    2015-01-01

    The neonatal Fc receptor (FcRn) is expressed by cells of epithelial, endothelial and myeloid lineages and performs multiple roles in adaptive immunity. Characterizing the FcRn/IgG interaction is fundamental to designing therapeutic antibodies because IgGs with moderately increased binding affinities for FcRn exhibit superior serum half-lives and efficacy. It has been hypothesized that 2 FcRn molecules bind an IgG homodimer with disparate affinities, yet their affinity constants are inconsistent across the literature. Using surface plasmon resonance biosensor assays that eliminated confounding experimental artifacts, we present data supporting an alternate hypothesis: 2 FcRn molecules saturate an IgG homodimer with identical affinities at independent sites, consistent with the symmetrical arrangement of the FcRn/Fc complex observed in the crystal structure published by Burmeister et al. in 1994. We find that human FcRn binds human IgG1 with an equilibrium dissociation constant (KD) of 760 ± 60 nM (N = 14) at 25°C and pH 5.8, and shows less than 25% variation across the other human subtypes. Human IgG1 binds cynomolgus monkey FcRn with a 2-fold higher affinity than human FcRn, and binds both mouse and rat FcRn with a 10-fold higher affinity than human FcRn. FcRn/IgG interactions from multiple species show less than a 2-fold weaker affinity at 37°C than at 25°C and appear independent of an IgG's variable region. Our in vivo data in mouse and rat models demonstrate that both affinity and avidity influence an IgG's serum half-life, which should be considered when choosing animals, especially transgenic systems, as surrogates. PMID:25658443

  12. Carcinogenic heavy metals replace Ca{sup 2+} for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer

    SciTech Connect

    Hirata, Aiko; Corcoran, George B.; Hirata, Fusao

    2010-10-01

    Mono-ubiquitinated annexin A1 was purified from rat liver nuclei. The homodimer form of mono-ubiquitinated annexin A1 was able to unwind dsDNA in a Mg{sup 2+}- and ATP-dependent manner, and to anneal ssDNA in a Ca{sup 2+}-dependent manner. Phospholipids decreased the concentration of Ca{sup 2+} required for maximal annealing activity. Heavy metals such as As{sup 3+}, Cr{sup 6+}, Pb{sup 2+} and Cd{sup 2+} substituted for Ca{sup 2+} in the ssDNA binding and annealing activities of annexin A1. While these metals inhibited the unwinding of dsDNA by nuclear annexin A1 in the presence of Mg{sup 2+} and ATP, they enhanced dsDNA-dependent ATPase activity of annexin A1. Heavy metals may have produced dsDNA, a substrate for the DNA unwinding reaction, via the DNA annealing reaction. DNA synthesomes were isolated from L5178Y tk(+/-) mouse lymphoma cells in exponential growth, and were found to contain helicase activities. The As{sup 3+}- or Cr{sup 6+}-induced increases in ssDNA binding activity of DNA synthesomes were reduced by a mono-specific anti-annexin A1 antibody, but not by anti-Ig antibody. Anti-annexin A1 antibody also blocked the inhibitory and stimulatory effects of As{sup 3+} or Cr{sup 6+} towards DNA unwinding and annealing activities of DNA synthesomes. Based on these observations, it can be concluded that the effects of heavy metals on DNA annealing and unwinding activities are mediated, at least in substantial part, through actions of the mono-ubiquitinated annexin A1 homodimer.

  13. Distinctive Leukocyte Subpopulations According to Organ Type in Cynomolgus Macaques.

    PubMed

    Zitsman, Jonah S; Alonso-Guallart, Paula; Ovanez, Christopher; Kato, Yojiro; Rosen, Joanna F; Weiner, Joshua I; Duran-Struuck, Raimon

    2016-01-01

    Cynomolgus macaques (CYNO; Macaca fascicularis) are a well-established NHP model used for studies in immunology. To provide reference values on the baseline cell distributions in the hematopoietic and lymphoid organs (HLO) of these animals, we used flow cytometry to analyze the peripheral blood, bone marrow, mesenteric lymph nodes, spleen, and thymus of a cohort of male, adult, research-naïve, Mauritian CYNO. Our findings demonstrate that several cell distribution patterns differ between CYNO and humans. First, the CD4(+):CD8(+) T-cell ratio is lower in CYNO compared with humans. Second, the peripheral blood of CYNO contains a population of CD4(+)CD8(+) T cells. Third, the CD31 level was elevated in all organs studied, suggesting that CD31 may not be an accurate marker of recent thymic emigrants within the CD4(+) T cells of CYNO. Finally the B-cell population is lower in CYNO compared with humans. In summary, although the majority of immune cell populations are similar between cynomolgus macaques and humans, several important differences should be considered when using CYNO in immunologic studies. Our current findings provide valuable information to not only researchers but also veterinarians working with CYNO at research centers, in zoos, or in the wild. PMID:27538862

  14. 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.

  15. Age and sexual behavior of Japanese macaques (Macaca fuscata).

    PubMed

    Wolfe, L

    1978-01-01

    The sexual behavior of the Arashiyama West troop, a natural semi-free-ranging troop of Japanese macaques, was studied during the 1973-1974 and 1974-1975 breeding seasons. The troop was transported intact from Japan to its current location in South Texas. There they have been free to move about in a 42.2-hectare electric fence enclosure. This report describes the relationships among age, aging, and sexual behavior. Males beginning at the age of 2.5 years were observed to series-mount estrous females in the double foot clasp mount position. Mounting in series in the double foot position is the normal pattern for Japanese macaque males. The ejaculation of semen with concomitant body movements indicative of orgasm begins at age 4.5 years at the earliest and continues until death. Males 4.5 and 5.5 years of age, sexually mature in the physiological sense, were not consistently sexually mature in the behavioral sense. The oldest male displayed traits that appear analogous to traits observed in aging human males. Females begin to experience estrus at 3.5 years of age. However, like pubescent males, pubescent females display behavioral patterns of sexual immaturity. The oldest female of the troop has remained sexually active. The attainment of sexual maturity by adulthood can be viewed as a learned process leading to efficiency and prowess, followed in old age by sexual involution.

  16. [Recent advances in social neuroscience research using macaques].

    PubMed

    Isoda, Masaki

    2013-06-01

    The last decade has seen a surge of interest in the study of social brain functions. Research in this field, called social neuroscience, has been mostly carried out on human subjects by using a functional neuroimaging technique. This is largely because of the fact that humans have sophisticated social abilities and are capable of performing various demanding tasks in a scanner. However, given the limited spatiotemporal resolution inherent in the methodology, a systems neuroscience approach using macaque monkeys may provide a useful platform that promotes the understanding of social brain functions at the cellular level, thereby complementing neuroimaging techniques. Recently, it has been demonstrated to be technically feasible to train macaque monkeys to perform socially oriented behavioral tasks and directly examine cellular activity in their brains. In this paper, we review the literature on this new branch of social neuroscience. Emerging evidence now suggests that diverse aspects of social cognition, such as social valuation, gaze following, joint attention, monitoring of other's behavior, and social comparison are implemented by distributed neuronal networks, including the orbital, lateral, and medial sectors of the prefrontal cortex, premotor cortex, posterior parietal cortex, amygdala, and superior temporal sulcus. Continuing efforts in this research direction could uncover the neural basis whereby primates have become such successful social beings in the animal kingdom.

  17. Polyostotic fibrous dysplasia in a cynomolgus Macaque (Macaca fascicularis).

    PubMed

    Bauer, Cassondra; Dunn, Betty G; Brothman, Arthur R; Dick, Edward J; Christensen, Chris; Voges, Andra; Moore, Charleen M

    2012-04-01

    A 2.3-y-old female cynomolgus macaque (Macaca fascicularis) presented with a broken right tibia and fibula. Radiographs showed multiple cyst-like defects in all long bones. We suspected that both fractures were pathologic because they occurred through these defects. Ultrasonography, MRI, and dual X-ray absorptiometry revealed that the defects were filled with soft tissue. Grossly, the bones were abnormal in shape, and a gelatinous material filled the defects and the surrounding marrow cavity. Histologically, the gelatinous material was composed of fibrin and cartilage; few normal bone cells were seen. Genetic testing revealed extra material on the short arm of chromosome 8 in all tissues examined, but no copy number alterations of likely clinical significance were observed, and no abnormalities were found that were unique to the lesions. In light of the clinical signs and radiographic and pathologic findings, polyostotic fibrous dysplasia was diagnosed. This report represents the first documented case of fibrous dysplasia in a cynomolgus macaque.

  18. A chronic neural interface to the macaque dorsal column nuclei.

    PubMed

    Richardson, Andrew G; Weigand, Pauline K; Sritharan, Srihari Y; Lucas, Timothy H

    2016-05-01

    The dorsal column nuclei (DCN) of the brain stem contain secondary afferent neurons, which process ascending somatosensory information. Most of the known physiology of the DCN in primates has been acquired in acute experiments with anesthetized animals. Here, we developed a technique to implant a multielectrode array (MEA) chronically in the DCN of macaque monkeys to enable experiments with the animals awake. Two monkeys were implanted with brain-stem MEAs for 2-5 mo with no major adverse effects. Responses of the cuneate and gracile nuclei were quantified at the level of both field potentials and single units. Tactile receptive fields (RFs) were identified for 315 single units. A subset of these units had very regular spiking patterns with spike frequencies predominantly in the alpha band (8-14 Hz). The stability of the neuronal recordings was assessed with a novel analysis that identified units by their mean spike waveform and by the spike-triggered average of activity on all other electrodes in the array. Fifty-six identified neurons were observed over two or more sessions and in a few cases for as long as 1 mo. RFs of stable neurons were largely consistent across days. The results demonstrate that a chronic DCN implant in a macaque can be safe and effective, yielding high-quality unit recording for several months. The unprecedented access to these nuclei in awake primates should lead to a better understanding of their role in sensorimotor behavior. PMID:26912601

  19. 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

  20. 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

  1. 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

  2. Male Tibetan macaques' (Macaca thibetana) choice of infant bridging partners

    PubMed Central

    Briana, BAUER; Lori K., SHEERAN; Megan D., MATHESON; Jin-Hua, LI; R., Steven WAGNER

    2014-01-01

    Adult male Tibetan (Macaca thibetana), Barbary (M. sylvanus), and stump-tailed macaques (M. arctoides) engage in bridging, a ritualized infant-handling behavior. Previous researchers found a bias toward the use of male infants for this behavior, but its function is debated. Explanations include three hypotheses: paternal care, mating effort, and agonistic buffering. We studied a group of habituated, provisioned Tibetan macaques to test whether adult males’ affiliative relationships with females predicted their use of an infant for bridging. We also examined biases for sex, age, and individual in males’ choice of bridging infant. We collected data via all occurrences, focal animal, and scan methods, from August to September 2011 at the Valley of the Wild Monkeys, China. We found that male infants were significantly preferred over females for bridging, but of three male infants in the group, only one was used by all males, while one male infant was used less often than expected. Adult males had females they were significantly more likely to be proximate to and/or to groom, but these corresponded to the mother of the bridging infant for only one male. Our results are most consistent with the agonistic buffering hypothesis: lower-ranked males used the alpha male’s preferred bridging infant in an attempt to regulate their interactions with the alpha. PMID:24866493

  3. 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

  4. 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.

  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.

  6. Growth rates in a captive population of Tonkean macaques.

    PubMed

    Sanna, Andrea; De Marco, Arianna; Thierry, Bernard; Cozzolino, Roberto

    2015-07-01

    Measuring variations in body mass is necessary to gain a deeper understanding of the evolution of life-history patterns, and it provides information on the timing of sexual maturity and the development of sexual dimorphism. In this study, we collected longitudinal data on body mass from infancy to adulthood in a captive population of Tonkean macaques (Macaca tonkeana). Tests to evaluate whether social group, maternal age, and dominance rank influenced growth rates showed that they had no significant effect. We investigated the timing and magnitude of breaking points in the growth paths of males and females, and checked whether these breaking points could correspond to specific reproductive and morphological developmental events. We found that male and female Tonkean macaques have roughly equivalent body masses until around the age of four, when males go through an adolescent growth spurt and females continue to grow at a constant rate. Males not only grow faster than females, but they also continue to grow for nearly one and a half years after females have attained their full body mass. Growth rate differences account for approximately two-thirds of the body mass sexual dimorphism; only the remaining third results from continued male growth beyond the age where full body mass is reached in females. We also discovered remarkable correspondences between the timing of testicular enlargement and the adolescent growth spurt in males, and between dental development and slowdown breaking points in both sexes.

  7. Grooming reciprocity in female tibetan macaques macaca thibetana.

    PubMed

    Xia, Dongpo; Li, Jinhua; Garber, Paul A; Sun, Lixing; Zhu, Yong; Sun, Binghua

    2012-06-01

    Grooming among nonhuman primates is widespread and may represent an important service commodity that is exchanged within a biological marketplace. In this study, using focal animal sampling methods, we recorded grooming relationships among 12 adult females in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China, to determine the influence of rank and kinship on grooming relationships, and whether females act as reciprocal traders (exchange grooming received for grooming given) or interchange traders (interchange grooming for social tolerance or other commodities). The results showed that: (1) grooming given was positively correlated with grooming received; (2) kinship did not exert a significant influence on grooming reciprocity; and (3) grooming reciprocity occurred principally between individuals of adjacent rank; however, when females of different rank groomed, females tended to groom up the hierarchy (lower ranking individuals groomed higher ranking individuals more than vice versa). Our results support the contention that both grooming reciprocity and the interchange of grooming for tolerance represent important social tactics used by female Tibetan macaques.

  8. Quantitative MRI Measures in SIV-Infected Macaque Brains.

    PubMed

    Zhang, Xiaodong; Li, Chunxia

    2013-01-01

    Multiple MRI modalities including Diffusion Tensor Imaging (DTI), perfusion MRI, in vivo MR Spectroscopy (MRS), volumetric MRI, contrast-enhanced MRI, and functional MRI have demonstrated abnormalities of the structural and functional integrity as well as neurochemical alterations of the HIV-infected central nervous system (CNS). MRI has been proposed as a robust imaging approach for the characterization of the stage of progression in HIV infection. However, the interpretation of the MRI findings of HIV patients is complicated by the fact that these clinical studies cannot readily be controlled. Simian immunodeficiency virus (SIV) infected macaques exhibit neuropathological symptoms similar to those of HIV patients, and are an important model for studying the course of CNS infection, cognitive impairment, and neuropathology of HIV disease as well as treatment efficacy. MRI of non-human primates (NHPs) is of limited benefit on most clinical scanners operating at or below 1.5 Tesla because this low field strength does not produce high-quality images of the relatively small NHP brain. Contemporary high field MRI (3T or more) for clinical use provides impressive sensitivity for magnetic resonance signal detection and is now accessible in many imaging centers and hospitals, facilitating the use of various MRI techniques in NHP studies. In this article, several high field MRI techniques and applications in macaque models of neuroAIDS are reviewed and the relation between quantitative MRI measures and blood T-cell alterations is discussed. PMID:24244892

  9. 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

  10. Polyostotic Fibrous Dysplasia in a Cynomolgus Macaque (Macaca fascicularis)

    PubMed Central

    Bauer, Cassondra; Dunn, Betty G; Brothman, Arthur R; Jr, Edward J Dick; Christensen, Chris; Voges, Andra; Moore, Charleen M

    2012-01-01

    A 2.3-y-old female cynomolgus macaque (Macaca fascicularis) presented with a broken right tibia and fibula. Radiographs showed multiple cyst-like defects in all long bones. We suspected that both fractures were pathologic because they occurred through these defects. Ultrasonography, MRI, and dual X-ray absorptiometry revealed that the defects were filled with soft tissue. Grossly, the bones were abnormal in shape, and a gelatinous material filled the defects and the surrounding marrow cavity. Histologically, the gelatinous material was composed of fibrin and cartilage; few normal bone cells were seen. Genetic testing revealed extra material on the short arm of chromosome 8 in all tissues examined, but no copy number alterations of likely clinical significance were observed, and no abnormalities were found that were unique to the lesions. In light of the clinical signs and radiographic and pathologic findings, polyostotic fibrous dysplasia was diagnosed. This report represents the first documented case of fibrous dysplasia in a cynomolgus macaque. PMID:22546922

  11. Gonadectomy increases neurogenesis in the male adolescent rhesus macaque hippocampus.

    PubMed

    Allen, K M; Fung, S J; Rothmond, D A; Noble, P L; Weickert, C Shannon

    2014-02-01

    New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset.

  12. 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

  13. 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

  14. 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

  15. Gastric hypomotility in chronic upper gastrointestinal disease of Japanese macaques (Macaca fuscata).

    PubMed

    Yamaoka, Arao; Koie, Hiroshi; Iwaki, Shunsaku; Sato, Tsuneo; Kanayama, Kiichi; Taira, Masato; Sakai, Takeo

    2011-01-01

    Japanese macaques bred indoor for laboratory use often show chronic anorexia and intermittent vomiting. In some of our macaques gastric air was observed on physical examination, and we suspected abnormality of gastric motility. We therefore performed contrast radiographic examinations of the gastrointestinal tract without anesthesia of 8 macaques with gastrointestinal symptoms and 9 asymptomatic controls from the same laboratory. Changes of abdominal radiography over time were observed following oral administration of contrast medium. In all control animals, contrast medium had completely passed from the stomach within 150 min after administration. However, all animals with gastrointestinal symptoms retained some contrast medium in the stomach. Gastric emptying time of contrast medium was associated with excessive gastric air in Japanese macaques; therefore, gastric emptying time seems to be associated with decreased gastric motility.

  16. Development of a new device for artificial insemination in cynomolgus macaques

    PubMed Central

    KOYAMA, Shuzo; FUKUDA, Koji; WATANABE, Sho; KOHARA, Sakae; TSUCHIYA, Hideaki; FUKUZAKI, Koichiro; NAGANO, Masashi; UNO, Yasuhiro; HOSOI, Yoshihiko

    2016-01-01

    In cynomolgus macaques, an important animal species for biomedical research, efficient reproduction has been hampered partly due to the difficulties of artificial insemination (AI) using straw tubes developed for humans or farm animals, because cynomolgus macaques have a complex cervical canal structure. In this study, taking into consideration the unique structure of the macaque cervical canal, we developed a novel device for AI, comprised of a syringe and an outer cylinder. At 24 and 48 h after using this device to inject semen into one female, viable sperm were observed in the oviduct where the sperm meets the oocytes. We then attempted AI using this new device on 10 females that were at pre-ovulation, and pregnancy was successful in three animals (30% pregnancy rate). These results show that the newly developed device can be used for AI in cynomolgus macaques. PMID:27319580

  17. Effects of Ketamine on Metabolomics of Serum and Urine in Cynomolgus Macaques (Macaca fascicularis).

    PubMed

    Pan, Xueying; Zeng, Xiancheng; Hong, Jiehua; Yuan, Congli; Cui, Li; Ma, Jing; Chang, Yan; Hua, Xiuguo

    2016-01-01

    In this study, a metabolomics approach based on nuclear magnetic resonance spectroscopy and pertinent multivariate data analyses was used to evaluate the effect of ketamine on metabolic markers in cynomolgus macaques. Principal component analysis and orthogonal projection to latent structure with discriminant analysis showed that ketamine (10 mg/kg) induced metabolic perturbations. Compared with the control group, ketamine-treated macaques had lower serum levels of α-glucose, myoinositol, lactate and succinate and lower urine levels of pyruvate and lactate. In contrast, the levels of leucine in serum and arginine in urine were significantly higher in the ketamine group. Our results also demonstrated that a single injection of ketamine influenced the major energy and amino acid metabolic pathways in cynomolgus macaques. Our study suggests that these influences should be considered in the design of experiments and the interpretation related blood and urine data from ketamine-sedated cynomolgus macaques. PMID:27657710

  18. Improving the welfare of captive macaques (Macaca sp.) through the use of water as enrichment.

    PubMed

    Robins, James G; Waitt, Corri D

    2011-01-01

    This review evaluates the use of water as a tool for enriching the environments of macaques (Macaca sp.) in captivity. Many macaque species are known to swim and forage in water in the wild, and in-situ reports suggest that access to water promotes activity and cultural behavior. Yet, there is a relative dearth of information on water enrichment, covering only a small number of macaque species in both laboratory and zoo settings. Previous studies in captivity report high levels of usage of water enrichment as well as further behavioral benefits, including increases in play, exploratory behavior, and tool use. Subsequently, there is a clear need for more research on the potential benefits of water enrichment for both macaques and other primate species, especially given that small water troughs and pools provide an inexpensive method for enriching nonhuman primate lives in captivity.

  19. 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

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

    PubMed

    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

    2015-03-06

    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.

  1. The biogeography and evolution of female homosexual behavior in Japanese macaques.

    PubMed

    Vasey, Paul L; Jiskoot, Hester

    2010-12-01

    In certain Japanese macaque (Macaca fuscata) populations, females routinely engage in same-sex courtship, mounting, and consortship activity. Drawing on behavioral, biogeographic, and genetic research, we suggest that female homosexual behavior may be associated with genetically distinct free-ranging populations of Japanese macaques. In addition, we briefly discuss the implications of this research for the evolution of female homosexual behavior in this species.

  2. Evidence for visual cortical area homologs in cat and macaque monkey.

    PubMed

    Payne, B R

    1993-01-01

    The maps of visuotopically discrete visual cerebral cortical areas in the cat and the macaque monkey are compared and gaps in knowledge are identified that limit such comparisons. Cat areas 17, 18, and 19 can be equated with macaque areas V1, V2, and V3, respectively, based on criteria of relative position in the cortical mantle, internal organization of visual field representations, and trans- and subcortical connections. Using these same criteria, a visual area on the medial bank of the lateral suprasylvian sulcus (area PMLS) in the cat can be equated with macaque area V5. The equivalences are supported by data on neuronal receptive field properties and the contributions the areas make to visual behavior. Although the data are scanty for most other visual areas, there are enough data tentatively to equate collectively cat areas 20a and 20b with macaque areas TF and TH and to liken cat areas 21a and 21b with macaque area V4. What is not clear is if there is a region in cat that is equivalent to area TE in the macaque monkey. If there is, it likely lies on the banks of the posterior suprasylvian sulcus between areas 20 and 21 and the polysensory cortex of the posterior ectosylvian gyrus. Knowledge gained from prior research on macaque areas V4 and TE can be used to formulate specific additional investigations of cat area 21 and the uncharted posterior suprasylvian sulcus. In addition, prior investigations carried out on cat area 20 can be used to devise specific explorations of macaque areas TF and TH.

  3. 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

  4. Sensitivity to first-order relations of facial elements in infant rhesus macaques.

    PubMed

    Paukner, Annika; Bower, Seth; Simpson, Elizabeth A; Suomi, Stephen J

    2013-05-01

    Faces are visually attractive to both human and nonhuman primates. Human neonates are thought to have a broad template for faces at birth and prefer face-like to non-face-like stimuli. To better compare developmental trajectories of face processing phylogenetically, here we investigated preferences for face-like stimuli in infant rhesus macaques using photographs of real faces. We presented infant macaques aged 15-25days with human, macaque, and abstract faces with both normal and linear arrangements of facial features, and measured infants' gaze durations, number of fixations, and latency to look to each face using eye-tracking technology. There was an overall preference for normal over linear facial arrangements for abstract and monkey faces, but not human faces. Moreover, infant macaques looked less at monkey faces than at abstract or human faces. These results suggest that species and facial configurations affect face processing in infant macaques, and we discuss potential explanations for these findings. Further, carefully controlled studies are required to ascertain whether infant macaques' face template can be considered as broad as human infants' face template. PMID:23997657

  5. Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.

    PubMed

    Daniel, M D; Letvin, N L; Sehgal, P K; Schmidt, D K; Silva, D P; Solomon, K R; Hodi, F S; Ringler, D J; Hunt, R D; King, N W

    1988-04-15

    The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme-linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero-positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. A Genetic Comparison of Two Alleged Subspecies of Philippine Cynomolgus Macaques

    PubMed Central

    Smith, David Glenn; Ng, Jillian; George, Debra; Trask, Jessica Satkoski; Houghton, Paul; Singh, Balbir; Villano, Jason; Kanthaswamy, Sreetharan

    2014-01-01

    Two subspecies of cynomolgus macaques (Macaca fascicularis) are alleged to co-exist in the Philippines, M. f. philippensis in the north and M. f. fascicularis in the south. However, genetic differences between the cynomolgus macaques in the two regions have never been studied to document the propriety of their subspecies status. We genotyped samples of cynomolgus macaques from Batangas in southwestern Luzon and Zamboanga in southwestern Mindanao for 15 short tandem repeat (STR) loci and sequenced an 835 bp fragment of the mtDNA of these animals. The STR genotypes were compared with those of cynomolgus macaques from southern Sumatra, Singapore, Mauritius and Cambodia, and the mtDNA sequences of both Philippine populations were compared with those of cynomolgus macaques from southern Sumatra, Indonesia and Sarawak, Malaysia. We conducted STRUCTURE and PCA analyses based on the STRs and constructed a median joining network based on the mtDNA sequences. The Philippine population from Batangas exhibited much less genetic diversity and greater genetic divergence from all other populations, including the Philippine population from Zamboanga. Sequences from both Batangas and Zamboanga were most closely related to two different mtDNA haplotypes from Sarawak from which they are apparently derived. Those from Zamboanga were more recently derived than those from Batangas, consistent with their later arrival in the Philippines. However, clustering analyses do not support a sufficient genetic distinction of cynomolgus macaques from Batangas from other regional populations assigned to subspecies M. f. fascicularis to warrant the subspecies distinction M. f. philippensis. PMID:24979664

  11. Topography-specific seed dispersal by Japanese macaques in a lowland forest on Yakushima Island, Japan.

    PubMed

    Tsujino, Riyou; Yumoto, Takakazu

    2009-01-01

    1. We investigated patterns of seed dispersal (i.e. dispersal distances and topography of seed-deposition sites) via the cheek pouches of Japanese macaques (Macaca fuscata yakui) during three seasons in a lowland forest on Yakushima Island, Japan. 2. The mean seed-dispersal distances were 16.7, 26.1, 41.8, and 32.4 m from the trunks of mother trees of Myrica rubra, Persea thunbergii, Neolitsea sericea, and Litsea acuminata, respectively. 3. We assessed the possible effect of macaque foraging patterns and the spatial distribution of fruiting trees on topography-specific seed dispersal. The topography of the locations of macaques differed across seasons, likely because the spatial distribution of fruiting trees determined the seasonal foraging patterns of macaques. 4. In early summer, macaques foraged on a ridge and fed on fruits of M. rubra and P. thunbergii, which were primarily distributed and dispersed within this area. In contrast, during the winter, macaques foraged within a valley and fed on fruits of L. acuminata, which were chiefly distributed and dispersed within the valley. 5. Seeds of M. rubra, P. thunbergii, and L. acuminata were directly dispersed to the specific topographic areas in which adult trees were distributed and in which juveniles have a predictably high probability of survival relative to random sites.

  12. Complete mitochondrial genome of the crested black macaque (Macaca nigra).

    PubMed

    Du, Li-Na; Shi, Fang-Lei; Liu, Zhi-Jin; Zhou, Qi-Hai

    2014-12-01

    Abstract The complete mitochondrial sequence of the crested black macaque (Macaca nigra) has been determined by mapping the raw data to previously published mitochondrial assemblies of the corresponding species. The total sequence length is 16,564 bp and includes 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 D-loop control region. The base composition of mtDNA genome is 31.76% A, 25.27% T, 30.17% C, and 12.80% G, with an AT content of 57.03%. The arrangement of genes in M. nigra is identical to that of M. mulatta. All genes are encoded on the heavy strand with the exception of ND6 and eight tRNA genes. The mitochondrial genome of M. nigra presented here will contribute to a better understanding of the population genetics, help to protect its genetic diversity and resolve phylogenetic relationships within the family.

  13. Optogenetic Activation of Normalization in Alert Macaque Visual Cortex.

    PubMed

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

    2015-06-17

    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.

  14. Maternal aggression by lactating group-living Japanese macaque females.

    PubMed

    Troisi, A; D'Amato, F R; Carnera, A; Trinca, L

    1988-12-01

    This study analyzed the influence of lactation on aggression by group-living Japanese macaque females. Data collected during 268 hr of observation showed that lactating females exhibited much more aggression than did females in any other reproductive condition under investigation. This postpartum aggression showed distinctive features in terms of time course during lactation and target selectivity but it was not characterized by a higher intensity and severity. Aggression increased progressively during the first 6 weeks of lactation, reached its highest levels between 7th and 9th weeks postpartum, and thereafter diminished. The relative percentages of threat, chase, and physical attack did not change with the reproductive condition. Lactating females were selective in their choice of targets, with young females being the recipients of nearly 90% of the total of their aggression.

  15. Taming desynchronized bursting with delays in the Macaque cortical network

    NASA Astrophysics Data System (ADS)

    Wang, Qing-Yun; Murks, Aleksandra; Perc, Matjaž; Lu, Qi-Shao

    2011-04-01

    Inhibitory coupled bursting Hindmarsh—Rose neurons are considered as constitutive units of the Macaque cortical network. In the absence of information transmission delay the bursting activity is desynchronized, giving rise to spatiotemporally disordered dynamics. This paper shows that the introduction of finite delays can lead to the synchronization of bursting and thus to the emergence of coherent propagating fronts of excitation in the space-time domain. Moreover, it shows that the type of synchronous bursting is uniquely determined by the delay length, with the transitions from one type to the other occurring in a step-like manner depending on the delay. Interestingly, as the delay is tuned close to the transition points, the synchronization deteriorates, which implies the coexistence of different bursting attractors. These phenomena can be observed by different but fixed coupling strengths, thus indicating a new role for information transmission delays in realistic neuronal networks.

  16. 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.

  17. Neurologic melioidosis in an imported pigtail macaque (Macaca nemestrina).

    PubMed

    Ritter, J M; Sanchez, S; Jones, T L; Zaki, S R; Drew, C P

    2013-11-01

    Burkholderia pseudomallei is the cause of melioidosis in humans and other animals. Disease occurs predominately in Asia and Australia. It is rare in North America, and affected people and animals typically have a history of travel to (in human cases) or importation from (in animal cases) endemic areas. We describe the gross and histopathologic features and the microbiologic, molecular, and immunohistochemical diagnoses of a case of acute meningoencephalomyelitis and focal pneumonia caused by B. pseudomallei infection in a pigtail macaque that was imported from Indonesia to the United States for research purposes. This bacterium has been classified as a Tier 1 overlap select agent and toxin; therefore, recognition of pathologic features, along with accurate and timely confirmatory diagnostic testing, in naturally infected research animals is imperative to protect animals and personnel in the laboratory animal setting.

  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.

  19. Comparative Pathology of Smallpox and Monkeypox in Man and Macaques

    PubMed Central

    Cann, J. A.; Jahrling, P. B.; Hensley, L. E.; Wahl-Jensen, V.

    2012-01-01

    Summary In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. PMID:22884034

  20. Optogenetic Activation of Normalization in Alert Macaque Visual Cortex.

    PubMed

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

    2015-06-17

    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

  1. 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

  2. Medial Axis Shape Coding in Macaque Inferotemporal Cortex

    PubMed Central

    Hung, Chia-Chun; Carlson, Eric T.; Connor, Charles E.

    2012-01-01

    SUMMARY The basic, still unanswered question about visual object representation is this: what specific information is encoded by neural signals? Theorists have long predicted that neurons would encode medial axis or skeletal object shape, yet recent studies reveal instead neural coding of boundary or surface shape. Here, we addressed this theoretical/experimental disconnect, using adaptive shape sampling to demonstrate for the first time explicit coding of medial axis shape in high-level object cortex (macaque monkey inferotemporal cortex or IT). Our metric shape analyses revealed a coding continuum, along which most neurons represent a configuration of both medial axis and surface components. Thus IT response functions embody a rich basis set for simultaneously representing skeletal and external shape of complex objects. This would be especially useful for representing biological shapes, which are often characterized by both complex, articulated skeletal structure and specific surface features. PMID:22726839

  3. Proton-bound dimers of nitrogen heterocyclic molecules: Substituent effects on the structures and binding energies of homodimers of diazine, triazine, and fluoropyridine

    NASA Astrophysics Data System (ADS)

    Attah, Isaac K.; Platt, Sean P.; Meot-Ner Mautner, Michael; El-Shall, M. S.; Aziz, Saadullah G.; Alyoubi, Abdulrahman O.

    2014-03-01

    The bonding energies of proton-bound homodimers BH+B were measured by ion mobility equilibrium studies and calculated at the DFT B3LYP/6-311++G** level, for a series of nitrogen heterocyclic molecules (B) with electron-withdrawing in-ring N and on-ring F substituents. The binding energies (ΔH°dissoc) of the proton-bound dimers (BH+B) vary significantly, from 29.7 to 18.1 kcal/mol, decreasing linearly with decreasing the proton affinity of the monomer (B). This trend differs significantly from the constant binding energies of most homodimers of other organic nitrogen and oxygen bases. The experimentally measured ΔH°dissoc for (1,3-diazine)2H+, i.e., (pyrimidine)2H+ and (3-F-pyridine)2H+ are 22.7 and 23.0 kcal/mol, respectively. The measured ΔH°dissoc for the pyrimidine.+(3-F-pyridine) radical cation dimer (19.2 kcal/mol) is signifcantly lower than that of the proton-bound homodimers of pyrimidine and 3-F-pyridine, reflecting the stronger interaction in the ionic H-bond of the protonated dimers. The calculated binding energies for (1,2-diazine)2H+, (pyridine)2H+, (2-F-pyridine)2H+, (3-F-pyridine)2H+, (2,6-di-F-pyridine)2H+, (4-F-pyridine)2H+, (1,3-diazine)2H+, (1,4-diazine)2H+, (1,3,5-triazine)2H+, and (pentafluoropyridine)2H+ are 29.7, 24.9, 24.8, 23.3, 23.2, 23.0, 22.4, 21.9, 19.3, and 18.1 kcal/mol, respectively. The electron-withdrawing substituents form internal dipoles whose electrostatic interactions contribute to both the decreased proton affinities of (B) and the decreased binding energies of the protonated dimers BH+B. The bonding energies also vary with rotation about the hydrogen bond, and they decrease in rotamers where the internal dipoles of the components are aligned efficiently for inter-ring repulsion. For compounds substituted at the 3 or 4 (meta or para) positions, the lowest energy rotamers are T-shaped with the planes of the two rings rotated by 90° about the hydrogen bond, while the planar rotamers are weakened by repulsion between the

  4. Pathology of experimental aerosol Zaire ebolavirus infection in rhesus macaques.

    PubMed

    Twenhafel, N A; Mattix, M E; Johnson, J C; Robinson, C G; Pratt, W D; Cashman, K A; Wahl-Jensen, V; Terry, C; Olinger, G G; Hensley, L E; Honko, A N

    2013-05-01

    There is limited knowledge of the pathogenesis of human ebolavirus infections and no reported human cases acquired by the aerosol route. There is a threat of ebolavirus as an aerosolized biological weapon, and this study evaluated the pathogenesis of aerosol infection in 18 rhesus macaques. Important and unique findings include early infection of the respiratory lymphoid tissues, early fibrin deposition in the splenic white pulp, and perivasculitis and vasculitis in superficial dermal blood vessels of haired skin with rash. Initial infection occurred in the respiratory lymphoid tissues, fibroblastic reticular cells, dendritic cells, alveolar macrophages, and blood monocytes. Virus spread to regional lymph nodes, where significant viral replication occurred. Virus secondarily infected many additional blood monocytes and spread from the respiratory tissues to multiple organs, including the liver and spleen. Viremia, increased temperature, lymphocytopenia, neutrophilia, thrombocytopenia, and increased alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, total bilirubin, serum urea nitrogen, creatinine, and hypoalbuminemia were measurable mid to late infection. Infection progressed rapidly with whole-body destruction of lymphoid tissues, hepatic necrosis, vasculitis, hemorrhage, and extravascular fibrin accumulation. Hypothermia and thrombocytopenia were noted in late stages with the development of disseminated intravascular coagulation and shock. This study provides unprecedented insight into pathogenesis of human aerosol Zaire ebolavirus infection and suggests development of a medical countermeasure to aerosol infection will be a great challenge due to massive early infection of respiratory lymphoid tissues. Rhesus macaques may be used as a model of aerosol infection that will allow the development of lifesaving medical countermeasures under the Food and Drug Administration's animal rule.

  5. 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

  6. Wide-field ganglion cells in macaque retinas

    PubMed Central

    YAMADA, ELIZABETH S.; BORDT, ANDREA S.; MARSHAK, DAVID W.

    2012-01-01

    To describe the wide-field ganglion cells, they were injected intracellularly with Neurobiotin using an in vitro preparation of macaque retina and labeled with streptavidin-Cy3. The retinas were then labeled with antibodies to choline acetyltransferase and other markers to indicate the depth of the dendrites within the inner plexiform layer (IPL) and analyzed by confocal microscopy. There were eight different subtypes of narrowly unistratified cells that ramified in each of the 5 strata, S1–5, including narrow thorny, large sparse, large moderate, large dense, large radiate, narrow wavy, large very sparse, and fine very sparse. There were four types of broadly stratified cells with dendritic trees extending from S4 to S2. One type resembled the parvocellular giant cell and another the broad thorny type described previously in primates. Another broadly stratified cell was called multi-tufted based on its distinctive dendritic branching pattern. The fourth type had been described previously, but not named; we called it broad wavy. There was a bistratified type with its major arbor in S5, the same level as the blue cone bipolar cell; it resembled the large, bistratified cell with blue ON-yellow OFF responses described recently. Two wide-field ganglion cell types were classified as diffuse because they had dendrites throughout the IPL. One had many small branches and was named thorny diffuse. The second was named smooth diffuse because it had straighter dendrites that lacked these processes. Dendrites of the large moderate and multi-tufted cells cofasciculated with ON-starburst cell dendrites and were, therefore, candidates to be ON- and ON–OFF direction-selective ganglion cells, respectively. We concluded that there are at least 15 morphoplogical types of wide-field ganglion cells in macaque retinas. PMID:16212697

  7. 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

  8. Emotional states after grooming interactions in Japanese macaques (Macaca fuscata).

    PubMed

    Ueno, Masataka; Yamada, Kazunori; Nakamichi, Masayuki

    2015-11-01

    In animal societies, the effect of grooming interactions on anxiety reduction is unclear. This study examined the effects of giving and receiving grooming on anxiety reduction in free ranging female Japanese macaques (Macaca fuscata) by measuring rates of self-scratching as an index of anxiety. In this study, the authors used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama prefecture, Japan. They evaluated affiliative relationships, which were defined by standard proximity rates, and found that females' self-scratching rates were lower after grooming affiliated partners than during matched-control periods (occurring on another day, beginning at approximately the same time of day as the corresponding postgrooming period) and not after grooming unaffiliated partners. Moreover, regardless of affiliative relationships, self-scratching rates were lower after receiving grooming than during matched-control periods. These findings did not change after excluding data in which groomer and groomee were in proximity after the grooming interaction. In addition, multivariable analysis showed that affiliative relationships, but not kinship or rank distances, were related to differences in the rates of self-scratching between giving grooming and matched-control periods. In contrast, neither affiliative relationships nor kinship nor rank distances affected differences in self-scratching rates between receiving grooming and matched-control periods. Therefore, individuals' anxiety levels decreased both after giving grooming to affiliated partners and after receiving grooming, regardless of affiliative relationships. This is the first empirical study to support the notion that giving grooming to affiliated partners is self-rewarding in Japanese macaques.

  9. Ecogeographical and phylogenetic effects on craniofacial variation in macaques.

    PubMed

    Ito, Tsuyoshi; Nishimura, Takeshi; Takai, Masanaru

    2014-05-01

    The widespread and complex ecogeographical diversity of macaques may have caused adaptive morphological convergence among four phylogenetic subgroups, making their phylogenetic relationships unclear. We used geometric morphometrics and multivariate analyses to test the null hypothesis that craniofacial morphology does not vary with ecogeographical and phylogenetic factors. As predicted by Bergmann's rule, size was larger for the fascicularis and sinica groups in colder environments. No clear size cline was observed in the silenus and sylvanus groups. An allometric pattern was observed across macaques, indicating that as size increases, rounded faces become more elongated. However, the elevation was differentiated within each of the former two groups and between the silenus and sylvanus groups, and the slope decreased in each of the two northern species of the fascicularis group. All allometric changes resulted in the similar situation of the face being more rounded in animals inhabiting colder zones and/or in animals having a larger body size than that predicted from the overarching allometric pattern. For non-allometric components, variations in prognathism were significantly correlated with dietary differences; variations in localized shape components in zygomatics and muzzles were significantly correlated with phylogenetic differences among the subgroups. The common allometric pattern was probably influenced directly or indirectly by climate-related factors, which are pressures favoring a more rounded face in colder environments and/or a more elongated face in warmer environments. Allometric dissociation could have occurred several times in Macaca even within a subgroup because of their wide latitudinal distributions, critically impairing the taxonomic utility of craniofacial elongation. PMID:24449333

  10. 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.

  11. Depth perception from moving cast shadow in macaque monkey.

    PubMed

    Mizutani, Saneyuki; Usui, Nobuo; Yokota, Takanori; Mizusawa, Hidehiro; Taira, Masato; Katsuyama, Narumi

    2015-07-15

    In the present study, we investigate whether the macaque monkey can perceive motion in depth using a moving cast shadow. To accomplish this, we conducted two experiments. In the first experiment, an adult Japanese monkey was trained in a motion discrimination task in depth by binocular disparity. A square was presented on the display so that it appeared with a binocular disparity of 0.12 degrees (initial position), and moved toward (approaching) or away from (receding) the monkey for 1s. The monkey was trained to discriminate the approaching and receding motion of the square by GO/delayed GO-type responses. The monkey showed a significantly high accuracy rate in the task, and the performance was maintained when the position, color, and shape of the moving object were changed. In the next experiment, the change in the disparity was gradually decreased in the motion discrimination task. The results showed that the performance of the monkey declined as the distance of the approaching and receding motion of the square decreased from the initial position. However, when a moving cast shadow was added to the stimulus, the monkey responded to the motion in depth induced by the cast shadow in the same way as by binocular disparity; the reward was delivered randomly or given in all trials to prevent the learning of the 2D motion of the shadow in the frontal plane. These results suggest that the macaque monkey can perceive motion in depth using a moving cast shadow as well as using binocular disparity.

  12. Dorsal Root Ganglia Damage in SIV-Infected Rhesus Macaques

    PubMed Central

    Burdo, Tricia H.; Orzechowski, Krystyna; Knight, Heather L.; Miller, Andrew D.; Williams, Kenneth

    2012-01-01

    HIV-associated sensory neuropathy (HIV-SN) is currently the most common neurological complication of chronic HIV infection and continues to substantially affect patient quality of life. Mechanisms underlying the neuronal damage and loss observed in sensory ganglia of HIV-infected individuals have not been sufficiently studied. The present study aimed to develop and characterize a model of HIV-SN using SIV-infected CD8 T-lymphocyte-depleted rhesus macaques (Macaca mulatta). Uninfected controls (n = 5), SIV-infected CD8-depleted (n = 4), and SIV-infected non-CD8-depleted (n = 6) animals were used. Of the six non-CD8-depleted animals, three were conventional progressors (progressing to AIDS >1 year after infection) and three were rapid progressors (AIDS within 6 months). Dorsal root ganglia (DRG) were examined for histological hallmarks of HIV-SN, including satellitosis, presence of Nageotte nodules, and neuronophagia, as well as increased numbers of CD68+ macrophages and abundant viral replication. In contrast to non-CD8-depleted animals, which had mild to moderate DRG pathology, the CD8-depleted SIV-infected animals had moderate to severe DRG damage, with increased numbers of CD68+ satellite cells. Additionally, there was marked active viral replication in the affected DRG. These findings confirm that many features of HIV-SN can be recapitulated in the CD8-depleted SIV-infected rhesus macaque model within a short time frame and illustrate the importance of this model for study of sensory neuropathy. PMID:22322298

  13. 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.

  14. 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

  15. Diversity and Molecular Phylogeny of Mitochondrial DNA of Rhesus Macaques (Macaca mulatta) in Bangladesh

    PubMed Central

    HASAN, M. KAMRUL; FEEROZ, M. MOSTAFA; JONES-ENGEL, LISA; ENGEL, GREGORY A.; KANTHASWAMY, SREE; SMITH, DAVID GLENN

    2015-01-01

    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

  16. 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

  17. 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.

  18. Delineation of multiple subpopulations of natural killer cells in rhesus macaques

    PubMed Central

    Webster, Ramothea L; Johnson, R Paul

    2005-01-01

    Natural killer (NK) cells in rhesus macaques have been variably defined as CD3− CD16+ or CD3− CD8+, although only limited efforts have been made to validate these definitions rigorously. To better understand the role of NK cells in macaque disease models, we undertook a multiparameter analysis of macaque NK cells employing four-colour flow cytometry and a panel of lineage-specific and non-lineage-specific lymphocyte markers. Using this approach, we identified two distinct populations of candidate NK cells: a major CD8bright CD16+ population and a minor CD8bright CD16− population. Further analysis of the major and minor NK cell populations revealed the expression of multiple markers characteristic of NK cells, including CD2, CD7, CD16, CD161, NKG2A and granzyme B. In addition, a CD56+ subset of cells within the minor rhesus NK population was identified which expressed chemokine and lymph node homing receptors similar to those expressed by the CD56bright NK cell population identified in humans. Cytolytic assays confirmed that the phenotypically defined rhesus NK cells lysed NK-susceptible target cells. Our observations support the existence of several distinct subpopulations of rhesus macaque NK cells, which have significant phenotypic and functional similarities to their human counterparts. These improved immunophenotypic definitions of macaque NK cells should facilitate future analysis of innate immune responses in rhesus macaques and the role of NK cells in AIDS pathogenesis in Simian immunodeficiency virus (SIV)-infected macaques. PMID:15885126

  19. Plasmodium knowlesi: Reservoir Hosts and Tracking the Emergence in Humans and Macaques

    PubMed Central

    Lee, Kim-Sung; Divis, Paul C. S.; Zakaria, Siti Khatijah; Matusop, Asmad; Julin, Roynston A.; Conway, David J.; Cox-Singh, Janet; Singh, Balbir

    2011-01-01

    Plasmodium knowlesi, a malaria parasite originally thought to be restricted to macaques in Southeast Asia, has recently been recognized as a significant cause of human malaria. Unlike the benign and morphologically similar P. malariae, these parasites can lead to fatal infections. Malaria parasites, including P. knowlesi, have not yet been detected in macaques of the Kapit Division of Malaysian Borneo, where the majority of human knowlesi malaria cases have been reported. In order to extend our understanding of the epidemiology and evolutionary history of P. knowlesi, we examined 108 wild macaques for malaria parasites and sequenced the circumsporozoite protein (csp) gene and mitochondrial (mt) DNA of P. knowlesi isolates derived from macaques and humans. We detected five species of Plasmodium (P. knowlesi, P. inui, P. cynomolgi, P. fieldi and P. coatneyi) in the long-tailed and pig-tailed macaques, and an extremely high prevalence of P. inui and P. knowlesi. Macaques had a higher number of P. knowlesi genotypes per infection than humans, and some diverse alleles of the P. knowlesi csp gene and certain mtDNA haplotypes were shared between both hosts. Analyses of DNA sequence data indicate that there are no mtDNA lineages associated exclusively with either host. Furthermore, our analyses of the mtDNA data reveal that P. knowlesi is derived from an ancestral parasite population that existed prior to human settlement in Southeast Asia, and underwent significant population expansion approximately 30,000–40,000 years ago. Our results indicate that human infections with P. knowlesi are not newly emergent in Southeast Asia and that knowlesi malaria is primarily a zoonosis with wild macaques as the reservoir hosts. However, ongoing ecological changes resulting from deforestation, with an associated increase in the human population, could enable this pathogenic species of Plasmodium to switch to humans as the preferred host. PMID:21490952

  20. Replication-specific conversion of the Staphylococcus aureus pT181 initiator protein from an active homodimer to an inactive heterodimer.

    PubMed Central

    Rasooly, A; Wang, P Z; Novick, R P

    1994-01-01

    The Staphylococcus aureus rolling circle plasmid pT181 regulates its replication by controlling the synthesis of its initiator protein RepC. RepC is inactivated during pT181 replication by the addition of an oligodeoxynucleotide, giving rise to a new form, RepC*. We analyzed RepC and RepC* in four classes of mutants: plasmid copy number mutants, two classes of RepC mutants affecting different portions of the protein and oriC (origin) mutants. We have found that in the cell with wild-type RepC there are similar relative amounts of RepC and RepC*, regardless of copy number, and that the conversion of RepC to RepC* is replication dependent. Genetic and biochemical evidence is presented that RepC functions as a dimer and that during replication the RepC homodimer is converted to the RepC/RepC* heterodimer. Images PMID:7957090

  1. Mimic me while playing! Social tolerance and rapid facial mimicry in macaques (Macaca tonkeana and Macaca fuscata).

    PubMed

    Scopa, Chiara; Palagi, Elisabetta

    2016-05-01

    Social play and tolerance are positively correlated and playful signals are more freely expressed in egalitarian than in despotic species. Macaque species are organized along a continuum from intolerant to tolerant social systems and, for this reason, they are good models to test some hypotheses about the possible linkage between communication and tolerance. We compared facial playful communication in 2 macaque species at opposite ends of the continuum: despotic Japanese macaques, Macaca fuscata, and tolerant Tonkean macaques, Macaca tonkeana. We predicted that tolerance has favored larger facial display repertoires and playful cooperative tendency. Moreover, we evaluated if tolerance could also reflect in the selection for emotional sharing expressed through rapid facial mimicry (RFM). RFM is an automatic, unconscious, and fast (<1 s) motor mirror response which favors emotional communication between subjects. Although M. fuscata and M. tonkeana performed play faces (PF) at comparable levels, only Tonkean macaques showed the phenomenon of RFM. The playful sessions characterized by RFM lasted longer than those characterized by the presence of playful signals perceived by a playmate but not followed by mimicry. Interestingly, the duration of playful sessions in Tonkean macaques overcame that of the sessions in Japanese macaques. It is likely that RFM improves communicative exchanges between the playmates and, at the same time, promotes behavioral coordination and cooperation in the sequence of actions. The tolerant nature of Tonkean macaques, also expressed in play, can foster RFM which, at the same time, positively enhances the propensity to cooperate in a sort of positive feedback. (PsycINFO Database Record

  2. Coprophagy-related interspecific nocturnal interactions between Japanese macaques (Macaca fuscata yakui) and sika deer (Cervus nippon yakushimae).

    PubMed

    Nishikawa, Mari; Mochida, Koji

    2010-04-01

    The influence of sympatric large animals on the sleeping behavior of primates in the wild is still largely unknown. In this study, we observed behaviors of wild Japanese macaques (Macaca fuscata yakui) at their sleeping sites, using a highly sensitive video camera. We found evidence of nocturnal interspecific interactions, such as agonistic interactions, between Japanese macaques and sika deer (Cervus nippon yakushimae). Deer approached sleeping clusters of macaques, which slept on the ground, to eat their feces or unidentified materials near the sleeping clusters, and as a result, the macaques were often quickly displaced from their sleeping site. There was a significant difference in the occurrence of macaque-deer agonistic interactions between seasons. Our results suggested that the size of the sleeping cluster, the number of adult macaques in the cluster, and the existence of adult males in the cluster did not influence the occurrence of the agonistic interactions. Finally, we discuss the influence of this interaction on macaques and speculate on the influential factors leading to nocturnal coprophagy of macaques' feces by deer.

  3. 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

  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.

  5. Psychogenic Alopecia in Rhesus Macaques Presenting as Focally Extensive Alopecia of the Distal Limb

    PubMed Central

    Kramer, Joshua A; Mansfield, Keith G; Simmons, Joe H; Bernstein, Joseph A

    2011-01-01

    Focally extensive alopecia affecting the distal limbs is a common clinical finding in rhesus macaque (Macaca mulatta) colonies and is both a regulatory and colony-health concern. We performed diagnostic examinations including physical exams, bloodwork, skin scrapes, surface cytology, and surface bacterial–fungal cultures on 17 rhesus macaques with this presentation of alopecia. Skin biopsies from alopecic skin obtained from each macaque were compared with those of normal skin from the same animal. Immunohistochemistry and metachromatic staining for inflammatory cells were performed to compare alopecic and normal skin. In addition, we compared these biopsies with those previously obtained from macaques with generalized alopecia and dermal inflammatory infiltrates consistent with cutaneous hypersensitivity disorders and with those from animals with normal haircoats. Bacterial and fungal cultures, skin scrapes, surface cytology, and bloodwork were unremarkable. Affected skin showed only mild histologic alteration, with rare evidence of trichomalacia and follicular loss. Numbers of mast cells and CD3+ lymphocytes did not differ between alopecic and normally haired skin from the same animal. The number of mast cells in alopecic skin from animals in the current cohort was significantly lower than that in skin of animals previously diagnosed with a cutaneous hypersensitivity disorder. Numbers of both mast cells and CD3+ lymphocytes in alopecic skin from the current cohort were similar to those from biopsies of animals with normal haircoats. Together, the clinical findings and pathology are consistent with a psychogenic origin for this pattern of alopecia in rhesus macaques. PMID:21819697

  6. Comparison of physiologic and pharmacologic parameters in Asian and mauritius cynomolgus macaques.

    PubMed

    Kozlosky, John C; Mysore, Jagannatha; Clark, Shawn P; Burr, Holly N; Li, Jinze; Aranibar, Nelly; Vuppugalla, Ragini; West, Ronald C; Mangipudy, Raja S; Graziano, Michael J

    2015-10-01

    This comparative study was conducted to assess background physiologic and pharmacologic parameters of cynomolgus macaques (Macaca fascicularis) from Cambodia, from a mixed Asian source (Cambodia, Vietnam and Indonesia), and from Mauritius. This evaluation provides a comprehensive assessment of several of these parameters in a single study. Ten male and 10 female captive-bred, age-matched macaques from each source were evaluated. Criteria for evaluation included weight gain, assessment of drug metabolizing enzyme activity, metabolomic analysis, immunologic assessments (lymphocyte subsets, TDAR, and serum Ig isotyping), clinical pathology evaluations, physical (respiratory, neurologic, cardiovascular, and ophthalmologic) examinations, pathogen screening, organ weights, and gross and microscopic pathology analyses. The results of this evaluation indicate that, compared to macaques of Asian origin, macaques from Mauritius had the lowest incidence and/or severity of spontaneous pathologic findings in several organs and tissues (lymphoid organs, stomach, kidney, urothelium, heart, arteries and lung) and better testicular maturity at a given age with minimal variability in organ weights. Although slight differences were observed in other parameters, none were considered detrimental to the use of macaques of Asian or Mauritius origin in pharmaceutical candidate safety studies with the use of a consistent source, concomitant controls, and appropriate background knowledge and screening.

  7. Planar covariation of limb elevation angles during bipedal walking in the Japanese macaque.

    PubMed

    Ogihara, Naomichi; Kikuchi, Takeo; Ishiguro, Yutaro; Makishima, Haruyuki; Nakatsukasa, Masato

    2012-09-01

    We investigated the planar covariation of lower limb segment elevation angles during bipedal walking in macaques to elucidate the mechanisms underlying the origin and evolution of the planar law in human walking. Two Japanese macaques and four adult humans walking on a treadmill were recorded, and the time course of the elevation angles at the thigh, shank and foot segments relative to the vertical axis were calculated. Our analyses indicated that the planar law also applies to macaque bipedal walking. However, planarity was much lower in macaques, and orientations of the plane differed between the two species because of differences in the foot elevation angle. The human foot is rigidly structured to form a longitudinal arch, whereas the macaque's foot is more flexible and bends at the midtarsal region in the stance phase. This difference in midfoot flexibility between the two species studied was the main source of the difference in the planar law. Thus, the evolution of a stable midfoot in early hominins may have preceded the acquisition of the strong planar intersegmental coordination and possibly facilitated the subsequent emergence of habitual bipedal walking in the human lineage.

  8. Relationship between ovarian cycle phase and sexual behavior in female Japanese macaques (Macaca fuscata).

    PubMed

    O'Neill, Ann C; Fedigan, Linda M; Ziegler, Toni E

    2004-12-01

    We conducted behavioral observations simultaneously with fecal sample collection on eight nonlactating females 2-3 times per week, October 1997-March 1998, to examine the relationship between ovarian hormones and the sexual behavior of female Japanese macaques (Macaca fuscata) during the mating season. We analyzed samples by enzyme immunoassay for fecal hormone levels. Hormone profiles of estrone-glucuronide (E1) and pregnanediol-glucuronide (PdG) were used to separate ovarian cycles into three phases (follicular, periovulatory, and luteal). Hormonal profiles indicate average cycle lengths of 27.6 +/- 4.2 days (+/- SD; n = 26). Average lengths of the luteal and follicular phases were 12.3 +/- 3.8 days (+/- SD) and 8.3 +/- 3.4 days (+/- SD), respectively. We observed female Japanese macaques engaging in sexual activity throughout the ovarian cycle, with the highest rates occurring during the follicular and periovulatory phases as compared to the luteal phase. The attractivity of female Japanese macaques increased significantly during the follicular and periovulatory phases of the ovarian cycle, when E1 levels are peaking and PdG levels drop to baseline. In addition, females displayed a significant increase in proceptive behavior during the follicular and periovulatory phases. Grooming bouts, as well as proximity between female and male macaques, also increased significantly during the follicular and periovulatory phases. We conclude that fluctuating levels of ovarian hormones in different phases of the cycle are significantly associated with variable rates of copulatory and pericopulatory behaviors in these Japanese macaque females.

  9. Adenocarcinoma of the ileocolic junction and multifocal hepatic sarcomas in an aged rhesus macaque (Macaca mulatta).

    PubMed

    Lang, Cynthia D; Daviau, Judith S; Merton, Daniel A; Caraker, Susan M

    2013-08-01

    An aged male rhesus macaque in our colony had decreased appetite and a loss of interest in behavioral testing. CBC analysis revealed a regenerative, microcytic, hypochromic anemia with thrombocytosis, consistent with iron deficiency. A fecal occult blood test was positive. Ultrasound imaging revealed numerous, vascularized focal liver lesions that suggested metastases. The macaque's appetite continued to decrease, and he became more lethargic. At this point, the investigator elected to euthanize the macaque. At necropsy, the ileocolic junction was white and abnormally thickened, and the liver was pale tan with approximately 18 discrete white masses randomly scattered throughout the hepatic parenchyma. Histologically, the mass at the ileocolic junction was identified as an intestinal adenocarcinoma, whereas the liver masses were confirmed to be undifferentiated hepatic sarcomas. This case report describes a rhesus macaque that had 2 unrelated primary neoplasms. A review of the literature indicates that this rhesus macaque is the first reported to have an adenocarcinoma of the ileocolic junction and multiple hepatic sarcomas simultaneously.

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

    PubMed

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

    2008-01-01

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

  11. Training Rhesus Macaques for Venipuncture Using Positive Reinforcement Techniques: A Comparison with Chimpanzees

    PubMed Central

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

    2008-01-01

    As more emphasis is placed on enhancing the psychological well-being of nonhuman primates, many research facilities have started using positive reinforcement training (PRT) techniques to train primates to voluntarily participate in husbandry and research procedures. PRT increases the animal's control over its environment and desensitizes the animal to stressful stimuli. Blood draw is a common husbandry and research procedure that can be particularly stressful for nonhuman primate subjects. Although studies have demonstrated that chimpanzees can be trained for in-cage venipuncture using PRT only, fewer studies have demonstrated success using similar techniques to train macaques. It is often assumed that macaques cannot be trained in the same manner as apes. In this study, we compare PRT data from singly housed adult rhesus macaques (Macaca mulatta; n = 8) with data from group-housed adult chimpanzees (Pan troglodytes; n = 4). All subjects were trained to place an arm in a ‘blood sleeve’ and remain stationary for venipuncture. Both facilities used similar PRT techniques. We were able to obtain repeated blood samples from 75% of the macaques and all of the chimpanzees. The training time did not differ significantly between the 2 species. These data demonstrate that macaques can be trained for venipuncture in a manner similar to that used for chimpanzees. PMID:18210997

  12. Minor contributions of the maxillary sinus to the air-conditioning performance in macaque monkeys.

    PubMed

    Mori, Futoshi; Hanida, Sho; Kumahata, Kiyoshi; Miyabe-Nishiwaki, Takako; Suzuki, Juri; Matsuzawa, Teruo; Nishimura, Takeshi D

    2015-08-01

    The nasal passages mainly adjust the temperature and humidity of inhaled air to reach the alveolar condition required in the lungs. By contrast to most other non-human primates, macaque monkeys are distributed widely among tropical, temperate and subarctic regions, and thus some species need to condition the inhaled air in cool and dry ambient atmospheric areas. The internal nasal anatomy is believed to have undergone adaptive modifications to improve the air-conditioning performance. Furthermore, the maxillary sinus (MS), an accessory hollow communicating with the nasal cavity, is found in macaques, whereas it is absent in most other extant Old World monkeys, including savanna monkeys. In this study, we used computational fluid dynamics simulations to simulate the airflow and heat and water exchange over the mucosal surface in the nasal passage. Using the topology models of the nasal cavity with and without the MS, we demonstrated that the MS makes little contribution to the airflow pattern and the air-conditioning performance within the nasal cavity in macaques. Instead, the inhaled air is conditioned well in the anterior portion of the nasal cavity before reaching the MS in both macaques and savanna monkeys. These findings suggest that the evolutionary modifications and coetaneous variations in the nasal anatomy are rather independent of transitions and variations in the climate and atmospheric environment found in the habitats of macaques.

  13. Noninvasive Temporal Artery Thermometry as an Alternative to Rectal Thermometry in Research Macaques (Macaca spp.)

    PubMed Central

    Woods, Stephanie E; Marini, Robert P; Patterson, Mary M

    2013-01-01

    Obtaining an animal's body temperature is essential for the assessment of its clinical status. For many species, rectal thermometry is the technique used most often; however, this method in macaques typically requires sedation or considerable physical restraint. A noninvasive and inexpensive temporal artery (TA) thermometer was evaluated as an alternative method for collecting body temperature measurements from macaques used in neuroscience research. Rectal and arterial temperatures were obtained from 86 macaques (mean age, 10.2 y) that had received ketamine (10 mg/kg IM) or Telazol (5 mg/kg IM); the arterial measurements were taken from behind the right ear. In addition, arterial temperatures were measured behind both ears in a cohort of awake, chaired macaques with cephalic restraint pedestals only (n = 8) or with cephalic restraint pedestals and recording chambers (n = 14). Within-subject repeatability for TA thermometry and agreement between rectal and arterial temperature measurements were assessed by using the Bland–Altman method. Temperature measurements indicated that values from TA thermometry were lower than those from rectal thermometry by 1.57 °C with a 95% agreement limit of ± 1.27 °C. Results show satisfactory repeatability with TA thermometry and agreement between arterial and rectal temperatures, demonstrating that TA thermometry can be a valuable tool in conscious, chaired macaques with restrained heads. PMID:23849413

  14. Influence of heavy snow on the feeding behavior of Japanese macaques (macaca fuscata) in northern Japan.

    PubMed

    Enari, Hiroto; Sakamaki-Enari, Haruka

    2013-06-01

    Natural disasters can degrade primate habitat and alter feeding behavior. Here, we examined the influence of unusually heavy snow on diet and feeding-site use by Japanese macaques (Macaca fuscata) in northern Japan. To compare the winter-feeding behavior under different snow conditions, we recorded the plant species foraged on by macaques in multiple transects of the Shirakami Mountains from 2008 to 2012 (excluding 2011). We used cluster analysis to describe foraged plant assemblages, and applied multiple dimensional scaling and decision tree modeling to evaluate annual variation in feeding-site use by macaques. Our cluster analysis revealed five types of foraged plant assemblages. The proportion of each type present in transects varied considerably across the years, indicating that the diet of macaques in heavy snow conditions was influenced more by resource accessibility than by preference. Multiple dimensional scaling and decision tree modeling demonstrated that heavy snow conditions restricted feeding-site use. Moreover, the distribution of refuges relative to severe external ambient environments was a stronger limiting factor for feeding-site use than was the availability of food resources. While most primate species facing unexpected starvation employ risk-prone foraging tactics (i.e., choosing the option with higher pay-off by accepting risk), Japanese macaques have a tendency to adopt risk-averse foraging behavior (i.e., minimizing energy loss when searching for preferred diet items under long-lasting heavy snow conditions), because winters with temperatures below freezing have higher thermoregulatory costs.

  15. Amino Acid 72 of Mouse and Human GDF9 Mature Domain Is Responsible for Altered Homodimer Bioactivities but Has Subtle Effects on GDF9:BMP15 Heterodimer Activities1

    PubMed Central

    Peng, Jia; Wigglesworth, Karen; Rangarajan, Adithya; Eppig, John J.; Thompson, Thomas B.; Matzuk, Martin M.

    2014-01-01

    ABSTRACT Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted paralogs of the transforming growth factor beta (TGFbeta) superfamily. In mammals, these two growth factors play critical roles in folliculogenesis. As previously reported, an arginine in the pre-helix loop of GDF5 defines the high binding specificity to its type 1 receptor. Interestingly, bioactive mouse GDF9 and human BMP15 share the conserved arginine in the pre-helix loop, but their low-activity counterparts (mouse BMP15 and human GDF9) have a glycine or a proline instead. To address the question of whether the arginine residue defines the different activities of GDF9 and BMP15 homodimers and their heterodimers in human and mouse, we used site-directed mutagenesis to change the species-specific residues in human and mouse proteins, and examined their activities in our in vitro assays. Although amino acid 72 of mature GDF9 is responsible for altered homodimer bioactivities, neither the corresponding BMP15 amino acid 62 nor the intact pre-helix loop is indispensable for BMP15 homodimer activity. However, amino acid 72 in GDF9 only has only subtle effects on GDF9:BMP15 heterodimer activity. Based on previous studies and our recent findings, we provide hypothetical models to understand the molecular mechanism to define activities of the homodimeric and heterodimeric ligands. The arginine residue in the pre-helix loop of GDF9 homodimer may prevent the inhibition from its pro-domain or directly alter receptor binding, but this residue in GDF9 does not significantly affect the heterodimer activity, because of suggested conformational changes during heterodimer formation. PMID:25253739

  16. Risperidone-induced inactivation and clozapine-induced reactivation of rat cortical astrocyte 5-hydroxytryptamine₇ receptors: evidence for in situ G protein-coupled receptor homodimer protomer cross-talk.

    PubMed

    Smith, Carol; Toohey, Nicole; Knight, Jessica A; Klein, Michael T; Teitler, Milt

    2011-02-01

    We have reported previously novel drug-induced inactivation and reactivation of human 5-hydroxytryptamine₇ (5-HT₇) receptors in a recombinant cell line. To explain these novel observations, a homodimer structure displaying protomer-protomer cross-talk was proposed. To determine whether these novel observations and interpretations are due to an artifactual G protein-coupled receptor (GPCR) mechanism unique to the recombinant cell line, we explored the properties of r5-HT₇ receptors expressed by cortical astrocytes in primary culture. As in the recombinant cell line, risperidone, 9-OH-risperidone, methiothepin, and bromocriptine were found to potently inactivate r5-HT₇ receptors. As in the recombinant cell line, exposure of risperidone-inactivated astrocyte r5-HT₇ receptors to competitive antagonists resulted in the reactivation of r5-HT₇ receptors. The potencies of the reactivating drugs closely correlated with their affinities for h5-HT₇ receptors. These results indicate the novel inactivating and reactivating property of drugs is not due to an artifact of the recombinant cell line expressing h5-HT₇ receptors but is an intrinsic property of 5-HT₇ receptors in vitro and ex vivo. This evidence suggests that a native (nonmutated) GPCR, in its native membrane environment (cortical astrocyte primary culture), can function as a homodimer with protomer-protomer cross-talk. Homodimers may be a common GPCR structure. The experimental design used in our studies can be used to explore the properties of other GPCRs in their native forms in recombinant cells, primary cultures expressing the endogenous GPCRs, and possibly in vivo. The homodimer structure and protomer-protomer cross-talk offer new avenues of research into receptor dysfunction in disease states and the development of novel drugs. PMID:21062995

  17. Bipedal locomotion of bonnet macaques after spinal cord injury.

    PubMed

    Babu, Rangasamy Suresh; Anand, P; Jeraud, Mathew; Periasamy, P; Namasivayam, A

    2007-10-01

    Experimental studies concerning the analysis of locomotor behavior in spinal cord injury research are widely performed in rodent models. The purpose of this study was to quantitatively evaluate the degree of functional recovery in reflex components and bipedal locomotor behavior of bonnet macaques (Macaca radiata) after spinal contusive injury. Six monkeys were tested for various reflex components (grasping, righting, hopping, extension withdrawal) and were trained preoperatively to walk in bipedal fashion on the simple and complex locomotor runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The overall performance of the animals'motor behavior and the functional status of limb movements during bipedal locomotion were graded by the Combined Behavioral Score (CBS) system. Using the simple Allen weight-drop technique, a contusive injury was produced by dropping a 13-g weight from a height of 30 cm to the exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the monkeys showed significant impairments in every reflex activity and in walking behavior during the early part of the postoperative period. In subsequent periods, the animals displayed mild alterations in certain reflex responses, such as grasping, extension withdrawal, and placing reflexes, which persisted through a 1-year follow-up. The contused animals traversed locomotor runways--narrow beam, incline plane, and grid runways--with more steps and few errors, as evaluated with the CBS system. Eventually, the behavioral performance of all spinal-contused monkeys recovered to near-preoperative level by the fifth postoperative month. The findings of this study reveal the recovery time course of various reflex components and bipedal locomotor behavior of spinal-contused macaques on runways for a postoperative period of up to 1 year. Our spinal cord research in primates is advantageous in understanding the characteristics of hind limb functions only, which possibly

  18. Investigation of cadmium contamination using hair of the Japanese macaque, Macaca fuscata, from Shimokita Peninsula, Aomori Prefecture in Japan.

    PubMed

    Mochizuki, Mariko; Anahara, Reiko; Mano, Tomoki; Nakayama, Yuri; Kobori, Mutsumi; Omi, Toshinori; Matsuoka, Shiro; Ueda, Fukiko

    2012-09-01

    The cadmium (Cd) contents in hair of macaques (n = 45, Macaca fuscata) living on the Shimokita Peninsula were investigated. The mean Cd contents in the hair of Japanese (n = 34, 5.01 μg/g) and macaques (3.05 μg/g) tendency to be higher than those of animals living other areas. The Cd contents of hair of wild macaques were significantly (p < 0.01) lower than that of humans, although three were no significant difference between Cd contents of humans and that of the macaque in captivity. The hair of the macaque was suggested as a useful sample for measurement of Cd contamination in the environment.

  19. 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

  20. 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

    2014-07-15

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

  1. Seasonal changes in the structure of rhesus macaque social networks

    PubMed Central

    Brent, Lauren J.N.; MacLarnon, Ann.; Platt, Michael L.; Semple, Stuart

    2012-01-01

    Social structure emerges from the patterning of interactions between individuals and plays a critical role in shaping some of the main characteristics of animal populations. The topological features of social structure, such as the extent to which individuals interact in clusters, can influence many biologically important factors, including the persistence of cooperation, and the rate of spread of disease. Yet the extent to which social structure topology fluctuates over relatively short periods of time in relation to social, demographic or environmental events remains unclear. Here, we use social network analysis to examine seasonal changes in the topology of social structures that emerge from socio-positive associations in adult female rhesus macaques (Macaca mulatta). Behavioral data for two different association types (grooming, spatial proximity) were collected for females in two free-ranging groups during two seasons: the mating and birth seasons. Stronger dyadic bonds resulted in social structures that were more tightly connected (i.e. of greater density) in the mating season compared to the birth season. Social structures were also more centralized around a subset of individuals, and were more clustered in the mating season than the birth season, although the latter differences were mostly driven by differences in density alone. Our results suggest a degree of temporal variation in the topological features of social structure in this population. Such variation may feed back on interactions, hence affecting the behaviors of individuals, and may therefore be important to take into account in studies of animal behavior. PMID:23565026

  2. Economic choices reveal probability distortion in macaque monkeys.

    PubMed

    Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-02-18

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing.

  3. 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

  4. Economic Choices Reveal Probability Distortion in Macaque Monkeys

    PubMed Central

    Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-01-01

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. PMID:25698750

  5. 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

  6. Macaque accessory optic system: II. Connections with the pretectum

    SciTech Connect

    Baleydier, C.; Magnin, M.; Cooper, H.M. )

    1990-12-08

    Connections of the accessory optic system (AOS) with the pretectum are described in the macaque monkey. Injections of tritiated amino acids in the pretectum demonstrate a major contralateral projection to the dorsal (DTN), lateral (LTN), and medial (MTN) terminal nuclei of the AOS and a sparser projection to the ipsilateral LTN. Injections of retrograde tracers, Fast Blue (FB), or wheat germ agglutinin horseradish peroxidase (WGA-HRP) plus nonconjugated horseradish peroxidase (HRP) in the LTN show that the pretectal-LTN projection originates from two nuclei. The main source of pretectal efferents to the LTN is from the pretectal olivary nucleus (OPN) and is entirely contralateral. This projection, which appears unique to primates, originates from the large multipolar cells of the OPN. In addition to this projection, the nucleus of the optic tract (NOT) projects to the ipsilateral LTN, as in nonprimates. Injection of WGA-HRP in the pretectum shows a reciprocal predominantely ipsilateral projection from the LTN to the pretectum. Retinas were observed after injection of FB in the LTN. The retinal ganglion cells projecting to the AOS are mainly distributed near the fovea and in the nasal region of the contralateral eye, suggesting a nasotemporal pattern of decussation. The demonstration of a direct connection between LTN and OPN forces to a reconsideration of the functional role of the AOS. Previous descriptions of luminance responsive cells in the LTN support a possible participation of this nucleus in the control of the pupillary light reflex.

  7. The whole mitochondrial genome of the Cynomolgus macaque (Macaca fascicularis).

    PubMed

    Li, Ruilei; Wang, Huawei; Yang, Liqin; Zhang, Baoming; Li, Yijiang; Hu, Jiansheng; Kong, Qingpeng

    2015-04-01

    Macaca fascicularis, known as the long-tailed macaque, is widely distributed in southern of East Asia and Southeast Asia. It was one of the most commonly used non-human primates in biomedical research. Thus, to illustrate the maternal phylogenetic status of M. fascicularis in primates based on the whole mitochondrial DNA (mtDNA) genome and determine a reference sequence for future population genetic studies by taking mtDNA as molecular marker, in this study, the high quality whole mtDNA genome of M. fascicularis was amplified and sequenced. Our data showed that the whole mtDNA genome of M. fascicularis includes 16,571 base pairs (bps). Further phylogenetic analyses of M. fascicularis were performed by incorporating the 83 available whole mtDNA genomes belonging to 77 primate species with Tupaia belangeri as out-group. Our result supported that M. fascicularis belongs to Macaca. Cercopithecinae. Cercopithecidae. Anthropoidea. Primates, which has the closest genetic affinity with Macaca mulatta. In addition, the ancestral divergence between the tarsier and other primate species was supported with evidence from the whole mtDNA genomes.

  8. Perceptual color map in macaque visual area V4.

    PubMed

    Li, Ming; Liu, Fang; Juusola, Mikko; Tang, Shiming

    2014-01-01

    Colors distinguishable with trichromatic vision can be defined by a 3D color space, such as red-green-blue or hue-saturation-lightness (HSL) space, but it remains unclear how the cortex represents colors along these dimensions. Using intrinsic optical imaging and electrophysiology, and systematically choosing color stimuli from HSL coordinates, we examined how perceptual colors are mapped in visual area V4 in behaving macaques. We show that any color activates 1-4 separate cortical patches within "globs," millimeter-sized color-preferring modules. Most patches belong to different hue or lightness clusters, in which sequential representations follow the color order in HSL space. Some patches overlap greatly with those of related colors, forming stacks, possibly representing invariable features, whereas few seem positioned irregularly. However, for any color, saturation increases the activity of all its patches. These results reveal how the color map in V4 is organized along the framework of the perceptual HSL space, whereupon different multipatch activity patterns represent different colors. We propose that such distributed and combinatorial representations may expand the encodable color space of small cortical maps and facilitate binding color information to other image features. PMID:24381282

  9. 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

  10. 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

  11. Distributions of transmitter receptors in the macaque cingulate cortex.

    PubMed

    Bozkurt, Ahmet; Zilles, Karl; Schleicher, Axel; Kamper, Lars; Arigita, Ernesto Sanz; Uylings, Harry B M; Kötter, Rolf

    2005-03-01

    The primate cingulate cortex is structurally and functionally complex. Although no studies have investigated the regional densities of multiple neurotransmitter receptor systems, such information would be useful for assessing its functions and disease vulnerabilities. We quantified nine different receptors in five transmitter systems by in vitro autoradiographic mapping of the cingulate cortex of macaque monkeys with the aim to link cytoarchitectonic regions and functional specialization. Receptor mapping substantiated the subdivision of the cingulate cortex into anterior versus posterior regions. In anterior cingulate cortex (ACC) AMPA glutamatergic receptors and GABA(A) inhibitory receptors were present in significantly higher concentrations than the modulatory alpha-adrenergic and muscarinic receptors. These differences were absent in the posterior cingulate cortex (PCC). By contrast, NMDA receptor densities were significantly higher than AMPA receptor densities in PCC, but not in ACC. The midcingulate area 24' shared more features with ACC than PCC. This area was characterized by the highest ratios of NMDA receptors to alpha-adrenergic, muscarinic and 5-HT2 receptors among all cingulate regions. Compared to rostrocaudal divisions, the differences between dorsoventral subdivisions a-c were small in all regions of cingulate cortex, and only muscarinic and alpha-adrenergic receptor densities followed the degree of cytoarchitectonic differentiation. We conclude that multiple receptor mapping reveals a highly differentiated classification of cingulate cortex with a characteristic predominance of fast ionotropic excitatory and inhibitory receptors in ACC, but a strong and varied complement of NMDA and metabotropic receptors in PCC.

  12. 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.

  13. Distress prevention by grooming others in crested black macaques.

    PubMed

    Aureli, Filippo; Yates, Kerrie

    2010-02-23

    Allogrooming is probably one of the most common and most studied social behaviours in a variety of animals. Whereas the short-term benefits for the groomee have often been investigated, little is known about the effects for the groomer. Our study focused on the short-term effects of grooming another group member in seven adult female crested black macaques (Macaca nigra). We found reductions in self-directed behaviour, an indicator of anxiety, and aggressive tendencies soon after grooming, when compared to matched-control periods. These findings can be interpreted as evidence of distress prevention, possibly mediated by an increase in tolerance. Indeed, a former groomee was more likely to be the nearest neighbour of the former groomer in the 10 min after grooming ended. Thus, the role of grooming in short-term distress alleviation can be applicable to the groomer as well as the groomee. These short-term effects, together with the longer-term effects of large and/or strong grooming networks confirm that grooming, as well as receiving grooming, has great importance for social dynamics.

  14. 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

  15. 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

  16. Sleep duration is affected by social relationships among sleeping partners in wild Japanese macaques.

    PubMed

    Mochida, Koji; Nishikawa, Mari

    2014-03-01

    Co-sleeping behaviour, such as sharing a sleeping site or bed, should play an important role in determining sleep structure in mammals by mitigating predation pressure and harsh abiotic conditions during sleep. Although environmental factors surrounding sleeping sites have been studied, there is very little information on the effects of the social environment within the site on sleep in animals other than humans. Here, we quantified the duration of nighttime sleep of wild primates during behavioural observations. Wild Japanese macaques (Macaca fuscata yakui) form clusters at sleeping sites, where they huddle with group members. Macaques slept for longer when huddled in sleeping clusters with natal members than in those with non-natal members. A high degree of synchronisation of wakefulness in pairs of macaques huddling in non-natal clusters suggested that their sleep was often interrupted by the wakefulness of huddling members at night. Our results suggest that familiarity and closeness to huddling partners influence sleep duration.

  17. Variations in fundamental frequency peak position in Japanese macaque (Macaca fuscata) coo calls.

    PubMed

    Owren, M J; Casale, T M

    1994-09-01

    Japanese macaques (Macaca fuscata) produce coo calls whose use in various contexts is correlated with differences in the relative temporal position of the peak value of a call's fundamental frequency (Green, 1975). Studies have produced conflicting results about both the location of the category boundary between smooth early high and smooth late high coo subtypes and macaques' perceptual sensitivity to variations in peak position. In this study, fundamental frequency peak positions were measured in 578 coos produced by 8 captive adult female Japanese macaques in order to test whether calls with peak positions close to either of 2 hypothesized boundaries occurred at low rates. Overall, such calls were found to occur at rate equal to or higher than predicted by chance. Peak position varied more consistently between animals than by behavioral context. The results may indicate that peak position in coos does not form 2 distinct categories.

  18. 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

  19. Genetic characterization of Indian-origin and Chinese-origin rhesus macaques (Macaca mulatta).

    PubMed

    Smith, David Glenn

    2005-06-01

    Genetic differences between Indian-origin and Chinese-origin rhesus macaques are as great as those between some primate species and can influence the results of experiments in which both are used as animal models for the study of the same human diseases. Unfortunately, many breeding facilities do not know with certainty the origin of the founders of their rhesus breeding colonies. Here I summarize the most definitive of the genetic traits among the microsatellite (STR) loci and mitochondrial DNA sequences that my laboratory previously reported to characterize Indian-origin and Chinese-origin rhesus macaques and then estimate the frequencies of these traits and their reliability as indicators of country of origin. The expression of diagnostic traits at two or more of four different unlinked loci provides a nearly 100% reliability in distinguishing rhesus macaques of Indian and Chinese origin.

  20. Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis).

    PubMed

    Saito, Akatsuki; Kono, Ken; Nomaguchi, Masako; Yasutomi, Yasuhiro; Adachi, Akio; Shioda, Tatsuo; Akari, Hirofumi; Nakayama, Emi E

    2012-03-01

    The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone, NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses.

  1. In-vivo stimulation of macaque natural killer T cells with α-galactosylceramide.

    PubMed

    Fernandez, C S; Jegaskanda, S; Godfrey, D I; Kent, S J

    2013-09-01

    Natural killer T cells are a potent mediator of anti-viral immunity in mice, but little is known about the effects of manipulating NKT cells in non-human primates. We evaluated the delivery of the NKT cell ligand, α-galactosylceramide (α-GalCer), in 27 macaques by studying the effects of different dosing (1-100 μg), and delivery modes [directly intravenously (i.v.) or pulsed onto blood or peripheral blood mononuclear cells]. We found that peripheral NKT cells were depleted transiently from the periphery following α-GalCer administration across all delivery modes, particularly in doses of ≥10 μg. Furthermore, NKT cell numbers frequently remained depressed at i.v. α-GalCer doses of >10 μg. Levels of cytokine expression were also not enhanced after α-GalCer delivery to macaques. To evaluate the effects of α-GalCer administration on anti-viral immunity, we administered α-GalCer either together with live attenuated influenza virus infection or prior to simian immunodeficiency virus (SIV) infection of two macaques. There was no clear enhancement of influenza-specific T or B cell immunity following α-GalCer delivery. Further, there was no modulation of pathogenic SIVmac251 infection following α-GalCer delivery to a further two macaques in a pilot study. Accordingly, although macaque peripheral NKT cells are modulated by α-GalCer in vivo, at least for the dosing regimens tested in this study, this does not appear to have a significant impact on anti-viral immunity in macaque models.

  2. Mixed-complexity artificial grammar learning in humans and macaque monkeys: evaluating learning strategies.

    PubMed

    Wilson, Benjamin; Smith, Kenny; Petkov, Christopher I

    2015-03-01

    Artificial grammars (AG) can be used to generate rule-based sequences of stimuli. Some of these can be used to investigate sequence-processing computations in non-human animals that might be related to, but not unique to, human language. Previous AG learning studies in non-human animals have used different AGs to separately test for specific sequence-processing abilities. However, given that natural language and certain animal communication systems (in particular, song) have multiple levels of complexity, mixed-complexity AGs are needed to simultaneously evaluate sensitivity to the different features of the AG. Here, we tested humans and Rhesus macaques using a mixed-complexity auditory AG, containing both adjacent (local) and non-adjacent (longer-distance) relationships. Following exposure to exemplary sequences generated by the AG, humans and macaques were individually tested with sequences that were either consistent with the AG or violated specific adjacent or non-adjacent relationships. We observed a considerable level of cross-species correspondence in the sensitivity of both humans and macaques to the adjacent AG relationships and to the statistical properties of the sequences. We found no significant sensitivity to the non-adjacent AG relationships in the macaques. A subset of humans was sensitive to this non-adjacent relationship, revealing interesting between- and within-species differences in AG learning strategies. The results suggest that humans and macaques are largely comparably sensitive to the adjacent AG relationships and their statistical properties. However, in the presence of multiple cues to grammaticality, the non-adjacent relationships are less salient to the macaques and many of the humans.

  3. 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

  4. Effective spatial scales for evaluating environmental determinants of population density in Yakushima macaques.

    PubMed

    Agetsuma, Naoki; Koda, Ryosuke; Tsujino, Riyou; Agetsuma-Yanagihara, Yoshimi

    2015-02-01

    Population densities of wildlife species tend to be correlated with resource productivity of habitats. However, wildlife density has been greatly modified by increasing human influences. For effective conservation, we must first identify the significant factors that affect wildlife density, and then determine the extent of the areas in which the factors should be managed. Here, we propose a protocol that accomplishes these two tasks. The main threats to wildlife are thought to be habitat alteration and hunting, with increases in alien carnivores being a concern that has arisen recently. Here, we examined the effect of these anthropogenic disturbances, as well as natural factors, on the local density of Yakushima macaques (Macaca fuscata yakui). We surveyed macaque densities at 30 sites across their habitat using data from 403 automatic cameras. We quantified the effect of natural vegetation (broad-leaved forest, mixed coniferous/broad-leaved forest, etc.), altered vegetation (forestry area and agricultural land), hunting pressure, and density of feral domestic dogs (Canis familiaris). The effect of each vegetation type was analyzed at numerous spatial scales (between 150 and 3,600-m radii from the camera locations) to determine the best scale for explaining macaque density (effective spatial scale). A model-selection procedure (generalized linear mixed model) was used to detect significant factors affecting macaque density. We detected that the most effective spatial scale was 400 m in radius, a scale that corresponded to group range size of the macaques. At this scale, the amount of broad-leaved forest was selected as a positive factor, whereas mixed forest and forestry area were selected as negative factors for macaque density. This study demonstrated the importance of the simultaneous evaluation of all possible factors of wildlife population density at the appropriate spatial scale.

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

    PubMed

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

    2013-04-01

    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 principal components analysis to identify temperament components. The analysis identified four components, which we interpreted as Sociability toward 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 toward humans, long-tailed macaques are more cautious and fearful, and pigtailed macaques are more sociable toward 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. Am. J. Primatol. 75:303-313, 2013. © 2012 Wiley Periodicals, Inc.

  6. Effective spatial scales for evaluating environmental determinants of population density in Yakushima macaques.

    PubMed

    Agetsuma, Naoki; Koda, Ryosuke; Tsujino, Riyou; Agetsuma-Yanagihara, Yoshimi

    2015-02-01

    Population densities of wildlife species tend to be correlated with resource productivity of habitats. However, wildlife density has been greatly modified by increasing human influences. For effective conservation, we must first identify the significant factors that affect wildlife density, and then determine the extent of the areas in which the factors should be managed. Here, we propose a protocol that accomplishes these two tasks. The main threats to wildlife are thought to be habitat alteration and hunting, with increases in alien carnivores being a concern that has arisen recently. Here, we examined the effect of these anthropogenic disturbances, as well as natural factors, on the local density of Yakushima macaques (Macaca fuscata yakui). We surveyed macaque densities at 30 sites across their habitat using data from 403 automatic cameras. We quantified the effect of natural vegetation (broad-leaved forest, mixed coniferous/broad-leaved forest, etc.), altered vegetation (forestry area and agricultural land), hunting pressure, and density of feral domestic dogs (Canis familiaris). The effect of each vegetation type was analyzed at numerous spatial scales (between 150 and 3,600-m radii from the camera locations) to determine the best scale for explaining macaque density (effective spatial scale). A model-selection procedure (generalized linear mixed model) was used to detect significant factors affecting macaque density. We detected that the most effective spatial scale was 400 m in radius, a scale that corresponded to group range size of the macaques. At this scale, the amount of broad-leaved forest was selected as a positive factor, whereas mixed forest and forestry area were selected as negative factors for macaque density. This study demonstrated the importance of the simultaneous evaluation of all possible factors of wildlife population density at the appropriate spatial scale. PMID:25231752

  7. SIV/HIV Nef recombinant virus (SHIVnef) produces simian AIDS in rhesus macaques.

    PubMed

    Mandell, C P; Reyes, R A; Cho, K; Sawai, E T; Fang, A L; Schmidt, K A; Luciw, P A

    1999-12-20

    The simian immunodeficiency virus (SIV) nef gene is an important determinant of viral load and acquired immunodeficiency syndrome (AIDS) in macaques. A role(s) for the HIV-1 nef gene in infection and pathogenesis was investigated by constructing recombinant viruses in which the nef gene of the pathogenic molecular clone SIVmac239 nef was replaced with either HIV-1sf2nef or HIV-1sf33nef. These chimeras, designated SHIV-2nef and SHIV-33nef, expressed HIV-1 Nef protein and replicated efficiently in cultures of rhesus macaque lymphoid cells. In two SHIV-2nef-infected juvenile rhesus macaques and in one of two SHIV-33nef-infected juvenile macaques, virus loads remained at low levels in both peripheral blood and lymph nodes in acute and chronic phases of infection (for >83 weeks). In striking contrast, the second SHIV-33nef-infected macaque showed high virus loads during the chronic stage of infection (after 24 weeks). CD4+ T-cell numbers declined dramatically in this latter animal, which developed simian AIDS (SAIDS) at 47-53 weeks after inoculation; virus was recovered at necropsy at 53 weeks and designated SHIV-33Anef. Sequence analysis of the HIV-1sf33 nef gene in SHIV-33Anef revealed four consistent amino acid changes acquired during passage in vivo. Interestingly, one of these consensus mutations generated a tyr-x-x-leu (Y-X-X-L) motif in the HIV-1sf33 Nef protein. This motif is characteristic of certain endocytic targeting sequences and also resembles a src-homology region-2 (SH-2) motif found in many cellular signaling proteins. Four additional macaques infected with SHIV-33Anef contained high virus loads, and three of these animals progressed to fatal SAIDS. Several of the consensus amino acid changes in Nef, including Y-X-X-L motif, were retained in these recipient animals exhibiting high virus load and disease. In summary, these findings indicate that the SHIV-33Anef chimera is pathogenic in rhesus macaques and that this approach, i.e., construction of

  8. Establishment of vertebral heart scale in the growth period of the Japanese macaque (Macaca fuscata).

    PubMed

    Harada, Mai; Koie, Hiroshi; Iwaki, Shunsaku; Sato, Tsuneo; Kanayama, Kiichi; Taira, Masato; Sakai, Takeo

    2010-04-01

    We performed a thoracic X-ray examination of 56 Japanese macaques to obtain normal reference values for vertebral heart scale (VHS). Mean VHS was 10.25 +/- 0.94 v. In males, mean VHS was 10.56 +/- 0.73 v, with no significant correlation to age or weight. In contrast, mean VHS in females was 9.97 +/- 1.03 v, and tended to decrease with increasing age and weight. These findings will facilitate the diagnosis of cardiac disease in Japanese macaques in the future.

  9. [Isolation and characterization of twenty-one polymorphic microsatellite loci in the Tibetan macaque (Macaca thibetana)].

    PubMed

    Jia, X D; Yang, B D; Yue, B S; Yin, H L; Wang, H X; Zhang, X Y

    2011-07-01

    Twenty-one microsatellite loci were isolated from AC-enriched library of Tibetan macaque (Macaca thibetana). The number of alleles at the 21 microsatellite loci ranged from 8 to 15, with an average of 12.2 per locus. Polymorphism information content (PIC) ranged from 0.805 to 0.910 with an average of 0.873. The observed and expected heterozygosities ranged from 0.208 to 0.792 and from 0.843 to 0.938, respectively. These microsatellite loci will be useful for future studies that relate to the genetic diversity and population structure of Tibetan macaque.

  10. Meningoencephalitis due to Listeria monocytogenes in a pregnant rhesus macaque (Macaca mulatta).

    PubMed

    Lemoy, Marie-Josee M F; Lopes, Danielle A; Reader, J Rachel; Westworth, Diccon R; Tarara, Ross P

    2012-10-01

    We here report a spontaneous case of meningoencephalitis due to Listeria monocytogenes in an adult primiparous rhesus macaque (Macaca mulatta) during an outbreak of listeriosis in an outdoor enclosure. Clinical signs included tremors, abnormal posture, and altered mental status. Hematology and analyses of cerebrospinal fluid were consistent with bacterial infection. Pure cultures of L. monocytogenes were recovered from the placenta-abortus, cerebrospinal fluid, and brain tissue. The macaque did not respond to treatment and was euthanized. Histopathologic examination of the brain revealed acute meningoencephalitis. This case represents an unusual clinical and pathologic presentation of listeriosis in a nonhuman primate in which the dam and fetus both were affected.

  11. Clinical allograft of a calcaneal tendon in a rhesus macaque (Macaca mulatta).

    PubMed

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

    2014-09-01

    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.

  12. Peripartum sex steroid changes and maternal style in rhesus and Japanese macaques.

    PubMed

    Bardi, Massimo; Shimizu, Keiko; Barrett, Gordon M; Borgognini-Tarli, Silvana M; Huffman, Michael A

    2003-10-01

    The subtle and complex relationships between the sequential maturation of the endocrine systems during pregnancy and parturition, and the hormonal role in activating the central nervous system to express maternal behavior in primates, are far from being completely understood. Recent studies on the association between sex steroids and maternal behavior have yielded conflicting results in this group. Here we use a comparative approach to assess the correlation between changes in the peripartum endocrine profiles and maternal styles in two closely related macaque species, housed in analogous environments. We included in this study the first seven Japanese macaque and seven rhesus macaque mother-infant pairs born during the birth season of 2001 at the Primate Research Institute, Kyoto University, Japan. We observed each pair 3h/week (six weekly 30-min observation sessions) during the first 12 weeks of lactation. We collected fecal samples twice a week from each mother, starting 4 weeks before parturition and ending 4 weeks after parturition. We tested the hypothesis that neuroendocrine changes during pregnancy and lactation might specifically contribute to the regulation and timing of infant rejection. Despite their biological similarities, we observed a clear difference in maternal style between the two groups concerning rejection rates: rhesus macaque mothers rejected their infants earlier and more frequently throughout the whole 12 weeks of study. On the other hand, protectiveness showed similar patterns and values in the two groups, and maternal warmth was significantly higher in the rhesus group, but it followed a similar pattern over time. We also confirmed an association between maternal rejection and excreted estrogen, but not excreted progesterone, for Japanese macaques. This association was not apparent for the rhesus macaques. This result, coupled with the observation that rhesus mothers are more rejecting than Japanese macaque mothers, tends to support our

  13. 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

  14. 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

  15. Variability of tail length in hybrids of the Japanese macaque (Macaca fuscata) and the Taiwanese macaque (Macaca cyclopis).

    PubMed

    Hamada, Yuzuru; Yamamoto, Ayumi; Kunimatsu, Yutaka; Tojima, Sayaka; Mouri, Toshio; Kawamoto, Yoshi

    2012-10-01

    In primates, tail length is subject to wide variation, and the tail may even be absent. Tail length varies greatly between each species group of the genus Macaca, which is explained by climatic factors and/or phylogeographic history. Here, tail length variability was studied in hybrids of the Japanese (M. fuscata) and Taiwanese (Macaca cyclopis) macaque, with various degrees of hybridization being evaluated through autosomal allele typing. Relative tail length (percent of crown-rump length) correlated well with the number of caudal vertebrae. Length profiles of caudal vertebrae of hybrids and parent species revealed a common pattern: the length of several proximal-most vertebrae do not differ greatly; then from the third or fourth vertebra, the length rapidly increases and peaks at around the fifth to seventh vertebra; then the length plateaus for several vertebrae and finally shows a gentle decrease. As the number of caudal vertebrae and relative tail length increase, peak vertebral length and lengths of proximal vertebrae also increase, except that of the first vertebra, which only shows a slight increase. Peak vertebral length and the number of caudal vertebrae explained 92 % of the variance in the relative tail length of hybrids. Relative tail length correlated considerably well with the degree of hybridization, with no significant deviation from the regression line being observed. Thus, neither significant heterosis nor hybrid depression occurred.

  16. Grooming-related feeding motivates macaques to groom and affects grooming reciprocity and episode duration in Japanese macaques (Macaca fuscata).

    PubMed

    Onishi, Kenji; Yamada, Kazunori; Nakamichi, Masayuki

    2013-01-01

    Allogrooming is considered as an altruistic behavior wherein primates exchange grooming as a tradable commodity for reciprocal grooming or other commodities such as support during aggression and tolerance during co-feeding. First, we report a case of the grooming relationships of the lowest-ranking adult female in a group of Japanese macaques (Macaca fuscata). The female (Lp) had lost a portion of the fur and was groomed by higher-ranking individuals without providing reciprocal grooming or other commodities. The groomers probably fed on lice eggs from the fur of Lp more frequently than from that of other adult groomees. This suggests that grooming-related feeding (GRF) motivated many individuals to groom Lp and influenced grooming reciprocity in dyads. Second, we investigated quantitative grooming data for adult females. A high GRF rate was found to lengthen the duration of grooming, suggesting that GRF motivates groomers to groom. From these results, we proposed 2 possible reasons for groomers' sensitivity to GRF rate: (1) the nutritional benefit from GRF compensates for part of the cost of giving grooming and facilitates giving grooming and (2) groomer's sensitivity to the GRF rate maintains the efficiency of removing lice eggs and ensures the groomee's hygienic benefit in receiving grooming.

  17. 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

  18. Natural infection of Burkholderia pseudomallei in an imported pigtail macaque (Macaca nemestrina) and management of the exposed colony.

    PubMed

    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.

  19. 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.

  20. 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

  1. 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.

  2. Independent evolution of an antiviral TRIMCyp in rhesus macaques.

    PubMed

    Wilson, Sam J; Webb, Benjamin L J; Ylinen, Laura M J; Verschoor, Ernst; Heeney, Jonathan L; Towers, Greg J

    2008-03-01

    The antiretroviral restriction factor TRIM5 has recently emerged as an important mediator of innate immunity and species-specific inhibition of retroviral replication in mammals. Selection pressure from pathogenic infection has driven rapid evolution of TRIM5 genes, leading to the antiviral specificities we see today. Remarkably, the New World owl monkey (Aotus trivirgatus) encodes a TRIM5 protein in which the antiviral determinants in the B30.2 domain have been replaced by cyclophilin A (CypA) encoded by a retrotransposed cDNA. The owl monkey TRIMCyp protein restricts infection by a subset of lentiviruses that recruit CypA to their capsids, including HIV-1 and feline immunodeficiency virus. Here, we show that the Old World monkey, rhesus macaque (Macaca mulatta), also encodes a TRIMCyp protein that has arisen independently from that in owl monkeys. The rhesus TRIMCyp is encoded by a single, but common, allele (Mamu7) of the rhesus TRIM5 gene, among at least six further alleles that encode full-length TRIM5 proteins with no homology to CypA. The antiviral specificity of the rhesus TRIMCyp is distinct, restricting infection of HIV-2 and feline immunodeficiency virus but not HIV-1. Restriction by rhesus TRIMCyp is before reverse transcription and inhibited by blocking CypA binding, with cyclosporine A, or by mutation of the capsid CypA binding site. These observations suggest a mechanism of restriction that is conserved between TRIMCyp proteins. The lack of activity against HIV-1 suggests that Mamu7 homozygous animals will be null for TRIM5-mediated restriction of HIV-1 and could contribute to improved animal models for HIV/AIDS. PMID:18287035

  3. Neural processing of biological motion in the macaque temporal cortex

    NASA Astrophysics Data System (ADS)

    Oram, Michael W.; Perrett, David I.

    1994-03-01

    Cells have been found in the superior temporal polysensory area (STPa) of the macaque temporal cortex which are selectively responsive to the sight of particular whole body movements (e.g., walking) under normal lighting. These cells typically discriminate the direction of walking and the view of the body (e.g., left profile walking left). We investigated the extent to which these cells are responsive under `biological motion' conditions where the form of the body is defined only by the movement of light patches attached to the points of limb articulation. One third of the cells (25/72) selective for the form and motion of waling bodies, showed sensitivity to the moving light displays. Seven of these cells showed only partial sensitivity to form from motion, in so far as the cells responded more to moving light displays than to moving controls but failed to discriminate body view. These seven cells exhibited directional selectivity. Eighteen cells showed statistical discrimination for both direction of movement and body view under biological motion conditions. Most of these cells showed reduced responses to the impoverished moving light stimuli compared to full light conditions. The 18 cells were thus sensitive to detailed form information (body view) from the pattern of articulating motion. Cellular processing of the global pattern of articulation was indicated by the observations that none of the cells were found sensitive to movement of individual limbs and that jumbling the pattern of moving limbs reduced response magnitude. The cell responses thus provide direct evidence for neural mechanisms computing form from non-rigid motion. The selectivity of the cells was for body view, specific direction and specific type of body motion presented by moving light displays and is not predicted by many current computational approaches to the extraction of form from motion.

  4. 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

  5. The medial parietal occipital areas in the macaque monkey.

    PubMed

    Gamberini, Michela; Fattori, Patrizia; Galletti, Claudio

    2015-01-01

    The number, location, extent, and functional properties of the cortical areas that occupy the medial parieto-occipital cortex (mPOC) have been, and still is, a matter of scientific debate. The mPOC is a convoluted region of the brain that presents a high level of individual variability, and the fact that many areas of mPOC are located within very deep sulci further limits the possibility to investigate their anatomo-functional properties. In the present review, we summarize the location and extent of mPOC areas in the macaque brain as obtained by architectural, connectional, and functional data. The different approaches lead to a subdivision of mPOC that includes areas V2, V3, V6, V6Av, and V6Ad. Extrastriate areas V2 and V3 occupy the posterior wall of the parieto-occipital sulcus (POs). The fundus of POs and the ventralmost part of the anterior wall of the sulcus are occupied by a retinotopically organized visual area, called V6, which represents the contralateral part of the visual field and emphasizes its periphery. The remaining part of the anterior wall of POs is occupied by two areas, V6Av and V6Ad, which contain visual as well as arm reaching neurons. Our analyses suggest that areas V6 and V6Av, together, occupy the cortical territory previously described as area PO. Functionally, area V6 is a motion area particularly sensitive to the real motion of objects in the animal's field of view, while V6Av and V6Ad are visuomotor areas likely involved in the visual guidance of arm movement and object prehension. PMID:26241957

  6. Cholinergic synaptic circuitry in the macaque prefrontal cortex.

    PubMed

    Mrzljak, L; Pappy, M; Leranth, C; Goldman-Rakic, P S

    1995-07-10

    Surprisingly little is known about the synaptic architecture of the cholinergic innervation in the primate cerebral cortex in spite of its acknowledged relevance to cognitive processing and Alzheimer's disease. To address this knowledge gap, we examined serially sectioned cholinergic axons in supra- and infragranular layers of the macaque prefrontal cortex by using an antibody against the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). The tissue bound antibody was visualized with both immunoperoxidase and silver-enhanced diaminobenzidine sulfide (SEDS) techniques. Both methods revealed that cholinergic axons make synapses in all cortical layers and that these synapses are exclusively symmetric. Cholinergic axons formed synapses primarily on dendritic shafts (70.5%), dendritic spines (25%), and, to a lesser extent, cell bodies (4.5%). Both pyramidal neurons and cells exhibiting the morphological features of GABAergic cells were targets of the cholinergic innervation. Some spiny dendritic shafts received multiple, closely spaced synapses, suggesting that a subset of pyramidal neurons may be subject to a particularly strong cholinergic influence. Analysis of synaptic incidence of cholinergic profiles in the supragranular layers of the prefrontal cortex by the SEDS technique revealed that definitive synaptic junctions were formed by 44% of the cholinergic boutons. An unexpected finding was that cholinergic boutons were frequently apposed to spines and small dendrites without making any visible synaptic specializations. These same spines and dendrites often received asymmetric synapses, presumably of thalamocortical or corticocortical origin. Present ultrastructural findings suggest that acetylcholine may have a dual modulatory effect in the neocortex: one through classical synaptic junctions on dendritic shafts and spines, and the other through nonsynaptic appositions in close vicinity to asymmetric synapses. Further physiological studies are

  7. 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

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

    PubMed Central

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

    1998-01-01

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

  9. 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

  10. High-sensitivity two-color detection of double-stranded DNA with a confocal fluorescence gel scanner using ethidium homodimer and thiazole orange.

    PubMed

    Rye, H S; Quesada, M A; Peck, K; Mathies, R A; Glazer, A N

    1991-01-25

    Ethidium homodimer (EthD; lambda Fmax 620 nm) at EthD:DNA ratios up to 1 dye:4-5 bp forms stable fluorescent complexes with double-stranded DNA (dsDNA) which can be detected with high sensitivity using a confocal fluorescence gel scanner (Glazer, A.N., Peck, K. & Mathies, R.A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3851-3855). However, on incubation with unlabeled DNA partial migration of EthD takes place from its complex with dsDNA to the unlabeled DNA. It is shown here that this migration is dependent on the fractional occupancy of intercalating sites in the original dsDNA-EthD complex and that there is no detectable transfer from dsDNA-EthD complexes formed at 50 bp: 1 dye. The monointercalator thiazole orange (TO; lambda Fmax 530 nm) forms readily dissociable complexes with dsDNA with a large fluorescence enhancement on binding (Lee, L.G., Chen, C. & Liu, L.A. (1986) Cytometry 7, 508-517). However, a large molar excess of TO does not displace EthD from its complex with dsDNA. When TO and EthD are bound to the same dsDNA molecule, excitation of TO leads to efficient energy transfer from TO to EthD. This observation shows the practicability of 'sensitizing' EthD fluorescence with a second intercalating dye having a very high absorption coefficient and efficient energy transfer characteristics. Electrophoresis on agarose gels, with TO in the buffer, of preformed linearized M13mp18 DNA-EthD complex together with unlabeled linearized pBR322 permits sensitive fluorescence detection in the same lane of pBR322 DNA-TO complex at 530 nm and of M13mp18 DNA-EthD complex at 620 nm. These observations lay the groundwork for the use of stable DNA-dye intercalation complexes carrying hundreds of chromophores in two-color applications such as the physical mapping of chromosomes.

  11. The Human Sodium-Glucose Cotransporter (hSGLT1) Is a Disulfide-Bridged Homodimer with a Re-Entrant C-Terminal Loop

    PubMed Central

    Sasseville, Louis J.; Morin, Michael; Coady, Michael J.; Blunck, Rikard; Lapointe, Jean-Yves

    2016-01-01

    Na-coupled cotransporters are proteins that use the trans-membrane electrochemical gradient of Na to activate the transport of a second solute. The sodium-glucose cotransporter 1 (SGLT1) constitutes a well-studied prototype of this transport mechanism but essential molecular characteristics, namely its quaternary structure and the exact arrangement of the C-terminal transmembrane segments, are still debated. After expression in Xenopus oocytes, human SGLT1 molecules (hSGLT1) were labelled on an externally accessible cysteine residue with a thiol-reactive fluorophore (tetramethylrhodamine-C5-maleimide, TMR). Addition of dipicrylamine (DPA, a negatively-charged amphiphatic fluorescence “quencher”) to the fluorescently-labelled oocytes is used to quench the fluorescence originating from hSGLT1 in a voltage-dependent manner. Using this arrangement with a cysteine residue introduced at position 624 in the loop between transmembrane segments 12 and 13, the voltage-dependent fluorescence signal clearly indicated that this portion of the 12–13 loop is located on the external side of the membrane. As the 12–13 loop begins on the intracellular side of the membrane, this suggests that the 12–13 loop is re-entrant. Using fluorescence resonance energy transfer (FRET), we observed that different hSGLT1 molecules are within molecular distances from each other suggesting a multimeric complex arrangement. In agreement with this conclusion, a western blot analysis showed that hSGLT1 migrates as either a monomer or a dimer in reducing and non-reducing conditions, respectively. A systematic mutational study of endogenous cysteine residues in hSGLT1 showed that a disulfide bridge is formed between the C355 residues of two neighbouring hSGLT1 molecules. It is concluded that, 1) hSGLT1 is expressed as a disulfide bridged homodimer via C355 and that 2) a portion of the intracellular 12–13 loop is re-entrant and readily accessible from the extracellular milieu. PMID:27137918

  12. 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

  13. Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation.

    PubMed

    He, Zhisong; Bammann, Hindrike; Han, Dingding; Xie, Gangcai; Khaitovich, Philipp

    2014-07-01

    The current annotation of the human genome includes more than 12,000 long intergenic noncoding RNAs (lincRNA). While a handful of lincRNA have been shown to play important regulatory roles, the functionality of most remains unclear. Here, we examined the expression conservation and putative functionality of lincRNA in human and macaque prefrontal cortex (PFC) development and maturation. We analyzed transcriptome sequence (RNA-seq) data from 38 human and 40 macaque individuals covering the entire postnatal development interval. Using the human data set, we detected the expression of 5835 lincRNA annotated in GENCODE and further identified 1888 novel lincRNA. Most of these lincRNA show low DNA sequence conservation, as well as low expression levels. Remarkably, developmental expression patterns of these lincRNA were as conserved between humans and macaques as those of protein-coding genes. Transfection of development-associated lincRNA into human SH-SY5Y cells affected gene expression, indicating their regulatory potential. In brain, expression of these putative target genes correlated with the expression of the corresponding lincRNA during human and macaque PFC development. These results support the potential functionality of lincRNA in primate PFC development.

  14. Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis).

    PubMed

    Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

    2016-01-01

    To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status. PMID:27657707

  15. Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis).

    PubMed

    Carlson, Amy M; Kelly Iii, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

    2016-01-01

    Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 μg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography-mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

  16. 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

  17. Training without reward: traditional training of pig-tailed macaques as coconut harvesters.

    PubMed

    Bertrand, M

    1967-01-27

    Macaca nemestrina, the pig-tailed macaque, is the only monkey regularly and extensively used for work. For centuries it has been trained in Southeast Asia to pick coconuts and other fruits. The training is based exclusively on punishment and avoidance of punishment.

  18. 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.

  19. Resource use of Japanese macaques in heavy snowfall areas: implications for habitat management.

    PubMed

    Enari, Hiroto; Sakamaki-Enari, Haruka

    2013-07-01

    Populations of Japanese macaque (Macaca fuscata) that inhabit the northernmost distribution of any nonhuman primates have been listed as endangered in Japan; however, macaques are widely known for being pests that cause agricultural damage. This study identified priority areas for the conservation and management of macaque habitats, by comparing the resource use of troops occupying remote mountains (montane troops) against troops inhabiting disturbed forests adjacent to settlements (rural troops). We collected species presence data across 2 years by radio-tracking two montane troops and two rural troops in the Shirakami Mountains. We developed seasonal utilization distributions by using the kernel method, and identified habitat characteristics by using ecological-niche factor analysis (ENFA). Our results indicate that environmental factors influencing the potential habitat varied widely with season in montane troops as compared with that in rural troops. ENFA results demonstrated that rural troops exhibited more biased resource use and narrower niche breadths than montane troops. Based on our findings, we propose that (1) primary broadleaf forests are the spring habitat conservation priority of montane troops; (2) the habitat unit--the product of habitat suitability index and its surface area--for montane troops is enhanced by removing old conifer plantations from the forest edge at low elevations; (3) such removal around settlements may also contribute toward removing a frontline refuge for rural troops intruding farmlands; and (4) intensive prevention measures against macaque intrusions into settlements during the bottleneck snowy season contribute toward reducing the habitat unit of rural troops.

  20. Impact assessment of dam construction and forest management for Japanese macaque habitats in snowy areas.

    PubMed

    Enari, Hiroto; Sakamaki-Enari, Haruka

    2014-03-01

    Japanese macaques (Macaca fuscata) in their northernmost habitats represent a keystone species and play a central role in heavy snowfall ecosystems. However, distributions have been restricted by pre-war hunting, and populations are facing issues of natural forest losses caused by new dam constructions and massive conifer plantations. In the present study, we predicted the influences of these environmental conditions on macaque habitats during each season, and evaluated the effect of natural forest restoration as a mitigation measure. We constructed multiple habitat suitability models on the basis of different forest change scenarios, by using maximum entropy modeling (Maxent). We predicted the influence of each scenario by calculating the habitat unit (habitat quality × habitat quantity). We made the following predictions: (1) the influences of environmental conditions on habitat models vary seasonally, but dam construction destroys the optimum macaque habitats in every season; (2) restoration of conifer plantations to semi-natural forests does not always contribute to the improvement of total habitat unit, except in snowy seasons; and (3) in comparison with encouraging natural forest restoration in plantation areas and maintaining the standard-rotation plantation management, the implementation of long-rotation plantation in existing plantation areas provides more suitable alternative habitats for macaques in non-snowy seasons.

  1. 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.

  2. Categorical perception of conspecific communication sounds by Japanese macaques, Macaca fuscata.

    PubMed

    May, B; Moody, D B; Stebbins, W C

    1989-02-01

    Field studies indicate that Japanese macaque (Macaca fuscata) communication signals vary with the social situation in which they occur [S. Green, "Variation of vocal pattern with social situation in the Japanese monkey (Macaca fuscata): A field study," in Primate Behavior, edited by L. A. Rosenblum (Academic, New York, 1975), Vol. 4]. A significant acoustic property of the contact calls produced by these primates is the temporal position of a frequency peak within the vocalization, that is, an inflection from rising to falling frequency [May et al., "Significant features of Japanese macaque communication sounds: A psychophysical study," Anim. Behav. 36, 1432-1444 (1988)]. The experiments reported here are based on the hypothesis that Japanese macaques derive meaning from this temporally graded feature by parceling the acoustic variation inherent in natural contact calls into two functional categories, and thus exhibit behavior that is analogous to the categorical perception of speech sounds by humans. To test this hypothesis, Japanese macaques were trained to classify natural contact calls by performing operant responses that signified either an early or late frequency peak position. Then, the subjects were tested in a series of experiments that required them to generalize this behavior to synthetic calls representing a continuum of peak positions. Demonstration of the classical perceptual effects noted for human listeners suggests that categorical perception reflects a principle of auditory information processing that influences the perception of sounds in the communication systems not only of humans, but of animals as well.

  3. 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

  4. Shape of, and body direction in, huddles of Japanese macaques (Macaca fuscata) in Arashiyama, Japan.

    PubMed

    Ogawa, Hideshi; Wada, Kazuo

    2011-07-01

    We studied huddles of Japanese macaques (Macaca fuscata) in the Arashiyama E troop at the "Arashiyama Monkey Park, Iwatayama" of Kyoto, central Japan. The macaques made physical contact with other individuals and formed huddles when the air was cold. The 99-101 adult females and 26-36 adult males in the study troop formed 345 huddles during 42 scan samples in the winter of 2001 and 376 huddles during 52 scan samples in the winter of 2002. The average size of huddles was 2.3 (range 2-7) individuals. Males huddled less frequently than females. Maternal kin-related dyads formed 2-female huddles more frequently than unrelated dyads. Choice of huddling partners might restrict the size of huddles. The most frequently observed 3 and 4-member huddles were triangular and diamond-shaped. Macaques usually huddled ventro-ventrally, ventro-laterally, and ventro-dorsally. A third individual frequently placed the ventral part of its body against the first individual and simultaneously put the lateral part of its body against the second individual, so that the 3 individuals formed a triangular huddle. This behaviour indicates that Japanese macaques choose their position and body direction in the huddle to reduce the area of body surface exposed to the air, thereby conserving body heat.

  5. 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…

  6. 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…

  7. 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…

  8. 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.

  9. 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…

  10. Septic arthritis due to moraxella osloensis in a rhesus macaque (Macaca mulatta).

    PubMed

    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.

  11. Development of an anatomically based whole-body musculoskeletal model of the Japanese macaque (Macaca fuscata).

    PubMed

    Ogihara, Naomichi; Makishima, Haruyuki; Aoi, Shinya; Sugimoto, Yasuhiro; Tsuchiya, Kazuo; Nakatsukasa, Masato

    2009-07-01

    We constructed a three-dimensional whole-body musculoskeletal model of the Japanese macaque (Macaca fuscata) based on computed tomography and dissection of a cadaver. The skeleton was modeled as a chain of 20 bone segments connected by joints. Joint centers and rotational axes were estimated by joint morphology based on joint surface approximation using a quadric function. The path of each muscle was defined by a line segment connecting origin to insertion through an intermediary point if necessary. Mass and fascicle length of each were systematically recorded to calculate physiological cross-sectional area to estimate the capacity of each muscle to generate force. Using this anatomically accurate model, muscle moment arms and force vectors generated by individual limb muscles at the foot and hand were calculated to computationally predict muscle functions. Furthermore, three-dimensional whole-body musculoskeletal kinematics of the Japanese macaque was reconstructed from ordinary video sequences based on this model and a model-based matching technique. The results showed that the proposed model can successfully reconstruct and visualize anatomically reasonable, natural musculoskeletal motion of the Japanese macaque during quadrupedal/bipedal locomotion, demonstrating the validity and efficacy of the constructed musculoskeletal model. The present biologically relevant model may serve as a useful tool for comprehensive understanding of the design principles of the musculoskeletal system and the control mechanisms for locomotion in the Japanese macaque and other primates.

  12. Immunohistochemical Characterization of Large Intestinal Adenocarcinoma in the Rhesus Macaque (Macaca mulatta).

    PubMed

    Harbison, C E; Taheri, F; Knight, H; Miller, A D

    2015-07-01

    In rhesus macaques, adenocarcinomas of either the ileocecal junction or colon are common spontaneous tumors in aging populations. The macaque tumors have similar gross and histologic characteristics compared with their human counterpart, but little is known regarding the immunohistochemical expression of proteins that are commonly implicated in the pathogenesis of these tumors in humans. We performed a retrospective review of 22 cases of large intestinal carcinoma in the rhesus macaque and evaluated the expression pattern of a panel of potentially prognostically significant proteins identified from human studies. Histologic characteristics of the tumors included abundant mucin deposition, transmural spread, and lymphatic invasion. All rhesus adenocarcinomas displayed altered expression of 1 or more of CD10, β-catenin, sirtuin 1, cytokeratin 17, and p53 compared with age-matched controls. Zymographic analysis of active matrix metalloproteinases 2 and 9 in the serum from 5 animals failed to reveal statistically significant differences between adenocarcinoma cases and controls. Based on the data presented herein, large intestinal carcinomas in the macaque share many histomorphologic and immunohistochemical similarities to large intestinal tumors in humans. Further validation of this animal model is considered important for the development of novel therapeutics and a better understanding of the pathogenesis.

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

    PubMed

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

    2015-04-01

    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.

  14. 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…

  15. Visual Recognition Memory in High- and Low-Risk Infant Pigtailed Macaques (Macaca Nemestrina).

    ERIC Educational Resources Information Center

    Gunderson, Virginia M.; And Others

    1987-01-01

    Study looks at pigtailed macaque in the context of visual recognition problems adapted from a standardized test developed for use with human infants. Results demonstrate that the low-risk group easily differentiated novel from previously seen targets; the high-risk group gave no evidence of recognition. (Author/RWB)

  16. [The protease inhibitor system of macaques. The identification of alleles using isoelectric focusing and family analysis].

    PubMed

    Samil'chuk, E I

    1989-01-01

    Five alpha-1-antitrypsin (alpha-1-AT) phenotypes have been revealed by isoelectrofocusing (IEF) in sera of 215 crab-eating macaques. Alpha-1-AT was monomorphic in sera of 250 Rhesus monkeys. A new allele of macaque Pi-system, designated as B' was postulated in addition to existing two (B and C) on the basis of IEF data. The above conclusion was supported by family analysis, based on 35 monkey birth cases. Alpha-1-AT phenotype frequencies were in agreement with Hardy-Weinberg equation both in wild and capture born crab-eating macaques. Alpha-1-AT was found to be microheterogeneous: several zones of the protein were revealed by IEF and Western blotting with anti human alpha-1-AT serum. The pregnancy caused a sharp increase of one band. This may lead to false identification of alpha-1-AT phenotypes, particularly when acid starch gel electrophoresis is used for alpha-1-AT identification. Such misinterpretation during alpha-1-AT phenotyping may explain the disagreement with Hardy-Weinberg equation described earlier for crab-eating macaques. PMID:2788967

  17. Identification of a novel CXCL1-like chemokine gene in macaques and its inactivation in hominids.

    PubMed

    Nomiyama, Hisayuki; Otsuka-Ono, Kaori; Miura, Retsu; Osada, Naoki; Terao, Keiji; Yoshie, Osamu; Kusuda, Jun

    2007-01-01

    Chemokines are a rapidly evolving cytokine gene family. Because of various genome rearrangements after divergence of primates and rodents, humans and mice have different sets of chemokine genes, with humans having members outnumbering those of mice. Here, we report the occurrence of lineage-specific chemokine gene generation or inactivation events within primates. By using human chemokine sequences as queries, we isolated a novel cynomolgus macaque CXC chemokine cDNA. The encoded chemokine, termed CXCL1L (from CXCL1-like) showed the highest similarity to human CXCL1. A highly homologous gene was also found in the rhesus macaque genome. By comparing the genome organization of the major CXC chemokine clusters among the primates, we found that one copy of the duplicated CXCL1 genes turned into a pseudogene in the hominids, whereas the gene in macaques has been maintained as a functionally active CXCL1L. In addition, cynomolgus macaque was found to contain an additional CXC chemokine highly homologous to CXCL3, termed CXCL3L (from CXCL3-like). These results demonstrate the birth-and-death process of a new gene in association with gene duplication within the primates.

  18. MHC class I A region diversity and polymorphism in macaque species

    PubMed Central

    de Vos-Rouweler, Annemiek J. M.; Heijmans, Corrine M. C.; de Groot, Natasja G.; Doxiadis, Gaby G. M.; Bontrop, Ronald E.

    2007-01-01

    The HLA-A locus represents a single copy gene that displays abundant allelic polymorphism in the human population, whereas, in contrast, a nonhuman primate species such as the rhesus macaque (Macaca mulatta) possesses multiple HLA-A-like (Mamu-A) genes, which parade varying degrees of polymorphism. The number and combination of transcribed Mamu-A genes present per chromosome display diversity in a population of Indian animals. At present, it is not clearly understood whether these different A region configurations are evolutionarily stable entities. To shed light on this issue, rhesus macaques from a Chinese population and a panel of cynomolgus monkeys (Macaca fascicularis) were screened for various A region-linked variations. Comparisons demonstrated that most A region configurations are old entities predating macaque speciation, whereas most allelic variation (>95%) is of more recent origin. The latter situation contrasts the observations of the major histocompatibility complex class II genes in rhesus and cynomolgus macaques, which share a high number of identical alleles (>30%) as defined by exon 2 sequencing. Electronic supplementary material The online version of this article (doi:10.1007/s00251-007-0201-2) contains supplementary material, which is available to authorized users. PMID:17334754

  19. High prevalence of Entamoeba infections in captive long-tailed macaques in China.

    PubMed

    Feng, Meng; Yang, Bin; Yang, Liu; Fu, Yongfeng; Zhuang, Yijun; Liang, Longgan; Xu, Qing; Cheng, Xunjia; Tachibana, Hiroshi

    2011-10-01

    Long-tailed macaques (Macaca fascicularis) are bred in China for export and for use in experiments. Entamoeba infections in captive long-tailed macaques were surveyed in one of the biggest colonies located in Guangxi Province, China. One stool sample was obtained from each of the 152 different cages representing >3,000 macaques in the colony. The samples were examined by PCR for five Entamoeba species. The number of detected Entamoeba coli infections comprised 94% of the samples, 93% for Entamoeba chattoni, and 83% for Entamoeba dispar. In contrast, Entamoeba histolytica and Entamoeba nuttalli were not detected. Six isolates of E. dispar were obtained by culture in Tanabe-Chiba medium. Analysis of serine-rich protein genes in these isolates showed two genotypes, one of which is identical to that of the E. dispar SAW760 strain in humans. This suggests transmission of E. dispar between humans and nonhuman primates. These results demonstrate that Entamoeba infections are common, but virulent Entamoeba species are absent in this colony. This work also confirms the need for monitoring with PCR-based identification of Entamoeba species for captive macaques in breeding colonies to ensure animal health and protection of humans from zoonotic hazards.

  20. Videotape-Versus Pellet-Reward Preferences in Joystick Tasks by Macaques

    NASA Technical Reports Server (NTRS)

    Washburn, David A.; Hopkins, William D.

    1994-01-01

    Andrews and Rosenblum (1993) convincingly demonstrated the effectiveness of live-social-video reward for joystick-task performance by bonnet macaques. We performed a similar series of experiments with quite different results. Taken together, these experiments emphasize the importance of the variability in individual preferences for reward effectiveness.

  1. 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

  2. Signaling context modulates social function of silent bared-teeth displays in rhesus macaques (Macaca mulatta).

    PubMed

    Beisner, Brianne A; McCowan, Brenda

    2014-02-01

    The signaling context has been found to change the meaning of the silent bared-teeth display (SBT) in pigtail macaques (Macaca nemestrina) such that the SBT in apparently peaceful contexts communicates subordination, a long-term pattern of behavior, whereas in conflict contexts it communicates immediate submission (PNAS, 104: 1581-1586). However, the context dependent nature of the SBT has not yet been explored in other species. We investigated SBT usage with respect to grooming, severe aggression, and signaler-receiver sex, rank difference, and body size in seven captive groups of rhesus macaques. Peaceful SBTs were given most often to male receivers by male and female signalers whereas conflict SBTs were given to both male and female receivers primarily by female signalers. Male signalers rarely gave SBTs (peaceful or conflict) to female receivers. Unlike pigtail macaques, peaceful SBTs in rhesus were often accompanied by withdrawal behavior (referred to as peaceful SBT-leave), which influenced grooming, but not aggression, at the dyadic level. Severe aggression was less frequent among dyads using peaceful SBTs (regardless of withdrawal behavior) than those using conflict SBTs. In contrast, grooming was more frequent among dyads using peaceful SBT-stay signals than those using peaceful SBT-leave signals or conflict SBTs. In total, our results indicate that peaceful SBTs are a functionally different signal from conflict SBTs in rhesus macaques.

  3. 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.

  4. Entamoeba histolytica and E. dispar infections in captive macaques (Macaca fascicularis) in the Philippines.

    PubMed

    Rivera, Windell L; Yason, John Anthony D L; Adao, Davin Edric V

    2010-01-01

    Entamoeba histolytica is a protozoan parasite that infects man and animals. This parasite has a global distribution and the disease it causes is usually characterized by diarrhea. In order to detect the parasite, it is necessary to differentiate it from Entamoeba dispar. E. dispar appears morphologically similar to E. histolytica but does not cause disease and tissue invasion. This study reports on the prevalence of E. histolytica and E. dispar among captive macaques in a primate facility in the Philippines. PCR was used to correctly identify both Entamoeba species. Indirect fluorescent antibody test (IFAT) was also performed to determine the seroprevalence of amebiasis in the captive macaques. Based on PCR targeting of the peroxiredoxin gene, of the 96 stool samples collected, 23 (24%) contained E. histolytica while 32 (33%) contained E. dispar. IFAT revealed 26 (27%) serum samples positive for antibodies against E. histolytica. Sequence analysis of the 18S rRNA gene showed that the 23 E. histolytica isolates were identical to human E. histolytica isolates deposited in the GenBank and not Entamoeba nuttalli as found in macaques in other recent reports. The Philippines is a major exporter of monkeys for biomedical research purposes, so screening animals before transporting them to other locations lessens the risk of spreading zoonoses to a wider area. This is the first report of the molecular detection of E. histolytica and E. dispar among macaques in the Philippines. This study complements the limited information available on the animal hosts of E. histolytica in the Philippines.

  5. 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.

  6. 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…

  7. Altitudinal and seasonal variations in the diet of Japanese macaques in Yakushima.

    PubMed

    Hanya, Goro; Noma, Naohiko; Agetsuma, Naoki

    2003-01-01

    Altitudinal and seasonal variations in the diet of Japanese macaques in Yakushima, southwestern Japan, were studied for 2 years by means of fecal analysis. The altitudinal range of fecal samples collected was 30 m to 1,203 m above sea level, and it was divided into three zones: low-zone forest (0-399 m), middle-zone forest (400-799 m), and high-zone forest (800 m-1,230 m). There was a considerable altitudinal and seasonal variation in the macaques' diet. Seed/fruit and animal matter were eaten more in the lower zones, whereas more fiber and fungi were consumed in the higher zones. In all of the zones, they ate seed/fruits the most in autumn (September-November) and the least in spring (March-April). They ate fibrous food the most in spring and the least in autumn. Macaques relied on seed/fruits heavily in the lower zone for a longer period than in the higher zones. Macaques in the high-zone forest ate almost no seed/fruit foods from March to May. Altitudinal variations in availability of seed/fruit foods seem to have influenced the altitudinal variations in diet. Total basal area of seed/fruit-food trees, species richness of seed/fruit-foods, main seed/fruit-food types available, and annual fleshy-fruit production all decreased with increasing altitude. Both interannual variation and annual cyclicity of diet were found in all zones.

  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. Elimination of Schistosoma mansoni Adult Worms by Rhesus Macaques: Basis for a Therapeutic Vaccine?

    PubMed Central

    Wilson, R. Alan; Langermans, Jan A. M.; van Dam, Govert J.; Vervenne, Richard A.; Hall, Stephanie L.; Borges, William C.; Dillon, Gary P.; Thomas, Alan W.; Coulson, Patricia S.

    2008-01-01

    Background Among animal models of schistosomiasis, the rhesus macaque is unique in that an infection establishes but egg excretion rapidly diminishes, potentially due to loss of adult worms from the portal system via shunts or death by immune attack. Principal Findings To investigate this, six rhesus macaques were exposed to Schistosoma mansoni cercariae and the infection monitored until portal perfusion at 18 weeks. Despite a wide variation in worm numbers recovered, fecal egg output and circulating antigen levels indicated that a substantial population had established in all animals. Half the macaques had portal hypertension but only one had portacaval shunts, ruling out translocation to the lungs as the reason for loss of adult burden. Many worms had a shrunken and pallid appearance, with degenerative changes in intestines and reproductive organs. Tegument, gut epithelia and muscles appeared cytologically intact but the parenchyma was virtually devoid of content. An early and intense IgG production correlated with low worm burden at perfusion, and blood-feeding worms cultured in the presence of serum from these animals had stunted growth. Using immunoproteomics, gut digestive enzymes, tegument surface hydrolases and antioxidant enzymes were identified as targets of IgG in the high responder animals. Significance It appears that worms starve to death after cessation of blood feeding, as a result of antibody-mediated processes. We suggest that proteins in the three categories above, formulated to trigger the appropriate mechanisms operating in rhesus macaques, would have both prophylactic and therapeutic potential as a human vaccine. PMID:18820739

  10. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    PubMed

    Dorsey, Jamie L; Mangus, Lisa M; Hauer, Peter; Ebenezer, Gigi J; Queen, Suzanne E; Laast, Victoria A; Adams, Robert J; Mankowski, Joseph L

    2015-11-01

    Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed. To study these intercurrent PNS disease processes, we first established a simian immunodeficiency virus (SIV)/pigtailed macaque model in which more than 90% of animals developed PNS changes closely resembling those seen in HIV-infected individuals with distal sensory neuropathy. To determine whether cART alters the progression of SIV-induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated in SIV-infected macaques after long-term suppressive cART. Although cART effectively suppressed SIV replication and reduced macrophage activation in the dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve fibers in the plantar surface of the feet of treated SIV-infected macaques clearly showed that cART did not normalize epidermal nerve fiber density. These findings illustrate that significant PNS damage persists in SIV-infected macaques on suppressive cART.

  11. New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

    PubMed

    Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

    2015-08-01

    A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

  12. 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…

  13. 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

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

    PubMed

    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.

  15. Flexibility in Food Extraction Techniques in Urban Free-Ranging Bonnet Macaques, Macaca radiata

    PubMed Central

    Mangalam, Madhur; Singh, Mewa

    2013-01-01

    Non-human primate populations, other than responding appropriately to naturally occurring challenges, also need to cope with anthropogenic factors such as environmental pollution, resource depletion, and habitat destruction. Populations and individuals are likely to show considerable variations in food extraction abilities, with some populations and individuals more efficient than others at exploiting a set of resources. In this study, we examined among urban free-ranging bonnet macaques, Macaca radiata (a) local differences in food extraction abilities, (b) between-individual variation and within-individual consistency in problem-solving success and the underlying problem-solving characteristics, and (c) behavioral patterns associated with higher efficiency in food extraction. When presented with novel food extraction tasks, the urban macaques having more frequent exposure to novel physical objects in their surroundings, extracted food material from PET bottles and also solved another food extraction task (i.e., extracting an orange from a wire mesh box), more often than those living under more natural conditions. Adults solved the tasks more frequently than juveniles, and females more frequently than males. Both solution-technique and problem-solving characteristics varied across individuals but remained consistent within each individual across the successive presentations of PET bottles. The macaques that solved the tasks showed lesser within-individual variation in their food extraction behavior as compared to those that failed to solve the tasks. A few macaques appropriately modified their problem-solving behavior in accordance with the task requirements and solved the modified versions of the tasks without trial-and-error learning. These observations are ecologically relevant – they demonstrate considerable local differences in food extraction abilities, between-individual variation and within-individual consistency in food extraction techniques among

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

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

    PubMed

    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

  5. 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

  6. Viral Decay Kinetics in the Highly Active Antiretroviral Therapy-Treated Rhesus Macaque Model of AIDS

    PubMed Central

    Deere, Jesse D.; Higgins, Joanne; Cannavo, Elda; Villalobos, Andradi; Adamson, Lourdes; Fromentin, Emilie; Schinazi, Raymond F.; Luciw, Paul A.; North, Thomas W.

    2010-01-01

    To prevent progression to AIDS, persons infected with human immunodeficiency virus type 1 (HIV-1) must remain on highly active antiretroviral therapy (HAART) indefinitely since this modality does not eradicate the virus. The mechanisms involved in viral persistence during HAART are poorly understood, but an animal model of HAART could help elucidate these mechanisms and enable studies of HIV-1 eradication strategies. Due to the specificity of non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for HIV-1, we have used RT-SHIV, a chimeric virus of simian immunodeficiency virus with RT from HIV-1. This virus is susceptible to NNRTIs and causes an AIDS-like disease in rhesus macaques. In this study, two groups of HAART-treated, RT-SHIV-infected macaques were analyzed to determine viral decay kinetics. In the first group, viral loads were monitored with a standard TaqMan RT-PCR assay with a limit of detection of 50 viral RNA copies per mL. Upon initiation of HAART, viremia decayed in a bi-phasic manner with half-lives of 1.7 and 8.5 days, respectively. A third phase was observed with little further decay. In the second group, the macaques were followed longitudinally with a more sensitive assay utilizing ultracentrifugation to concentrate virus from plasma. Bi-phasic decay of viral RNA was also observed in these animals with half-lives of 1.8 and 5.8 days. Viral loads in these animals during a third phase ranged from 2–58 RNA copies/mL, with little decay over time. The viral decay kinetics observed in these macaques are similar to those reported for HIV-1 infected humans. These results demonstrate that low-level viremia persists in RT-SHIV-infected macaques despite a HAART regimen commonly used in humans. PMID:20668516

  7. The role of charge and multiple faces of the CD8 alpha/alpha homodimer in binding to major histocompatibility complex class I molecules: support for a bivalent model.

    PubMed Central

    Giblin, P A; Leahy, D J; Mennone, J; Kavathas, P B

    1994-01-01

    The CD8 dimer interacts with the alpha 3 domain of major histocompatibility complex class I molecules through two immunoglobulin variable-like domains. In this study a crystal structure-informed mutational analysis has been performed to identify amino acids in the CD8 alpha/alpha homodimer that are likely to be involved in binding to class I. Several key residues are situated on the top face of the dimer within loops analogous to the complementarity-determining regions (CDRs) of immunoglobulin. In addition, other important amino acids are located in the A and B beta-strands on the sides of the dimer. The potential involvement of amino acids on both the top and the side faces of the molecule is consistent with a bivalent model for the interaction between a single CD8 alpha/alpha homodimer and two class I molecules and may have important implications for signal transduction in class I-expressing cells. This study also demonstrates a role for the positive surface potential of CD8 in class I binding and complements previous work demonstrating the importance of a negatively charged loop on the alpha 3 domain of class I for CD8 alpha/alpha-class I interaction. We propose a model whereby residues located on the CDR-like loops of the CD8 homodimer interact with the alpha 3 domain of MHC class I while amino acids on the side of the molecule containing the A and B beta-strands contact the alpha 2 domain of class I. Images PMID:8127870

  8. Intermolecular disulfide bonds stabilize VirB7 homodimers and VirB7/VirB9 heterodimers during biogenesis of the Agrobacterium tumefaciens T-complex transport apparatus.

    PubMed

    Spudich, G M; Fernandez, D; Zhou, X R; Christie, P J

    1996-07-23

    The Agrobacterium tumefaciens VirB7 lipoprotein contributes to the stabilization of VirB proteins during biogenesis of the putative T-complex transport apparatus. Here, we report that stabilization of VirB7 itself is correlated with its ability to form disulfide cross-linked homodimers via a reactive Cys-24 residue. Three types of beta-mercaptoethanol-dissociable complexes were visualized with VirB7 and/or a VirB7::PhoA41 fusion protein: (i) a 9-kDa complex corresponding in size to a VirB7 homodimer, (ii) a 54-kDa complex corresponding in size to a VirB7/VirB7::PhoA41 mixed dimer, and (iii) a 102-kDa complex corresponding to a VirB7::PhoA41 homodimer. A VirB7C24S mutant protein was immunologically undetectable, whereas the corresponding VirB7C24S::PhoA41 derivative accumulated to detectable levels but failed to form dissociable homodimers or mixed dimers with wild-type VirB7. We further report that VirB7-dependent stabilization of VirB9 is correlated with the ability of these two proteins to dimerize via formation of a disulfide bridge between reactive Cys-24 and Cys-262 residues, respectively. Two types of dissociable complexes were visualized: (i) a 36-kDa complex corresponding in size to a VirB7/VirB9 heterodimer and (ii) an 84-kDa complex corresponding in size to a VirB7/VirB9::PhoA293 heterodimer. A VirB9C262S mutant protein was immunologically undetectable, whereas the corresponding VirB9C262S::PhoA293 derivative accumulated to detectable levels but failed to form dissociable heterodimers with wild-type VirB7. Taken together, these results support a model in which the formation of disulfide cross-linked VirB7 dimers represent critical early steps in the biogenesis of the T-complex transport apparatus. PMID:8755505

  9. Prefrontal connections of the parabelt auditory cortex in macaque monkeys.

    PubMed

    Hackett, T A; Stepniewska, I; Kaas, J H

    1999-01-30

    In the present study, we determined connections of three newly defined regions of auditory cortex with regions of the frontal lobe, and how two of these regions in the frontal lobe interconnect and connect to other portions of frontal cortex and the temporal lobe in macaque monkeys. We conceptualize auditory cortex as including a core of primary areas, a surrounding belt of auditory areas, a lateral parabelt of two divisions, and adjoining regions of temporal cortex with parabelt connections. Injections of several different fluorescent tracers and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were placed in caudal (CPB) and rostral (RPB) divisions of the parabelt, and in cortex of the superior temporal gyrus rostral to the parabelt with parabelt connections (STGr). Injections were also placed in two regions of the frontal lobe that were labeled by a parabelt injection in the same case. The results lead to several major conclusions. First, CPB injections label many neurons in dorsal prearcuate cortex in the region of the frontal eye field and neurons in dorsal prefrontal cortex of the principal sulcus, but few or no neurons in orbitofrontal cortex. Fine-grain label in these same regions as a result of a WGA-HRP injection suggests that the connections are reciprocal. Second, RPB injections label overlapping prearcuate and principal sulcus locations, as well as more rostral cortex of the principal sulcus, and several locations in orbitofrontal cortex. Third, STGr injections label locations in orbitofrontal cortex, some of which overlap those of RPB injections, but not prearcuate or principal sulcus locations. Fourth, injections in prearcuate and principal sulcus locations labeled by a CPB injection labeled neurons in CPB and RPB, with little involvement of the auditory belt and no involvement of the core. In addition, the results indicated that the two frontal lobe regions are densely interconnected. They also connect with largely separate

  10. 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

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

    PubMed

    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. 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

  13. 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

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

    PubMed

    Brunell, Marla K

    2012-07-01

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

  15. Neisseria infection of rhesus macaques as a model to study colonization, transmission, persistence, and horizontal gene transfer.

    PubMed

    Weyand, Nathan J; Wertheimer, Anne M; Hobbs, Theodore R; Sisko, Jennifer L; Taku, Nyiawung A; Gregston, Lindsay D; Clary, Susan; Higashi, Dustin L; Biais, Nicolas; Brown, Lewis M; Planer, Shannon L; Legasse, Alfred W; Axthelm, Michael K; Wong, Scott W; So, Magdalene

    2013-02-19

    The strict tropism of many pathogens for man hampers the development of animal models that recapitulate important microbe-host interactions. We developed a rhesus macaque model for studying Neisseria-host interactions using Neisseria species indigenous to the animal. We report that Neisseria are common inhabitants of the rhesus macaque. Neisseria isolated from the rhesus macaque recolonize animals after laboratory passage, persist in the animals for at least 72 d, and are transmitted between animals. Neisseria are naturally competent and acquire genetic markers from each other in vivo, in the absence of selection, within 44 d after colonization. Neisseria macacae encodes orthologs of known or presumed virulence factors of human-adapted Neisseria, as well as current or candidate vaccine antigens. We conclude that the rhesus macaque model will allow studies of the molecular mechanisms of Neisseria colonization, transmission, persistence, and horizontal gene transfer. The model can potentially be developed further for preclinical testing of vaccine candidates.

  16. 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

  17. Self-Injurious Behavior Secondary to Cytomegalovirus-Induced Neuropathy in an SIV-Infected Rhesus Macaque (Macaca mulatta).

    PubMed

    Clemmons, Elizabeth A; Gumber, Sanjeev; Strobert, Elizabeth; Bloomsmith, Mollie A; Jean, Sherrie M

    2015-06-01

    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.

  18. 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

    2016-04-01

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

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

    PubMed Central

    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

  20. Identification and Simian Immunodeficiency Virus Infection of CD1d-Restricted Macaque Natural Killer T Cells

    PubMed Central

    Motsinger, Alison; Azimzadeh, Agnes; Stanic, Aleksandar K.; Johnson, R. Paul; Van Kaer, Luc; Joyce, Sebastian; Unutmaz, Derya

    2003-01-01

    Natural killer T (NKT) cells express a highly conserved T-cell receptor (TCR) and recognize glycolipids in the context of CD1d molecules. We recently demonstrated that CD4+ NKT cells are highly susceptible to human immunodeficiency virus type 1 (HIV-1) infection and are selectively depleted in HIV-infected individuals. Here, we identified macaque NKT cells using CD1d tetramers and human Vα24 antibodies. Similar to human NKT cells, α-galactosylceramide (α-GalCer)-pulsed dendritic cells activate and expand macaque NKT cells. Upon restimulation with α-GalCer-pulsed CD1d+ cells, macaque NKT cells secreted high levels of cytokines, a characteristic of these T cells. Remarkably, the majority of resting and activated macaque NKT cells expressed CD8, and a smaller portion expressed CD4. Macaque NKT cells also expressed the HIV-1/simian immunodeficiency virus (SIV) coreceptor CCR5, and the CD4+ subset was susceptible to SIV infection. Identification of macaque NKT cells has major implications for delineating the role of these cells in nonhuman primate disease models of HIV as well as other pathological conditions, such as allograft rejection and autoimmunity. PMID:12829854

  1. 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

    2016-04-01

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

  2. The Organization of Collective Group Movements in Wild Barbary Macaques (Macaca sylvanus): Social Structure Drives Processes of Group Coordination in Macaques

    PubMed Central

    Seltmann, Anne; Majolo, Bonaventura

    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

  3. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus.

    PubMed

    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

    2014-03-01

    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).

  4. IgG Binding Characteristics of Rhesus Macaque FcγR.

    PubMed

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

    2016-10-01

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

  5. Single-neuron and genetic correlates of autistic behavior in macaque

    PubMed Central

    Yoshida, Kyoko; Go, Yasuhiro; Kushima, Itaru; Toyoda, Atsushi; Fujiyama, Asao; Imai, Hiroo; Saito, Nobuhito; Iriki, Atsushi; Ozaki, Norio; Isoda, Masaki

    2016-01-01

    Atypical neurodevelopment in autism spectrum disorder is a mystery, defying explanation despite increasing attention. We report on a Japanese macaque that spontaneously exhibited autistic traits, namely, impaired social ability as well as restricted and repetitive behaviors, along with our single-neuron and genomic analyses. Its social ability was measured in a turn-taking task, where two monkeys monitor each other’s actions for adaptive behavioral planning. In its brain, the medial frontal neurons responding to others’ actions, abundant in the controls, were almost nonexistent. In its genes, whole-exome sequencing and copy number variation analyses identified rare coding variants linked to human neuropsychiatric disorders in 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C) and adenosine triphosphate (ATP)–binding cassette subfamily A13 (ABCA13). This combination of systems neuroscience and cognitive genomics in macaques suggests a new, phenotype-to-genotype approach to studying mental disorders. PMID:27679817

  6. IgG Binding Characteristics of Rhesus Macaque FcγR.

    PubMed

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

    2016-10-01

    Indian rhesus macaques (Macaca mulatta) are routinely used in preclinical studies to evaluate therapeutic Abs and candidate vaccines. The efficacy of these interventions in many cases is known to rely heavily on the ability of Abs to interact with a set of Ab FcγR expressed on innate immune cells. Yet, despite their presumed functional importance, M. mulatta Ab receptors are largely uncharacterized, posing a fundamental limit to ensuring accurate interpretation and translation of results from studies in this model. In this article, we describe the binding characteristics of the most prevalent allotypic variants of M. mulatta FcγR for binding to both human and M. mulatta IgG of varying subclasses. The resulting determination of the affinity, specificity, and glycan sensitivity of these receptors promises to be useful in designing and evaluating studies of candidate vaccines and therapeutic Abs in this key animal model and exposes significant evolutionary divergence between humans and macaques. PMID:27559046

  7. Developmental and cross-situational stability in infant pigtailed macaque temperament.

    PubMed

    Sussman, Adrienne; Ha, James

    2011-05-01

    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 10 months of development showed a trend toward calmer and bolder behavior with age, with significant individual variation in the pattern of change. Boldness showed a quadratic pattern of change, whereas reactivity decreased linearly. We also studied the relationship between temperament and response to a novelty probe. The magnitude of the response to the novelty probe decreased slightly over time, and boldness and reactivity in a familiar setting did not predict these changes in response to novelty. In a 2nd principal components analysis, reactivity to novelty represented a distinct aspect of temperament. Our results demonstrate developmental changes and context dependency in macaque behavior.

  8. 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.

  9. Behavioral and emotional response of Japanese macaque (Macaca fuscata) mothers after their offspring receive an aggression.

    PubMed

    Schino, Gabriele; Geminiani, Simona; Rosati, Luca; Aureli, Filippo

    2004-09-01

    The authors of this study investigated the behavioral and emotional response of female Japanese macaques (Macaca fuscata) to an aggression received by their offspring to evaluate the existence of cognitive empathic responses in a naturalistic setting. After their offspring received an aggression, mothers did not direct increased affiliative contacts to them. The factors likely to affect the degree of distress in the offspring or the perceived risk for the mother failed to appropriately modulate maternal behavior. Finally, mothers did not increase their frequency of scratching (a behavioral indicator of anxiety) after their offspring had received an aggression. The results suggest Japanese macaque mothers may be unable to understand their offspring's need for distress alleviation after the receipt of aggression.

  10. Ovarian cycle phase and same-sex mating behavior in Japanese macaque females.

    PubMed

    O'Neill, Ann C; Fedigan, Linda M; Ziegler, Toni E

    2004-05-01

    The relationship of the ovarian cycle phase to same-sex mounting activity in adult female Japanese macaques (Macaca fuscata) was studied during the 1997/1998 mating season. Fecal samples were collected from eight female subjects two to three times per week and analyzed by enzyme immunoassay for fecal hormone levels. Hormone profiles of estrone (E1) and pregnanediol (PdG) were used to separate ovarian cycles into three phases: follicular, periovulatory, and luteal. Patterns of same-sex and heterosexual mounting behavior in the females were analyzed for phase variation during conceptive cycles. Same-sex mounting among female Japanese macaques occurred most frequently during the follicular and periovulatory phases of the cycle, and not at all during the luteal phase, paralleling the pattern found in heterosexual mounting behavior. These findings suggest a link between hormonal fluctuations and patterns of sexual mounting, regardless of whether the partner is of the same or opposite sex.

  11. Acrylamide effects on the macaque visual system. I. Psychophysics and electrophysiology

    SciTech Connect

    Merigan, W.H.; Barkdoll, E.; Maurissen, J.P.J.; Eskin, T.A.; Lapham, L.W.

    1985-03-01

    Oral acrylamide produces axonal swelling and later degeneration and gliosis in the distal optic tract, especially within the lateral geniculate nucleus, of macaque monkeys. Measures of visual thresholds and cortical-evoked potentials were used to study the time course of visual changes during exposure to acrylamide in macaque monkeys. Contrast sensitivity, visual acuity, and flicker fusion frequency were reduced during exposure, and only flicker fusion recovered rapidly and completely after exposure. Pattern-reversal-evoked responses exhibited increased latency and reduced amplitude during dosing but substantially recovered after exposure. Visual acuity and contrast sensitivity for high spatial frequencies were decreased throughout the 140 days of testing after dosing. These results suggest an acute general depression of visual capacities as the initial effect of acrylamide exposure, whereas later effects were confined to high spatial frequencies. 29 references, 6 figures.

  12. Lip salivary-gland hamartoma in a cynomolgus macaque (Macaca fascicularis).

    PubMed

    Radi, Zaher A; Morton, Daniel G

    2014-02-01

    An incidental, asymptomatic, well-circumscribed, solitary, submucosal nodular mass was detected on the mucosal surface of the inner lower lip in a female cynomolgus macaque (age, approximately 2.4 y) during a juvenile chronic toxicology study. Grossly, the nodule was soft with brown to tan discoloration and measured approximately 4 mm in diameter. Microscopically, the nodule was covered by normal stratified squamous epithelium and composed of well-circumscribed irregular lobules containing hyperplastic and normal-appearing mucinous salivary gland acini and ducts, which were separated by thick connective tissue septae. In light of the gross pathology and results of microscopic examination, salivary gland hamartoma was diagnosed. This lesion resembles adenomatoid hyperplasia of mucous salivary glands in humans, which is a rare nonneoplastic swelling. To our knowledge, this case description is the first report of a cynomolgus macaque with the rare entity of lip salivary gland hamartoma, which likely represents adenomatous hyperplasia in humans.

  13. 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

  14. Biogeography of the intestinal mucosal and lumenal microbiome in the rhesus macaque.

    PubMed

    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; Morgan, Xochitl C

    2015-03-11

    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 ten 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 and 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.

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

    PubMed

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

    2014-02-01

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

  16. 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

  17. 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

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

    PubMed Central

    Bertrand, Henri; Mindus, Claire; Flecknell, Paul

    2016-01-01

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

  19. Single-neuron and genetic correlates of autistic behavior in macaque

    PubMed Central

    Yoshida, Kyoko; Go, Yasuhiro; Kushima, Itaru; Toyoda, Atsushi; Fujiyama, Asao; Imai, Hiroo; Saito, Nobuhito; Iriki, Atsushi; Ozaki, Norio; Isoda, Masaki

    2016-01-01

    Atypical neurodevelopment in autism spectrum disorder is a mystery, defying explanation despite increasing attention. We report on a Japanese macaque that spontaneously exhibited autistic traits, namely, impaired social ability as well as restricted and repetitive behaviors, along with our single-neuron and genomic analyses. Its social ability was measured in a turn-taking task, where two monkeys monitor each other’s actions for adaptive behavioral planning. In its brain, the medial frontal neurons responding to others’ actions, abundant in the controls, were almost nonexistent. In its genes, whole-exome sequencing and copy number variation analyses identified rare coding variants linked to human neuropsychiatric disorders in 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C) and adenosine triphosphate (ATP)–binding cassette subfamily A13 (ABCA13). This combination of systems neuroscience and cognitive genomics in macaques suggests a new, phenotype-to-genotype approach to studying mental disorders.

  20. Selective serotonin reuptake inhibitor and bleeding in a cynomolgus macaque (Macaca fascicularis).

    PubMed

    Silverstein, Marnie G; El-Amin, Colette Kirk; Shively, Carol A

    2014-06-01

    Selective serotonin reuptake inhibitors (SSRI) are associated with an increased bleeding risk in humans. This report describes a bleeding event in a cynomolgus macaque (Macaca fascicularis) treated with the SSRI sertraline HCl (Zoloft). During the treatment course, the subject presented with a maculopapular rash, cutaneous bleeding, epistaxis, bleeding from the eye, melena, and a severe thrombocytopenia. To our knowledge, this report is the first description of an SSRI-related adverse event in a nonhuman primate. This report demonstrates that the clinical presentation of SSRI-associated bleeding in cynomolgus macaques is consistent with that reported in humans and that complications from SSRI treatment should be considered as a differential diagnosis for maculopapular dermatitis or spontaneous bleeding in this species.

  1. Selective Serotonin Reuptake Inhibitor and Bleeding in a Cynomolgus Macaque (Macaca fascicularis)

    PubMed Central

    Silverstein, Marnie G; El-Amin, Colette Kirk; Shively, Carol A

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRI) are associated with an increased bleeding risk in humans. This report describes a bleeding event in a cynomolgus macaque (Macaca fascicularis) treated with the SSRI sertraline HCl (Zoloft). During the treatment course, the subject presented with a maculopapular rash, cutaneous bleeding, epistaxis, bleeding from the eye, melena, and a severe thrombocytopenia. To our knowledge, this report is the first description of an SSRI-related adverse event in a nonhuman primate. This report demonstrates that the clinical presentation of SSRI-associated bleeding in cynomolgus macaques is consistent with that reported in humans and that complications from SSRI treatment should be considered as a differential diagnosis for maculopapular dermatitis or spontaneous bleeding in this species. PMID:24956214

  2. Fear reactions to snakes in naïve mouse lemurs and pig-tailed macaques.

    PubMed

    Weiss, Lucie; Brandl, Pavel; Frynta, Daniel

    2015-07-01

    Primates have been predated on by snakes throughout their evolution and as a result, antipredator responses accompanied by signs of fear are often witnessed in the wild. In captivity, however, the fear of snakes is less clear, as experiments with naïve nonhuman primates have given inconsistent results. In this study, we present evidence that naïve mouse lemurs (Microcebus murinus) and putatively naïve pig-tailed macaques (Macaca nemestrina) do exhibit fear of snakes, even though the apparent reactions are mild. In an experiment with control- or snake-odoured boxes, mouse lemurs clearly avoided feeding in the latter. When the latency of touching rubber models was measured, pig-tailed macaques took longer to touch a toy snake compared with a toy lizard. Our findings that fear of snakes is shown by naïve individuals support the hypothesis that it is innate in primates.

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

    PubMed Central

    Bertrand, Henri; Mindus, Claire; Flecknell, Paul

    2016-01-01

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

  4. 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

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

    PubMed

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

    2002-03-01

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

  6. 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

  7. Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys.

    PubMed

    Ito, T; Inoue, K; Takada, M

    2015-12-01

    Macaque monkeys use complex communication calls and are regarded as a model for studying the coding and decoding of complex sound in the auditory system. However, little is known about the distribution of excitatory and inhibitory neurons in the auditory system of macaque monkeys. In this study, we examined the overall distribution of cell bodies that expressed mRNAs for VGLUT1, and VGLUT2 (markers for glutamatergic neurons), GAD67 (a marker for GABAergic neurons), and GLYT2 (a marker for glycinergic neurons) in the auditory system of the Japanese macaque. In addition, we performed immunohistochemistry for VGLUT1, VGLUT2, and GAD67 in order to compare the distribution of proteins and mRNAs. We found that most of the excitatory neurons in the auditory brainstem expressed VGLUT2. In contrast, the expression of VGLUT1 mRNA was restricted to the auditory cortex (AC), periolivary nuclei, and cochlear nuclei (CN). The co-expression of GAD67 and GLYT2 mRNAs was common in the ventral nucleus of the lateral lemniscus (VNLL), CN, and superior olivary complex except for the medial nucleus of the trapezoid body, which expressed GLYT2 alone. In contrast, the dorsal nucleus of the lateral lemniscus, inferior colliculus, thalamus, and AC expressed GAD67 alone. The absence of co-expression of VGLUT1 and VGLUT2 in the medial geniculate, medial superior olive, and VNLL suggests that synaptic responses in the target neurons of these nuclei may be different between rodents and macaque monkeys.

  8. Topographic effects on spatial data at a Japanese macaque study site.

    PubMed

    Sprague, D S

    2000-11-01

    In mountainous topography, actual travel distances and home range areas are larger than those measured on a flat map. This paper analyzed the increase in spatial measures that occurred when topography was taken into account for data collected at a mountainous study site of the Japanese macaque. Both travel distances and home range areas increased when measured on a computerized terrain model compared to those measured on a flat map. The travel distance changes varied among troops as well as individual travel routes.

  9. [State of equilibrium among agonistic behaviour patterns in a group of Japanese macaques (Macaca fuscata)].

    PubMed

    Thierry, B

    1990-01-01

    The degree of aggressive intensity, the degree of contest asymmetry and the development of conciliatory patterns were studied in a captive group of Japanese macaques (Macaca fuscata). The state of equilibrium among these components varied according to relatedness of interacting individuals, the observed variations being analogous to those found in interspecific comparisons. It is concluded that the relations linking these components result from epigenetic processes which govern the emergence of a social organization.

  10. Emergence of Small-World and Limitations to Its Maximization in a Macaque Cerebral Cortical Network

    NASA Astrophysics Data System (ADS)

    Zhao, Qing-Bai; Liao, Meng-Jie; Chen, Qi-Cai

    2011-06-01

    We study both the emergence of small-world topology in a macaque cerebral cortical network and the limitations to maximization of small-worldness. The results show that the maximization of neural complexity leads to a small-world topology, but it also limits the maximization of small-worldness. It is suggested that the modular organization that corresponds to different functions may be a limitation. Additionally, the need for strong resilience against attacks may be another limitation.

  11. Social object play among young Japanese macaques (Macaca fuscata) in Arashiyama, Japan.

    PubMed

    Shimada, Masaki

    2006-10-01

    Social object play (SOP), i.e., social play using portable object(s), among young Japanese macaques (Macaca fuscata; 0-4 years old) in the Arashiyama E troop was studied using a modified sequence sampling method from July to October 2000. SOP was a relatively common activity for most of the young macaques and often continued for long periods. Participants used many kinds of object, including edible natural objects and artificial objects, such as plastic bottles, but they never used provisioned food or wild fruit in SOP bouts. An analysis of long bouts (>/=0.5 min) revealed the following interactive SOP features: (1) at any given time, participants used only one object, and only one participant held the object; (2) during SOP play-chasing, the object holder was likely to be chased by others; (3) during long bouts, the object changed hands frequently; and (4) agonistic competition for an object among young macaques was rare. Combinations of sexes, ages, relative ranks, or matrilines of the object holder and non-holder did not affect the tendency that the holder was chased by non-holder(s) during play-chasing. Even when there was a change in object holders, the repetitiveness of this interactive pattern, i.e., that the holder would be chased during SOP bouts, distinguished the SOP structure from that of other types of social play without object(s). General proximate social play mechanisms, such as self-handicapping or role taking, were associated with SOP. Other mechanisms that affected SOP included the following: (1) young macaques treated an object as a target in play competition, and (2) 'being the holder of a target object' was associated with the 'role of the chasee.'

  12. Cryptosporidiosis in rhesus macaques challenged during acute and chronic phases of SIV infection.

    PubMed

    Singh, Inderpal; Carville, Angela; Tzipori, Saul

    2011-09-01

    The intestinal immune dysfunction due to loss of mucosal and peripheral CD4(+) T cells in individuals with HIV/AIDS is presumably responsible for the establishment of persistent cryptosporidiosis. Simian immunodeficiency virus (SIV)-infected macaques were used to investigate the phase/timing in SIV infection, which permits a self-limiting Cryptosporidium parvum infection to become persistent in immunodeficient hosts because of significant mucosal immune defects. Two groups of SIV-infected macaques were challenged with C. parvum; one was challenged during the acute SIV infection phase (2 weeks post-SIV infection) and the second was challenged during the chronic SIV phase (CD4 counts 200-500 cells/μl of blood). Samples (fecal, blood, biopsy, and necropsy) were collected at different time points after infection to correlate the progression of disease with the immune status of the animals. All seven SIV-infected macaques challenged during the acute phase of SIV infection became persistently infected and excreted oocysts for 1-4 months. However, four of the six in the chronic SIV phase became infected with cryptosporidiosis, of which one survived 2 weeks and one became naturally infected. Sequential analysis of CD4(+) in blood and intestines of coinfected macaques exhibited pronounced losses of CD4 T cells during the first 2 weeks after SIV infection, followed by transient rebound of CD4 T cells in the gut after C. parvum infection, and then a gradual loss over subsequent months. Persistent cryptosporidiosis was more consistently induced during the acute SIV phase indicating that profound viral damage to gut lymphoid tissue during the acute phase was more conducive, compared with the chronic phase, to establishing persistent cryptosporidiosis than low circulating CD4 T cells.

  13. 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

  14. 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

  15. Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses.

    PubMed

    Lauck, Michael; Alkhovsky, Sergey V; Bào, Yīmíng; Bailey, Adam L; Shevtsova, Zinaida V; Shchetinin, Alexey M; Vishnevskaya, Tatyana V; Lackemeyer, Matthew G; Postnikova, Elena; Mazur, Steven; Wada, Jiro; Radoshitzky, Sheli R; Friedrich, Thomas C; Lapin, Boris A; Deriabin, Petr G; Jahrling, Peter B; Goldberg, Tony L; O'Connor, David H; Kuhn, Jens H

    2015-08-01

    Simian hemorrhagic fever (SHF) is lethal for macaques. Based on clinical presentation and serological diagnosis, all reported SHF outbreaks were thought to be caused by different strains of the same virus, simian hemorrhagic fever virus (SHFV; Arteriviridae). Here we show that the SHF outbreaks in Sukhumi in 1964 and in Alamogordo in 1989 were caused not by SHFV but by two novel divergent arteriviruses. Our results indicate that multiple divergent simian arteriviruses can cause SHF. PMID:25972539

  16. 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

  17. Historical Outbreaks of Simian Hemorrhagic Fever in Captive Macaques Were Caused by Distinct Arteriviruses

    PubMed Central

    Lauck, Michael; Alkhovsky, Sergey V.; Bào, Yīmíng; Bailey, Adam L.; Shevtsova, Zinaida V.; Shchetinin, Alexey M.; Vishnevskaya, Tatyana V.; Lackemeyer, Matthew G.; Postnikova, Elena; Mazur, Steven; Wada, Jiro; Radoshitzky, Sheli R.; Friedrich, Thomas C.; Lapin, Boris A.; Deriabin, Petr G.; Jahrling, Peter B.; Goldberg, Tony L.; O'Connor, David H.

    2015-01-01

    Simian hemorrhagic fever (SHF) is lethal for macaques. Based on clinical presentation and serological diagnosis, all reported SHF outbreaks were thought to be caused by different strains of the same virus, simian hemorrhagic fever virus (SHFV; Arteriviridae). Here we show that the SHF outbreaks in Sukhumi in 1964 and in Alamogordo in 1989 were caused not by SHFV but by two novel divergent arteriviruses. Our results indicate that multiple divergent simian arteriviruses can cause SHF. PMID:25972539

  18. Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study.

    PubMed

    Pinsk, Mark A; Arcaro, Michael; Weiner, Kevin S; Kalkus, Jan F; Inati, Souheil J; Gross, Charles G; Kastner, Sabine

    2009-05-01

    Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between

  19. 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

  20. 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

  1. 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

  2. Standard trivalent influenza virus protein vaccination does not prime antibody-dependent cellular cytotoxicity in macaques.

    PubMed

    Jegaskanda, Sinthujan; Amarasena, Thakshila H; Laurie, Karen L; Tan, Hyon-Xhi; Butler, Jeff; Parsons, Matthew S; Alcantara, Sheilajen; Petravic, Janka; Davenport, Miles P; Hurt, Aeron C; Reading, Patrick C; Kent, Stephen J

    2013-12-01

    Yearly vaccination with the trivalent inactivated influenza vaccine (TIV) is recommended, since current vaccines induce little cross neutralization to divergent influenza strains. Whether the TIV can induce antibody-dependent cellular cytotoxicity (ADCC) responses that can cross-recognize divergent influenza virus strains is unknown. We immunized 6 influenza-naive pigtail macaques twice with the 2011-2012 season TIV and then challenged the macaques, along with 12 control macaques, serially with H1N1 and H3N2 viruses. We measured ADCC responses in plasma to a panel of H1 and H3 hemagglutinin (HA) proteins and influenza virus-specific CD8 T cell (CTL) responses using a sensitive major histocompatibility complex (MHC) tetramer reagent. The TIV was weakly immunogenic and, although binding antibodies were detected by enzyme-linked immunosorbent assay (ELISA), did not induce detectable influenza virus-specific ADCC or CTL responses. The H1N1 challenge elicited robust ADCC to both homologous and heterologous H1 HA proteins, but not influenza virus HA proteins from different subtypes (H2 to H7). There was no anamnestic influenza virus-specific ADCC or CTL response in vaccinated animals. The subsequent H3N2 challenge did not induce or boost ADCC either to H1 HA proteins or to divergent H3 proteins but did boost CTL responses. ADCC or CTL responses were not induced by TIV vaccination in influenza-naive macaques. There was a marked difference in the ability of infection compared to that of vaccination to induce cross-reactive ADCC and CTL responses. Improved vaccination strategies are needed to induce broad-based ADCC immunity to influenza.

  3. 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

  4. 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

  5. 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

  6. 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

  7. Evaluation of Functional NK Cell Responses in Vaccinated and SIV-Infected Rhesus Macaques.

    PubMed

    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. PMID:27630641

  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. Role of vocal tract characteristics in individual discrimination by Japanese macaques (Macaca fuscata).

    PubMed

    Furuyama, Takafumi; Kobayasi, Kohta I; Riquimaroux, Hiroshi

    2016-08-23

    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.

  10. The influence of rearing conditions on the physical growth of captive Japanese macaques (Macaca fuscata).

    PubMed

    Suzuki, J; Miwa, N; Kumazaki, K; Abe, M; Kamanaka, Y; Matsubayashi, N; Gotoh, S; Matsubayashi, K

    2001-04-01

    To clarify the influence of rearing conditions on the growth of various body parts of Japanese macaques (Macaca fuscata), two groups reared under different conditions, i.e., a group born and reared in open enclosures (Enclosure group) and another consisting of macaques born and reared in cages (Caged group), were somatometrically analyzed. Somatometric data on 36 measures of various body parts were collected from 77 males and 92 females. Growth in many body parts was smaller in the Caged group than in the Enclosure group. Body parts that exhibited large incremental increases were more sensitive to differences in rearing space at the infantile growth stage in both sexes. Recovery from delayed growth at the pubertal growth stage was found in many body parts. However, the size of some locomotor elements such as the wrist and hand, and ankle and foot strongly reflected limitations of space and changes due to this were irreversible. Females were more sensitive than males to such differences in rearing conditions. We conclude that open enclosures with ample rearing space are necessary for the innate growth of Japanese macaques to occur.

  11. Biomechanical analysis of vertical climbing in the spider monkey and the Japanese macaque.

    PubMed

    Hirasaki, E; Kumakura, H; Matano, S

    2000-12-01

    Climbing is one of the most important components of primate locomotor modes. We previously reported that the kinesiological characteristics of vertical climbing by the spider monkey and Japanese macaque are clearly different, based on their kinetics and kinematics. In this study, a more detailed analysis using inverse dynamics was conducted to estimate the biomechanical characteristics of vertical climbing in the spider monkey and Japanese macaque. One of the main findings was the difference in forelimb use by the two species. The results of a joint moment analysis and estimates of muscular force indicate that the spider monkey uses its forelimbs to keep the body close to the substrate, rather than to generate propulsion. The forelimb of the Japanese macaque, on the other hand, likely contributes more to propulsion. This supports the idea that "forelimb-hindlimb differentiation" is promoted in the spider monkey. The estimated muscular force also suggests that the spider monkey type of climbing could develop the hindlimb extensor muscles, which are important in bipedal posture and walking. As a result, we conclude that the spider monkey type of climbing could be functionally preadaptive for human bipedalism. This type of climbing would develop the hip and knee extensor muscles, and result in more extended lower limb joints, a more erect trunk posture, and more functionally differentiated fore- and hindlimbs, all of which are important characteristics of human bipedalism.

  12. 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.

  13. Severe Acquired Idiopathic Thrombocytopenia in a Female Cynomolgus Macaque (Macaca fascicularis).

    PubMed

    Parrula, Cecilia M; Mysore, Jagannatha; Burr, Holly; Freebern, Wendy; Neef, Natasha

    2015-06-01

    A 4-y-old female cynomolgus macaque presented for veterinary evaluation prior to placement in a preclinical study showed markedly low platelet counts that continued to decrease over time. Physical examination over the next several days showed areas of pale red discoloration in forelimbs, anterior thorax, and inguinal area and multifocal pinpoint areas of erythema or scabs. An area of dark red discoloration approximately 2 cm in diameter on the dorsal surface of the tongue was discovered on day 9. The macaque was euthanized, and histopathologic evaluation showed multifocal, ulcerative or erosive, hemorrhagic, lymphohistiocytic and neutrophilic glossitis and tonsillitis. The lesions on the tongue were associated with opportunistic fungi consistent with Candida albicans. The bone marrow showed megakaryocytic hyperplasia. There was no evidence of increased consumption of platelets, sequestration of platelets, or bone marrow suppression. The monkey was serologically negative for simian retrovirus, SIV, and simian T-lymphotropic virus. In light of cases reported in humans, immune-mediated destruction of platelets due to autoantibodies secondary to Candida albicans infection was considered. However, we were unable to detect antiplatelet antibodies on the platelet surface or in serum to support this etiology; therefore idiopathic thrombocytopenia was diagnosed. To our knowledge, this case represents the second reported observation of acquired thrombocytopenia in a nonhuman primate and the first reported observation in a cynomolgus macaque.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in newborn macaques

    PubMed Central

    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.

    2016-01-01

    Prevention of mother to child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested anti-HIV-1 human neutralizing monoclonal antibodies (NmAb) as post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with 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 following administration. Replicating virus was found in multiple tissues by day 1 in animals without treatment. All NmAb-treated macaques were free of virus in blood and tissues at 6 months post-exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged following CD8+ T cell depletion. These results suggest early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

  19. 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).

  20. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    PubMed

    Wahl-Jensen, Victoria; Cann, Jennifer A; Rubins, Kathleen H; Huggins, John W; Fisher, Robert W; Johnson, Anthony J; de Kok-Mercado, Fabian; Larsen, Thomas; Raymond, Jo Lynne; Hensley, Lisa E; Jahrling, Peter B

    2011-01-01

    Smallpox, caused by variola virus (VARV), is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  1. Using Porches to Decrease Feces Painting in Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Gottlieb, Daniel H; O'Connor, Jillann Rawlins; Coleman, Kristine

    2014-01-01

    The goal of this project was to evaluate the efficacy of a porch in decreasing feces painting in captive rhesus macaques. The porch is a small extension that is hung on the outside of a monkey's primary home cage. Porches provide many potential benefits to indoor-housed macaques, including opportunities to perch above the ground, additional space, and increased field of view. Rates of feces painting, an abnormal behavior in which the animal smears or rubs feces on a surface, were compared in 3 situations: with porch enrichment, with ‘smear board’ enrichment (a foraging device commonly used to decrease feces painting), and without either enrichment item. Feces painting was evaluated daily by using a 5-point scale that ranged from 0, no feces present, to 4, multiple large areas of feces. We found that subjects received significantly lower feces painting scores when given porch enrichment or smear board enrichment compared with baseline. Furthermore, subjects received significantly lower feces painting scores with porch enrichment than smear board enrichment. These results demonstrate that the porch is an effective tool to decrease feces painting in captive macaques. PMID:25650971

  2. Experimental Infection of Rhesus Macaques and Common Marmosets with a European Strain of West Nile Virus

    PubMed Central

    Verstrepen, Babs E.; Fagrouch, Zahra; van Heteren, Melanie; Buitendijk, Hester; Haaksma, Tom; Beenhakker, Niels; Palù, Giorgio; Richner, Justin M.; Diamond, Michael S.; Bogers, Willy M.; Barzon, Luisa; Chabierski, Stefan; Ulbert, Sebastian; Kondova, Ivanela; Verschoor, Ernst J.

    2014-01-01

    West Nile virus (WNV) is a mosquito-borne flavivirus that infects humans and other mammals. In some cases WNV causes severe neurological disease. During recent years, outbreaks of WNV are increasing in worldwide distribution and novel genetic variants of the virus have been detected. Although a substantial amount of data exists on WNV infections in rodent models, little is known about early events during WNV infection in primates, including humans. To gain a deeper understanding of this process, we performed experimental infections of rhesus macaques and common marmosets with a virulent European WNV strain (WNV-Ita09) and monitored virological, hematological, and biochemical parameters. WNV-Ita09 productively infected both monkey species, with higher replication and wider tissue distribution in common marmosets compared to rhesus macaques. The animals in this study however, did not develop clinical signs of WNV disease, nor showed substantial deviations in clinical laboratory parameters. In both species, the virus induced a rapid CD56dimCD16bright natural killer response, followed by IgM and IgG antibody responses. The results of this study show that healthy rhesus macaques and common marmosets are promising animal models to study WNV-Ita09 infection. Both models may be particularly of use to evaluate potential vaccine candidates or to investigate WNV pathogenesis. PMID:24743302

  3. Evaluation of Cynomolgus Macaque (Macaca fascicularis) Endogenous Retrovirus Expression Following Simian Immunodeficiency Virus Infection

    PubMed Central

    Marsh, Angie K.; Willer, David O.; Skokovets, Olena; Iwajomo, Oluwadamilola H.; Chan, Jacqueline K.; MacDonald, Kelly S.

    2012-01-01

    Human endogenous retrovirus type K (HERV-K) transcripts are upregulated in the plasma of HIV-infected individuals and have been considered as targets for an HIV vaccine. We evaluated cynomolgus macaque endogenous retrovirus (CyERV) mRNA expression by RT-qPCR in PBMCs isolated from a cohort of animals previously utilized in a live attenuated SIV vaccine trial. CyERV env transcript levels decreased following vaccination (control and vaccine groups) and CyERV env and gag mRNA expression was decreased following acute SIV-infection, whereas during chronic SIV infection, CyERV transcript levels were indistinguishable from baseline. Reduced susceptibility to initial SIV infection, as measured by the number of SIV challenges required for infection, was associated with increased CyERV transcript levels in PBMCs. In vitro analysis revealed that SIV infection of purified CD4+ T-cells did not alter CyERV gene expression. This study represents the first evaluation of ERV expression in cynomolgus macaques following SIV infection, in an effort to assess the utility of cynomolgus macaques as an animal model to evaluate ERVs as a target for an HIV/SIV vaccine. This non-human primate model system does not recapitulate what has been observed to date in the plasma of HIV-infected humans suggesting that further investigation at the cellular level is required to elucidate the impact of HIV/SIV infection on endogenous retrovirus expression. PMID:22768246

  4. Chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques (Macaca mulatta).

    PubMed

    Strait, Karen R; Orkin, Jack L; Anderson, Daniel C; Muly, E Chris

    2010-03-01

    As part of a study of antipsychotic drug treatment in monkeys, we developed a technique to provide chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques. This method allowed us to mimic the osmotic release oral delivery system currently used in humans for continuous enteral drug delivery. Rhesus macaques (n = 5) underwent gastric catheter placement by laparotomy. After the catheters were secured to the stomach, the remaining catheter length was exited through the lateral abdomen, tunneled subcutaneously along the back, and connected to a 2-mL osmotic pump enclosed in a subcutaneous pocket. Osmotic pumps were changed every 2 to 4 wk for 1 y and remained patent for the duration of the study. Four complications (including cutting of the catheter, incisional dehiscence at the pump site, and loss of 1 catheter into the abdominal cavity requiring catheter replacement) occurred among the 80 pump changes performed during the year-long study. At necropsy, histopathologic examination of the catheter implant sites revealed mild changes consistent with a foreign-body reaction. Our results indicate that the gastric catheter and osmotic pump system was well tolerated in rhesus macaques for as long as 12 mo after placement and suggest that this system will be an attractive option for use in studies that require chronic, constant-rate, gastric drug infusion in nontethered monkeys. PMID:20353697

  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. 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.

  7. 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

  8. 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. PMID:27630641

  9. Using porches to decrease feces painting in rhesus macaques (Macaca mulatta).

    PubMed

    Gottlieb, Daniel H; O'Connor, Jillann Rawlins; Coleman, Kristine

    2014-11-01

    The goal of this project was to evaluate the efficacy of a porch in decreasing feces painting in captive rhesus macaques. The porch is a small extension that is hung on the outside of a monkey's primary home cage. Porches provide many potential benefits to indoor-housed macaques, including opportunities to perch above the ground, additional space, and increased field of view. Rates of feces painting, an abnormal behavior in which the animal smears or rubs feces on a surface, were compared in 3 situations: with porch enrichment, with 'smear board' enrichment (a foraging device commonly used to decrease feces painting), and without either enrichment item. Feces painting was evaluated daily by using a 5-point scale that ranged from 0, no feces present, to 4, multiple large areas of feces. We found that subjects received significantly lower feces painting scores when given porch enrichment or smear board enrichment compared with baseline. Furthermore, subjects received significantly lower feces painting scores with porch enrichment than smear board enrichment. These results demonstrate that the porch is an effective tool to decrease feces painting in captive macaques.

  10. 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.

  11. Individual and social learning processes involved in the acquisition and generalization of tool use in macaques

    PubMed Central

    Macellini, S.; Maranesi, M.; Bonini, L.; Simone, L.; Rozzi, S.; Ferrari, P. F.; Fogassi, L.

    2012-01-01

    Macaques can efficiently use several tools, but their capacity to discriminate the relevant physical features of a tool and the social factors contributing to their acquisition are still poorly explored. In a series of studies, we investigated macaques' ability to generalize the use of a stick as a tool to new objects having different physical features (study 1), or to new contexts, requiring them to adapt the previously learned motor strategy (study 2). We then assessed whether the observation of a skilled model might facilitate tool-use learning by naive observer monkeys (study 3). Results of study 1 and study 2 showed that monkeys trained to use a tool generalize this ability to tools of different shape and length, and learn to adapt their motor strategy to a new task. Study 3 demonstrated that observing a skilled model increases the observers' manipulations of a stick, thus facilitating the individual discovery of the relevant properties of this object as a tool. These findings support the view that in macaques, the motor system can be modified through tool use and that it has a limited capacity to adjust the learnt motor skills to a new context. Social factors, although important to facilitate the interaction with tools, are not crucial for tool-use learning. PMID:22106424

  12. 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

  13. Distributions of Cells and Neurons across the Cortical Sheet in Old World Macaques.

    PubMed

    Turner, Emily C; Young, Nicole A; Reed, Jamie L; Collins, Christine E; Flaherty, David K; Gabi, Mariana; Kaas, Jon H

    2016-01-01

    According to previous research, cell and neuron densities vary across neocortex in a similar manner across primate taxa. Here, we provide a more extensive examination of this effect in macaque monkeys. We separated neocortex from the underlying white matter in 4 macaque monkey hemispheres (1 Macaca nemestrina, 2 Macaca radiata, and 1 Macaca mulatta), manually flattened the neocortex, and divided it into smaller tissue pieces for analysis. The number of cells and neurons were determined for each piece across the cortical sheet using flow cytometry. Primary visual cortex had the most densely packed neurons and primary motor cortex had the least densely packed neurons. With respect to differences in brain size between cases, there was little variability in the total cell and neuron numbers within specific areas, and overall trends were similar to what has been previously described in Old World baboons and other primates. The average hemispheric total cell number per hemisphere ranged from 2.9 to 3.7 billion, while the average total neuron number ranged from 1.3 to 1.7 billion neurons. The visual cortex neuron densities were predictably higher, ranging from 18.2 to 34.7 million neurons/cm2 in macaques, in comparison to a range of 9.3-17.7 million neurons/cm2 across cortex as a whole. The results support other evidence that neuron surface densities vary across the cortical sheet in a predictable pattern within and across primate taxa. PMID:27547956

  14. Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers.

    PubMed

    Iyer, Anita K; Zhang, Yao-Hua; McCabe, Edward R B

    2006-10-01

    Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1), and small heterodimer partner (SHP) (NR0B2) are atypical nuclear receptor superfamily members that function primarily as corepressors through heterodimeric interactions with other nuclear receptors. Mutations in DAX1 cause adrenal hypoplasia congenita, and mutations in SHP lead to mild obesity and insulin resistance, but the mechanisms are unclear. We investigated the existence and subcellular localization of DAX1 and SHP homodimers and the dynamics of homodimerization. We demonstrated DAX1 homodimerization in the nucleus and cytoplasm, and dissociation of DAX1 homodimers upon heterodimerization with steroidogenic factor 1 (SF1) or ligand-activated estrogen receptor-alpha (ERalpha). DAX1 homodimerization involved an interaction between its amino and carboxy termini involving its LXXLL motifs and activation function (AF)-2 domain. We observed SHP homodimerization in the nucleus of mammalian cells and showed dissociation of SHP homodimers upon heterodimerization with ligand-activated ERalpha. We observed DAX1-SHP heterodimerization in the nucleus of mammalian cells and demonstrated the involvement of the LXXLL motifs and AF-2 domain of DAX1 in this interaction. We further demonstrate heterodimerization of DAX1 with its alternatively spliced isoform, DAX1A. This is the first evidence of homodimerization of individual members of the unusual NR0B nuclear receptor family and heterodimerization between its members. Our results suggest that DAX1 forms antiparallel homodimers through the LXXLL motifs and AF-2 domain. These homodimers may function as holding reservoirs in the absence of heterodimeric partners. The formation of DAX1 and SHP homodimers and DAX1-SHP and DAX1-DAX1A heterodimers suggests the possibility of novel functions independent of their coregulator roles, suggesting additional complexity in the molecular mechanisms of DAX1 and SHP action

  15. Flow cytometric characterizations of leukocyte subpopulations in the peripheral blood of northern pig-tailed macaques (Macaca leonina).

    PubMed

    Zheng, Hong-Yi; Zhang, Ming-Xu; Zhang, Lin-Tao; Zhang, Xiao-Liang; Pang, Wei; Lyu, Long-Bao; Zheng, Yong-Tang

    2014-11-18

    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.

  16. Functions of an unreported "rocking-embrace" gesture between female Japanese Macaques (Macaca fuscata) in Kinkazan Island, Japan.

    PubMed

    Shimooka, Yukiko; Nakagawa, Naofumi

    2014-04-01

    Recently, research has focused on the effects of the concurrence of multimodal signals and their efficacy and meaning. We observed an unreported behaviour, a ventro-ventral "rocking-embrace" gesture that is always accompanied by lip smacking as the facial expression and sometimes by a girney call, in wild Japanese macaques (Macaca fuscata) living in Kinkazan Island, northern Japan. This study examined the form and contexts of the occurrence of such multimodal signals in order to elucidate its functions. Eighty-eight cases of rocking embrace were recorded during 183 h of observation over 22 days. Adult females were involved in all of the cases. Of the 71 cases between adult females in which behaviours prior to the rocking embrace could be identified, 13 cases were allogrooming interruptions, 11 were aggression, and 42 were approaches, most of which occurred between non-kin grooming partners. The rocking embrace was often followed by allogrooming. This suggests that rocking embraces occur under stressful conditions and may function to reduce tensions. This conclusion is consistent with the contexts and functions of lip smacking and girneys shown in previous studies. In contrast with lip smacking and girneys, neither a rocking embrace nor a ventro-ventral embrace (without rocking) between anoestrous adult females has been previously shown in Japanese macaques. In other macaque species, however, the latter gesture is often observed as an affiliative behaviour that immediately follows conflict; it functions to reconcile or as a greeting when it occurs immediately after an approach. Rocking embraces among the Kinkazan macaques occur in contexts similar to, and have a similar function to, the ancestral gesture of ventro-ventral embracing (which is hidden in Japanese macaques) and the ancestral display of lip smacking (which is still observed in Japanese macaques). The ventro-ventral embrace as a tactile signal might have been hidden since it was made redundant by the

  17. 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

  18. 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

  19. 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

  20. Interactions between visitors and Formosan macaques (Macaca cyclopis) at Shou-Shan Nature Park, Taiwan.

    PubMed

    Hsu, Minna J; Kao, Chien-Ching; Agoramoorthy, Govindasamy

    2009-03-01

    Ecotourism involving feeding wildlife has raised public attention and is a controversial issue, especially concerning nonhuman primates. Between July 2002 and April 2005, the behavior of monkeys and tourists was collected through scan samplings, focal samplings and behavior samplings at the Shou-Shan Nature Park located in Taiwan's second largest city--Kaohsiung. In addition, the number of tourists and monkeys was counted in different hours and plac