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Sample records for macaque lgn implications

  1. Responses of primate LGN cells to moving stimuli involve a constant background modulation by feedback from area MT.

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    Jones, H E; Andolina, I M; Grieve, K L; Wang, W; Salt, T E; Cudeiro, J; Sillito, A M

    2013-08-29

    The feedback connections from the cortical middle temporal (MT) motion area, to layer 6 of the primary visual cortex (V1), have the capacity to drive a cascaded feedback influence from the layer 6 cortico-geniculate cells back to the lateral geniculate nucleus (LGN) relay cells. This introduces the possibility of a re-entrant motion signal affecting the relay of the retinal input through the LGN to the visual cortex. The question is whether the response of LGN cells to moving stimuli involves a component derived from this feedback. By producing a reversible focal pharmacological block of the activity of an MT direction column we show the presence of such an influence from MT on the responses of magno, parvo and koniocellular cells in the macaque LGN. The pattern of effect in the LGN reflects the direction bias of the MT location inactivated. This suggests a moving stimulus is captured by iterative interactions in the circuit formed by visual cortical areas and visual thalamus.

  2. Transfer of Timing Information from RGC to LGN Spike Trains

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    Teich, Malvin C.; Lowen, Steven B.; Saleh, Bahaa E. A.; Kaplan, Ehud

    1998-03-01

    We have studied the firing patterns of retinal ganglion cells (RGCs) and their target lateral geniculate nucleus (LGN) cells. We find that clusters of spikes in the RGC neural firing pattern appear at the LGN output essentially unchanged, while isolated RGC firing events are more likely to be eliminated; thus the LGN action-potential sequence is therefore not merely a randomly deleted version of the RGC spike train. Employing information-theoretic techniques we developed for point processes,(B. E. A. Saleh and M. C. Teich, Phys. Rev. Lett.) 58, 2656--2659 (1987). we are able to estimate the information efficiency of the LGN neuronal output --- the proportion of the variation in the LGN firing pattern that carries information about its associated RGC input. A suitably modified integrate-and-fire neural model reproduces both the enhanced clustering in the LGN data (which accounts for the increased coefficient of variation) and the measured value of information efficiency, as well as mimicking the results of other observed statistical measures. Reliable information transmission therefore coexists with fractal fluctuations, which appear in RGC and LGN firing patterns.(M. C. Teich, C. Heneghan, S. B. Lowen, T. Ozaki, and E. Kaplan, J. Opt. Soc. Am. A) 14, 529--546 (1997).

  3. Dynamic encoding of natural luminance sequences by LGN bursts.

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    Nicholas A Lesica

    2006-07-01

    Full Text Available In the lateral geniculate nucleus (LGN of the thalamus, visual stimulation produces two distinct types of responses known as tonic and burst. Due to the dynamics of the T-type Ca(2+ channels involved in burst generation, the type of response evoked by a particular stimulus depends on the resting membrane potential, which is controlled by a network of modulatory connections from other brain areas. In this study, we use simulated responses to natural scene movies to describe how modulatory and stimulus-driven changes in LGN membrane potential interact to determine the luminance sequences that trigger burst responses. We find that at low resting potentials, when the T channels are de-inactivated and bursts are relatively frequent, an excitatory stimulus transient alone is sufficient to evoke a burst. However, to evoke a burst at high resting potentials, when the T channels are inactivated and bursts are relatively rare, prolonged inhibitory stimulation followed by an excitatory transient is required. We also observe evidence of these effects in vivo, where analysis of experimental recordings demonstrates that the luminance sequences that trigger bursts can vary dramatically with the overall burst percentage of the response. To characterize the functional consequences of the effects of resting potential on burst generation, we simulate LGN responses to different luminance sequences at a range of resting potentials with and without a mechanism for generating bursts. Using analysis based on signal detection theory, we show that bursts enhance detection of specific luminance sequences, ranging from the onset of excitatory sequences at low resting potentials to the offset of inhibitory sequences at high resting potentials. These results suggest a dynamic role for burst responses during visual processing that may change according to behavioral state.

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

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

    2017-01-01

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

  5. Integrate-and-fire vs Poisson models of LGN input to V1 cortex: noisier inputs reduce orientation selectivity.

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    Lin, I-Chun; Xing, Dajun; Shapley, Robert

    2012-12-01

    One of the reasons the visual cortex has attracted the interest of computational neuroscience is that it has well-defined inputs. The lateral geniculate nucleus (LGN) of the thalamus is the source of visual signals to the primary visual cortex (V1). Most large-scale cortical network models approximate the spike trains of LGN neurons as simple Poisson point processes. However, many studies have shown that neurons in the early visual pathway are capable of spiking with high temporal precision and their discharges are not Poisson-like. To gain an understanding of how response variability in the LGN influences the behavior of V1, we study response properties of model V1 neurons that receive purely feedforward inputs from LGN cells modeled either as noisy leaky integrate-and-fire (NLIF) neurons or as inhomogeneous Poisson processes. We first demonstrate that the NLIF model is capable of reproducing many experimentally observed statistical properties of LGN neurons. Then we show that a V1 model in which the LGN input to a V1 neuron is modeled as a group of NLIF neurons produces higher orientation selectivity than the one with Poisson LGN input. The second result implies that statistical characteristics of LGN spike trains are important for V1's function. We conclude that physiologically motivated models of V1 need to include more realistic LGN spike trains that are less noisy than inhomogeneous Poisson processes.

  6. Chronic morphine exposure induces degradation of receptive field properties of LGN cells in cats

    Institute of Scientific and Technical Information of China (English)

    Li-hua HE; Guang-xing LI; Xiang-rui LI; Yi-feng ZHOU

    2005-01-01

    Aim: To investigate the effect of chronic morphine exposure on the receptive field properties of lateral geniculate nucleus (LGN) neurons in cats. Methods: Cats were injected with morphine (10 mg/kg) or saline twice daily, for 10 d. Subsequently,extracellular single-unit recording techniques were used to examine the sensitivity of LGN neurons to visual stimuli in chronic morphine-treated and saline-treated cats. Results: Compared with saline-treated cats (as controls), LGN neurons in morphine-treated cats had decreased signal-to-noise ratios (1.9 vs 3.1), and orientation and direction sensitivity (0.103 vs 0.135 and 0.074 vs 0.10, respectively),accompanied by significant increases in spontaneous (27.4 vs 17.5) and evoked activity (preferred: 42.2 vs 38.1; average: 28.1 vs 22.3). Conclusion: Chronic morphine exposure can lead to the functional degradation of LGN neurons in cats,which might result from the effects of chronic morphine exposure on inhibitory neurotransmission.

  7. Can the Outputs of LGN Y-Cells Support Emotion Recognition? A Computational Study

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    Andrea De Cesarei

    2015-01-01

    Full Text Available It has been suggested that emotional visual input is processed along both a slower cortical pathway and a faster subcortical pathway which comprises the lateral geniculate nucleus (LGN, the superior colliculus, the pulvinar, and finally the amygdala. However, anatomical as well as functional evidence concerning the subcortical route is lacking. Here, we adopt a computational approach in order to investigate whether the visual representation that is achieved in the LGN may support emotion recognition and emotional response along the subcortical route. In four experiments, we show that the outputs of LGN Y-cells support neither facial expression categorization nor the same/different expression matching by an artificial classificator. However, the same classificator is able to perform at an above chance level in a statistics-based categorization of scenes containing animals and scenes containing people and of light and dark patterns. It is concluded that the visual representation achieved in the LGN is insufficient to allow for the recognition of emotional facial expression.

  8. Recovery from optic neuritis: an ROI-based analysis of LGN and visual cortical areas

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Madsen, Kristoffer Hougaard; Frederiksen, Jette L

    2007-01-01

    and neuronal plasticity in the cortical and subcortical visual pathways. To assess where recovery takes place along the visual pathway, visual activation was studied in the lateral geniculate nucleus (LGN), the main thalamic relay nucleus in the visual pathway and in three areas of the visual cortex......: the lateral occipital complexes (LOC), V1 and V2. We conducted a longitudinal functional magnetic resonance imaging (fMRI) study of regions of interest (ROI) of activation in LGN and visual cortex in 19 patients with acute ON at onset, 3 and 6 months from presentation. With fMRI we measured the activation......Optic neuritis (ON) is the first clinical manifestation in approximately 20% of patients with multiple sclerosis (MS). The inflammation and demyelination of the optic nerve are characterized by symptomatic visual impairment and retrobulbar pain, and associated with decreased visual acuity...

  9. Expression profile of hepatic genes in cynomolgus macaques bred in Cambodia, China, and Indonesia: implications for cytochrome P450 genes.

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    Ise, Ryota; Nakanishi, Yasuharu; Kohara, Sakae; Yamashita, Hiroyuki; Yoshikawa, Tsuyoshi; Iwasaki, Kazuhide; Nagata, Ryoichi; Fukuzaki, Koichiro; Utoh, Masahiro; Nakamura, Chika; Yamazaki, Hiroshi; Uno, Yasuhiro

    2012-01-01

    Cynomolgus macaques, frequently used in drug metabolism studies, are bred mainly in the countries of Asia; however, comparative studies of drug metabolism between cynomolgus macaques bred in these countries have not been conducted. In this study, hepatic gene expression profiles of cynomolgus macaques bred in Cambodia (mfCAM), China (mfCHN), and Indonesia (mfIDN) were analyzed. Microarray analysis revealed that expression of most hepatic genes, including drug-metabolizing enzyme genes, was not substantially different between mfCAM, mfCHN, and mfIDN; only 1.1% and 3.0% of all the gene probes detected differential expression (>2.5-fold) in mfCAM compared with mfCHN and mfIDN, respectively. Quantitative polymerase chain reaction showed that the expression levels of 14 cytochromes P450 (P450s) important for drug metabolism did not differ (>2.5-fold) in mfCAM, mfCHN, and mfIDN, validating the microarray data. In contrast, expression of CYP2B6 and CYP3A4 differed (>2.5-fold, p profiles, including drug-metabolizing enzyme genes such as P450 genes, are similar in mfCAM, mfCHN, and mfIDN.

  10. Female homosexual behavior and inter-sexual mate competition in Japanese macaques: possible implications for sexual selection theory.

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    Vasey, Paul L; Leca, Jean-Baptiste; Gunst, Noëlle; VanderLaan, Doug P

    2014-10-01

    In this paper, we review research related to female homosexual behavior in Japanese macaques (Macaca fuscata), including our 20-year program of research on this species. Multiple lines of evidence indicate that female homosexual behavior in this species is sexually motivated. In contrast, many sociosexual hypotheses have been tested in relation to female homosexual behavior in Japanese macaques, but none have been supported. Female Japanese macaques sometimes engage in same-sex sexual activity even when motivated opposite-sex alternatives are available. Within this context of mate choice, males compete inter-sexually for opportunities to copulate with females above and beyond any intra-sexual competition that is required. Anecdotal evidence suggests that inter-sexual competition for female sexual partners has been observed in a number of other species, including humans. At present it is unclear whether inter-sexual competition for sexual partners influences patterns of reproduction. Our understanding of sexual selection and the evolution of mating systems may be improved by investigating whether inter-sexual mate competition influences the acquisition and maintenance of reproductive partners in those species in which such interactions occur.

  11. An autoinhibited conformation of LGN reveals a distinct interaction mode between GoLoco motifs and TPR motifs.

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    Pan, Zhu; Zhu, Jinwei; Shang, Yuan; Wei, Zhiyi; Jia, Min; Xia, Caihao; Wen, Wenyu; Wang, Wenning; Zhang, Mingjie

    2013-06-01

    LGN plays essential roles in asymmetric cell divisions via its N-terminal TPR-motif-mediated binding to mInsc and NuMA. This scaffolding activity requires the release of the autoinhibited conformation of LGN by binding of Gα(i) to its C-terminal GoLoco (GL) motifs. The interaction between the GL and TPR motifs of LGN represents a distinct GL/target binding mode with an unknown mechanism. Here, we show that two consecutive GL motifs of LGN form a minimal TPR-motif-binding unit. GL12 and GL34 bind to TPR0-3 and TPR4-7, respectively. The crystal structure of a truncated LGN reveals that GL34 forms a pair of parallel α helices and binds to the concave surface of TPR4-7, thereby preventing LGN from binding to other targets. Importantly, the GLs bind to TPR motifs with a mode distinct from that observed in the GL/Gα(i)·GDP complexes. Our results also indicate that multiple and orphan GL motif proteins likely respond to G proteins with distinct mechanisms.

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

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

    2015-06-01

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

  13. Semi-Automatic Segmentation of Optic Radiations and LGN, and Their Relationship to EEG Alpha Waves

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    Descoteaux, Maxime; Bernier, Michaël; Garyfallidis, Eleftherios; Whittingstall, Kevin

    2016-01-01

    At rest, healthy human brain activity is characterized by large electroencephalography (EEG) fluctuations in the 8-13 Hz range, commonly referred to as the alpha band. Although it is well known that EEG alpha activity varies across individuals, few studies have investigated how this may be related to underlying morphological variations in brain structure. Specifically, it is generally believed that the lateral geniculate nucleus (LGN) and its efferent fibres (optic radiation, OR) play a key role in alpha activity, yet it is unclear whether their shape or size variations contribute to its inter-subject variability. Given the widespread use of EEG alpha in basic and clinical research, addressing this is important, though difficult given the problems associated with reliably segmenting the LGN and OR. For this, we employed a multi-modal approach and combined diffusion magnetic resonance imaging (dMRI), functional magnetic resonance imaging (fMRI) and EEG in 20 healthy subjects to measure structure and function, respectively. For the former, we developed a new, semi-automated approach for segmenting the OR and LGN, from which we extracted several structural metrics such as volume, position and diffusivity. Although these measures corresponded well with known morphology based on previous post-mortem studies, we nonetheless found that their inter-subject variability was not significantly correlated to alpha power or peak frequency (p >0.05). Our results therefore suggest that alpha variability may be mediated by an alternative structural source and our proposed methodology may in general help in better understanding the influence of anatomy on function such as measured by EEG or fMRI. PMID:27383146

  14. Semi-Automatic Segmentation of Optic Radiations and LGN, and Their Relationship to EEG Alpha Waves.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Renauld

    Full Text Available At rest, healthy human brain activity is characterized by large electroencephalography (EEG fluctuations in the 8-13 Hz range, commonly referred to as the alpha band. Although it is well known that EEG alpha activity varies across individuals, few studies have investigated how this may be related to underlying morphological variations in brain structure. Specifically, it is generally believed that the lateral geniculate nucleus (LGN and its efferent fibres (optic radiation, OR play a key role in alpha activity, yet it is unclear whether their shape or size variations contribute to its inter-subject variability. Given the widespread use of EEG alpha in basic and clinical research, addressing this is important, though difficult given the problems associated with reliably segmenting the LGN and OR. For this, we employed a multi-modal approach and combined diffusion magnetic resonance imaging (dMRI, functional magnetic resonance imaging (fMRI and EEG in 20 healthy subjects to measure structure and function, respectively. For the former, we developed a new, semi-automated approach for segmenting the OR and LGN, from which we extracted several structural metrics such as volume, position and diffusivity. Although these measures corresponded well with known morphology based on previous post-mortem studies, we nonetheless found that their inter-subject variability was not significantly correlated to alpha power or peak frequency (p >0.05. Our results therefore suggest that alpha variability may be mediated by an alternative structural source and our proposed methodology may in general help in better understanding the influence of anatomy on function such as measured by EEG or fMRI.

  15. Structural basis for the recognition of the scaffold protein Frmpd4/Preso1 by the TPR domain of the adaptor protein LGN.

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    Takayanagi, Hiroki; Yuzawa, Satoru; Sumimoto, Hideki

    2015-02-01

    The adaptor protein LGN interacts via the N-terminal domain comprising eight tetratricopeptide-repeat (TPR) motifs with its partner proteins mInsc, NuMA, Frmpd1 and Frmpd4 in a mutually exclusive manner. Here, the crystal structure of the LGN TPR domain in complex with human Frmpd4 is described at 1.5 Å resolution. In the complex, the LGN-binding region of Frmpd4 (amino-acid residues 990-1011) adopts an extended structure that runs antiparallel to LGN along the concave surface of the superhelix formed by the TPR motifs. Comparison with the previously determined structures of the LGN-Frmpd1, LGN-mInsc and LGN-NuMA complexes reveals that these partner proteins interact with LGN TPR1-6 via a common core binding region with consensus sequence (E/Q)XEX4-5(E/D/Q)X1-2(K/R)X0-1(V/I). In contrast to Frmpd1, Frmpd4 makes additional contacts with LGN via regions N- and C-terminal to the core sequence. The N-terminal extension is replaced by a specific α-helix in mInsc, which drastically increases the direct contacts with LGN TPR7/8, consistent with the higher affinity of mInsc for LGN. A crystal structure of Frmpd4-bound LGN in an oxidized form is also reported, although oxidation does not appear to strongly affect the interaction with Frmpd4.

  16. Temporal response properties to second-order visual stimuli in the LGN of cats

    Institute of Scientific and Technical Information of China (English)

    XU PengJing; YE Xiang; ZHOU Yifeng

    2007-01-01

    Visual stimuli occurring naturally are rich in instances of objects delineated from the backgrounds only by differences in luminance, which is called first-order stimuli, as well as those defined by differences of contrast or texture, referred to as second-order stimuli.The neuronal mechanism for processing second-order stimuli is still unclear.In this study, we compared the responses of cat LGN (lateral geniculate nucleus) cells to second-order stimuli at five temporal frequencies to their responses to first-order stimuli.Our results showed that most LGN cells can be evoked by second-order stimuli, and their firing rates to second-order stimuli decreased relative to first-order stimuli as temporal frequency increased from 0.5 to 8 Hz; moreover the ratio of a nonlinear to linear factor had a higher value in the responses to second-order stimuli than to first-order stimuli.We also found that the responses of Y-cells to second-order stimuli were significantly higher than the responses of X-cells, suggesting the Y-cells have a more important role in the processing of second-order stimuli.All these results reveal that first-order and second-order signals might be processed in separate 'streams' of the visual system.

  17. Pigtail macaque performance on a challenging joystick task has important implications for enrichment and anxiety within a captive environment.

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    Lincoln, H; Andrews, M W; Rosenblum, L A

    1995-06-01

    The purpose of this study was to extend previous findings on joystick task engagement by a group of pigtail macaques. The goals were to determine the influence of task difficulty on daily levels of task activity and to test the hypothesis that previously identified preferences among identical devices at different locations derived largely from the level of anxiety induced at each location. It was found that the number of daily trials decreased when the task was made more difficult, with more time required to complete each trial with the difficult task. Preferences among locations became more pronounced with the more difficult task. Analysis of errors made on devices at different locations supported the view that preferences did derive, at least in part, from levels of induced anxiety. Locations of enrichment devices may influence not only amount of use but also levels of anxiety in captive monkeys.

  18. Human Exposure to Herpesvirus B–Seropositive Macaques, Bali, Indonesia

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    Engel, Gregory A.; Schillaci, Michael A.; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-01-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a “monkey forest” (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B. PMID:12141963

  19. Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

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    Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

    2002-08-01

    Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

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

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

    2010-02-01

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

  1. Effects of pattern shape on adaptation of dLGN cell

    Institute of Scientific and Technical Information of China (English)

    JIN Jianzhong; XU Pengjing; LI Xiangrui; ZHOU Yifeng

    2003-01-01

    Pattern adaptation is one of the fundamental sensory processes in the visual system. In this study, we compared pattern adaptation induced by two types of sinusoidal drifting grating in dLGN cells of cat. The two types ofgrating have the same parameters (e.g. spatial frequency, temporal frequency and contrast) except their pattern shapes, one of which is normal grating and the other annular grating. The results suggested that the annular grating elicited stronger response and stronger pattern adaptation than the normal grating. This is consistent with the adaptation and aftereffect to the two types of drifting gratings seen in psychology and may reflect the subcortical neural mechanism underlying these psychological phenomena.

  2. A CORF computational model of a simple cell that relies on LGN input outperforms the Gabor function model

    NARCIS (Netherlands)

    Azzopardi, George; Petkov, Nicolai

    Simple cells in primary visual cortex are believed to extract local contour information from a visual scene. The 2D Gabor function (GF) model has gained particular popularity as a computational model of a simple cell. However, it short-cuts the LGN, it cannot reproduce a number of properties of real

  3. Crystal Structures of the Scaffolding Protein LGN Reveal the General Mechanism by Which GoLoco Binding Motifs Inhibit the Release of GDP from Gαi *

    Science.gov (United States)

    Jia, Min; Li, Jianchao; Zhu, Jinwei; Wen, Wenyu; Zhang, Mingjie; Wang, Wenning

    2012-01-01

    GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Gα subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Gαi/o during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Gαi·GDP. The crystal structures of Gαi·GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Gαi interaction features when compared with the only high resolution structure known with GL/Gαi interaction between RGS14 and Gαi1. Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to Gαi·GDP. A highly conserved “double Arg finger” sequence (RΨ(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to Gαi. Together with the sequence alignment, we suggest that the LGN GL/Gαi interaction represents a general binding mode between GL motifs and Gαi. We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors. PMID:22952234

  4. Diversification of both KIR and NKG2 natural killer cell receptor genes in macaques - implications for highly complex MHC-dependent regulation of natural killer cells.

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    Walter, Lutz; Petersen, Beatrix

    2017-02-01

    The killer immunoglobulin-like receptors (KIR) as well as their MHC class I ligands display enormous genetic diversity and polymorphism in macaque species. Signals resulting from interaction between KIR or CD94/NKG2 receptors and their cognate MHC class I proteins essentially regulate the activity of natural killer (NK) cells. Macaque and human KIR share many features, such as clonal expression patterns, gene copy number variations, specificity for particular MHC class I allotypes, or epistasis between KIR and MHC class I genes that influence susceptibility and resistance to immunodeficiency virus infection. In this review article we also annotated publicly available rhesus macaque BAC clone sequences and provide the first description of the CD94-NKG2 genomic region. Besides the presence of genes that are orthologous to human NKG2A and NKG2F, this region contains three NKG2C paralogues. Hence, the genome of rhesus macaques contains moderately expanded and diversified NKG2 genes in addition to highly diversified KIR genes. The presence of two diversified NK cell receptor families in one species has not been described before and is expected to require a complex MHC-dependent regulation of NK cells. © 2016 John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Poster: the macaque genome.

    Science.gov (United States)

    2007-04-13

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

  7. Structural Analysis of Human and Macaque Monoclonal Antibodies 2909 and 2.5B: Implications for the Configuration of the Quaternary Neutralizing Epitope of HIV-1 gp120

    Energy Technology Data Exchange (ETDEWEB)

    B Spurrier; J Sampson; M Totrov; H Li; T ONeal; C Williams; J Robinson; M Gorny; S Zolla-Pazner; X Kong

    2011-12-31

    The quaternary neutralizing epitope (QNE) of HIV-1 gp120 is preferentially expressed on the trimeric envelope spikes of intact HIV virions, and QNE-specific monoclonal antibodies (mAbs) potently neutralize HIV-1. Here, we present the crystal structures of the Fabs of human mAb 2909 and macaque mAb 2.5B. Both mAbs have long beta hairpin CDR H3 regions >20 {angstrom} in length that are each situated at the center of their respective antigen-binding sites. Computational analysis showed that the paratopes include the whole CDR H3, while additional CDR residues form shallow binding pockets. Structural modeling suggests a way to understand the configuration of QNEs and the antigen-antibody interaction for QNE mAbs. Our data will be useful in designing immunogens that may elicit potent neutralizing QNE Abs.

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

    Directory of Open Access Journals (Sweden)

    Parham Peter

    2011-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Pedersen Niels C

    2007-04-01

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

  10. Illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, Daan

    2014-01-01

    While Morocco is well known as the main port between Africa and the EU for the illegal drugs trade and migration, the illegal trade in wildlife is flourishing as well. Next to the illegal large-scale trafficking of tortoises and birds, it is estimated that as few as 5,000 Barbary macaques remain in

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

    Science.gov (United States)

    Riley, Erin P; Wade, Tiffany W

    2016-04-01

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

  12. Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey

    Science.gov (United States)

    Hannibal, J.; Kankipati, L.; Strang, C.E.; Peterson, B.B.; Dacey, D.; Gamlin, P.D.

    2014-01-01

    Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are entrained to the environmental light/dark cycle via intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin and the neuropeptide PACAP. The ipRGCs regulate other non-image-forming visual functions such as the pupillary light reflex, masking behaviour and light induced melatonin suppression. To evaluate whether PACAP immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we characterized the occurrence of PACAP in melanopsin expressing ipRGCs and in the retinal target areas in the brain visualized by the anterograde tracer Cholera Toxin subunit B (CtB) in combination with PACAP staining. In the retina, PACAP and melanopsin were found to be co-stored in 99% of melanopsin expressing cells characterized as inner and outer stratifying melanopsin RGCs. Two macaque monkeys were anesthetized and received a unilateral intravitreal injection of CtB. Bilateral retinal projections containing co-localized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex (LGN) including the pregeniculate nucleus (PrGC), the pretectal olivary nucleus (PON), the nucleus of the optic tract (NOT), the brachium of the superior colliculus (BSC), and the superior colliculus (SC). In conclusion, PACAP immunoreactive projections with co-localized CtB represent retinal projections of ipRGCs in the macaque monkey, and support previous retrograde tracer studies demonstrating that melanopsin containing retinal projections reach areas in the primate brain involved in both image and non-image-forming visual processing. PMID:24752373

  13. Metabotropic glutamate receptor 5 shows different patterns of localization within the parallel visual pathways in macaque and squirrel monkeys

    Directory of Open Access Journals (Sweden)

    Shostak Y

    2014-09-01

    Full Text Available Yuri Shostak,1,5 Ashley Wenger,4 Julia Mavity-Hudson,1 Vivien A Casagrande1–3 1Department of Cell and Developmental Biology, 2Department of Psychology, 3Department of Ophthalmology and Visual Sciences, 4Undergraduate Neuroscience Program, Vanderbilt University, Nashville, TN, USA; 5Foreign Trade Unitary Enterprise, Minsk, Belarus Abstract: Glutamate is used as an excitatory neurotransmitter by the koniocellular (K, magnocellular (M, and parvocellular (P pathways to transfer signals from the primate lateral geniculate nucleus (LGN to primary visual cortex (V1. Glutamate acts through both fast ionotropic receptors, which appear to carry the main sensory message, and slower, modulatory metabotropic receptors (mGluRs. In this study, we asked whether mGluR5 relates in distinct ways to the K, M, and P LGN axons in V1. To answer this question, we used light microscopic immunocytochemistry and preembedding electron microscopic immunogold labeling to determine the localization of mGluR5 within the layers of V1 in relation to the K, M, and P pathways in macaque and squirrel monkeys. These pathways were labeled separately via wheat germ agglutinin–horseradish peroxidase (WGA–HRP injections targeting the LGN layers. mGluR5 is of interest because it: 1 has been shown to be expressed in the thalamic input layers; 2 appears to be responsible for some types of oscillatory firing, which could be important in the binding of visual features; and 3 has been associated with a number of sensory-motor gating-related pathologies, including schizophrenia and autism. Our results demonstrated the presence of mGluR5 in the neuropil of all V1 layers. This protein was lowest in IVCa (M input and the infragranular layers. In layer IVC, mGluR5 also was found postsynaptic to about 30% of labeled axons, but the distribution was uneven, such that postsynaptic mGluR5 label tended to occur opposite smaller (presumed P, and not larger (presumed M axon terminals. Only in the K

  14. Cortical activity influences geniculocortical spike efficacy in the macaque monkey

    Directory of Open Access Journals (Sweden)

    Farran Briggs

    2007-11-01

    Full Text Available Thalamocortical communication is a dynamic process influenced by both presynaptic and postsynaptic mechanisms. In this study, we recorded single-unit responses from cortical neurons that received direct input from the lateral geniculate nucleus (LGN to address the question of whether prior patterns of cortical activity affect the ability of LGN inputs to drive cortical responses. By examining the ongoing activity that preceded the arrival of electrically evoked spikes from the LGN, we identified a number of activity patterns that were predictive of suprathreshold communication. Namely, cortical neurons were more likely to respond to LGN stimulation when their activity levels increased to 30-40Hz and/or their activity displayed rhythmic patterns (30 ms intervals with increased power in the gamma frequency band. Cortical neurons were also more likely to respond to LGN stimulation when their activity increased 30-40 ms prior to stimulation, suggesting that the phase of gamma activity also contributes to geniculocortical communication. Based on these results, we conclude that ongoing activity in the cortex is not random, but rather organized in a manner that can influence the dynamics of thalamocortical communication.

  15. Structural Analysis of Human and Macaque mAbs 2909 and 2.5B: Implications for the Configuration of the Quaternary Neutralizing Epitope of HIV-1 gp120

    Energy Technology Data Exchange (ETDEWEB)

    Spurrier, Brett; Sampson, Jared M.; Totrov, Maxim; Li, Huiguang; O; Neal, Timothy; Williams, Constance; Robinson, James; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Kong, Xiang-Peng (Molsoft); (Tulane); (NYUSM)

    2011-08-25

    The quaternary neutralizing epitope (QNE) of HIV-1 gp120 is preferentially expressed on the trimeric envelope spikes of intact HIV virions, and QNE-specific monoclonal antibodies (mAbs) potently neutralize HIV-1. Here, we present the crystal structures of the Fabs of human mAb 2909 and macaque mAb 2.5B. Both mAbs have long beta hairpin CDR H3 regions >20 {angstrom} in length that are each situated at the center of their respective antigen-binding sites. Computational analysis showed that the paratopes include the whole CDR H3, while additional CDR residues form shallow binding pockets. Structural modeling suggests a way to understand the configuration of QNEs and the antigen-antibody interaction for QNE mAbs. Our data will be useful in designing immunogens that may elicit potent neutralizing QNE Abs.

  16. A macaque model for hantavirus infection.

    NARCIS (Netherlands)

    J. Groen (Jan); M.N. Gerding; J.P. Koeman; P.J.M. Roholl (Paul); G. van Amerongen (Geert); H.G.M. Jordans; A.D.M.E. Osterhaus (Albert); H.G.M. Niesters (Bert)

    1995-01-01

    textabstractCynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hallnas), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild pro

  17. Elevated Cerebrospinal fluid 5-hydroxyindoleacetic acid in Macaques Following Early Life Stress (ELS and Inverse Association with Hippocampal Volume: Preliminary Implications for Serotonin-Related Function in Mood and Anxiety Disorders

    Directory of Open Access Journals (Sweden)

    Jeremy D Coplan

    2014-12-01

    Full Text Available Background: Early life stress (ELS is cited as a risk for mood and anxiety disorders, potentially through altered serotonin neurotransmission. We examined the effects of ELS, utilizing the variable foraging demand (VFD macaque model, on adolescent monoamine metabolites. We sought to replicate an increase in cerebrospinal fluid (CSF 5-hydroxyindoleacetic acid (5-HIAA observed in two previous VFD cohorts. We hypothesized that elevated cisternal 5-HIAA was associated with reduced neurotrophic effects , conceivably due to excessive negative feedback at somatodendritic 5-HT1A autoreceptors. A putatively decreased serotonin neurotransmission would be reflected by reductions in hippocampal volume and white matter (WM fractional anisotropy (FA. Methods: When infants were 2-6 months of age, bonnet macaque mothers were exposed to VFD. We employed cisternal CSF taps to measure monoamine metabolites in VFD (N = 22 and non-VFD (N = 14 offspring (mean age = 2.61 years. Metabolites were correlated with hippocampal volume obtained by MRI and WM FA by diffusion tensor imaging in young adulthood in 17 males [10 VFD (mean age = 4.57 years].Results: VFD subjects exhibited increased CSF 5-HIAA compared to non-VFD controls. An inverse correlation between right hippocampal volume and 5-HIAA was noted in VFD- but not controls. CSF HVA and MHPG correlated inversely with hippocampal volume only in VFD. CSF 5-HIAA correlated inversely with FA of the WM tracts of the anterior limb of the internal capsule (ALIC only in VFD. Conclusions: Elevated cisternal 5-HIAA in VFD may reflect increased dorsal raphe serotonin, potentially inducing excessive autoreceptor activation, inducing a putative serotonin deficit in terminal fields. Resultant reductions in neurotrophic activity are reflected by smaller right hippocampal volume. Convergent evidence of reduced neurotrophic activity in association with high CSF 5-HIAA in VFD was reflected by reduced FA of the ALIC.

  18. Intrasulcal electrocorticography in macaque monkeys with minimally invasive neurosurgical protocols

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    Takeshi eMatsuo

    2011-05-01

    Full Text Available Electrocorticography (ECoG, multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate’s brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems (MEMS technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the

  19. Intrasulcal electrocorticography in macaque monkeys with minimally invasive neurosurgical protocols.

    Science.gov (United States)

    Matsuo, Takeshi; Kawasaki, Keisuke; Osada, Takahiro; Sawahata, Hirohito; Suzuki, Takafumi; Shibata, Masahiro; Miyakawa, Naohisa; Nakahara, Kiyoshi; Iijima, Atsuhiko; Sato, Noboru; Kawai, Kensuke; Saito, Nobuhito; Hasegawa, Isao

    2011-01-01

    Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting-edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain.

  20. Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2008-07-01

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

  3. Cholinergic control of visual categorisation in macaques

    Directory of Open Access Journals (Sweden)

    Nikolaos C. Aggelopoulos

    2011-11-01

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

  4. Altered β-Catenin Accumulation in Hepatocellular Carcinomas of Diethynitrosamine-Exposed Rhesus Macaques

    Science.gov (United States)

    Wei, Bih-Rong; Edwards, Jennifer B.; Hoover, Shelley B.; Tillman, Heather S.; Reed, L. Tiffany; Sills, Robert C.; Simpson, R. Mark

    2008-01-01

    Chemical exposures are important risks for development of hepatocellular carcinoma (HCC). One such chemical, diethylnitrosamine (DENA), is present in food products as well as in industrial and research settings. Further examination of tumors induced by DENA may yield clues to human risk. HCC from seven rhesus macaques exposed to DENA were selected from a tissue archive to examine for evidence of Wnt/β-catenin signaling events, which are frequently associated with HCC. DENA exposure durations ranged from 8 to 207 months, and total accumulated dose ranged from 0.7 to 4.08 mg. Unexposed colony breeder macaques served as controls. Previously unrecognized HCC metastases were discovered in lungs of three macaques. Overexpression of β-catenin and glutamine synthetase was detected by immunohistochemistry in six confirmed primary HCC and all metastatic HCC, which implicated Wnt/β-catenin activation. Concomitant β-catenin gene mutation was detected in one primary HCC; similar findings have been reported in human and rodent HCC. Neither β-catenin mutation nor β-catenin overexpression appeared to influence metastatic potential. Accumulation of intracellular proteins involved in Wnt/β-catenin signaling during HCC oncogenesis in rhesus macaques exposed to DENA appears to include other mechanisms, in addition to mutation of β-catenin gene. PMID:18978308

  5. Macaque monkeys experience visual crowding.

    Science.gov (United States)

    Crowder, Erin A; Olson, Carl R

    2015-01-01

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

  6. Ambiguity aversion in rhesus macaques

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    Benjamin eHayden

    2010-09-01

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

  7. Comparative Pathobiology of Macaque Lymphocryptoviruses

    Science.gov (United States)

    Carville, Angela; Mansfield, Keith G

    2008-01-01

    Lymphocryptoviruses (LCVs) have been identified as naturally occurring infections of both Old and New World nonhuman primates. These viruses are closely related to Epstein–Barr virus (EBV, Human herpesvirus 4) and share similar genomic organization and biological properties. Nonhuman primate LCVs have the ability to immortalize host cells and express a similar complement of viral lytic and latent genes as those found in EBV. Recent evidence indicates that nonhuman primate LCVs can immortalize B cells from genetically related species, suggesting a close evolutionary relationship between these viruses and their respective hosts. Early work with EBV in tamarins and owl monkeys revealed that cross species transmission of lymphocryptoviruses from the natural to inadvertent host may be associated with oncogenesis and the development of malignant lymphoma. Moreover, simian LCVs have the ability to induce malignant lymphomas in immunodeficient hosts and have been associated with posttransplantation lymphoproliferative disease in cynomolgus macaques undergoing solid organ transplantation. This review will focus on the comparative pathobiology of lymphocryptoviral infection and discuss the derivation of specific pathogen-free animals. PMID:19793458

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  9. Gene targeting in adult rhesus macaque fibroblasts

    Directory of Open Access Journals (Sweden)

    Wolf Don P

    2008-03-01

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

  10. A macaque model for hantavirus infection

    NARCIS (Netherlands)

    Groen, J; Gerding, M; Koeman, J P; Roholl, P J; van Amerongen, G; Jordans, H G; Niesters, H G; Osterhaus, A D

    1995-01-01

    Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hällnäs), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Emily J Bethell

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

  14. Surgical technique for allogeneic uterus transplantation in macaques

    OpenAIRE

    Hideaki Obara; Iori Kisu; Yojiro Kato; Yohei Yamada; Kentaro Matsubara; Katsura Emoto; Masataka Adachi; Yusuke Matoba; Kiyoko Umene; Yuya Nogami; Kouji Banno; Hideaki Tsuchiya; Iori Itagaki; Ikuo Kawamoto; Takahiro Nakagawa

    2016-01-01

    No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac art...

  15. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta)

    OpenAIRE

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

    2011-01-01

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

  16. Vicarious Reinforcement in Rhesus Macaques (Macaca Mulatta)

    OpenAIRE

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

    2011-01-01

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

  17. Gravity orientation tuning in macaque anterior thalamus.

    Science.gov (United States)

    Laurens, Jean; Kim, Byounghoon; Dickman, J David; Angelaki, Dora E

    2016-12-01

    Gravity may provide a ubiquitous allocentric reference to the brain's spatial orientation circuits. Here we describe neurons in the macaque anterior thalamus tuned to pitch and roll orientation relative to gravity, independently of visual landmarks. We show that individual cells exhibit two-dimensional tuning curves, with peak firing rates at a preferred vertical orientation. These results identify a thalamic pathway for gravity cues to influence perception, action and spatial cognition.

  18. Inhalational Monkeypox Virus Infection in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roy eBarnewall

    2012-09-01

    Full Text Available An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV, and a nonhuman primate (NHP inhalation monkeypox model was developed in cynomologus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD was for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 µm, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 x 104 to 9.28 x 105 plaque forming units (pfu inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD50 was determined to be approximately 7.8 x 104 pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data.

  19. Fructosamine reference ranges in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Williams-Fritze, Misty J; Smith, Peter C; Zelterman, Daniel; Scholz, Jodi A Carlson

    2011-07-01

    Naturally occurring diabetes mellitus (DM) is common in several species of Old and New World nonhuman primates. Fructosamine values provide important information about recent glycemic control and can be useful in the diagnosis and management of DM. However, despite an abundance of reports in the literature describing spontaneous and induced DM in monkeys, few reference ranges are available for fructosamine. Reference ranges have been published for woolly monkeys (Lagothrix lagotricha), cynomolgus macaques (Macaca fascicularis), and stumptail macaques (Macaca arctoides) but currently are not available for rhesus macaques. At our institution, DM is a common diagnosis in aging rhesus macaques. Here we report a reference range for fructosamine in rhesus macaques. The overall range was 157 to 230 μmol/L, with male rhesus and macaques 10 y or older having significantly higher values than do female rhesus and macaques younger than 10 y, respectively. This range provides clinical veterinarians with an additional tool for evaluating glycemic control in rhesus macaques. Copyright 2011 by the American Association for Laboratory Animal Science

  20. Effects of tourists on Barbary macaques at Gibraltar.

    Science.gov (United States)

    O'Leary, H; Fa, J E

    1993-01-01

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

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

    Science.gov (United States)

    Li, Cheng; Zhao, Chao; Fan, Peng-Fei

    2015-07-01

    We describe a newly discovered Macaca species from the Medog, in southeastern Tibet, China, Macaca leucogenys sp. nov or the "white-cheeked macaque". Based on 738 photos taken during direct observations and captured by camera traps this new species appears to be distinct from the Macaca sinica species group. Moreover, the species is distinguished from all potential sympatric macaque species (M. mulatta, M. thibetana, M. assamensis, and M. munzala) in exhibiting a suite of pelage characteristics including relatively uniform dorsal hair pattern, hairy ventral pelage, relative hairless short tail, prominent pale to white side- and chin-whiskers creating a white cheek and round facial appearance, dark facial skin on the muzzle, long and thick hairs on its neck, and a round rather than arrow-shaped male genitalia. This new macaque species was found to exploit a diverse set of habitat types from tropical forest at 1395 m, to primary and secondary evergreen broad-leaved forest at 2000 m, as well as mixed broadleaf-conifer forest at 2700 m. Its range may extend to neighboring counties in Tibet and the part of southeastern Tibet controlled by India. The white-cheeked macaque is threatened by illegal hunting and the construction of hydropower stations. Discovery of this new primate species further highlights the high value for biodiversity conservation of southeastern Tibet and calls for more intensive surveys, studies, and environmental protection in this area.

  2. Ulcerative cheilitis in a rhesus macaque.

    Science.gov (United States)

    Bailey, C C; Miller, A D

    2012-03-01

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

  3. Grooming reciprocity in male Tibetan macaques.

    Science.gov (United States)

    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.

  4. Condylomatous genital lesions in cynomolgus macaques from Mauritius.

    Science.gov (United States)

    Harari, Ariana; Wood, Charles E; Van Doorslaer, Koenraad; Chen, Zigui; Domaingue, Marie Claire; Elmore, David; Koenig, Patricia; Wagner, Janice D; Jennings, Ryan N; Burk, Robert D

    2013-08-01

    Genital condyloma-like lesions were observed on male and female cynomolgus macaque monkeys (Macaca fascicularis) originating from the island of Mauritius. Cytobrush and/or biopsy samples were obtained from lesions of 57 affected macaques. Primary histologic features included eosinophilic, neutrophilic, and lymphoplasmacytic penile and vulvar inflammation, epidermal hyperplasia with acanthosis, and increased collagenous stroma. Polymerase chain reaction-based assays to amplify viral DNA revealed the presence of macaque lymphocryptovirus (LCV) DNA but not papillomavirus or poxvirus DNA. Subsequent DNA analyses of 3 genomic regions of LCV identified isolates associated with lesions in 19/25 (76%) biopsies and 19/57 (33%) cytology samples. Variable immunolabeling for proteins related to the human LCV Epstein Barr Virus was observed within intralesional plasma cells, stromal cells, and epithelial cells. Further work is needed to characterize the epidemiologic features of these lesions and their association with LCV infection in Mauritian-origin macaques.

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

    Science.gov (United States)

    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.

  6. Co-transplantation of macaque autologous Schwann cells and human embryonic nerve stem cells in treatment of macaque Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Ying Xia; Chengchuan Jiang; Zuowei Cao; Keshan Shi; Yang Wang

    2012-01-01

    Objective:To investigate the therapeutic effects of co-transplantation with Schwann cells (SCs) and human embryonic nerve stem cells (NSCs) on macaque Parkinson's disease (PD). Methods:Macaque autologous SCs and human embryonic NSCs were adopted for the treatment of macaque PD. Results: Six months after transplantation, positron emission computerized tomography showed that 18F-FP-β-CIT was significantly concentrated in the injured striatum in the co-transplanted group. Immunohistochemical staining of transplanted area tissue showed migration of tyroxine hydroxylase positive cells from the transplant area to the surrounding area was significantly increased in the co-transplanted group. Conclusions: Co-transplantation of SCs and NSCs could effectively cure PD in macaques. SCs harvested from the autologous peripheral nerves can avoid rejection and the ethics problems, so it is expected to be applied clinically.

  7. Keep children away from macaque monkeys!

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  9. Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Steve W. C. Chang

    2011-03-01

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

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

    Science.gov (United States)

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

    2008-02-01

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

  11. Characterization and phylogenetic epitope mapping of CD38 ADPR cyclase in the cynomolgus macaque

    Directory of Open Access Journals (Sweden)

    Titti Fausto

    2004-09-01

    Full Text Available Abstract Background The CD38 transmembrane glycoprotein is an ADP-ribosyl cyclase that moonlights as a receptor in cells of the immune system. Both functions are independently implicated in numerous areas related to human health. This study originated from an inherent interest in studying CD38 in the cynomolgus monkey (Macaca fascicularis, a species closely related to humans that also represents a cogent animal model for the biomedical analysis of CD38. Results A cDNA was isolated from cynomolgus macaque peripheral blood leukocytes and is predicted to encode a type II membrane protein of 301 amino acids with 92% identity to human CD38. Both RT-PCR-mediated cDNA cloning and genomic DNA PCR surveying were possible with heterologous human CD38 primers, demonstrating the striking conservation of CD38 in these primates. Transfection of the cDNA coincided with: (i surface expression of cynomolgus macaque CD38 by immunofluorescence; (ii detection of ~42 and 84 kDa proteins by Western blot and (iii the appearance of ecto-enzymatic activity. Monoclonal antibodies were raised against the cynomolgus CD38 ectodomain and were either species-specific or cross-reactive with human CD38, in which case they were directed against a common disulfide-requiring conformational epitope that was mapped to the C-terminal disulfide loop. Conclusion This multi-faceted characterization of CD38 from cynomolgus macaque demonstrates its high genetic and biochemical similarities with human CD38 while the immunological comparison adds new insights into the dominant epitopes of the primate CD38 ectodomain. These results open new prospects for the biomedical and pharmacological investigations of this receptor-enzyme.

  12. Lack of prophylactic efficacy of oral maraviroc in macaques despite high drug concentrations in rectal tissues.

    Science.gov (United States)

    Massud, Ivana; Aung, Wutyi; Martin, Amy; Bachman, Shanon; Mitchell, James; Aubert, Rachael; Solomon Tsegaye, Theodros; Kersh, Ellen; Pau, Chou-Pong; Heneine, Walid; García-Lerma, J Gerardo

    2013-08-01

    Maraviroc (MVC) is a potent CCR5 coreceptor antagonist that is in clinical testing for daily oral pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model consisting of weekly SHIV162p3 exposures to evaluate the efficacy of oral MVC in preventing rectal SHIV transmission. MVC dosing was informed by the pharmacokinetic profile seen in blood and rectal tissues and consisted of a human-equivalent dose given 24 h before virus exposure, followed by a booster postexposure dose. In rectal secretions, MVC peaked at 24 h (10,242 ng/ml) with concentrations at 48 h that were about 40 times those required to block SHIV infection of peripheral blood mononuclear cells (PBMCs) in vitro. Median MVC concentrations in rectal tissues at 24 h (1,404 ng/g) were 30 and 10 times those achieved in vaginal or lymphoid tissues, respectively. MVC significantly reduced macrophage inflammatory protein 1β-induced CCR5 internalization in rectal mononuclear cells, an indication of efficient binding to CCR5 in rectal lymphocytes. The half-life of CCR5-bound MVC in PBMCs was 2.6 days. Despite this favorable profile, 5/6 treated macaques were infected during five rectal SHIV exposures as were 3/4 controls. MVC treatment was associated with a significant increase in the percentage of CD3(+)/CCR5(+) cells in blood. We show that high and durable MVC concentrations in rectal tissues are not sufficient to prevent SHIV infection in macaques. The increases in CD3(+)/CCR5(+) cells seen during MVC treatment point to unique immunological effects of CCR5 inhibition by MVC. The implications of these immunological effects on PrEP with MVC require further evaluation.

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

    Science.gov (United States)

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

    2014-12-01

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

  14. Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.

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    A Gregory Bruce

    Full Text Available Two gammaherpesviruses, Epstein-Barr virus (EBV (Lymphocryptovirus genus and Kaposi's sarcoma-associated herpesvirus (KSHV (Rhadinovirus genus have been implicated in the etiology of AIDS-associated lymphomas. Homologs of these viruses have been identified in macaques and other non-human primates. In order to assess the association of these viruses with non-human primate disease, archived lymphoma samples were screened for the presence of macaque lymphocryptovirus (LCV homologs of EBV, and macaque rhadinoviruses belonging to the RV1 lineage of KSHV homologs or the more distant RV2 lineage of Old World primate rhadinoviruses. Viral loads were determined by QPCR and infected cells were identified by immunolabeling for different viral proteins. The lymphomas segregated into three groups. The first group (n = 6 was associated with SIV/SHIV infections, contained high levels of LCV (1-25 genomes/cell and expressed the B-cell antigens CD20 or BLA.36. A strong EBNA-2 signal was detected in the nuclei of the neoplastic cells in one of the LCV-high lymphomas, indicative of a type III latency stage. None of the lymphomas in this group stained for the LCV viral capsid antigen (VCA lytic marker. The second group (n = 5 was associated with D-type simian retrovirus-2 (SRV-2 infections, contained high levels of RV2 rhadinovirus (9-790 genomes/cell and expressed the CD3 T-cell marker. The third group (n = 3 was associated with SIV/SHIV infections, contained high levels of RV2 rhadinovirus (2-260 genomes/cell and was negative for both CD20 and CD3. In both the CD3-positive and CD3/CD20-negative lymphomas, the neoplastic cells stained strongly for markers of RV2 lytic replication. None of the lymphomas had detectable levels of retroperitoneal fibromatosis herpesvirus (RFHV, the macaque RV1 homolog of KSHV. Our data suggest etiological roles for both lymphocryptoviruses and RV2 rhadinoviruses in the development of simian AIDS-associated lymphomas and indicate that

  15. A neural circuit covarying with social hierarchy in macaques.

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    MaryAnn P Noonan

    2014-09-01

    Full Text Available Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI, which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI data in 25 group-living macaques. First, a deformation-based morphometric (DBM approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

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

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    Donald K. Nichols

    2012-10-01

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

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

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    Angie K Marsh

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

  18. Rank-dependent grooming patterns and cortisol alleviation in Barbary macaques.

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    Sonnweber, Ruth S; Ravignani, Andrea; Stobbe, Nina; Schiestl, Gisela; Wallner, Bernard; Fitch, W Tecumseh

    2015-06-01

    Flexibly adapting social behavior to social and environmental challenges helps to alleviate glucocorticoid (GC) levels, which may have positive fitness implications for an individual. For primates, the predominant social behavior is grooming. Giving grooming to others is particularly efficient in terms of GC mitigation. However, grooming is confined by certain limitations such as time constraints or restricted access to other group members. For instance, dominance hierarchies may impact grooming partner availability in primate societies. Consequently specific grooming patterns emerge. In despotic species focusing grooming activity on preferred social partners significantly ameliorates GC levels in females of all ranks. In this study we investigated grooming patterns and GC management in Barbary macaques, a comparably relaxed species. We monitored changes in grooming behavior and cortisol (C) for females of different ranks. Our results show that the C-amelioration associated with different grooming patterns had a gradual connection with dominance hierarchy: while higher-ranking individuals showed lowest urinary C measures when they focused their grooming on selected partners within their social network, lower-ranking individuals expressed lowest C levels when dispersing their grooming activity evenly across their social partners. We argue that the relatively relaxed social style of Barbary macaque societies allows individuals to flexibly adapt grooming patterns, which is associated with rank-specific GC management.

  19. Decoding target distance and saccade amplitude from population activity in the macaque lateral intraparietal area (LIP

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    Frank Bremmer

    2016-08-01

    Full Text Available Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades towards moving targets are computationally more demanding since the oculomotor system must use speed and direction information about the target as well as knowledge about its own processing latency to program an adequate, predictive saccade vector. In monkeys, different brain regions have been implicated in the control of voluntary saccades, among them the lateral intraparietal area (LIP. Here we asked, if activity in area LIP reflects the distance between fovea and saccade target, or the amplitude of an upcoming saccade, or both. We recorded single unit activity in area LIP of two macaque monkeys. First, we determined for each neuron its preferred saccade direction. Then, monkeys performed visually guided saccades along the preferred direction towards either stationary or moving targets in pseudo-randomized order. LIP population activity allowed to decode both, the distance between fovea and saccade target as well as the size of an upcoming saccade. Previous work has shown comparable results for saccade direction (Graf and Andersen, 2014a, b. Hence, LIP population activity allows to predict any two-dimensional saccade vector. Functional equivalents of macaque area LIP have been identified in humans. Accordingly, our results provide further support for the concept of activity from area LIP as neural basis for the control of an oculomotor brain-machine interface.

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

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    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.

  1. Craniodental variation among Macaques (Macaca, nonhuman primates

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    Pan Ruliang

    2002-05-01

    Full Text Available Abstract Background In terms of structure and function, the skull is one of the most complicated organs in the body. It is also one of the most important parts in terms of developmental and evolutionary origins. This complexity makes it difficult to obtain evolutionary assessments if, as is usually the case with fossils, only part of the skull is available. For this reason this study involves a set of comparisons whereby the smallest functional units are studied first, and these built up, through a triple-nested hierarchical design, into more complex anatomical regions and eventually into the skull-as-a-whole. This design has been applied to macaques (Macaca in order to reveal patterns of variation at the different levels. The profiles of such variation have been obtained both within and between species. This has lead to a search for the skull parts that have undergone similar selection pressures during evolution and comparable development patterns in both ontogeny and phylogeny. Results Morphometric analysis (Principal Components was used to obtain these profiles of species and sex separations based on 77 cranial variables from 11 species of macaques. The results showed that 7 functional units could be aggregated into three functionally reasonable anatomical regions on the basis of similarities in profiles. These were: the masticatory apparatus containing mandible, lower teeth and upper teeth, the face as a whole combining maxilla (actually lower face and upper face, and the cranium as a whole involving cranium and calvaria. Twenty-six variables were finally selected for analyzing the morphology of the whole skull. This last showed an overall profile similar to that revealed in the masticatory apparatus but also contained additional information pertaining to individual species and species-groups separations. Conclusions The study provides a model for carrying out analysis of species separations and sex variation simultaneously. Through this

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

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    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.

  3. A potential aphrodisiac for female macaques.

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    Pertovaara, Antti; Linnankoski, Ilkka; Artchakov, Denis; Rämä, Pia; Carlson, Synnöve

    2004-09-01

    Earlier studies suggest that alpha2-adrenoceptor antagonists and dopamine receptor agonists may enhance sexual activity in human and nonhuman male primates. It is not known whether these compounds influence the sexual behavior of female primates. We determined whether the administration of a selective alpha2-adrenoceptor antagonist (atipamezole), a dopamine receptor agonist (apomorphine), or their combination to female Macaca arctoides (stumptail macaque) monkeys produces changes in sexual behavior of the female with a male. Following the administration of drugs to the female, the behavior of the female with a male stumptail was observed for 30 min. Atipamezole dose dependently (0.03-0.3 mg/kg im) increased short-time mounting behavior of the male and the total number of copulations. Apomorphine alone (0.125-0.25 mg/kg) or in combination with atipamezole had no significant effects on sexual behavior. The result indicates that a selective alpha2-adrenoceptor antagonist administered in the female stumptail increases sexual behavior of the male with the female. A plausible explanation for this finding is that a selective alpha2-adrenoceptor antagonist increases sexual arousal in female stumptails and this, possibly due to a change in psychosocial behavior of the female, triggers increased sexual activity in males.

  4. Retinotopy versus face selectivity in macaque visual cortex.

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    Rajimehr, Reza; Bilenko, Natalia Y; Vanduffel, Wim; Tootell, Roger B H

    2014-12-01

    Retinotopic organization is a ubiquitous property of lower-tier visual cortical areas in human and nonhuman primates. In macaque visual cortex, the retinotopic maps extend to higher-order areas in the ventral visual pathway, including area TEO in the inferior temporal (IT) cortex. Distinct regions within IT cortex are also selective to specific object categories such as faces. Here we tested the topographic relationship between retinotopic maps and face-selective patches in macaque visual cortex using high-resolution fMRI and retinotopic face stimuli. Distinct subregions within face-selective patches showed either (1) a coarse retinotopic map of eccentricity and polar angle, (2) a retinotopic bias to a specific location of visual field, or (3) nonretinotopic selectivity. In general, regions along the lateral convexity of IT cortex showed more overlap between retinotopic maps and face selectivity, compared with regions within the STS. Thus, face patches in macaques can be subdivided into smaller patches with distinguishable retinotopic properties.

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

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

    2015-02-01

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

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

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    Matthew T Aliota

    2016-12-01

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

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

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    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. © 2014 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  10. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

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

    2017-01-01

    Tuberculosis (TB) is a common opportunistic infection and the leading cause of death for human immunodeficiency virus (HIV)-infected patients. Thus, it is necessary to understand the pathogenetic interactions between M.tb and HIV infection. In this study, we examined M.tb and/or simian immunodeficiency virus (SIV) infection of Chinese rhesus macaques. While there was little evidence that M.tb enhanced SIV infection of macaques, SIV could facilitate M.tb infection as demonstrated by X-rays, pa...

  11. Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data

    Science.gov (United States)

    Peng, Xinxia; Pipes, Lenore; Xiong, Hao; Green, Richard R.; Jones, Daniel C.; Ruzzo, Walter L.; Schroth, Gary P.; Mason, Christopher E.; Palermo, Robert E.; Katze, Michael G.

    2014-01-01

    Background The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common nonhuman primate animal models, are limited. Methods We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. Results For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely ‘missing’ from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. Conclusions For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies. PMID:24810475

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

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    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.

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

    Science.gov (United States)

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

    2016-03-01

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

  14. Asynchronous onset of clinical disease in BSE-infected macaques.

    Science.gov (United States)

    Montag, Judith; Schulz-Schaeffer, Walter; Schrod, Annette; Hunsmann, Gerhard; Motzkus, Dirk

    2013-07-01

    To estimate the effect of the variability of prion disease onset on primary bovine spongiform encephalopathy transmission to humans, we studied 6 cynomolgus macaques. The preclinical incubation period was significantly prolonged in 2 animals, implying that onset of variant Creutzfeldt-Jacob disease in humans could be more diverse than previously expected.

  15. Surgical technique for allogeneic uterus transplantation in macaques

    Science.gov (United States)

    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

  16. Testosterone Correlates with Venezuelan Equine Encephalitis Virus in Macaques

    Science.gov (United States)

    2006-03-29

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

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

    Science.gov (United States)

    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…

  18. Evolutionary and biomedical insights from the rhesus macaque genome

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

  20. Experimental inoculation of juvenile rhesus macaques with primate enteric caliciviruses.

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    Karol Sestak

    Full Text Available BACKGROUND: Tissue culture-adapted Tulane virus (TV, a GI.1 rhesus enteric calicivirus (ReCV, and a mixture of GII.2 and GII.4 human norovirus (NoV-containing stool sample were used to intrastomacheally inoculate juvenile rhesus macaques (Macaca mulatta in order to evaluate infection caused by these viruses. METHODOLOGY & FINDINGS: Two of the three TV-inoculated macaques developed diarrhea, fever, virus-shedding in stools, inflammation of duodenum and 16-fold increase of TV-neutralizing (VN serum antibodies but no vomiting or viremia. No VN-antibody responses could be detected against a GI.2 ReCV strain FT285, suggesting that TV and FT285 represent different ReCV serotypes. Both NoV-inoculated macaques remained asymptomatic but with demonstrable virus shedding in one animal. Examination of duodenum biopsies of the TV-inoculated macaques showed lymphocytic infiltration of the lamina propria and villous blunting. TV antigen-positive (TV+ cells were detected in the lamina propria. In most of the TV+ cells TV co-localized perinuclearly with calnexin--an endoplasmic reticulum protein. A few CD20+TV+ double-positive B cells were also identified in duodenum. To corroborate the authenticity of CD20+TV+ B cells, in vitro cultures of peripheral blood mononuclear cells (PBMCs from healthy macaques were inoculated with TV. Multicolor flow cytometry confirmed the presence of TV antigen-containing B cells of predominantly CD20+HLA-DR+ phenotype. A 2-log increase of viral RNA by 6 days post inoculation (p<0.05 suggested active TV replication in cultured lymphocytes. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show that ReCVs represent an alternative cell culture and animal model to study enteric calicivirus replication, pathogenesis and immunity.

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

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

    2011-05-01

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

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

    Science.gov (United States)

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

    2005-10-01

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

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

    Science.gov (United States)

    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.

  4. Multimodal Advertisement of Pregnancy in Free-Ranging Female Japanese Macaques (Macaca fuscata.

    Directory of Open Access Journals (Sweden)

    Lucie Rigaill

    Full Text Available The role of multiple sexual signals in indicating the timing of female ovulation, and discrimination of this timing by males, has been particularly well studied among primates. However the exhibition of pregnancy signals, and how such signals might modulate male post-conception mating decisions, is still poorly understood. Here we aimed to determine if Japanese macaque males use changes in female sexual signals (behavioral, visual and auditory to discriminate pregnancy and adjust their socio-sexual behaviors. We combined behavioral observations, digital photography and endocrinological (progestogen and estrogen data, collected systematically during three one-month periods: the pre-conceptive period, the 1st month of pregnancy and the 2nd month of pregnancy. We analyzed variation in the probability of detecting male and female socio-sexual behaviors and estrus calls, as well as changes in female face color parameters, in relation to female reproductive state. Based on our focal observations, we found that males did not copulate during the pregnancy period, and that female socio-sexual behaviors generally decreased from the pre-conceptive to post-conceptive periods. Female face luminance decreased from the pre-conceptive month to the pregnancy period whereas face color only varied between the 1st and 2nd month of gestation. Our results suggest that Japanese macaque females display sexual cues of pregnancy that males might use to reduce energy wasted on non-reproductive copulations with pregnant females. We hypothesize that females advertize their pregnancy through changes in behavioral, visual and potential auditory signals that males can use to adjust their mating behaviors. We finish by discussing implications for male and female post-conception strategies.

  5. Multimodal Advertisement of Pregnancy in Free-Ranging Female Japanese Macaques (Macaca fuscata).

    Science.gov (United States)

    Rigaill, Lucie; MacIntosh, Andrew J J; Higham, James P; Winters, Sandra; Shimizu, Keiko; Mouri, Keiko; Furuichi, Takeshi; Garcia, Cécile

    2015-01-01

    The role of multiple sexual signals in indicating the timing of female ovulation, and discrimination of this timing by males, has been particularly well studied among primates. However the exhibition of pregnancy signals, and how such signals might modulate male post-conception mating decisions, is still poorly understood. Here we aimed to determine if Japanese macaque males use changes in female sexual signals (behavioral, visual and auditory) to discriminate pregnancy and adjust their socio-sexual behaviors. We combined behavioral observations, digital photography and endocrinological (progestogen and estrogen) data, collected systematically during three one-month periods: the pre-conceptive period, the 1st month of pregnancy and the 2nd month of pregnancy. We analyzed variation in the probability of detecting male and female socio-sexual behaviors and estrus calls, as well as changes in female face color parameters, in relation to female reproductive state. Based on our focal observations, we found that males did not copulate during the pregnancy period, and that female socio-sexual behaviors generally decreased from the pre-conceptive to post-conceptive periods. Female face luminance decreased from the pre-conceptive month to the pregnancy period whereas face color only varied between the 1st and 2nd month of gestation. Our results suggest that Japanese macaque females display sexual cues of pregnancy that males might use to reduce energy wasted on non-reproductive copulations with pregnant females. We hypothesize that females advertize their pregnancy through changes in behavioral, visual and potential auditory signals that males can use to adjust their mating behaviors. We finish by discussing implications for male and female post-conception strategies.

  6. Increased neuronal firing in resting and sleep in areas of the macaque medial prefrontal cortex.

    Science.gov (United States)

    Gabbott, Paul L; Rolls, Edmund T

    2013-06-01

    The medial prefrontal cortex (mPFC) of humans and macaques is an integral part of the default mode network and is a brain region that shows increased activation in the resting state. A previous paper from our laboratory reported significantly increased firing rates of neurons in the macaque subgenual cingulate cortex, Brodmann area (BA) 25, during disengagement from a task and also during slow wave sleep [E.T. Rolls et al. (2003) J. Neurophysiology, 90, 134-142]. Here we report the finding that there are neurons in other areas of mPFC that also increase their firing rates during disengagement from a task, drowsiness and eye-closure. During the neurophysiological recording of single mPFC cells (n = 249) in BAs 9, 10, 13 m, 14c, 24b and especially pregenual area 32, populations of neurons were identified whose firing rates altered significantly with eye-closure compared with eye-opening. Three types of neuron were identified: Type 1 cells (28.1% of the total population) significantly increased (mean + 329%; P ≪ 0.01) their average firing rate with eye-closure, from 3.1 spikes/s when awake to 10.2 spikes/s when asleep; Type 2 cells (6.0%) significantly decreased (mean -68%; P areas of mPFC, implicated in the anterior default mode network, there is a substantial population of neurons that significantly increase their firing rates during periods of eye-closure. Such neurons may be part of an interconnected network of distributed brain regions that are more active during periods of relaxed wakefulness than during attention-demanding tasks. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  7. Establishing the reliability of rhesus macaque social network assessment from video observations.

    Science.gov (United States)

    Feczko, Eric; Mitchell, Thomas A J; Walum, Hasse; Brooks, Jenna M; Heitz, Thomas R; Young, Larry J; Parr, Lisa A

    2015-09-01

    Understanding the properties of a social environment is important for understanding the dynamics of social relationships. Understanding such dynamics is relevant for multiple fields, ranging from animal behaviour to social and cognitive neuroscience. To quantify social environment properties, recent studies have incorporated social network analysis. Social network analysis quantifies both the global and local properties of a social environment, such as social network efficiency and the roles played by specific individuals, respectively. Despite the plethora of studies incorporating social network analysis, methods to determine the amount of data necessary to derive reliable social networks are still being developed. Determining the amount of data necessary for a reliable network is critical for measuring changes in the social environment, for example following an experimental manipulation, and therefore may be critical for using social network analysis to statistically assess social behaviour. In this paper, we extend methods for measuring error in acquired data and for determining the amount of data necessary to generate reliable social networks. We derived social networks from a group of 10 male rhesus macaques, Macaca mulatta, for three behaviours: spatial proximity, grooming and mounting. Behaviours were coded using a video observation technique, where video cameras recorded the compound where the 10 macaques resided. We collected, coded and used 10 h of video data to construct these networks. Using the methods described here, we found in our data that 1 h of spatial proximity observations produced reliable social networks. However, this may not be true for other studies due to differences in data acquisition. Our results have broad implications for measuring and predicting the amount of error in any social network, regardless of species.

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

    Science.gov (United States)

    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

  9. Testosterone correlates with Venezuelan equine encephalitis virus infection in macaques

    Directory of Open Access Journals (Sweden)

    Koterski James

    2006-03-01

    Full Text Available Abstract Here we briefly report testosterone and cytokine responses to Venezuelan equine encephalitis virus (VEEV in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

  10. Chronic lymphocytic thyroiditis in a cynomolgus macaque (Macaca fascicularis).

    Science.gov (United States)

    Guzman, Roberto E; Radi, Zaher A

    2007-02-01

    Chronic lymphocytic thyroiditis characterized by multifocal follicular lymphoid cell infiltrates with germinal centers, thyroid acinar atrophy and pituitary cell hyperplasia/hypertrophy of the adenohypophysis was detected in a vehicle control, 4-year-old female Cynomolgus macaque in a routine toxicology study. Lymphoid cells of germinal centers were positive for the B-cell marker CD20 by immunohistochemistry (IHC), while remaining lymphocytes were positive for the T-cell marker CD3. Hypertrophied/hyperplastic pituitary cells were positive for thyroid stimulating hormone (TSH) by IHC, consistent with an adaptive response due to removal of hormonal negative feedback from the diseased thyroid gland. Features of this case are similar to chronic lymphocytic thyroiditis in humans, an autoimmune disorder also known as Hashimoto's disease. Chronic lymphocytic thyroiditis with compensatory pituitary changes may occur spontaneously in young, clinically normal cynomolgus macaques and its presence in drug treated animals should be interpreted with caution.

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

    Science.gov (United States)

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

    2007-04-13

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

  12. The human homologue of macaque area V6A.

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Richard McFarland

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

  14. Intersegmental Coordination in the Kinematics of Prehension Movements of Macaques

    Science.gov (United States)

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

    2015-01-01

    The most popular model to explain how prehensile movements are organized assumes that they comprise two “components”, the reaching component encoding information regarding the object’s spatial location and the grasping component encoding information on the object’s intrinsic properties such as size and shape. Comparative kinematic studies on grasping behavior in the humans and in macaques have been carried out to investigate the similarities and differences existing across the two species. Although these studies seem to favor the hypothesis that macaques and humans share a number of kinematic features it remains unclear how the reaching and grasping components are coordinated during prehension movements in free-ranging macaque monkeys. Twelve hours of video footage was filmed of the monkeys as they snatched food items from one another (i.e., snatching) or collect them in the absence of competitors (i.e., unconstrained). The video samples were analyzed frame-by-frame using digitization techniques developed to perform two-dimensional post-hoc kinematic analyses of the two types of actions. The results indicate that only for the snatching condition when the reaching variability increased there was an increase in the amplitude of maximum grip aperture. Besides, the start of a break-point along the deceleration phase of the velocity profile correlated with the time at which maximum grip aperture occurred. These findings suggest that macaques can spatially and temporally couple the reaching and the grasping components when there is pressure to act quickly. They offer a substantial contribution to the debate about the nature of how prehensile actions are programmed. PMID:26176232

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

    2007-01-01

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

  17. Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis)

    Science.gov (United States)

    Laffins, Michael M; Mellal, Nacera; Almlie, Cynthia L; Regalia, Douglas E

    2017-01-01

    Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations. Infrared measurements were taken 5 cm from the chest and inguinal areas. We evaluated 10 (9 functional devices) sedated cynomolgus macaques (5 male, 5 female) implanted with telemetry units in a muscular pouch between the internal and external abdominal oblique muscles. We determined that the mean body temperature acquired by using telemetry did not differ from either the mean of inguinal and chest infrared measurements but did differ from the mean of temperature obtained rectally. In addition, the mean rectal temperature differed from the mean of the inguinal reading but not the mean of the chest temperature. The results confirm our hypothesis that the infrared thermometer can be used to replace standard rectal thermometry. PMID:28905720

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

    Science.gov (United States)

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

    2013-11-27

    Artificial grammars (AG) are designed to emulate aspects of the structure of language, and AG learning (AGL) paradigms can be used to study the extent of nonhuman animals' structure-learning capabilities. However, different AG structures have been used with nonhuman animals and are difficult to compare across studies and species. We developed a simple quantitative parameter space, which we used to summarize previous nonhuman animal AGL results. This was used to highlight an under-studied AG with a forward-branching structure, designed to model certain aspects of the nondeterministic nature of word transitions in natural language and animal song. We tested whether two monkey species could learn aspects of this auditory AG. After habituating the monkeys to the AG, analysis of video recordings showed that common marmosets (New World monkeys) differentiated between well formed, correct testing sequences and those violating the AG structure based primarily on simple learning strategies. By comparison, Rhesus macaques (Old World monkeys) showed evidence for deeper levels of AGL. A novel eye-tracking approach confirmed this result in the macaques and demonstrated evidence for more complex AGL. This study provides evidence for a previously unknown level of AGL complexity in Old World monkeys that seems less evident in New World monkeys, which are more distant evolutionary relatives to humans. The findings allow for the development of both marmosets and macaques as neurobiological model systems to study different aspects of AGL at the neuronal level.

  19. Acquisition and functional consequences of social knowledge in macaques.

    Science.gov (United States)

    Tiddi, Barbara; di Sorrentino, Eugenia Polizzi; Fischer, Julia; Schino, Gabriele

    2017-02-01

    To manoeuvre in complex societies, it is beneficial to acquire knowledge about the social relationships existing among group mates, so as to better predict their behaviour. Although such knowledge has been firmly established in a variety of animal taxa, how animals acquire such knowledge, as well as its functional significance, remains poorly understood. In order to understand how primates acquire and use their social knowledge, we studied kin-biased redirected aggression in Japanese macaques (Macaca fuscata) relying on a large database of over 15 000 aggressive episodes. Confirming previous research, macaques redirected aggression preferentially to the kin of their aggressor. An analysis that controlled for the rate of affiliation between aggressors and targets of redirection showed that macaques identified the relatives of group mates on the basis of the frequency of their ongoing associations. By contrast, having observed group mates interact with their mother as infants did not increase the monkeys' success in correctly identifying kin relationships among third parties. Inter-individual variation in the successful identification of the kin of aggressors and in redirecting aggression accordingly translated into differences in the amount of aggression received, highlighting a selective advantage for those individuals that were better able to acquire and use social knowledge.

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Michael Valentine

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

  2. Age, but not anthelmintic treatment, is associated with urinary neopterin levels in semi-free ranging Barbary macaques

    Science.gov (United States)

    Müller, Nadine; Heistermann, Michael; Strube, Christina; Schülke, Oliver; Ostner, Julia

    2017-01-01

    Studying host parasite interactions and their implications for evolution and ecology recently received increasing attention, particularly with regard to host physiology and immunity. Here we assess variation of urinary neopterin (uNEO), a marker of cellular immune activation and iummunosenescence, in response to age and anthelmintic treatment in semi-free ranging Barbary macaques (Macaca sylvanus). Urinary NEO levels were measured via enzyme-immunoassay from 179 urine samples of 43 individuals between 5–29 years of age. Efficiency of treatment was assessed by Mc Master flotation on repeated faecal samples, including 18 untreated individuals as control group. We used linear mixed models with age and parasite status as main effects, controlling for sex and physical condition, assessed through urinary C-Peptide-levels, with social group and ID as random factors. Urinary NEO levels significantly increased with age, suggesting that changes in aging Barbary macaque immune responses are consistent with immunosenescence described in human and nonhuman primates and can be detected via uNEO measurements. Anthelmintic treatment, however, had no influence on uNEO levels, potentially due to quick reinfections or attenuated immune responses in repeated infections. We conclude that uNEO is a potential non-invasive marker for immune function and particularly immunosenescence in wildlife. PMID:28155915

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

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  7. Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Kai-tao Hu

    2015-04-01

    Conclusions: Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  9. High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus

    Science.gov (United States)

    Nalca, Aysegul; Rossi, Franco D.; Miller, Lynn J.; Wiley, Michael R.; Perez-Sautu, Unai; Washington, Samuel C.; Norris, Sarah L.; Wollen-Roberts, Suzanne E.; Shamblin, Joshua D.; Kimmel, Adrienne E.; Bloomfield, Holly A.; Valdez, Stephanie M.; Sprague, Thomas R.; Principe, Lucia M.; Bellanca, Stephanie A.; Cinkovich, Stephanie S.; Lugo-Roman, Luis; Cazares, Lisa H.; Pratt, William D.; Palacios, Gustavo F.; Bavari, Sina; Pitt, M. Louise; Nasar, Farooq

    2017-01-01

    Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present. PMID:28548637

  10. Tenofovir disoproxil fumarate intravaginal ring protects high-dose depot medroxyprogesterone acetate-treated macaques from multiple SHIV exposures.

    Science.gov (United States)

    Smith, James M; Srinivasan, Priya; Teller, Ryan S; Lo, Yungtai; Dinh, Chuong T; Kiser, Patrick F; Herold, Betsy C

    2015-01-01

    Preclinical HIV prevention models use either a single high-dose viral challenge in depot medroxyprogesterone acetate-treated macaques or repeated viral challenges in cycling macaques. We tested the efficacy of an intravaginal tenofovir disoproxil fumarate (TDF) ring in a model combining repeated 30-mg injections of depot medroxyprogesterone acetate every 6 weeks with vaginal viral challenges weekly for 12 weeks. Twelve macaques were randomized to TDF or placebo rings. All placebo macaques became infected after a median of 2 exposures, whereas only 1 TDF macaque became infected at the eighth exposure (P = 0.0012). The TDF ring provides durable protection in a stringent challenge model.

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

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

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

  12. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques

    Science.gov (United States)

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

    2017-01-01

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

  13. SIV Infection Facilitates Mycobacterium tuberculosis Infection of Rhesus Macaques.

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nami Suzuki-Hashido

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  16. Focused-ultrasound termination of an early pregnancy in rhesus macaques (Macaca mulatta): a pilot study.

    Science.gov (United States)

    Du, Yong-Hong; Zou, Jian-Zhong; Bai, Jin; Zhan, Yang; Wu, Feng; Wang, Zhi-Biao

    2012-12-01

    We explored the effectiveness, safety, and feasibility of focused ultrasound in terminating undesired pregnancy. A high-intensity focused ultrasound therapeutic unit was employed to terminate early pregnancies in rhesus macaques. B-mode ultrasound incorporated within the system was used to locate and study the gestational sacs of 6 rhesus macaques with gestation ages of 37 to 66 days, and varying modes of ultrasound exposure were adopted in the termination of the early pregnancies of the rhesus macaques. After focused ultrasound exposure, B-mode ultrasound of the gestational sacs showed significant lethal changes. Of the 6 rhesus macaques, 5 underwent complete abortions whereas 1 rhesus macaque underwent an incomplete abortion. The rhesus macaques resumed their menstrual cycles 50 days after focused-ultrasound treatment. The results suggested that focused ultrasound could be safe, feasible, and effective in terminating early pregnancies in rhesus macaques. As a novel physical method, it may be a promising ablation for a potentially clinical application. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  17. The enigmatic Arunachal macaque: its biogeography, biology and taxonomy in Northeastern India.

    Science.gov (United States)

    Biswas, Jihosuo; Borah, Dhiraj K; Das, Abhijit; Das, Jayanta; Bhattacharjee, P C; Mohnot, S M; Horwich, Robert H

    2011-05-01

    The purpose of this study was to determine the taxonomic status of an unidentified enigmatic macaque seen by scientists since the late 1990s in Arunachal Pradesh, India. We surveyed 49 troops of enigmatic macaques in four districts of Arunachal Pradesh. The population studied is from the macaque sinica-group as defined by the reproductive organs. The main species-separating trait in the sinica-group is tail length to head and body length ratio that decreases with latitude and elevation. We gathered data on morphology, pelage descriptions, tail to head and body ratios and tail to hind foot ratios from photos and live animals (43 individuals from 36 areas) within the range of and between the two subspecies of the Assamese macaque (Macaca assamensis). We compared the data to six western Assamese macaques and studies of Assamese macaques and related species. We found great variability in tail length, pelage color, facial skin color, and facial and hair patterns. The tail/head-body and tail/foot ratios, although varied, supported the hypothesis that these enigmatic forms were part of a population of Assamese macaques found in the gap between the two subspecies ranges and were not a new species as described earlier. Instead, we found evidence that darker pelage, larger body size, and shorter tails occur at higher elevations and latitudes similar to the general trend in the sinica-group's adaptations to colder climates. Thus, the population may be important for its variation, throwing light on the speciation process and how the northern species of Tibetan macaques evolved from an ancestor similar to the Assamese macaques as adaptations to a colder climate. © 2011 Wiley-Liss, Inc.

  18. Modelling Niche Differentiation of Co-Existing, Elusive and Morphologically Similar Species: A Case Study of Four Macaque Species in Nakai-Nam Theun National Protected Area, Laos

    Directory of Open Access Journals (Sweden)

    Camille N. Z. Coudrat

    2013-01-01

    Full Text Available Species misidentification often occurs when dealing with co-existing and morphologically similar species such as macaques, making the study of their ecology challenging. To overcome this issue, we use reliable occurrence data from camera-trap images and transect survey data to model their respective ecological niche and potential distribution locally in Nakai-Nam Theun National Protected Area (NNT NPA, central-Eastern Laos. We investigate niche differentiation of morphologically similar species using four sympatric macaque species in NNT NPA, as our model species: rhesus Macaca mulatta (Taxonomic Serial Number, TSN 180099, Northern pig-tailed M. leonina (TSN not listed; Assamese M. assamensis (TSN 573018 and stump-tailed M. arctoides (TSN 573017. We examine the implications for their conservation. We obtained occurrence data of macaque species from systematic 2006–2011 camera-trapping surveys and 2011–2012 transect surveys and model their niche and potential distribution with MaxEnt software using 25 environmental and topographic variables. The respective suitable habitat predicted for each species reveals niche segregation between the four species with a gradual geographical distribution following an environmental gradient within the study area. Camera-trapping positioned at many locations can increase elusive-species records with a relatively reduced and more systematic sampling effort and provide reliable species occurrence data. These can be used for environmental niche modelling to study niche segregation of morphologically similar species in areas where their distribution remains uncertain. Examining unresolved species' niches and potential distributions can have crucial implications for future research and species' management and conservation even in the most remote regions and for the least-known species.

  19. Modelling Niche Differentiation of Co-Existing, Elusive and Morphologically Similar Species: A Case Study of Four Macaque Species in Nakai-Nam Theun National Protected Area, Laos.

    Science.gov (United States)

    Coudrat, Camille N Z; Nekaris, K Anne-Isola

    2013-01-30

    Species misidentification often occurs when dealing with co-existing and morphologically similar species such as macaques, making the study of their ecology challenging. To overcome this issue, we use reliable occurrence data from camera-trap images and transect survey data to model their respective ecological niche and potential distribution locally in Nakai-Nam Theun National Protected Area (NNT NPA), central-Eastern Laos. We investigate niche differentiation of morphologically similar species using four sympatric macaque species in NNT NPA, as our model species: rhesus Macaca mulatta (Taxonomic Serial Number, TSN 180099), Northern pig-tailed M. leonina (TSN not listed); Assamese M. assamensis (TSN 573018) and stump-tailed M. arctoides (TSN 573017). We examine the implications for their conservation. We obtained occurrence data of macaque species from systematic 2006-2011 camera-trapping surveys and 2011-2012 transect surveys and model their niche and potential distribution with MaxEnt software using 25 environmental and topographic variables. The respective suitable habitat predicted for each species reveals niche segregation between the four species with a gradual geographical distribution following an environmental gradient within the study area. Camera-trapping positioned at many locations can increase elusive-species records with a relatively reduced and more systematic sampling effort and provide reliable species occurrence data. These can be used for environmental niche modelling to study niche segregation of morphologically similar species in areas where their distribution remains uncertain. Examining unresolved species' niches and potential distributions can have crucial implications for future research and species' management and conservation even in the most remote regions and for the least-known species.

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

    Science.gov (United States)

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

    2012-01-17

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

  1. Testosterone increases circulating dehydroepiandrosterone sulfate levels in the male rhesus macaque

    Directory of Open Access Journals (Sweden)

    Krystina eSorwell

    2014-06-01

    Full Text Available The adrenal steroid dehydroepiandrosterone (DHEA and its sulfate (DHEAS are two of the most abundant hormones in the human circulation. Furthermore, they are released in a circadian pattern and show a marked age-associated decline. Adult levels of DHEA and DHEAS are significantly higher in males than in females, but the reason for this sexual dimorphism is unclear. In the present study, we administered supplementary androgens (DHEA, testosterone and 5α-dihydrotestosterone [DHT] to aged male rhesus macaques (Macaca mulatta. While this paradigm increased circulating DHEAS immediately after DHEA administration, an increase was also observed following either testosterone or DHT administration, resulting in hormonal profile resembling levels observed in young males in terms of both amplitude and circadian pattern. This stimulatory effect was limited to DHEAS, as an increase in circulating cortisol was not observed. Taken together, these data demonstrate an influence of the hypothalamo-pituitary-testicular axis on adrenal function in males, possibly by sensitizing the zona reticularis to the stimulating action of adrenocorticopic hormone. This represents a plausible mechanism to explain sex differences in circulating DHEA and DHEAS levels, and may have important implications in the development of hormone therapies designed for elderly men and women.

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

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    Rong Bao

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

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

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    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.

  4. Grooming reciprocity in female tibetan macaques macaca thibetana.

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    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.

  5. Risk factors for dystocia in pigtailed macaques (Macaca nemestrina).

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    Stockinger, Diane E; Torrence, Anne E; Hukkanen, Renee R; Vogel, Keith W; Hotchkiss, Charlotte E; Ha, James C

    2011-04-01

    Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources.

  6. Function and innervation of the locus ceruleus in a macaque model of Functional Hypothalamic Amenorrhea.

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    Bethea, Cynthia L; Kim, Aaron; Cameron, Judy L

    2013-02-01

    A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afterwards, the animals were rested until normal menstrual cycles resumed and then euthanized on day 5 of a new menstrual cycle [a] in the absence of further stress; or [b] after 5 days of resumed psychosocial and metabolic stress. In this study, parameters of the LC were examined in HSR and SS animals in the presence and absence of stress (2×2 block design) using ICC and image analysis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the synthesis of catecholamines; and the TH level was used to assess by inference, NE output. The pixel area of TH-positive dendrites extending outside the medial border of the LC was significantly increased by stress to a similar degree in both HSR and SS animals (p<0.0001). There is a significant CRF innervation of the LC. The positive pixel area of CRF boutons, lateral to the LC, was higher in SS than HSR animals in the absence of stress. Five days of moderate stress significantly increased the CRF-positive bouton pixel area in the HSR group (p<0.02), but not in the SS group. There is also a significant serotonin innervation of the LC. A marked increase in medial serotonin dendrite swelling and beading was observed in the SS+stress group, which may be a consequence of excitotoxicity. The dendrite beading interfered with analysis of axonal boutons. However, at one anatomical level, the serotonin-positive bouton area was obtained between the LC and the superior cerebellar peduncle. Serotonin-positive bouton pixel area was significantly

  7. CYP1B1 is polymorphic in cynomolgus and rhesus macaques.

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    Uno, Yasuhiro; Matsushita, Akinori; Yamazaki, Hiroshi

    2011-09-01

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

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

    Science.gov (United States)

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

    2011-06-01

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

  9. Influence of Early Pregnancy Termination by Focused Ultrasound Beams on Menstrual Recovery of Macaques

    Institute of Scientific and Technical Information of China (English)

    Yong-hong DU; Zheng-ai XIONG; Jian-zhong ZOU; Yi TAN; Jin BAI; Zhi-biao WANG

    2004-01-01

    Objective To explore the effects on macaques' menstrual recovery after terminating early pregnancy by focused ultrasound beams (FUB)Methods FUB was used to terminate early pregnancy in 5 macaques with gestation duration ranging from 37-66 d. Two circles after the recovery of menstruation, color Doppler flow imaging (CDFI) and magnetic resonance imaging (MRI) were used to estimate the shape, size and blood flow of uterus, and pathological examinations were performed to check against any lesions to uterine endometrium and ovary.Results Forty days after FUB abortion, menstruation recovered and the volume and duration of each macaque's menstruation were not changed compared with those before gestation. CDFI and MRI suggested that the siz.e and shape of uterus were normal.The endometrial line was clear and no lesions were found in adjacent organs.Conclusion FUB termination of early pregnancy in macaques did not damage their ovarian tissue and had no influence on subsequent menstrual recovery.

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

    Science.gov (United States)

    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

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

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    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.

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

    Science.gov (United States)

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

    1988-04-15

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

  13. Release of DEFB126 from macaque sperm and completion of capacitation are triggered by conditions that simulate periovulatory oviductal fluid.

    Science.gov (United States)

    Tollner, Theodore L; Vandevoort, Catherine A; Yudin, Ashley I; Treece, Cathy A; Overstreet, James W; Cherr, Gary N

    2009-05-01

    Capacitation of macaque sperm in vitro has been achieved efficiently only with the addition of both cyclic nucleotides and methylxanthines. The use of these exogenous sperm activators clouds an understanding of the normal mechanisms underlying capacitation and may slow early embryo development following in vitro fertilization (IVF). We demonstrate that culture medium which simulates periovulatory oviductal fluid with respect to bicarbonate (HCO(3)(-)) and glucose concentration induces capacitation in a high percentage of macaque sperm as determined by the ability of sperm to undergo both the release of coating protein DEFB126 and the zona pellucida-induced acrosome reaction (AR). Few sperm were able to undergo the AR following 6 hr incubation in medium containing either 35 mM HCO(3)(-) (approximately 7.2 pH) or 90 mM HCO(3)(-) (approximately pH 7.8) with 5 mM glucose. When glucose concentration was lowered to 0.5 mM to match levels reported for women at midcycle, the AR rate increased significantly in sperm incubated in both levels of HCO(3)(-), indicating that glucose interferes with sperm responsiveness to increasing HCO(3)(-) concentration observed in the primate oviduct during ovulation. Even greater synchronization of capacitation could be achieved with nonphysiologic extremes of alkalinity or energy substrate deprivation. In the latter case, sperm achieved high rates of IVF. A shift in pH from 7.2 to 7.8 in a HEPES-buffered medium was sufficient to remove DEFB126 from the surface of most sperm after only 3 hr. The loss of DEFB126 from sperm under periovulaory fluid conditions has implications for the timing of release of sperm from the oviductal reservoir.

  14. Alcohol-induced neuroapoptosis in the fetal macaque brain.

    Science.gov (United States)

    Farber, Nuri B; Creeley, Catherine E; Olney, John W

    2010-10-01

    The ability of brief exposure to alcohol to cause widespread neuroapoptosis in the developing rodent brain and subsequent long-term neurocognitive deficits has been proposed as a mechanism underlying the neurobehavioral deficits seen in fetal alcohol spectrum disorder (FASD). It is unknown whether brief exposure to alcohol causes apoptosis in the fetal primate brain. Pregnant fascicularis macaques at various stages of gestation (G105 to G155) were exposed to alcohol for 8h, then the fetuses were delivered by caesarean section and their brains perfused with fixative and evaluated for apoptosis. Compared to saline control brains, the ethanol-exposed brains displayed a pattern of neuroapoptosis that was widespread and similar to that caused by alcohol in infant rodent brain. The observed increase in apoptosis was on the order of 60-fold. We propose that the apoptogenic action of alcohol could explain many of the neuropathological changes and long-term neuropsychiatric disturbances associated with human FASD.

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

    Institute of Scientific and Technical Information of China (English)

    Wang Qing-Yun; Murks Aleksandra; Perc Matja(z); Lu Qi-Shao

    2011-01-01

    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 synchroization 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 be different but fixed coupling strengths, thus indicating a new role for information transmission delays in realistic neuronal networks.

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

    Science.gov (United States)

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

    2014-04-02

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    Science.gov (United States)

    Blomquist, Gregory E

    2009-03-01

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

  1. Decoding of visual attention from LFP signals of macaque MT.

    Science.gov (United States)

    Esghaei, Moein; Daliri, Mohammad Reza

    2014-01-01

    The local field potential (LFP) has recently been widely used in brain computer interfaces (BCI). Here we used power of LFP recorded from area MT of a macaque monkey to decode where the animal covertly attended. Support vector machines (SVM) were used to learn the pattern of power at different frequencies for attention to two possible positions. We found that LFP power at both low (<9 Hz) and high (31-120 Hz) frequencies contains sufficient information to decode the focus of attention. Highest decoding performance was found for gamma frequencies (31-120 Hz) and reached 82%. In contrast low frequencies (<9 Hz) could help the classifier reach a higher decoding performance with a smaller amount of training data. Consequently, we suggest that low frequency LFP can provide fast but coarse information regarding the focus of attention, while higher frequencies of the LFP deliver more accurate but less timely information about the focus of attention.

  2. Decoding of visual attention from LFP signals of macaque MT.

    Directory of Open Access Journals (Sweden)

    Moein Esghaei

    Full Text Available The local field potential (LFP has recently been widely used in brain computer interfaces (BCI. Here we used power of LFP recorded from area MT of a macaque monkey to decode where the animal covertly attended. Support vector machines (SVM were used to learn the pattern of power at different frequencies for attention to two possible positions. We found that LFP power at both low (<9 Hz and high (31-120 Hz frequencies contains sufficient information to decode the focus of attention. Highest decoding performance was found for gamma frequencies (31-120 Hz and reached 82%. In contrast low frequencies (<9 Hz could help the classifier reach a higher decoding performance with a smaller amount of training data. Consequently, we suggest that low frequency LFP can provide fast but coarse information regarding the focus of attention, while higher frequencies of the LFP deliver more accurate but less timely information about the focus of attention.

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

    Science.gov (United States)

    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.

  4. Development of a Zika Virus Infection Model in Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Fusataka Koide

    2016-12-01

    Full Text Available Limited availability of Indian rhesus macaques (IRM is a bottleneck to study Zika virus (ZIKV pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM model for ZIKV infection. In brief, six MCMs (seronegative for dengue and ZIKV were subdivided into 3 cohorts with a male and female each and challenged with different doses of Asian PRVABC59 (Puerto Rico or FSS13025 (Cambodia or African (IBH30656 lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva and urine and tissues (testes and brain were assessed for viral load by quantitative RT-PCR and neutralizing antibodies (Nab by 50% Plaque Reduction Neutralization Test (PRNT50 at various times post infection (p.i. PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2 to 3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 ×103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.

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

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    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.

  6. Plasmodium knowlesi: reservoir hosts and tracking the emergence in humans and macaques.

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    Kim-Sung Lee

    2011-04-01

    Full Text Available 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.

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

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

    2014-11-01

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

  8. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

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    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  9. Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

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    J Gerardo García-Lerma

    2008-02-01

    Full Text Available BACKGROUND: In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. METHODS AND FINDINGS: We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. CONCLUSIONS: This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising Pr

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

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    Kienesberger, Sabine; Perez-Perez, Guillermo I; Rivera-Correa, Juan L; Tosado-Acevedo, Rafael; Li, Huilin; Dubois, Andre; Gonzalez-Martinez, Janis A; Dominguez-Bello, Maria Gloria; Blaser, Martin J

    2012-08-24

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

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

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    Kienesberger Sabine

    2012-08-01

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

  12. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  13. Characterization of SIV in the Oral Cavity and in Vitro Inhibition of SIV by Rhesus Macaque Saliva

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    Thomas, Jessica S.; Lacour, Nedra; Kozlowski, Pamela A.; Nelson, Steve; Bagby, Gregory J.

    2010-01-01

    Abstract Human immunodeficiency virus (HIV) infections are rarely acquired via an oral route in adults. Previous studies have shown that human whole saliva inhibits HIV infection in vitro, and multiple factors present in human saliva have been shown to contribute to this antiviral activity. Despite the widespread use of simian immunodeficiency virus (SIV)-infected rhesus macaques as models for HIV pathogenesis and transmission, few studies have monitored SIV in the oral cavity of infected rhesus macaques and evaluated the viral inhibitory capacity of macaque saliva. Utilizing a cohort of rhesus macaques infected with SIVMac251, we monitored virus levels and genotypic diversity in the saliva throughout the course of the disease; findings were similar to previous observations in HIV-infected humans. An in vitro infectivity assay was utilized to measure inhibition of HIV/SIV infection by normal human and rhesus macaque whole saliva. Both human and macaque saliva were capable of inhibiting HIV and SIV infection. The inhibitory capacity of saliva samples collected from a cohort of animals postinfection with SIV increased over the course of disease, coincident with the development of SIV-specific antibodies in the saliva. These findings suggest that both innate and adaptive factors contribute to inhibition of SIV by whole macaque saliva. This work also demonstrates that SIV-infected rhesus macaques provide a relevant model to examine the innate and adaptive immune responses that inhibit HIV/SIV in the oral cavity. PMID:20672998

  14. Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

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    Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

    2017-02-18

    There are substantial differences across species in the organisation and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration 'thin' spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the expression of Kv3.1b in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labelled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. This article is protected by copyright. All rights reserved.

  15. Possible shift in macaque trophic level following a century of biodiversity loss in Singapore.

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    Gibson, Luke

    2011-07-01

    Biodiversity loss in tropical forests is a major problem in conservation biology, and nowhere is this more dire than in Southeast Asia. Deforestation and the associated loss of species may trigger shifts in habitat and feeding preferences of persisting species. In this study, I compared the habitat use and diet of long-tailed macaque (Macaca fascicularis) populations in Singapore from two time periods: museum specimens originally collected between 1893 and 1944, and living macaques sampled in 2009. I collected hair and used stable carbon and nitrogen isotope analysis to identify temporal changes in dietary source and trophic position, respectively. δ(13)C ratios were virtually identical, suggesting that macaques foraged in similar habitats during both time periods. However, δ(15)N ratios decreased considerably over time, suggesting that macaques today feed at a lower trophic level than previously. This decline in trophic level may be because of the disappearance or decline of other species that compete with macaques for fruit. This study highlights the effect of biodiversity loss on persisting species in degraded habitats of Southeast Asia, and improves our understanding of how species will adapt to further human-driven changes in tropical forest habitats.

  16. Allele frequency of antiretroviral host factor TRIMCyp in wild-caught cynomolgus macaques (Macaca fascicularis)

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    Saito, Akatsuki; Kawamoto, Yoshi; Higashino, Atsunori; Yoshida, Tomoyuki; Ikoma, Tomoko; Suzaki, Yuriko; Ami, Yasushi; Shioda, Tatsuo; Nakayama, Emi E.; Akari, Hirofumi

    2012-01-01

    A recent study showed that the frequency of an antiretroviral factor TRIM5 gene-derived isoform, TRIMCyp, in cynomolgus macaques (Macaca fascicularis) varies widely according to the particular habitat examined. However, whether the findings actually reflect the prevalence of TRIMCyp in wild cynomolgus macaques is still uncertain because the previous data were obtained with captive monkeys in breeding and rearing facilities. Here, we characterized the TRIM5 gene in cynomolgus macaques captured in the wild, and found that the frequency of the TRIMCyp allele was comparable to those in captive monkeys. This suggests that the previous results with captive monkeys do indeed reflect the natural allele frequency and that breeding and rearing facilities may not affect the frequency of TRIM5 alleles. Interestingly, the prevalence of a minor haplotype of TRIMCyp in wild macaques from the Philippines was significantly lower than in captive ones, suggesting that it is advantageous for wild monkeys to possess the major haplotype of TRIMCyp. Overall, our results add to our understanding of the geographic and genetic prevalence of cynomolgus macaque TRIMCyp. PMID:22969754

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

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    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. © 2015. Published by The Company of Biologists Ltd.

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

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    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.

  19. Variation in intergroup encounters among two provisioned free-ranging populations of Japanese macaques Macaca fuscata

    Institute of Scientific and Technical Information of China (English)

    Peng ZHANG; Kunio WATANABE

    2012-01-01

    Typically,Japanese macaques are thought to avoid encountering other groups wherever possible.Intergroup relations between macaques on Shodoshima Island,however,appear exceptional.We show that neighboring groups of Shodoshima monkeys spent 32.8% of their active time in proximity to (<100 m) and even foraged simultaneously at the same provisioning site with another group.The average duration and rate of intergroup encounters at Shodoshima (59.8 min,0.33 times/hour,n=269)were approximately ten times longer and 16.5 times more frequent than those at Jigokudani (6.1 min,0.02 times/hour,n=14).Since both populations have similar provisioning and ecological conditions,such variation cannot be explained by the socioecology model alone.Compared with other populations of Japanese macaques,intergroup relations of Shodoshima monkeys are also characterized by more frequent neutral encounters,less frequent agonistic encounters,more frequent unsuccessful displacement,a lower intensity of aggression,and more frequent counter-aggression between groups.These characteristics suggest that intergroup relationships on Shodoshima Island are more tolerant than those in other Japanese macaque populations.This study reveals considerable differences in intergroup encounters within local populations of Japanese macaques living in similar environments,and emphasizes the role of social factors in such intra-specific variation.

  20. Effects of age and sex on the hematology and blood chemistry of Tibetan macaques (Macaca thibetana).

    Science.gov (United States)

    Wu, Di; Yi, Yong; Sun, Fei; Zhou, Liang; Yang, Feng; Wang, Hongxing; Zhang, Guodong; Zhang, Yu Alex; Yue, Feng

    2014-01-01

    Tibetan macaques (Macaca thibetana), also known as Chinese stump-tailed macaques, are a threatened primate species. Although Tibetan macaques are Old World monkeys in the genus of Macaca, limited age- and sex-related physiologic data are available for this particular species. We used 69 apparently healthy Tibetan male and female macaques to explore the effect of age and sex on physiologic parameters. Somatometric measurements, biochemistry, and hematologic parameters were analyzed. Significant age-related differences were found for weight, BMI, RBC count, Hgb, Hct, neutrophils, eosinophil count, ALT, AST, ALP, GGT, creatine kinase (muscle and brain subtypes), LDH, α-amylase, creatinine, apolipoprotein A1, total protein, albumin, cholesterol, HDL, and potassium. Significant differences by sex were noted for weight, BMI, ALT, total bilirubin, and indirect bilirubin. An interaction between age and sex accounted for statistically significant differences in the values for weight, BMI, and lymphocyte and eosinophil counts. These physiologic data will provide veterinarians and researchers with important age- and sex-specific reference ranges for evaluating experimental results from Tibetan macaques.

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

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    Karli K Watson

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

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

    Science.gov (United States)

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

    2010-07-01

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

  3. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

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    Laura M J Ylinen

    Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  6. Feeding Behavior of Tonkean Macaques (Macaca tonkeana in Schmutzer Primates Center and Ragunan Zoo, Jakarta

    Directory of Open Access Journals (Sweden)

    Fery Dwi Riptianingsih

    2015-06-01

    Full Text Available Tonkean macaques are one of seven endemic macaque species on Sulawesi Island. Feeding management in captivity should pay attention to the quality, palatability, and feeding behavior patterns of animals. The goal of this study was to compare the feeding behavior of two social groups of Tonkean macaques at Schmutzer Primates Center (SPC and Ragunan Zoo (RZ with different captive management, which was expected to affect feeding behavior. Ad libitum sampling was used to observe daily behavior and hierarchy, while focal animal sampling was used to observe feeding behavior and feed preference. Data were collected from September 2013 until March 2014 with a total of 495 hours of observations. There were significant differences between the daily behavior of two groups of Tonkean macaques. Resting behavior was dominant in RZ group with non-enrichment feed cage, while feeding behavior was more common in the SPC group with an enrichment feed cage. The SPC group spent most of their feeding time in searching for feed, while choosing, carrying and refusing were greater in the RZ group. Both Tonkean macaque groups showed individual dominance in their feeding behavior. Provisioned feed in both locations had different diversity and preference values. The selection of feed required was based on preference values with attention to Tonkean macaques’ feed in nature. Cage construction, such as the SPC cage, was able to reduce abnormal behavior exhibited by individuals.

  7. Attention and normalization circuits in macaque V1.

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-04-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms.

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

    Science.gov (United States)

    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.

  9. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

    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. Copyright © 2015 Stauffer et al.

  10. Serial memory strategies in macaque monkeys: behavioral and theoretical aspects.

    Science.gov (United States)

    Orlov, Tanya; Yakovlev, Volodya; Amit, Daniel; Hochstein, Shaul; Zohary, Ehud

    2002-03-01

    Serial memory is the ability to encode and retrieve a list of items in their correct temporal order. To study nonverbal strategies involved in serial memory, we trained four macaque monkeys on a novel delayed sequence-recall task and analysed the mechanisms underlying their performance in terms of a neural network model. Thirty fractal images, divided into 10 triplets, were presented repeatedly in fixed temporal order. On each trial the monkeys viewed three sequentially presented sample images, followed by a test stimulus consisting of the same triplet of images and a distractor image (chosen randomly from the remaining 27). The task was to touch the three images in their original order, avoiding the distractor. The monkeys' most common error was touching the distractor when it had the same ordinal position (in its own triplet) as the correct image. This finding suggests that monkeys naturally categorize images by their ordinal number. Additional, secondary strategies were eventually used to avoid distractor images. These include memory of the sample images (working memory) and associations between triplet members. Further direct evidence for ordinal number categorization was provided by a transfer of learning to untrained images of the same ordinal category, following reassignment of image categories within each triplet. We propose a generic three-tier neuronal framework that can explain the components and complex set of characteristics of the observed behavior. This framework, with its intermediate level representing ordinal categories, can also explain the transfer of learning following category reassignment.

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

    Science.gov (United States)

    Blomquist, Gregory E

    2013-03-01

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

  12. Births in captive stump-tailed macaques (Macaca arctoides).

    Science.gov (United States)

    Solanki, G S; Zothansiama

    2013-01-01

    In this report, nighttime births of 3 stump-tailed macaques observed at the Aizawl Zoological Park, India, are described. Continuous focal observations were collected a long with video and still photographs, on the 3 parturitions, from the first observed onset of labour. The average time taken for infant birth, beginning with visibility of the head at the vaginal opening, was 45 s. The births observed were similar in many respects, regardless of parity and social context. The average time taken for consuming the placenta was 4 min 4 s and the average number of contractions was 6.3. In all cases births occurred with the infant emerging in the occiput posterior position, assisted by the mother. Individual variations existed in the number of contractions, intercontraction intervals, self-examination of the anogenital region, duration of labour and the interval between infant birth and the delivery of the placenta. Each mother ingested the placenta completely, while holding her neonate, but without paying much attention to the neonate during placentophagia. Placentophagia appears to provide nutrition to the mothers. Detailed data on parturition in non-human primates, and particularly for Macacaarctoides , are still scarce. Data, such as those presented here, contribute to our understanding of primate birth and the adaptive pressures that shape parturition behaviour and reproductive success.

  13. Attention and normalization circuits in macaque V1

    Science.gov (United States)

    Sanayei, M; Herrero, J L; Distler, C; Thiele, A

    2015-01-01

    Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. PMID:25757941

  14. Multimodal convergence within the intraparietal sulcus of the macaque monkey.

    Science.gov (United States)

    Guipponi, Olivier; Wardak, Claire; Ibarrola, Danielle; Comte, Jean-Christophe; Sappey-Marinier, Dominique; Pinède, Serge; Ben Hamed, Suliann

    2013-02-27

    The parietal cortex is highly multimodal and plays a key role in the processing of objects and actions in space, both in human and nonhuman primates. Despite the accumulated knowledge in both species, we lack the following: (1) a general description of the multisensory convergence in this cortical region to situate sparser lesion and electrophysiological recording studies; and (2) a way to compare and extrapolate monkey data to human results. Here, we use functional magnetic resonance imaging (fMRI) in the monkey to provide a bridge between human and monkey studies. We focus on the intraparietal sulcus (IPS) and specifically probe its involvement in the processing of visual, tactile, and auditory moving stimuli around and toward the face. We describe three major findings: (1) the visual and tactile modalities are strongly represented and activate mostly nonoverlapping sectors within the IPS. The visual domain occupies its posterior two-thirds and the tactile modality its anterior one-third. The auditory modality is much less represented, mostly on the medial IPS bank. (2) Processing of the movement component of sensory stimuli is specific to the fundus of the IPS and coincides with the anatomical definition of monkey ventral intraparietal area (VIP). (3) A cortical sector within VIP processes movement around and toward the face independently of the sensory modality. This amodal representation of movement may be a key component in the construction of peripersonal space. Overall, our observations highlight strong homologies between macaque and human VIP organization.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

    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.

  17. Estrogen enhances cystatin C expression in the macaque vagina.

    Science.gov (United States)

    Slayden, Ov D; Hettrich, Kevin; Carroll, Rebecca S; Otto, Lesley N; Clark, Amanda L; Brenner, Robert M

    2004-02-01

    Cystatin C is a secreted inhibitor of cysteine proteinases that participates in extracellular matrix remodeling. Whether hormones affect its expression in the vagina was unknown. Consequently, we examined the effects of estradiol (E(2)), progesterone (P), and raloxifene on vaginal cystatin C in rhesus macaques. In experiment 1, ovariectomized animals were treated sequentially with E(2) (14 d) and E(2) + P (14 d) to induce 28-d menstrual cycles. Vaginal samples were collected on d 6, 8, 14, and 28 of the induced cycle. Some cycled animals were deprived of both E(2) + P for 28 d. In experiment 2, ovariectomized animals were treated for 5 months with E(2) alone, E(2) + P, raloxifene, or left untreated. Total RNA from the vaginal wall was analyzed for the cystatin C transcript with a commercially prepared cDNA array and semiquantitative RT-PCR. Vaginal cryosections were analyzed by in situ hybridization for cystatin C transcript and by immunocytochemistry for the protein. E(2) treatment significantly (5-fold; P pelvic floor prolapse.

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

    Science.gov (United States)

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

    2014-07-15

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

  19. Giant neurons in the macaque pulvinar: a distinct relay subpopulation

    Directory of Open Access Journals (Sweden)

    Kosuke Imura

    2007-07-01

    Full Text Available Calbindin positive (CB+ giant neurons are known to occur within the pulvinar nucleus in subhuman primates. Here, we demonstrate by combined retrograde tracing and immunocytochemistry that at least some of these are pulvinocortical relay neurons, and further report several distinctive features. First, in contrast with non-giant relay neurons, the giant neurons are often solitary and isolated from a main projection focus. The question thus arises of whether their cortical projections may be non-reciprocal or otherwise distinctive. Second, these neurons are positive for GluR4; but third, they are otherwise neurochemically heterogeneous, in that about one-third are positive for both parvalbumin (PV and CB. Presumably, these subpopulations are also functionally heterogeneous. These results provide further evidence for the idea of multiple, interleaved organizations within the pulvinar; and they imply that thalamocortical projections are more disparate than has yet been appreciated. Finally, we found that giant CB+ neurons have a distinctive meshwork of large, PV+ terminations, prominent at the first dendritic branch point. In size and location, these resemble inhibitory terminations from the zona incerta or anterior pretectal nucleus (APT, as recently described in higher order thalamic nuclei in rats. One can speculate that giant neurons in the macaque pulvinar participate in a layer 5-APT-thalamus (giant neuron extrareticular pathway, functionally distinct from the layer 6-reticular nucleus-thalamus network.

  20. Transient inactivation of orbitofrontal cortex blocks reinforcer devaluation in macaques.

    Science.gov (United States)

    West, Elizabeth A; DesJardin, Jacqueline T; Gale, Karen; Malkova, Ludise

    2011-10-19

    The orbitofrontal cortex (OFC) and its interactions with the basolateral amygdala (BLA) are critical for goal-directed behavior, especially for adapting to changes in reward value. Here we used a reinforcer devaluation paradigm to investigate the contribution of OFC to this behavior in four macaques. Subjects that had formed associations between objects and two different primary reinforcers (foods) were presented with choices of objects overlying the two different foods. When one of the two foods was devalued by selective satiation, the subjects shifted their choices toward the objects that represented the nonsated food reward (devaluation effect). Transient inactivation of OFC by infusions of the GABA(A) receptor agonist muscimol into area 13 blocked the devaluation effect: the monkeys did not reduce their selection of objects associated with the devalued food. This effect was observed when OFC was inactivated during both satiation and the choice test, and during the choice test only. This supports our hypothesis that OFC activity is required during the postsatiety object choice period to guide the selection of objects. This finding sharply contrasts with the role of BLA in the same devaluation process (Wellman et al., 2005). Whereas activity in BLA was required during the selective satiation procedure, it was not necessary for guiding the subsequent object choice. Our results are the first to demonstrate that transient inactivation of OFC is sufficient to disrupt the devaluation effect, and to document a role for OFC distinct from that of BLA for the conditioned reinforcer devaluation process in monkeys.

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

    Science.gov (United States)

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

    2016-12-01

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

  2. Comparative analysis of the macroscale structural connectivity in the macaque and human brain.

    Directory of Open Access Journals (Sweden)

    Alexandros Goulas

    2014-03-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-05-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  8. Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Maréchal, Laëtitia; Levy, Xandria; Meints, Kerstin; Majolo, Bonaventura

    2017-01-01

    Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion) affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus, affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants' level of experience was defined as either: (1) naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2) exposed: shown pictures of the different Barbary macaques' facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3) expert: worked with Barbary macaques for at least two months. Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques' facial expressions improved the ability of inexperienced participants to better discriminate neutral and distressed faces, and a trend was found for

  9. Human Short Tandem Repeat (STR Markers for Paternity Testing in Pig-Tailed Macaques

    Directory of Open Access Journals (Sweden)

    DYAH PERWITASARI-FARAJALLAH

    2007-06-01

    Full Text Available This study investigated the use of human short tandem repeat (STR or microsatellite loci markers for assessing paternity and genetic structure of pig-tailed macaques (Macaca nemestrina breeding colony. Four human microsatellite primer pairs located at human map position D1S548, D3S1768, D5S820, and D2S1777, were amplified by polymerase chain reaction (PCR for pig-tailed macaques. Four loci were found to be clearly and reliably amplified, and three loci exhibited high levels of genetic heterogeneity. These loci were sufficiently informative to differentiate discretely between related and unrelated pairs.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Copyright © 2015. Published by Elsevier Ltd.

  12. Crossmodal integration of conspecific vocalizations in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Christa Payne

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

  13. Plasmodium knowlesi in humans, macaques and mosquitoes in peninsular Malaysia

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    NorParina Ismail

    2008-08-01

    Full Text Available Abstract Background Since a large focus of human infection with Plasmodium knowlesi, a simian malaria parasite naturally found in long-tailed and pig tailed macaques, was reported in Sarawak, Malaysian Borneo, it was pertinent to study the situation in peninsular Malaysia. A study was thus initiated to screen human cases of Plasmodium malariae using molecular techniques, to determine the presence of P. knowlesi in non- human primates and to elucidate its vectors. Methods Nested polymerase chain reaction (PCR was used to identify all Plasmodium species present in the human blood samples sent to the Parasitology laboratory of Institute for Medical Research. At the same time, non-human primates were also screened for malaria parasites and nested PCR was carried out to determine the presence of P. knowlesi. Mosquitoes were collected from Pahang by human landing collection and monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites and nested PCR was carried out on positive glands. Sequencing of the csp genes were carried on P. knowlesi samples from humans, monkeys and mosquitoes, positive by PCR. Results and Discussion Plasmodium knowlesi was detected in 77 (69.37% of the 111 human samples, 10 (6.90% of the 145 monkey blood and in 2 (1.7% Anopheles cracens. Sequence of the csp gene clustered with other P. knowlesi isolates. Conclusion Human infection with Plasmodium knowlesi is occurring in most states of peninsular Malaysia. An. cracens is the main vector. Economic exploitation of the forest is perhaps bringing monkeys, mosquitoes and humans into increased contact. A single bite from a mosquito infected with P. knowlesi is sufficient to introduce the parasite to humans. Thus, this zoonotic transmission has to be considered in the future planning of malaria control.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2012-11-01

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

  16. Hierarchical steepness, counter-aggression, and macaque social style scale.

    Science.gov (United States)

    Balasubramaniam, Krishna N; Dittmar, Katharina; Berman, Carol M; Butovskaya, Marina; Cooper, Mathew A; Majolo, Bonaventura; Ogawa, Hideshi; Schino, Gabriele; Thierry, Bernard; De Waal, Frans B M

    2012-10-01

    Nonhuman primates show remarkable variation in several aspects of social structure. One way to characterize this variation in the genus Macaca is through the concept of social style, which is based on the observation that several social traits appear to covary with one another in a linear or at least continuous manner. In practice, macaques are more simply characterized as fitting a four-grade scale in which species range from extremely despotic (grade 1) to extremely tolerant (grade 4). Here, we examine the fit of three core measures of social style-two measures of dominance gradients (hierarchical steepness) and another closely related measure (counter-aggression)-to this scale, controlling for phylogenetic relationships. Although raw scores for both steepness and counter-aggression correlated with social scale in predicted directions, the distributions appeared to vary by measure. Counter-aggression appeared to vary dichotomously with scale, with grade 4 species being distinct from all other grades. Steepness measures appeared more continuous. Species in grades 1 and 4 were distinct from one another on all measures, but those in the intermediate grades varied inconsistently. This confirms previous indications that covariation is more readily observable when comparing species at the extreme ends of the scale than those in intermediate positions. When behavioral measures were mapped onto phylogenetic trees, independent contrasts showed no significant consistent directional changes at nodes below which there were evolutionary changes in scale. Further, contrasts were no greater at these nodes than at neutral nodes. This suggests that correlations with the scale can be attributed largely to species' phylogenetic relationships. This could be due in turn to a structural linkage of social traits based on adaptation to similar ecological conditions in the distant past, or simply to unlinked phylogenetic closeness.

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

    Science.gov (United States)

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

    2012-01-01

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

  18. Multiple parietal-frontal pathways mediate grasping in macaque monkeys

    Science.gov (United States)

    Gharbawie, Omar A.; Stepniewska, Iwona; Qi, Huixin; Kaas, Jon H.

    2011-01-01

    The nodes of a parietal-frontal pathway that mediates grasping in primates are in anterior intraparietal area (AIP) and ventral premotor cortex (PMv). Nevertheless, multiple somatosensory and motor representations of the hand, respectively in parietal and frontal cortex, suggest that additional pathways remain unrealized. We explored this possibility in macaque monkeys by injecting retrograde tracers into grasp zones identified in M1, PMv, and area 2 with long train electrical stimulation. The M1 grasp zone was densely connected with other frontal cortex motor regions. The remainder of the connections originated from somatosensory areas 3a and S2/PV, and from the medial bank and fundus of the intraparietal sulcus (IPS). The PMv grasp zone was also densely connected with frontal cortex motor regions, albeit to a lesser extent than the M1 grasp zone. The remainder of the connections originated from areas S2/PV and aspects of the inferior parietal lobe such as PF, PFG, AIP, and the tip of the IPS. The area 2 grasp zone was densely connected with the hand representations of somatosensory areas 3b, 1, and S2/PV. The remainder of the connections was with areas 3a and 5 and the medial bank and fundus of the IPS. Connections with frontal cortex were relatively weak and concentrated in caudal M1. Thus, the three grasp zones may be nodes of parallel parietal-frontal pathways. Differential points of origin and termination of each pathway suggest varying functional specializations. Direct and indirect connections between those parietal-frontal pathways likely coordinate their respective functions into an accurate grasp. PMID:21832196

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

    Science.gov (United States)

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

    1998-01-01

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

  20. Fixations Gate Species-Specific Responses to Free Viewing of Faces in the Human and Macaque Amygdala

    Directory of Open Access Journals (Sweden)

    Juri Minxha

    2017-01-01

    Full Text Available Neurons in the primate amygdala respond prominently to faces. This implicates the amygdala in the processing of socially significant stimuli, yet its contribution to social perception remains poorly understood. We evaluated the representation of faces in the primate amygdala during naturalistic conditions by recording from both human and macaque amygdala neurons during free viewing of identical arrays of images with concurrent eye tracking. Neurons responded to faces only when they were fixated, suggesting that neuronal activity was gated by visual attention. Further experiments in humans utilizing covert attention confirmed this hypothesis. In both species, the majority of face-selective neurons preferred faces of conspecifics, a bias also seen behaviorally in first fixation preferences. Response latencies, relative to fixation onset, were shortest for conspecific-selective neurons and were ∼100 ms shorter in monkeys compared to humans. This argues that attention to faces gates amygdala responses, which in turn prioritize species-typical information for further processing.

  1. First Complete Genome Sequence of a Simian Foamy Virus Isolate from a Cynomolgus Macaque

    Science.gov (United States)

    Sakai, Koji; Ami, Yasushi; Suzaki, Yuriko

    2016-01-01

    We report here the first complete proviral genome sequence (DDBJ/ENA/GenBank accession no. LC094267) of a simian foamy virus, SFVmfa/Cy5061, isolated from a cynomolgus macaque (Macaca fascicularis). This proviral genome consists of 12,965 nucleotides and has five open reading frames, gag, pol, env, tas, and bet, as with other foamy viruses. PMID:27908992

  2. Dietary Variation of Long Tailed Macaques (Macaca fascicularis in Telaga Warna, Bogor, West Java

    Directory of Open Access Journals (Sweden)

    Sarah Nila

    2014-03-01

    Full Text Available The genus Macaca, member of sub-family Cercopithecinae, is the most widely distributed non-human primates in Asian countries. The habitats are strongly influence the dietary variation of the populations. The dietary variation of the macaques reflect ecological plasticity in coping with differences both in availability and abundance of food. The macaques are plastic in taking any kind of food that available in their home range and adjust their behaviour according to its abundance. Here, we present the dietary variation of long-tailed macaques (Macaca fascicularis in the high altitude rain forest of Telaga Warna, West Java, Indonesia. The proportion of their food from natural sources is greater than those from visitors. The natural food consisted of plants, small animals (insects and earthworm, fungi and water from lake. The plant food comprised of 29 species plus a few mosses. The frequency of eating artificial food was influenced by visitors who come for picnic. In this site, the macaques learned that the visiting of tourists is identical with food.

  3. Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

    NARCIS (Netherlands)

    de Boer, E.; Samuel, S.; French, D. N.; Warram, J. M.; Schoeb, T. R.; Rosenthal, E. L.; Zinn, K. R.

    2016-01-01

    Purpose: The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques. Procedures: Total IR700 and intact cetuximab-IR700

  4. Comparative diffusion tractography of corticostriatal motor pathways reveals differences between humans and macaques

    NARCIS (Netherlands)

    Neggers, S.F.W.; Zandbelt, B.B.; Schall, M.S.; Schall, J.D.

    2015-01-01

    The primate corticobasal ganglia circuits are understood to be segregated into parallel anatomically and functionally distinct loops. Anatomical and physiological studies in macaque monkeys are summarized as showing that an oculomotor loop begins with projections from the frontal eye fields (FEF) to

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

    Science.gov (United States)

    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.

  6. Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta)

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Lundsgaard, Jo F. H.; Bakker, Jaco

    2014-01-01

    Five acute-phase reactants—serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron—were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this specie...

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

    Science.gov (United States)

    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.

  8. Behavioral measurement of temperament in male nursery-raised infant macaques and baboons.

    Science.gov (United States)

    Heath-Lange, S; Ha, J C; Sackett, G P

    1999-01-01

    We define temperament as an individual's set of characteristic behavioral responses to novel or challenging stimuli. This study adapted a temperament scale used with rhesus macaques by Schneider and colleagues [American Journal of Primatology 25:137-155, 1991] for use with male pigtailed macaque (Macaca nemestrina, n = 7), longtailed macaque (M. fascicularis, n = 3), and baboon infants (Papio cynocephalus anubis, n = 4). Subjects were evaluated twice weekly for the first 5 months of age during routine removal from their cages for weighing. Behavioral measures were based on the subject's interactions with a familiar human caretaker and included predominant state before capture, response to capture, contact latency, resistance to tester's hold, degree of clinging, attention to environment, defecation/urination, consolability, facial expression, vocalizations, and irritability. Species differences indicated that baboons were more active than macaques in establishing or terminating contact with the tester. Temperament scores decreased over time for the variables Response to Capture and Contact Latency, indicating that as they grew older, subjects became less reactive and more bold in their interactions with the tester. Temperament scores changed slowly with age, with greater change occurring at younger ages. The retention of variability in reactivity between and within species may be advantageous for primates, reflecting the flexibility necessary to survive in a changing environment.

  9. Diet of the Assamese macaque Macaca assamensis in lime-stone habitats of Nonggang, China

    Directory of Open Access Journals (Sweden)

    Qihai ZHOU, Hua WEI, Zhonghao HUANG, Chengming HUANG

    2011-02-01

    Full Text Available To enhance our understanding of dietary adaptations in macaques we studied the diet of the Assamese macaque Macaca assamensis in limestone seasonal rain forests at Nonggang Nature Reserve, China from September 2005 to August 2006. Our results show that although macaques fed on many plant species, 85.2% of the diet came from only 12 species, of which a bamboo species, Indocalamus calcicolus contributed to 62% of the diet. Young leaves were staple food items (74.1% of the diet for Assamese macaques at Nonggang, and constituted the bulk of monthly diets almost year-round, ranging from 44.9% (July to 92.9% (May. Young parts of Indocalamus calcicolus unexpanded leaves contributed to a large proportion of the young leaf diet in most months. Fruit accounted for only 17.4% of the diet, with a peak of consumption in July. We suggest that this highly folivorous diet may be related to the long lean season of fruit availability in limestone habitats as well as the utilization of cliffs of low fruit availability [Current Zoology 57 (1: 18–25, 2011].

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

    Science.gov (United States)

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

    2011-02-03

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    Science.gov (United States)

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

    2011-03-15

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

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

    Directory of Open Access Journals (Sweden)

    Yumi Murata

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  15. Expression of the Memory Marker CD45RO on Helper T Cells in Macaques

    NARCIS (Netherlands)

    Valentine, Michael; Song, Kejing; Maresh, Grace A.; Mack, Heather; Huaman, Maria Cecilia; Polacino, Patricia; Ho, On; Cristillo, Anthony; Chung, Hye Kyung; Hu, Shiu-Lok; Pincus, Seth H.

    2013-01-01

    Background: In humans it has been reported that a major site of the latent reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO, defined by the mAb UCHL1. There are conflicting reports regarding the expression of this antigen in macaques, the most relevant animal species for s

  16. Two-item discrimination and Hamilton search learning in infant pigtailed macaque monkeys

    NARCIS (Netherlands)

    Ha, J.C.; Mandell, D.J.; Gray, J.

    2011-01-01

    This study investigated how infant pigtailed macaque monkeys performed on two separate learning assessments, two-object discrimination/reversal and Hamilton search learning. Although the learning tasks have been tested on several species, including non-human primates, there have been no normative

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  19. A 22-channel receive array with Helmholtz transmit coil for anesthetized macaque MRI at 3 T.

    Science.gov (United States)

    Janssens, Thomas; Keil, Boris; Serano, Peter; Mareyam, Azma; McNab, Jennifer A; Wald, Lawrence L; Vanduffel, Wim

    2013-11-01

    The macaque monkey is an important model for cognitive and sensory neuroscience that has been used extensively in behavioral, electrophysiological, molecular and, more recently, neuroimaging studies. However, macaque MRI has unique technical differences relative to human MRI, such as the geometry of highly parallel receive arrays, which must be addressed to optimize imaging performance. A 22-channel receive coil array was constructed specifically for rapid high-resolution anesthetized macaque monkey MRI at 3 T. A local Helmholtz transmit coil was used for excitation. Signal-to-noise ratios (SNRs) and noise amplification for parallel imaging were compared with those of single- and four-channel receive coils routinely used for macaque MRI. The 22-channel coil yielded significant improvements in SNR throughout the brain. Using this coil, the SNR in peripheral brain was 2.4 and 1.7 times greater than that obtained with single- or four-channel coils, respectively. In the central brain, the SNR gain was 1.5 times that of both the single- and four-channel coils. Finally, the performance of the array for functional, anatomical and diffusion-weighted imaging was evaluated. For all three modalities, the use of the 22-channel array allowed for high-resolution and accelerated image acquisition.

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

    Science.gov (United States)

    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. Severe Encephalitis in Cynomolgus Macaques Exposed to Aerosolized Eastern Equine Encephalitis Virus

    Science.gov (United States)

    2007-08-01

    report here that cynomolgus macaques are also suitable as a model for aerosol exposure to EEE viruses. MATERIALS AND METHODS Animals. Healthy, adult... trocar , the arterial catheter was routed through the subcuta- neous space to the inguinal incision. With an 18-gauge needle, the arterial catheter was

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2012-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Hsieh Fushing

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

  6. Two-item discrimination and Hamilton search learning in infant pigtailed macaque monkeys

    NARCIS (Netherlands)

    Ha, J.C.; Mandell, D.J.; Gray, J.

    2011-01-01

    This study investigated how infant pigtailed macaque monkeys performed on two separate learning assessments, two-object discrimination/reversal and Hamilton search learning. Although the learning tasks have been tested on several species, including non-human primates, there have been no normative re

  7. High maltose sensitivity of sweet taste receptors in the Japanese macaque (Macaca fuscata)

    Science.gov (United States)

    Nishi, Emiko; Tsutsui, Kei; Imai, Hiroo

    2016-01-01

    Taste sensitivity differs among animal species depending on feeding habitat. To humans, sucrose is one of the sweetest natural sugars, and this trait is expected to be similar in other primates. However, previous behavioral tests have shown that some primate species have equal preferences for maltose and sucrose. Because sweet tastes are recognized when compounds bind to the sweet taste receptor Tas1R2/Tas1R3, we evaluated the responses of human and Japanese macaque Tas1R2/Tas1R3 to various natural sugars using a heterologous expression system. Human Tas1R2/Tas1R3 showed high sensitivity to sucrose, as expected; however, Japanese macaque Tas1R2/Tas1R3 showed equally high sensitivity to maltose and sucrose. Furthermore, Japanese macaques showed equally high sensitivity to sucrose and maltose in a two-bottle behavioral experiment. These results indicate that Japanese macaques have high sensitivity to maltose, and this sensitivity is directly related to Tas1R2/Tas1R3 function. This is the first molecular biological evidence that for some primate species, sucrose is not the most preferable natural sugar, as it is for humans. PMID:27982108

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-05-13

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

  9. Thromboelastography values from pigtail macaques ( Macaca nemestrina): effects of age and sex.

    Science.gov (United States)

    Fong, Derek L; Ha, James C; Hotchkiss, Charlotte E

    2012-01-01

    Thromboelastography is a clinical laboratory test used to assess global hemostasis. With technologic advances and the test's reemergence in human medicine, its utility in veterinary medicine is being explored. Because assays for PT, aPTT, and d-dimers require platelet-poor plasma, whereas thromboelastography is performed on whole blood, thromboelastography provides a more accurate representation of coagulation and allows the identification of hypocoagulable, hypercoagulable, and hyperfibrinolytic states. Conflicting information has been reported about the effects of age and sex on thromboelastog- raphy in humans and animals. Human studies have reported significant effects of age and sex on thromboelastography more often than have animal studies, but few publications are available about thromboelastography in the nonhuman primate and laboratory animal literature. We used a sample of 50 pigtail macaques (Macaca nemestrina) to determine whether age or sex influence thromboelastography values. Of 5 measured and 2 calculated variables produced by thromboelastography, sex had a significant effect only on the lysis-30 parameter, which also showed significant interaction between age and sex; values increased with age in male macaques but decreased with age in female macaques. In addition, we used the data to define reference intervals for thromboelastography parameters in pigtail macaques.

  10. Mitochondrial DNA variation in Chinese and Indian rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Smith, David Glenn; McDonough, John

    2005-01-01

    DNA was extracted from the buffy coats or serum of 212 rhesus macaques (Macaca mulatta) sampled throughout the species' geographic range. An 835 base pair (bp) fragment of mitochondrial DNA (mtDNA) was amplified from each sample, sequenced, aligned, and used to estimate genetic distances from which phylogenetic trees were constructed. A tree that included sequences from rhesus macaques whose exact origins in China are known was used to determine the regional origin of clusters of haplotypes, or haplogroups, defined by the trees. Indian rhesus sequences formed one large homogeneous haplogroup with very low levels of nucleotide diversity and no geographic structure, and a second much smaller haplogroup apparently derived from Burma. The sequences from Burma and eastern and western China were quite divergent from those in the major haplogroup of India. Each of these sequences formed separate clusters of haplotypes that exhibited far greater nucleotide diversity and/or population structure. Correspondingly, sequences from Indian rhesus macaques that are considered to represent different subspecies (based on morphological differences) were intermingled in the tree, while those from China reflected some, but not all, aspects of subspecific taxonomy. Regional variation contributed 72% toward the paired differences between sequences in an analysis of molecular variance (AMOVA), and the average differences between the populations of eastern and western China were also statistically significant. These results suggest that Indian and Chinese rhesus macaques were reproductively isolated during most, if not all, of the Pleistocene, during which time Indian rhesus macaques experienced a severe genetic bottleneck, and that some gene flow westward into India was subsequently reestablished. Samples from breeding centers in three different provinces of China included sequences from rhesus macaques that originated in both eastern (or southern) and western China, confirming anecdotal

  11. Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques.

    Science.gov (United States)

    Hu, Kai-tao; Zheng, Jin-xin; Yu, Zhi-jian; Chen, Zhong; Cheng, Hang; Pan, Wei-guang; Yang, Wei-zhi; Wang, Hong-yan; Deng, Qi-wen; Zeng, Zhong-ming

    2015-04-01

    Sucrose gel was used to treat bacterial vaginosis in a phase III clinical trial. However, the changes of vaginal flora after treatment were only examined by Nugent score in that clinical trial, While the vaginal microbiota of rhesus macaques is characterized by anaerobic, Gram-negative bacteria, few lactobacilli, and pH levels above 4.6, similar to the microbiota of patients with bacterial vaginosis. This study is aimed to investigate the change of the vaginal microbiota of rehsus macaques after topical use of sucrose gel to reveal more precisely the bacterial population shift after the topical application of sucrose gel. Sixteen rhesus macaques were treated with 0.5 g sucrose gel vaginally and three with 0.5 g of placebo gel. Vaginal swabs were collected daily following treatment. Vaginal pH levels and Nugent scores were recorded. The composition of the vaginal micotbiota was tested by V3∼V4 16S rDNA metagenomic sequencing. Dynamic changes in the Lactobacillus genus were analyzed by qPCR. The vaginal microbiota of rhesus macaques are dominated by anaerobic Gram-negative bacteria, with few lactobacilli and high pH levels above 4.6. After five days' treatment with topical sucrose gel, the component percentage of Lactobacillus in vaginal microbiota increased from 1.31% to 81.59%, while the component percentage of Porphyromonas decreased from 18.60% to 0.43%, Sneathia decreased from 15.09% to 0.89%, Mobiluncus decreased from 8.23% to 0.12%, etc.. The average vaginal pH values of 16 rhesus macaques of the sucrose gel group decreased from 5.4 to 3.89. There were no significant changes in microbiota and vaginal pH observed in the placebo group. Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora. Copyright © 2015 The Authors. Published by

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

    Directory of Open Access Journals (Sweden)

    Yamato Tsuji

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  14. Nutritional content explains the attractiveness of cacao to crop raiding Tonkean macaques

    Institute of Scientific and Technical Information of China (English)

    Erin P.RILEY; Barbara TOLBERT; Wartika R.FARIDA

    2013-01-01

    Nutritional ecology has been linked to crop raiding behavior in a number of wildlife taxa.Here our goal is to explore the role nutrition plays in cacao crop raiding by Tonkean macaques Macaca tonkeana in Sulawesi,Indonesia.From June-Sept.2008 we collected fruit samples from 13 species known to be important Tonkean macaque foods and compared their nutritional value to that of cacao Theobroma cacao,an important cash crop in Sulawesi.Cacao pulp was significantly lower in protein,but lower in dietary fiber,and higher in digestible carbohydrates and energy content compared to forest fruits.These fmdings,combined with the fact that cacao fruits are spatially concentrated and available throughout the year,likely explain why Tonkean macaques are attracted to this cultivated resource.We use these data along with published feeding ecology data to propose strategies to minimize human-macaque conflict.Namely,we recommend the deliberate protection of Elmerillila tsiampaccca,Ficus spp.and Arenga pinnata,fruit species known to be regularly consumed and of considerable nutritional value.We also identify the A.pinnata palm as a potential buffer resource to curb cacao crop raiding by macaques.Cacao is a hard-to-process food because the pods have a thick outer skin that encases the seeds and pulp.Aren palm fruit,although lower in digestibility,is easier-to-process,higher in protein,and also available year round.In addition,because the palm has considerable cultural and economic significance for local people,the strategy of planting Aren palm in a buffer corridor is likely to garner local community support.

  15. Indocyanine green fluorescence imaging for evaluation of uterine blood flow in cynomolgus macaque.

    Directory of Open Access Journals (Sweden)

    Iori Kisu

    Full Text Available BACKGROUND: Uterine blood flow is an important factor in uterine viability, but the number of blood vessels required to maintain viability is uncertain. In this study, indocyanine green (ICG fluorescence imaging was used to examine uterine hemodynamics and vessels associated with uterine blood flow in cynomolgus macaque. METHODS: The uterus of a female cynomolgus macaque was cut from the vaginal canal to mimic a situation during trachelectomy or uterine transplantation surgery in which uterine perfusion is maintained only with uterine and ovarian vessels. Intraoperative uterine hemodynamics was observed using ICG fluorescence imaging under conditions in which various nutrient vessels were selected by clamping of blood vessels. A time-intensity curve was plotted using imaging analysis software to measure the T(max of uterine perfusion for selected blood vessel patterns. Open surgery was performed with the uterus receiving nutritional support only from uterine vessels on one side. The size of the uterus after surgery was monitored using transabdominal ultrasonography. RESULTS: The resulting time-intensity curves displayed the average intensity in the regions of the uterine corpus and uterine cervix, and in the entire uterus. Analyses of the uterine hemodynamics in the cynomolgus macaque showed that uterine vessels were significantly related to uterine perfusion (P=0.008, whereas ovarian vessels did not have a significant relationship (P=0.588. When uterine vessels were clamped, ovarian vessels prolonged the time needed to reach perfusion maximum. Postoperative transabdominal ultrasonography showed that the size of the uterus was not changed 2 months after surgery, with recovery of periodic menstruation. The cynomolgus macaque has got pregnant with favorable fetus well-being. CONCLUSION: Uterine vessels may be responsible for uterine blood flow, and even one uterine vessel may be sufficient to maintain uterine viability in cynomolgus macaque. Our

  16. Prevention of vaginal SHIV transmission in macaques by a coitally-dependent Truvada regimen.

    Directory of Open Access Journals (Sweden)

    Jessica Radzio

    Full Text Available BACKGROUND: Daily pre-exposure prophylaxis (PrEP with Truvada (a combination of emtricitabine (FTC and tenofovir (TFV disoproxil fumarate (TDF is a novel HIV prevention strategy recently found to prevent HIV transmission in men who have sex with men and heterosexual couples. We previously showed that a coitally-dependent Truvada regimen protected macaques against rectal SHIV transmission. Here we examined FTC and tenofovir TFV exposure in vaginal tissues after oral dosing and assessed if peri-coital Truvada also protects macaques against vaginal SHIV infection. METHODS: The pharmacokinetic profile of emtricitabine (FTC and tenofovir (TFV was evaluated at first dose. FTC and TFV levels were measured in blood plasma, rectal, and vaginal secretions. Intracellular concentrations of FTC-triphosphate (FTC-TP and TFV-diphosphate (TFV-DP were measured in PBMCs, rectal tissues, and vaginal tissues. Efficacy of Truvada in preventing vaginal SHIV infection was assessed using a repeat-exposure vaginal SHIV transmission model consisting of weekly exposures to low doses of SHIV162p3. Six pigtail macaques with normal menstrual cycles received Truvada 24 h before and 2 h after each weekly virus exposure and six received placebo. Infection was monitored by serology and PCR amplification of SHIV RNA and DNA. RESULTS: As in humans, the concentration of FTC was higher than the concentration of TFV in vaginal secretions. Also as in humans, TFV levels in vaginal secretions were lower than in rectal secretions. Intracellular TFV-DP concentrations were also lower in vaginal tissues than in rectal tissues. Despite the low vaginal TFV exposure, all six treated macaques were protected from infection after 18 exposures or 4 full menstrual cycles. In contrast, all 6 control animals were infected. CONCLUSIONS: We modeled a peri-coital regimen with two doses of Truvada and showed that it fully protected macaques from repeated SHIV exposures. Our results open the possibility

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Wheeler David A

    2011-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Foley, Brian T [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory

    2008-01-01

    Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

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

    Science.gov (United States)

    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.

  1. Distribution of N-Acetylgalactosamine-Positive Perineuronal Nets in the Macaque Brain: Anatomy and Implications

    Directory of Open Access Journals (Sweden)

    Adrienne L. Mueller

    2016-01-01

    Full Text Available Perineuronal nets (PNNs are extracellular molecules that form around neurons near the end of critical periods during development. They surround neuronal cell bodies and proximal dendrites. PNNs inhibit the formation of new connections and may concentrate around rapidly firing inhibitory interneurons. Previous work characterized the important role of perineuronal nets in plasticity in the visual system, amygdala, and spinal cord of rats. In this study, we use immunohistochemistry to survey the distribution of perineuronal nets in representative areas of the primate brain. We also document changes in PNN prevalence in these areas in animals of different ages. We found that PNNs are most prevalent in the cerebellar nuclei, surrounding >90% of the neurons there. They are much less prevalent in cerebral cortex, surrounding less than 10% of neurons in every area that we examined. The incidence of perineuronal nets around parvalbumin-positive neurons (putative fast-spiking interneurons varies considerably between different areas in the brain. Our survey indicates that the presence of PNNs may not have a simple relationship with neural plasticity and may serve multiple functions in the central nervous system.

  2. A neural circuit covarying with social hierarchy in macaques

    National Research Council Canada - National Science Library

    Noonan, MaryAnn P; Sallet, Jerome; Mars, Rogier B; Neubert, Franz X; O'Reilly, Jill X; Andersson, Jesper L; Mitchell, Anna S; Bell, Andrew H; Miller, Karla L; Rushworth, Matthew F S

    2014-01-01

    .... We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals...

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

    Science.gov (United States)

    Tsujino, Riyou; Yumoto, Takakazu

    2014-04-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Brunell, Marla K

    2012-07-01

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

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

    OpenAIRE

    2014-01-01

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

  7. Captive propagation of threatened primates - the example of the Lion-tailed Macaque Macaca silenus

    OpenAIRE

    W. Kaumanns; Singh, M; A. Silwa

    2013-01-01

    Many conservation-oriented breeding programs are not likely to reach their goal of establishing self-sustaining populations. Some zoo biologists propagate to reconsider zoo-based conservation policies and strategies. The Lion-tailed Macaque is a flagship species for in situ conservation and a high priority species in captive propagation. This article reviews the captive management history of the Lion-tailed Macaque, identifies management patterns that might have negatively influenced the d...

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

    Science.gov (United States)

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

    2008-04-15

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

  9. Experience-based human perception of facial expressions in Barbary macaques (Macaca sylvanus

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    Laëtitia Maréchal

    2017-06-01

    Full Text Available Background Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. Methods The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus, affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants’ level of experience was defined as either: (1 naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2 exposed: shown pictures of the different Barbary macaques’ facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3 expert: worked with Barbary macaques for at least two months. Results Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques’ facial expressions improved the ability of inexperienced participants to better discriminate neutral

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

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    Michael T Bethune

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

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

    Directory of Open Access Journals (Sweden)

    Washington Parks Robyn

    2001-07-01

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

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

    Science.gov (United States)

    Seltmann, Anne; Majolo, Bonaventura; Schülke, Oliver; Ostner, Julia

    2013-01-01

    Social animals have to coordinate activities and collective movements to benefit from the advantages of group living. Animals in large groups maintain cohesion by self-organization processes whereas in smaller groups consensus decisions can be reached. Where consensus decisions are relevant leadership may emerge. Variation in the organization of collective movements has been linked to variation in female social tolerance among macaque species ranging from despotic to egalitarian. Here we investigated the processes underlying group movements in a wild macaque species characterized by a degree of social tolerance intermediate to previously studied congeneric species. We focused on processes before, during and after the departure of the first individual. To this end, we observed one group of wild Barbary macaques (Macaca sylvanus) in the Middle Atlas, Morocco using all-occurrence behaviour sampling of 199 collective movements. We found that initiators of a collective movement usually chose the direction in which more individuals displayed pre-departure behavior. Dominant individuals contributed to group movements more than subordinates, especially juveniles, measured as frequencies of successful initiations and pre-departure behaviour. Joining was determined by affiliative relationships and the number of individuals that already joined the movement (mimetism). Thus, in our study group partially shared consensus decisions mediated by selective mimetism seemed to be prevalent, overall supporting the suggestion that a species' social style affects the organization of group movements. As only the most tolerant species show equally shared consensus decisions whereas in others the decision is partially shared with a bias to dominant individuals the type of consensus decisions seems to follow a stepwise relation. Joining order may also follow a stepwise, however opposite, relationship, because dominance only determined joining in highly despotic, but not in intermediate and

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

    Directory of Open Access Journals (Sweden)

    Anne Seltmann

    Full Text Available 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

  14. Intergroup interactions in Tibetan macaques at Mt. Emei, China.

    Science.gov (United States)

    Zhao, Q K

    1997-12-01

    Data on intergroup-interactions (I-I) were collected in 5 seasonally provisioned groups (A, B, D, D1, and E) of Tibetan macaques (Macaca thibetana) at Mt. Emei in three 70-day periods between 1991 April-June (P1), September-November (P2), December-1992 February (P3). The I-I were categorized as forewarning made by high-ranking males (including Branch Shaking and/or Loud Calls), long-distance interactions in space (specified by changes in their foraging movements), and close encounters (with Affinitive Behavior, Male's Herding Female, Sexual Interaction, Severe Conflict, Adult Male-male Conflict, Opportunistic Advance and Retreat, etc. performed by different age-sex classes). From periods P1 to P3, the I-I rate decreased with reduction in population density as a positive correlate of food clumpedness or the number of potential feeders along a pedestrian trail. On the other hand, from the birth season (BS, represented by P1 and P3) to the mating season (MS, represented by P2) the dominance relation between groups, which produced a winner and a loser in the encounters, became obscure; the proportion of close encounters in the I-I increased; the asymmetry (local groups over intruders) of forewarning signals disappeared; the rate of branch shaking decreased; and sometimes intergroup cohesion appeared. Considering that sexual interactions also occurred between the encountering groups, above changes in intergroup behaviors may be explained with a model of the way in which the competition for food (exclusion) and the sexual attractiveness between opposite sexes were in a dynamic equilibrium among the groups, with the former outweighing the latter in the BS, and conversely in the MS. Females made 93% of severe conflicts, which occurred in 18% of close encounters. Groups fissioned in the recent past shared the same home range, and showed the highest hostility to each other by females. In conspicuous contrast with females' great interest in intergroup food/range competition

  15. IgG Binding Characteristics of Rhesus Macaque FcγR.

    Science.gov (United States)

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

    2016-10-01

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

  16. High resolution karyotype of Thai crab-eating macaque (Macaca fascicularis

    Directory of Open Access Journals (Sweden)

    Fan Xiaobo

    2014-01-01

    Full Text Available Comparative chromosome banding analysis and/or fluorescence in situ hybridization (FISH studies are established approaches to compare human and ape chromosomes. FISH banding is a relatively new and not routinely applied method very well suited to provide to a better understanding of the evolutionary history of primate and human phylogeny. Here multicolor banding (MCB-applying probes derived from Homo sapiens were used to analyze the chromosomes of Thai crab-eating macaque (Macaca fascicularis. The results agree with those of previous studies in other macaques, e.g. Macaca sylvanus or Macaca nemestrina. This result highlights that morphological differences within the Cercopithecoidea must be found rather in subchromosomal changes or even in epigenetics than in gross structural alterations.

  17. High resolution karyotype of thai crab-eating macaque (Macaca fascicularis

    Directory of Open Access Journals (Sweden)

    Fan Xiaobo

    2014-01-01

    Full Text Available Comparative chromosome banding analysis and/or fluorescence in situ hybridization (FISH studies are established approaches to compare human and ape chromosomes. FISH-banding is a relatively new and not routinely applied method suited very well to provide to a better understanding of the evolutionary history of primate and human phylogeny. Here multicolor banding (MCB applying probes derived from Homo sapiens was used to analyze the chromosomes of Thai crab-eating macaque (Macaca fascicularis. The results agree with those of previous studies in other macaques, e.g. Macaca sylvanus or Macaca nemestrina. This result pinpoints, that morphological differences within the Ceropithecoidae must be founded rather in subchromosomal changes or even in epigenetics than in gross structural alterations.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

    Science.gov (United States)

    Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

    2017-08-15

    A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART.IMPORTANCE Resting CD4(+) T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV

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

    Science.gov (United States)

    Bertrand, Henri; Mindus, Claire; Flecknell, Paul

    2016-01-01

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

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

    Science.gov (United States)

    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.

  2. Fetal sex determination of macaque monkeys by a nested PCR using maternal plasma.

    Science.gov (United States)

    Mitsunaga, Fusako; Ueiwa, Miyuki; Kamanaka, Yoshirou; Morimoto, Mayumi; Nakamura, Shin

    2010-01-01

    Non-invasive fetal sex determination is required for biomedical studies, in which some sexual difference would be expected in fetal events, in order to make a choice of male or female fetus. To detect male fetal DNA of the sex-determining region Y gene (SRY) in maternal macaque plasma, nested real-time PCR using the SYBR Green system was developed. In all cases of pregnant macaques with male fetuses, a nested PCR product of SRY was amplified from the mother's plasma, while no amplicon was detected in any case of pregnancy with a female fetus. Interestingly, fetal SRY DNA appeared to be cleared rapidly from the maternal blood after parturition. The current method is sensitive and can be performed with a regular PCR machine.

  3. A Review of Plasmodium coatneyi-Macaque Models of Severe Malaria.

    Science.gov (United States)

    Lombardini, E D; Gettayacamin, M; Turner, G D H; Brown, A E

    2015-11-01

    Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.

  4. Central projections of intrinsically photosensitive retinal ganglion cells in the macaque monkey

    DEFF Research Database (Denmark)

    Hannibal, J; Kankipati, L; Strang, C E

    2014-01-01

    ). The ipRGCs regulate other nonimage-forming visual functions such as the pupillary light reflex, masking behavior, and light-induced melatonin suppression. To evaluate whether PACAP-immunoreactive retinal projections are useful as a marker for central projection of ipRGCs in the monkey brain, we......-expressing cells characterized as inner and outer stratifying melanopsin RGCs. Two macaque monkeys were anesthetized and received a unilateral intravitreal injection of CtB. Bilateral retinal projections containing colocalized CtB and PACAP immunostaining were identified in the SCN, the lateral geniculate complex...... including the pregeniculate nucleus, the pretectal olivary nucleus, the nucleus of the optic tract, the brachium of the superior colliculus, and the superior colliculus. In conclusion, PACAP-immunoreactive projections with colocalized CtB represent retinal projections of ipRGCs in the macaque monkey...

  5. Generous leaders and selfish underdogs: pro-sociality in despotic macaques.

    Directory of Open Access Journals (Sweden)

    Jorg J M Massen

    Full Text Available Actively granting food to a companion is called pro-social behavior and is considered to be part of altruism. Recent findings show that some non-human primates behave pro-socially. However, pro-social behavior is not expected in despotic species, since the steep dominance hierarchy will hamper pro-sociality. We show that some despotic long-tailed macaques do grant others access to food. Moreover, their dominance hierarchy determines pro-social behavior in an unexpected way: high-ranking individuals grant, while low-ranking individuals withhold their partner access to food. Surprisingly, pro-social behavior is not used by subordinates to obtain benefits from dominants, but by dominants to emphasize their dominance position. Hence, Machiavellian macaques rule not through "fear above love", but through "be feared when needed and loved when possible".

  6. Generous leaders and selfish underdogs: pro-sociality in despotic macaques.

    Science.gov (United States)

    Massen, Jorg J M; van den Berg, Lisette M; Spruijt, Berry M; Sterck, Elisabeth H M

    2010-03-17

    Actively granting food to a companion is called pro-social behavior and is considered to be part of altruism. Recent findings show that some non-human primates behave pro-socially. However, pro-social behavior is not expected in despotic species, since the steep dominance hierarchy will hamper pro-sociality. We show that some despotic long-tailed macaques do grant others access to food. Moreover, their dominance hierarchy determines pro-social behavior in an unexpected way: high-ranking individuals grant, while low-ranking individuals withhold their partner access to food. Surprisingly, pro-social behavior is not used by subordinates to obtain benefits from dominants, but by dominants to emphasize their dominance position. Hence, Machiavellian macaques rule not through "fear above love", but through "be feared when needed and loved when possible".

  7. An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes

    DEFF Research Database (Denmark)

    Jin, Xin; He, Mingze; Ferguson, Betsy;

    2012-01-01

    Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human...... primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab......-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger...

  8. Macaque cardiac physiology is sensitive to the valence of passively viewed sensory stimuli.

    Directory of Open Access Journals (Sweden)

    Eliza Bliss-Moreau

    Full Text Available Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period increased and parasympathetic activity (as measured by respiratory sinus arrhythmia decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2002-03-01

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

  11. High Infection Rates in Adult Macaques Following Intravaginal or Intrarectal Zika Virus Inoculation

    Science.gov (United States)

    2017-04-07

    instrument in macaque C4 failed). Notocord-hem Evolution software platform (Version 4.3.0.47, 132 Notocord Inc., Newark, NJ, USA) was used to...Ponlawat A, Jarman RG, Tesh RB, et al. Genetic 275 characterization of Spondweni and Zika viruses and susceptibility of geographically distinct 276...Tropical Medicine and Hygiene. 1952 Sep;46(5):509-20. 282 4. Haddow AD, Schuh AJ, Yasuda CY, Kasper MR, Heang V, Huy R, et al. Genetic 283

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

    OpenAIRE

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

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  14. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

    Science.gov (United States)

    Lin, Philana Ling; Maiello, Pauline; Gideon, Hannah P; Coleman, M Teresa; Cadena, Anthony M; Rodgers, Mark A; Gregg, Robert; O'Malley, Melanie; Tomko, Jaime; Fillmore, Daniel; Frye, L James; Rutledge, Tara; DiFazio, Robert M; Janssen, Christopher; Klein, Edwin; Andersen, Peter L; Fortune, Sarah M; Flynn, JoAnne L

    2016-07-01

    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.

  15. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections▿ †

    Science.gov (United States)

    Brown, Joseph N.; Palermo, Robert E.; Baskin, Carole R.; Gritsenko, Marina; Sabourin, Patrick J.; Long, James P.; Sabourin, Carol L.; Bielefeldt-Ohmann, Helle; García-Sastre, Adolfo; Albrecht, Randy; Tumpey, Terrence M.; Jacobs, Jon M.; Smith, Richard D.; Katze, Michael G.

    2010-01-01

    The host proteome response and molecular mechanisms that drive disease in vivo during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (Macaca fascicularis) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatography-tandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a “core” response to viral infection from a “high” response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process. PMID:20844032

  19. Macaque proteome response to highly pathogenic avian influenza and 1918 reassortant influenza virus infections.

    Science.gov (United States)

    Brown, Joseph N; Palermo, Robert E; Baskin, Carole R; Gritsenko, Marina; Sabourin, Patrick J; Long, James P; Sabourin, Carol L; Bielefeldt-Ohmann, Helle; García-Sastre, Adolfo; Albrecht, Randy; Tumpey, Terrence M; Jacobs, Jon M; Smith, Richard D; Katze, Michael G

    2010-11-01

    The host proteome response and molecular mechanisms that drive disease in vivo during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (Macaca fascicularis) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatography-tandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a "core" response to viral infection from a "high" response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process.

  20. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis

    Science.gov (United States)

    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

  1. PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

    Directory of Open Access Journals (Sweden)

    Philana Ling Lin

    2016-07-01

    Full Text Available 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.

  2. Divergent Simian Arteriviruses Cause Simian Hemorrhagic Fever of Differing Severities in Macaques

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    Victoria Wahl-Jensen

    2016-02-01

    Full Text Available 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.

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

    OpenAIRE

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

    2010-01-01

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

  4. Medroxyprogesterone Acetate Antagonizes the Effects of Estrogen Treatment on Social and Sexual Behavior in Female Macaques

    OpenAIRE

    2004-01-01

    Medroxyprogesterone acetate (MPA) commonly is used in contraception and hormone replacement therapy. However, little is known about its effects within the central nervous system. Using ovariectomized pigtail macaques (Macaca nemestrina), we evaluated the potential for MPA to antagonize estradiol (E2) effects on female sociosexual behavior. Subjects (n = 6) were treated sequentially with placebo, E2 alone, E2 + progesterone (P4), and E2 + MPA. The order of treatments was balanced among subject...

  5. A macaque model of mesial temporal lobe epilepsy induced by unilateral intrahippocampal injection of kainic Acid.

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    Ning Chen

    Full Text Available OBJECTIVE: In order to better investigate the cause/effect relationships of human mesial temporal lobe epilepsy (mTLE, we hereby describe a new non-human primate model of mTLE. METHODS: Ten macaques were studied and divided into 2 groups: saline control group (n = 4 and kainic acid (KA injection group (n = 6. All macaques were implanted bilaterally with subdural electrodes over temporal cortex and depth electrodes in CA3 hippocampal region. KA was stereotaxically injected into the right hippocampus of macaques. All animals were monitored by video and electrocorticography (ECoG to assess status epilepticus (SE and subsequent spontaneous recurrent seizures (SRS. Additionally, in order to evaluate brain injury produced by SE or SRS, we used both neuroimaging, including magnetic resonance image (MRI & magnetic resonance spectroscopy (MRS, and histological pathology, including Nissl stainning and glial fibrillary acid protein (GFAP immunostaining. RESULTS: The typical seizures were observed in the KA-injected animal model. Hippocampal sclerosis could be found by MRI & MRS. Hematoxylin and eosin (H&E staining and GFAP immunostaining showed neuronal loss, proliferation of glial cells, formation of glial scars, and hippocampal atrophy. Electron microscopic analysis of hippocampal tissues revealed neuronal pyknosis, partial ribosome depolymerization, an abnormal reduction in rough endoplasmic reticulum size, expansion of Golgi vesicles and swollen star-shaped cells. Furthermore, we reported that KA was able to induce SE followed by SRS after a variable period of time. Similar to human mTLE, brain damage is confined to the hippocampus. Accordingly, hippocampal volume is in positive correlations with the neuronal cells count in the CA3, especially the ratio of neuron/glial cell. CONCLUSIONS: The results suggest that a model of mTLE can be developed in macaques by intra-hippocampal injection of KA. Brain damage is confined to the hippocampus which

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

    Science.gov (United States)

    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

  7. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever.

    Science.gov (United States)

    Zapata, Juan C; Pauza, C David; Djavani, Mahmoud M; Rodas, Juan D; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S; Salvato, Maria S

    2011-11-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets.

  8. Identification of Hepatocystis species in a macaque monkey in northern Myanmar

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    Chang Q

    2011-11-01

    Full Text Available Qiaocheng Chang1,*, Xiaodong Sun2,*, Jian Wang2,*, Jigang Yin1, Junpeng Song1, Shuai Peng1, Huijun Lu1, Hongning Zhou2, Ning Jiang1, Qijun Chen1,31Key Laboratory of Zoonosis, Jilin University, Changchun; 2Institute for Parasitic Disease Control of Yunnan Province, Puer City, Yunnan; 3Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China *These authors contributed equally to this workBackground: Long-tailed and pig-tailed macaque monkeys are natural hosts of Plasmodium knowlesi, which has been identified as a fifth malaria parasite infecting humans. In this study, we investigated possible infection by this Plasmodium parasite in macaque monkeys using a combination of polymerase chain reaction amplification and sequencing.Methods: Forty-five blood samples were obtained in 2010 from macaques in northern Myanmar near Yunnan Province of China and investigated for possible infection with Plasmodium species using a nested polymerase chain reaction method for amplification of 18S SSU rRNA genes.Results: Positive amplification was obtained from one monkey, and both sequence and phylogenetic analysis indicated that the parasite was of the Hepatocystis species lineage.Conclusion: The results suggest that a combination of polymerase chain reaction amplification and sequence identification would be necessary for detection of Plasmodium knowlesi infection in both humans and its natural hosts.Keywords: Plasmodium knowlesi, monkey, parasite, malaria

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  11. Food provisioning and stone handling tradition in Japanese macaques: a comparative study of ten troops.

    Science.gov (United States)

    Leca, Jean-Baptiste; Gunst, Noëlle; Huffman, Michael A

    2008-08-01

    By addressing the influence of food provisioning on stone handling (SH), a behavioral tradition in Japanese macaques, this study contributes to the ongoing debate in cultural primatology by asking whether human intervention influences the emergence or propagation of behavioral traditions. SH is a form of object play consisting of the manipulation of stones by performing various behavioral patterns. We tested the hypothesis that the frequency of food provisioning affects the daily performance, form, and context of occurrence of SH by influencing a troop's feeding-related activity budget. We used a standardized observation procedure to investigate SH in ten troops of Japanese macaques. In troops provisioned several times a day, SH was more frequent, longer, and more prevalent during provisioning than nonprovisioning periods. These effects of provisioning were not significant in troops provisioned less frequently. SH was more frequently integrated with food-related activities in troops supplied with food several times a day than in the other troops. Food provisioning may be a key factor in the innovation and transformation phases of the SH tradition in Japanese macaques.

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

    Science.gov (United States)

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

    2015-08-01

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

  13. Genetic diversity and population structure of long-tailed macaque (Macaca fascicularis) populations in Peninsular Malaysia.

    Science.gov (United States)

    Nikzad, Sonia; Tan, Soon Guan; Yong Seok Yien, Christina; Ng, Jillian; Alitheen, Noorjahan Banu; Khan, Razib; Rovie-Ryan, Jeffrine J; Valdiani, Alireza; Khajeaian, Parastoo; Kanthaswamy, Sree

    2014-12-01

    The genetic diversity and structure of long-tailed macaques (Macaca fascicularis) in Peninsular Malaysia, a widely used non-human primate species in biomedical research, have not been thoroughly characterized. Thirteen sites of wild populations of long-tailed macaques representing six states were sampled and analyzed with 18 STR markers. The Sunggala and Penang Island populations showed the highest genetic diversity estimates, while the Jerejak Island population was the most genetically discrete due to isolation from the mainland shelf. Concordant with pairwise F(st) estimates, STRUCTURE analyses of the seven PCA-correlated clusters revealed low to moderate differentiation among the sampling sites. No association between geographic and genetic distances exists, suggesting that the study sites, including island study sites, are genetically if not geographically contiguous. The status of the genetic structure and composition of long-tailed macaque populations require further scrutiny to develop this species as an important animal model in biomedical research. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2010-01-01

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

  15. Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

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    Maria S. Salvato

    2007-01-01

    Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

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

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    Victoria Wahl-Jensen

    Full Text Available 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.

  17. Surface-based atlases of cerebellar cortex in the human, macaque, and mouse

    Science.gov (United States)

    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).

  18. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever

    Science.gov (United States)

    Zapata, Juan C.; Pauza, C. David; Djavani, Mahmoud M.; Rodas, Juan D.; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S.; Salvato, Maria S.

    2011-01-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets. PMID:21820469

  19. Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors.

    Science.gov (United States)

    Dobard, Charles; Sharma, Sunita; Parikh, Urvi M; West, Rolieria; Taylor, Andrew; Martin, Amy; Pau, Chou-Pong; Hanson, Debra L; Lipscomb, Jonathan; Smith, James; Novembre, Francis; Hazuda, Daria; Garcia-Lerma, J Gerardo; Heneine, Walid

    2014-03-12

    Coitally delivered microbicide gels containing antiretroviral drugs are important for HIV prevention. However, to date, microbicides have contained entry or reverse transcriptase inhibitors that block early steps in virus infection and thus need to be given as a preexposure dose that interferes with sexual practices and may limit compliance. Integrase inhibitors block late steps after virus infection and therefore are more suitable for post-coital dosing. We first determined the kinetics of strand transfer in vitro and confirmed that integration begins about 6 hours after infection. We then used a repeat-challenge macaque model to assess efficacy of vaginal gels containing integrase strand transfer inhibitors when applied before or after simian/human immunodeficiency virus (SHIV) challenge. We showed that gel containing the strand transfer inhibitor L-870812 protected two of three macaques when applied 30 min before SHIV challenge. We next evaluated the efficacy of 1% raltegravir gel and demonstrated its ability to protect macaques when applied 3 hours after SHIV exposure (five of six protected; P test). Breakthrough infections showed no evidence of drug resistance in plasma or vaginal secretions despite continued gel dosing after infection. We documented rapid vaginal absorption reflecting a short pharmacological lag time and noted that vaginal, but not plasma, virus load was substantially reduced in the breakthrough infection after raltegravir gel treatment. We provide a proof of concept that topically applied integrase inhibitors protect against vaginal SHIV infection when administered shortly before or 3 hours after virus exposure.

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

    Science.gov (United States)

    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

  1. A diffusion-tensor-based white matter atlas for rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Elizabeth Zakszewski

    Full Text Available Atlases of key white matter (WM structures in humans are widely available, and are very useful for region of interest (ROI-based analyses of WM properties. There are histology-based atlases of cortical areas in the rhesus macaque, but none currently of specific WM structures. Since ROI-based analysis of WM pathways is also useful in studies using rhesus diffusion tensor imaging (DTI data, we have here created an atlas based on a publicly available DTI-based template of young rhesus macaques. The atlas was constructed to mimic the structure of an existing human atlas that is widely used, making results translatable between species. Parcellations were carefully hand-drawn on a principle-direction color-coded fractional anisotropy image of the population template. The resulting atlas can be used as a reference to which registration of individual rhesus data can be performed for the purpose of white-matter parcellation. Alternatively, specific ROIs from the atlas may be warped into individual space to be used in ROI-based group analyses. This atlas will be made publicly available so that it may be used as a resource for DTI studies of rhesus macaques.

  2. Mapping the hierarchical layout of the structural network of the macaque prefrontal cortex.

    Science.gov (United States)

    Goulas, Alexandros; Uylings, Harry B M; Stiers, Peter

    2014-05-01

    A consensus on the prefrontal cortex (PFC) holds that it is pivotal for flexible behavior and the integration of the cognitive, affective, and motivational domains. Certain models have been put forth and a dominant model postulates a hierarchical anterior-posterior gradient. The structural connectivity principles of this model dictate that increasingly anterior PFC regions exhibit more efferent connections toward posterior ones than vice versa. Such hierarchical asymmetry principles are thought to pertain to the macaque PFC. Additionally, the laminar patterns of the connectivity of PFC regions can be used for defining hierarchies. In the current study, we formally tested the asymmetry-based hierarchical principles of the anterior-posterior model by employing an exhaustive dataset on macaque PFC connectivity and tools from network science. On the one hand, the asymmetry-based principles and predictions of the hierarchical anterior-posterior model were not confirmed. The wiring of the macaque PFC does not fully correspond to the principles of the model, and its asymmetry-based hierarchical layout does not follow a strict anterior-posterior gradient. On the other hand, our results suggest that the laminar-based hierarchy seems a more tenable working hypothesis for models advocating an anterior-posterior gradient. Our results can inform models of the human PFC.

  3. A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251.

    Science.gov (United States)

    Van Rompay, Koen K A; Hunter, Zoe; Jayashankar, Kartika; Peabody, Julianne; Montefiori, David; LaBranche, Celia C; Keele, Brandon F; Jensen, Kara; Abel, Kristina; Chackerian, Bryce

    2014-02-01

    As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque CCR5 could prevent or suppress vaginal infection with highly virulent SIVmac251. Twelve macaques were vaccinated with a bacteriophage Qß-based vaccine targeting macaque CCR5 (Qß.CCR5). Six control animals were immunized with the Qß platform alone. All animals immunized with Qß.CCR5 developed high-titer anti-CCR5 antibody responses. Macaques were vaginally challenged with a high dose of SIVmac251. The mean peak viral RNA levels in the vaccinated groups were 30-fold lower than in the control group (10(6.8) versus 10(8.3) copies/ml plasma). Three of the 12 vaccinated macaques dramatically suppressed simian immunodeficiency virus (SIV) replication: peak viral loads were low (10(3) to 10(4) RNA copies/ml), and SIV RNA became undetectable from 6 weeks onward. No viral RNA or DNA could be detected in colon and lymph node biopsy specimens collected 13 months after challenge. In vivo depletion of CD8(+) cells failed to induce a viral rebound. However, once anti-CCR5 antibody responses had waned, the 3 animals became infected after intravaginal and/or intravenous rechallenge. In conclusion, vaccination against CCR5 was associated with dramatic suppression of virus replication in a subset (25%) of macaques. These data support further research of vaccination against CCR5 to combat HIV infection.

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

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    Tamara Aliza Rachel Weinstein

    2014-08-01

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

  5. Somato-motor haptic processing in posterior inner perisylvian region (SII/pIC of the macaque monkey.

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    Hiroaki Ishida

    Full Text Available The posterior inner perisylvian region including the secondary somatosensory cortex (area SII and the adjacent region of posterior insular cortex (pIC has been implicated in haptic processing by integrating somato-motor information during hand-manipulation, both in humans and in non-human primates. However, motor-related properties during hand-manipulation are still largely unknown. To investigate a motor-related activity in the hand region of SII/pIC, two macaque monkeys were trained to perform a hand-manipulation task, requiring 3 different grip types (precision grip, finger exploration, side grip both in light and in dark conditions. Our results showed that 70% (n = 33/48 of task related neurons within SII/pIC were only activated during monkeys' active hand-manipulation. Of those 33 neurons, 15 (45% began to discharge before hand-target contact, while the remaining neurons were tonically active after contact. Thirty-percent (n = 15/48 of studied neurons responded to both passive somatosensory stimulation and to the motor task. A consistent percentage of task-related neurons in SII/pIC was selectively activated during finger exploration (FE and precision grasping (PG execution, suggesting they play a pivotal role in control skilled finger movements. Furthermore, hand-manipulation-related neurons also responded when visual feedback was absent in the dark. Altogether, our results suggest that somato-motor neurons in SII/pIC likely contribute to haptic processing from the initial to the final phase of grasping and object manipulation. Such motor-related activity could also provide the somato-motor binding principle enabling the translation of diachronic somatosensory inputs into a coherent image of the explored object.

  6. Tactile orientation perception: an ideal observer analysis of human psychophysical performance in relation to macaque area 3b receptive fields.

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    Peters, Ryan M; Staibano, Phillip; Goldreich, Daniel

    2015-12-01

    The ability to resolve the orientation of edges is crucial to daily tactile and sensorimotor function, yet the means by which edge perception occurs is not well understood. Primate cortical area 3b neurons have diverse receptive field (RF) spatial structures that may participate in edge orientation perception. We evaluated five candidate RF models for macaque area 3b neurons, previously recorded while an oriented bar contacted the monkey's fingertip. We used a Bayesian classifier to assign each neuron a best-fit RF structure. We generated predictions for human performance by implementing an ideal observer that optimally decoded stimulus-evoked spike counts in the model neurons. The ideal observer predicted a saturating reduction in bar orientation discrimination threshold with increasing bar length. We tested 24 humans on an automated, precision-controlled bar orientation discrimination task and observed performance consistent with that predicted. We next queried the ideal observer to discover the RF structure and number of cortical neurons that best matched each participant's performance. Human perception was matched with a median of 24 model neurons firing throughout a 1-s period. The 10 lowest-performing participants were fit with RFs lacking inhibitory sidebands, whereas 12 of the 14 higher-performing participants were fit with RFs containing inhibitory sidebands. Participants whose discrimination improved as bar length increased to 10 mm were fit with longer RFs; those who performed well on the 2-mm bar, with narrower RFs. These results suggest plausible RF features and computational strategies underlying tactile spatial perception and may have implications for perceptual learning.

  7. Lack of viral control and development of cART escape mutations in macaques after bone marrow transplantation

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    PETERSON, Christopher W.; HAWORTH, Kevin G.; POLACINO, Patricia; HUANG, Meei-Li; SYKES, Craig; OBENZA, Willimark M.; REPETTO, Andrea C.; KASHUBA, Angela; BUMGARNER, Roger; DeROSA, Stephen C.; WOOLFREY, Ann E.; JEROME, Keith R.; MULLINS, James I.; HU, Shiu-Lok; KIEM, Hans-Peter

    2015-01-01

    Objective We have previously demonstrated robust control of simian/human immunodeficiency virus (SHIV1157-ipd3N4) viremia following administration of combination antiretroviral therapy (cART) in pigtailed macaques. Here, we sought to determine the safety of hematopoietic stem cell transplantation (HSCT) in cART-suppressed and unsuppressed animals. Design We compared disease progression in animals challenged with SHIV 100 days post-transplant (PT), to controls that underwent transplant following SHIV challenge and stable, cART-dependent viral suppression. Methods SHIV viral load, combination antiretroviral therapy (cART) levels, and anti-SHIV antibodies were measured longitudinally from plasma/serum from each animal. Flow cytometry was used to assess T-cell subset frequencies in peripheral blood and gastrointestinal tract (GI). Deep sequencing was used to identify cART resistance mutations. Results In control animals, virus challenge induced transient peak viremia, viral set point, and durable suppression by cART. Subsequent HSCT was not associated with adverse events in these animals. PT animals were challenged during acute recovery following HSCT, and displayed sustained peak viremia and cART resistance. Although PT animals had comparable plasma levels of antiretroviral drugs and showed no evidence of enhanced infection of myeloid subsets in the periphery, they exhibited a drastic reduction in virus-specific antibody production and decreased T-cell counts. Conclusions These results suggest that virus challenge prior to complete transplant recovery impairs viral control and may promote drug resistance. These findings may also have implications for scheduled treatment interruption (STI) studies in patients on cART during post-HSCT recovery: premature STI could similarly result in lack of viral control and cART resistance. PMID:26372270

  8. Somato-motor haptic processing in posterior inner perisylvian region (SII/pIC) of the macaque monkey.

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    Ishida, Hiroaki; Fornia, Luca; Grandi, Laura Clara; Umiltà, Maria Alessandra; Gallese, Vittorio

    2013-01-01

    The posterior inner perisylvian region including the secondary somatosensory cortex (area SII) and the adjacent region of posterior insular cortex (pIC) has been implicated in haptic processing by integrating somato-motor information during hand-manipulation, both in humans and in non-human primates. However, motor-related properties during hand-manipulation are still largely unknown. To investigate a motor-related activity in the hand region of SII/pIC, two macaque monkeys were trained to perform a hand-manipulation task, requiring 3 different grip types (precision grip, finger exploration, side grip) both in light and in dark conditions. Our results showed that 70% (n = 33/48) of task related neurons within SII/pIC were only activated during monkeys' active hand-manipulation. Of those 33 neurons, 15 (45%) began to discharge before hand-target contact, while the remaining neurons were tonically active after contact. Thirty-percent (n = 15/48) of studied neurons responded to both passive somatosensory stimulation and to the motor task. A consistent percentage of task-related neurons in SII/pIC was selectively activated during finger exploration (FE) and precision grasping (PG) execution, suggesting they play a pivotal role in control skilled finger movements. Furthermore, hand-manipulation-related neurons also responded when visual feedback was absent in the dark. Altogether, our results suggest that somato-motor neurons in SII/pIC likely contribute to haptic processing from the initial to the final phase of grasping and object manipulation. Such motor-related activity could also provide the somato-motor binding principle enabling the translation of diachronic somatosensory inputs into a coherent image of the explored object.

  9. Within-Host Evolution of Simian Arteriviruses in Crab-Eating Macaques.

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    Moncla, Louise H; Weiler, Andrea M; Barry, Gabrielle; Weinfurter, Jason T; Dinis, Jorge M; Charlier, Olivia; Lauck, Michael; Bailey, Adam L; Wahl-Jensen, Victoria; Nelson, Chase W; Johnson, Joshua C; Caì, Yíngyún; Goldberg, Tony L; O'Connor, David H; Jahrling, Peter B; Kuhn, Jens H; Friedrich, Thomas C

    2017-02-15

    Simian arteriviruses are a diverse clade of viruses infecting captive and wild nonhuman primates. We recently reported that Kibale red colobus virus 1 (KRCV-1) causes a mild and self-limiting disease in experimentally infected crab-eating macaques, while simian hemorrhagic fever virus (SHFV) causes lethal viral hemorrhagic fever. Here we characterize how these viruses evolved during replication in cell culture and in experimentally infected macaques. During passage in cell culture, 68 substitutions that were localized in open reading frames (ORFs) likely associated with host cell entry and exit became fixed in the KRCV-1 genome. However, we did not detect any strong signatures of selection during replication in macaques. We uncovered patterns of evolution that were distinct from those observed in surveys of wild red colobus monkeys, suggesting that these species may exert different adaptive challenges for KRCV-1. During SHFV infection, we detected signatures of selection on ORF 5a and on a small subset of sites in the genome. Overall, our data suggest that patterns of evolution differ markedly among simian arteriviruses and among host species. Certain RNA viruses can cross species barriers and cause disease in new hosts. Simian arteriviruses are a diverse group of related viruses that infect captive and wild nonhuman primates, with associated disease severity ranging from apparently asymptomatic infections to severe, viral hemorrhagic fevers. We infected nonhuman primate cell cultures and then crab-eating macaques with either simian hemorrhagic fever virus (SHFV) or Kibale red colobus virus 1 (KRCV-1) and assessed within-host viral evolution. We found that KRCV-1 quickly acquired a large number of substitutions in its genome during replication in cell culture but that evolution in macaques was limited. In contrast, we detected selection focused on SHFV ORFs 5a and 5, which encode putative membrane proteins. These patterns suggest that in addition to diverse

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

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    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 places within the park. Four hundred visitors were interviewed using a questionnaire to gather data on sex, age, purpose and frequency of visit to the park. The number of tourists was significantly higher during weekends than in weekdays in all locations. Humans dominated in the initiation of interspecies interactions--the overall ratio of human-initiated and monkey-initiated interactions was 2.44:1. Human-monkey conflicts accounted for only 16.4% of the total interactions (n=2,166), and adult human males and adult male macaques participated in higher rates than other age/sex groups in these conflicts. Visitors showed more affiliative behavior (15.9%) than agonistic behavior (8%) toward the macaques. In response to visitors' threat or attack, the Formosan macaques mostly showed submissive behavior with bared teeth, squealed or ran away to avoid confrontation (69.1%)--only few responded with counteraggression (18.7%). This study for the first time provided evidence that food provisioning increased both the frequency and duration of aggression among Formosan macaques (P<0.001). During food provisioning, the average frequency and the duration of agonistic events of macaques were more than 4 times higher compared with those without food provisioning. The average frequency of food provision by tourists was 0.73 times/hr--more than twice the incident that monkeys grabbed the food from tourists (0.34 times/hr). If people refrain from feeding monkeys and destroying the city park's natural vegetation, monkeys can be used to educate

  11. Genomic plasticity of the immune-related Mhc class I B region in macaque species

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    Bontrop Ronald E

    2008-10-01

    Full Text Available Abstract Background In sharp contrast to humans and great apes, the expanded Mhc-B region of rhesus and cynomolgus macaques is characterized by the presence of differential numbers and unique combinations of polymorphic class I B genes per haplotype. The MIB microsatellite is closely linked to the single class I B gene in human and in some great apes studied. The physical map of the Mhc of a heterozygous rhesus monkey provides unique material to analyze MIB and Mamu-B copy number variation and then allows one to decipher the compound evolutionary history of this region in primate species. Results In silico research pinpointed 12 MIB copies (duplicons, most of which are associated with expressed B-genes that cluster in a separate clade in the phylogenetic tree. Generic primers tested on homozygous rhesus and pedigreed cynomolgus macaques allowed the identification of eight to eleven MIB copies per individual. The number of MIB copies present per haplotype varies from a minimum of three to six in cynomolgus macaques and from five to eight copies in rhesus macaques. Phylogenetic analyses highlight a strong transpecific sharing of MIB duplicons. Using the physical map, we observed that, similar to MIB duplicons, highly divergent Mamu-B genes can be present on the same haplotype. Haplotype variation as reflected by the copy number variation of class I B loci is best explained by recombination events, which are found to occur between MIBs and Mamu-B. Conclusion The data suggest the existence of highly divergent MIB and Mamu-B lineages on a given haplotype, as well as variable MIB and B copy numbers and configurations, at least in rhesus macaque. Recombination seems to occur between MIB and Mamu-B loci, and the resulting haplotypic plasticity at the individual level may be a strategy to better cope with pathogens. Therefore, evolutionary inferences based on the multiplicated MIB loci but also other markers close to B-genes appear to be promising for

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

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

    2017-01-01

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

  13. Variation in hair δ13C and δ15N values in long-tailed macaques (Macaca fascicularis) from Singapore

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    Schillaci, Michael A.; Castellini, J. Margaret; Stricker, Craig A.; Jones-Engel, Lisa; Lee, Benjamin P.Y.-H.

    2014-01-01

    Much of the primatology literature on stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) has focused on African and New World species, with comparatively little research published on Asian primates. Here we present hair δ13C and δ15N isotope values for a sample of 33 long-tailed macaques from Singapore. We evaluate the suggestion by a previous researcher that forest degradation and biodiversity loss in Singapore have led to a decline in macaque trophic level. The results of our analysis indicated significant spatial variability in δ13C but not δ15N. The range of variation in δ13C was consistent with a diet based on C3 resources, with one group exhibiting low values consistent with a closed canopy environment. Relative to other macaque species from Europe and Asia, the macaques from Singapore exhibited a low mean δ13C value but mid-range mean δ15N value. Previous research suggesting a decline in macaque trophic level is not supported by the results of our study.

  14. Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

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    Wang, Rong; Wu, Lingjie; Tang, Zuohua; Sun, Xinghuai; Feng, Xiaoyuan; Tang, Weijun; Qian, Wen; Wang, Jie; Jin, Lixin; Zhong, Yufeng; Xiao, Zebin

    2017-04-15

    Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices.

  15. Use of Femoral Head and Neck Ostectomy and Physical Therapy to Manage Osteoarthritis in a Rhesus Macaque (Macaca mulatta).

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    Uchihashi, Mayu; Hampel, Joseph A; Nemzek, Jean A; Saccone, Phillip A; Eaton, Kathryn A; Nowland, Megan H

    2015-06-01

    Osteoarthritis is associated with pain and immobility in both humans and animals. However, available resources for osteoarthritis management in captive NHP are limited. This case report describes a novel management strategy for a 10-y-old male macaque with unilateral hindlimb lameness, prominent muscle wasting, and severely limited range of motion. Radiographs of the affected limb showed lytic lesions of the femoral head. To relieve pain and improve mobility, femoral head and neck ostectomy (FHO) was performed, and multiple pharmacotherapies were initiated. The macaque also received a unique method of physical therapy that required no sedation, acted as enrichment, and was implemented by using a conventional caging system. The response to therapy was monitored by measuring thigh circumference in the operated and nonoperated limbs, which demonstrated improvement in both legs. The unique physical therapy in conjunction with surgery and pharmacotherapy benefited the macaque with osteoarthritis by reducing discomfort and improving mobility.

  16. Contrasting the edge- and surface-based theories of object recognition: behavioral evidence from macaques (Macaca mulatta).

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    Parron, Carole; Washburn, David

    2010-01-01

    This study assessed the contribution of edge and surface cues on object representation in macaques (Macaca mulatta). In Experiments 1 and 2, 5 macaques were trained to discriminate 4 simple volumetric objects (geons) and were subsequently tested for their ability to recognize line drawings, silhouettes, and light changes of these geons. Performance was above chance in all test conditions and was similarly high for the line drawings and silhouettes of geons, suggesting the use of the outline shape to recognize the original objects. In addition, transfer for the geons seen under new lighting was greater than for the other stimuli, stressing the importance of the shading information. Experiment 3, using geons filled with new textures, showed that a radical change in the surface cues does not prevent object recognition. It is concluded that these findings support a surface-based theory of object recognition in macaques, although it does not exclude the contribution of edge cues, especially when surface details are not available.

  17. Depot-medroxyprogesterone acetate does not reduce the prophylactic efficacy of emtricitabine and tenofovir disoproxil fumarate in macaques.

    Science.gov (United States)

    Radzio, Jessica; Hanley, Krisztina; Mitchell, James; Ellis, Shanon; Deyounks, Frank; Jenkins, Leecresia; Heneine, Walid; García-Lerma, J Gerardo

    2014-12-01

    Concerns that the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) may increase the risk of HIV acquisition in women led to questions on whether DMPA could reduce efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention. We used a macaque model to investigate the impact of prolonged DMPA exposure on PrEP with emtricitabine/tenofovir disoproxil fumarate. Twelve pigtail macaques treated with DMPA were exposed vaginally to simian HIV once a week for up to 5 months and received either placebo (n = 6) or emtricitabine/tenofovir disoproxil fumarate (n = 6). All control macaques were infected, whereas the PrEP-treated animals remained protected (P = 0.0007). This model suggests that women using DMPA will fully benefit from PrEP.

  18. Differences in compact bone tissue microscopic structure between adult humans (Homo sapiens) and Assam macaques (Macaca assamensis).

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    Nganvongpanit, Korakot; Phatsara, Manussabhorn; Settakorn, Jongkolnee; Mahakkanukrauh, Pasuk

    2015-09-01

    This study investigated the osteon structure of adult humans and Assam macaques, which served as a nonhuman primate model, to find an adequate key for species identification. Samples of compact bone from humans (n=5) and Assam macaques (n=5) - including humerus (n=20), radius (n=20), ulna (n=20), femur (n=20), tibia (n=20) and fibula (n=20) - were processed using conventional histological techniques. 100 secondary osteons from each sample were evaluated under light microscopy. Parameter measurements included: diameter, perimeter and area of Haversian canal and osteon; distance between centers of Haversian canals; and ratio between diameter of Haversian canal and osteon. Four parameters, including diameters and areas of Haversian canal and osteon, demonstrated significantly higher (P<0.05) values in humans than in Assam macaques. Therefore, compact bone microstructure could thus be used as a potential tool to differentiate human and nonhuman primates.

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

    Science.gov (United States)

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

    2016-01-01

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

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

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    Athe M N Tsibris

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

  1. Visualization of transepithelial passage of the immunogenic 33-residue peptide from alpha-2 gliadin in gluten-sensitive macaques.

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    Kaushiki Mazumdar

    Full Text Available BACKGROUND: Based on clinical, histopathological and serological similarities to human celiac disease (CD, we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2 antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from alpha(2-gliadin in the distal duodenum of gluten-sensitive macaques. METHODOLOGY/PRINCIPAL FINDINGS: Six rhesus macaques were selected for study from a pool of 500, including two healthy controls and four gluten-sensitive animals with elevated anti-gliadin or anti-TG2 antibodies as well as history of non-infectious chronic diarrhea. Pediatric endoscope-guided pinch biopsies were collected from each animal's distal duodenum following administration of a gluten-containing diet (GD and again after remission by gluten-free diet (GFD. Control biopsies always showed normal villous architecture, whereas gluten-sensitive animals on GD exhibited histopathology ranging from mild lymphocytic infiltration to villous atrophy, typical of human CD. Immunofluorescent microscopic analysis of biopsies revealed IgG+ and IgA+ plasma-like cells producing antibodies that colocalized with TG2 in gluten-sensitive macaques only. Following instillation in vivo, the Cy-3-labeled 33-residue gluten peptide colocalized with the brush border protein villin in all animals. In a substantially enteropathic macaque with "leaky" duodenum, the peptide penetrated beneath the epithelium into the lamina propria. CONCLUSIONS/SIGNIFICANCE: The rhesus macaque model of gluten sensitivity not only resembles the histopathology of CD but it also may provide a model for studying intestinal permeability in states of epithelial integrity and disrepair.

  2. Social network size affects neural circuits in macaques.

    Science.gov (United States)

    Sallet, J; Mars, R B; Noonan, M P; Andersson, J L; O'Reilly, J X; Jbabdi, S; Croxson, P L; Jenkinson, M; Miller, K L; Rushworth, M F S

    2011-11-04

    It has been suggested that variation in brain structure correlates with the sizes of individuals' social networks. Whether variation in social network size causes variation in brain structure, however, is unknown. To address this question, we neuroimaged 23 monkeys that had been living in social groups set to different sizes. Subject comparison revealed that living in larger groups caused increases in gray matter in mid-superior temporal sulcus and rostral prefrontal cortex and increased coupling of activity in frontal and temporal cortex. Social network size, therefore, contributes to changes both in brain structure and function. The changes have potential implications for an animal's success in a social context; gray matter differences in similar areas were also correlated with each animal's dominance within its social network.

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

    OpenAIRE

    2011-01-01

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

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

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    Yuan Qiaoping

    2012-06-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

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    Kanthaswamy S

    2008-05-01

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

  7. Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques.

    Science.gov (United States)

    Lindell, Stephen G; Schwandt, Melanie L; Sun, Hui; Sparenborg, Jeffrey D; Björk, Karl; Kasckow, John W; Sommer, Wolfgang H; Goldman, David; Higley, J Dee; Suomi, Stephen J; Heilig, Markus; Barr, Christina S

    2010-04-01

    Neuropeptide Y (NPY) counters stress and is involved in neuroadaptations that drive escalated alcohol drinking in rodents. In humans, low NPY expression predicts amygdala response and emotional reactivity. Genetic variation that affects the NPY system could moderate stress resilience and susceptibility to alcohol dependence. To determine whether functional NPY variation influences behavioral adaptation to stress and alcohol consumption in a nonhuman primate model of early adversity (peer rearing). We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays using nuclear extract from testes, brain, and hypothalamus. Levels of NPY in cerebrospinal fluid were measured by radioimmunoassay, and messenger RNA levels were assessed in the amygdala using real-time polymerase chain reaction. Animals were exposed to repeated social separation stress and tested for individual differences in alcohol consumption. Animals were genotyped for -1002 T > G, and the data were analyzed using analysis of variance. National Institutes of Health Animal Center. Subjects Ninety-six rhesus macaques. Main Outcome Measure Behavior arousal during social separation stress and ethanol consumption. The G allele altered binding of regulatory proteins in all nuclear extracts tested, and -1002 T > G resulted in lower levels of NPY expression in the amygdala. Macaques exposed to adversity had lower cerebrospinal fluid NPY levels and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation. Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining gene x environment interactions in humans.

  8. Novel Methodology for Creating Macaque Retinas with Sortable Photoreceptors and Ganglion Cells

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    Shreyasi Choudhury

    2016-12-01

    Full Text Available Purpose: The ability to generate macaque retinas with sortable cell populations would be of great benefit to both basic and translational studies of the primate retina. The purpose of our study was therefore to develop methods to achieve this goal by selectively labeling, in life, photoreceptors (PRs and retinal ganglion cells (RGCs with separate fluorescent markers. Methods: Labeling of macaque (Macaca fascicularis PRs and RGCs was accomplished by subretinal delivery of AAV5-hGRK1-GFP, and retrograde transport of micro-ruby™ from the lateral geniculate nucleus, respectively. Retinas were anatomically separated into different regions. Dissociation conditions were optimized, and cells from each region underwent fluorescent activated cell sorting (FACS. Expression of retinal cell type- specific genes was assessed by quantitative real-time PCR to characterize isolated cell populations. Results: We show that macaque PRs and RGCs can be simultaneously labeled in-life and enriched populations isolated by FACS. Recovery from different retinal regions indicated efficient isolation/enrichment for PRs and RGCs, with the macula being particularly amendable to this technique. Conclusions: The methods and materials presented here allow for the identification of novel reagents designed to target retinal ganglion cells and/or photoreceptors in a species that is phylogenetically and anatomically similar to human. These techniques will enable screening of intravitreally- delivered AAV capsid libraries for variants with increased tropism for PRs and/or RGCs and the evaluation of vector tropism and/or cellular promoter activity of gene therapy vectors in a clinically relevant species.

  9. Pharmacokinetics of 2 formulations of buprenorphine in macaques (Macaca mulatta and Macaca fascicularis).

    Science.gov (United States)

    Nunamaker, Elizabeth A; Halliday, Lisa C; Moody, David E; Fang, Wenfang B; Lindeblad, Matthew; Fortman, Jeffrey D

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tested doses. The low and high doses of buprenorphine had elimination half-lives of 2.6 ± 0.7 and 5.3 ± 2.0 h, respectively, but the low-dose data were constrained by the sensitivity of the analytical method. Sustained-release buprenorphine had an elimination half-life of 42.6 ± 26.2 h. The AUC0-Tlast of buprenorphine were 9.1 ± 4.3 and 39.0 ± 25.1 ng × h/mL for the low and high doses, respectively, and sustained-release buprenorphine had an AUC0-Tlast of 177 ± 74 ng × h/mL. Assuming a hypothesized therapeutic buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h. These results further demonstrate that a single 0.2-mg/kg SC injection of sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL for 5 d in macaques. These findings support a new dosing strategy using sustained-release buprenorphine to improve pain management, decrease animal stress, improve animal welfare, and simplify the postoperative management of nonhuman primates in laboratory animal and zoological settings.

  10. No-scalpel vasectomy by electrocauterization in free range rhesus macaques (Macaca mulatta

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    A. Raj

    2012-02-01

    Full Text Available The objective of the study was to standardize a new method of vasectomy in male rhesus macaques (Macaca mulatta. A total of 208 free range male rhesus macaques captured from different locations in Shivalik Hills in a population control programme of the rhesus macaques in India. General anaesthesia was achieved by using a combination of ketamine hydrochloride at 8 mg/kg body weight and xylazine hydrochloride at 2mg/kg body weight intramuscularly in squeeze cage. Surgical procedure of vasectomy was carried out by single-hole no-scalpel technique using a single pre-scrotal skin incision above the median raphae. Spermatic cord was grasped with ringed forceps and was pulled out through the single-hole incision. Vas deferens was separated from the artery-vein complexus and about 3-4 cm portion of vas deferens was resected. Cauterization of both ends of the vas deferens was achieved with electrocautery. The induction time for anaesthesia was 1.40±0.18 min while surgical time for vasectomy was found to be 5.09±0.22 min. Recovery from general anaesthesia was without side-effects after a mean duration of 36.07±1.22 min, whereas the duration of anaesthesia was observed to be 82.27±4.96 min. There were no major complications following the surgery and recovery of animals was smooth. Animals were kept in postoperative care for five days and released at the same capturing site.

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

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    James Andrew Solyst

    2014-11-01

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

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

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    Guang Tian

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

  13. Short-term costs and benefits of grooming in Japanese macaques.

    Science.gov (United States)

    Schino, Gabriele; Alessandrini, Alessandro

    2015-07-01

    This study investigated the short-term consequences of giving grooming in Japanese macaques (Macaca fuscata) in order to obtain information on its immediate costs and benefits. Giving grooming was associated with increased aggression received from groomees and decreased aggression received from third parties (but only as long as the groomer maintained proximity to the groomee). Grooming was also associated with decreased scratching rates. These results emphasize the unpredictable outcome of individual grooming interactions and the difficulties of social decision-making for monkeys living in despotic societies.

  14. Sexual signalling in female crested macaques and the evolution of primate fertility signals

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    Higham James P

    2012-06-01

    Full Text Available Abstract Background Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females’ interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. Results We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Conclusion Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these

  15. Pharmacokinetics of 2 Formulations of Buprenorphine in Macaques (Macaca mulatta and Macaca fascicularis)

    OpenAIRE

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the ...

  16. Captive propagation of threatened primates - the example of the Lion-tailed Macaque Macaca silenus

    Directory of Open Access Journals (Sweden)

    W. Kaumanns

    2013-10-01

    Full Text Available Many conservation-oriented breeding programs are not likely to reach their goal of establishing self-sustaining populations. Some zoo biologists propagate to reconsider zoo-based conservation policies and strategies. The Lion-tailed Macaque is a flagship species for in situ conservation and a high priority species in captive propagation. This article reviews the captive management history of the Lion-tailed Macaque, identifies management patterns that might have negatively influenced the development of the programs, and proposes to use this analysis to initiate a new management perspective. In the North American captive Lion-tailed Macaque population under the Species Survival Plan (SSP, the strong reduction in population size and group sizes due to space problems might have contributed to a decrease in population viability. The population over two decades has declined from almost 300 to less than 100 individuals. In the European population under the European Endangered Species Program (EEP, population size was not limited and larger groups were advocated. The population grew slowly but steadily to a present size of more than 350 individuals over about 23 years. The effective population size has remained low in both SSP and EEP populations. A general conceptual framework that focuses on individuals and their phenotypes for in situ and ex situ conservation recently developed by field conservationists is briefly introduced. It is used to suggest improvements in the management of the Lion-tailed Macaque. It is concluded that the size and structure of a breeding population is to be decided so as to provide conditions and materials for successful reproduction rather than by the available zoo space only. For this, large groups and populations with representation of all age-sex classes are advocated. This would result in a further reduction in the number of species kept in zoos. It is indicated that zoo biology needs to develop new concepts that

  17. Cerebello-thalamo-cortical projections to the posterior parietal cortex in the macaque monkey.

    Science.gov (United States)

    Amino, Y; Kyuhou, S; Matsuzaki, R; Gemba, H

    2001-08-17

    The cerebello-thalamo-posterior parietal cortical projections were investigated electrophysiologically and morphologically in macaque monkeys. In anesthetized monkeys, electrical stimulation of every cerebellar nucleus evoked marked surface-positive, depth-negative (s-P, d-N) cortical field potentials in the superior parietal lobule and the cortical bank of the intraparietal sulcus, but no responses in the inferior parietal lobule. Tract-tracing experiments combining the anterograde method with the retrograde one indicated that the interposed and lateral cerebellar nuclei projected to the posterior parietal cortex mainly through the nucleus ventral lateralis caudalis of the thalamus. The significance of the projections is discussed in connection with cognitive functions.

  18. Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in macaques

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Ji; Ke-Yi Sun; Yan-Hong Feng; Guo-Qing Yin

    2004-01-01

    AIM: To study changes of inflammation-associated cytokine expressions during early phase of endotoxic shock in macague.METHODS: Experiments were performed in Macaque mulatta treated with LPS 2.8 mg/kg in shock model group or with normal saline in control group. Blood samples were collected before, or 60 min, or 120 min after LPS injection,respectively. Liver and spleen tissues were obtained at 120 min after LPS injection. The plasma levels of TNF-α,IL-1 β, IL-10 and IL-12P40 were determined by doubleantibody sandwich ELISA with antibodies against human cytokines. The mRNA levels of TNF-α, IL-1 β, and IL-18 in peripheral blood mononuclear cells (PBMCs), liver and spleen were examined by real-time fluorescence semi-quantitative RT-PCR with the primers based on human genes.RESULTS: Mean systemic arterial pressure (MAP), systemic vascular resistance index (SVRI) and left ventricular work index (LVWI) of macaques were significant declined in shock model group on average 60 min after LPS injection. The plasma levels of TNF-α and IL-10 were significantly increased 60 min after LPS injection and then decreased.The plasma levels of IL-1 β and IL-12P40 were significantly increased at 120 min after LPS injection. The mRNA levels of TNF-α and IL-1 β were significantly increased 60 min after LPS stimulation in PBMCs and 120 min after LPS stimulation in livers. The mRNA level of IL-18 was significantly increased 120 min after LPS stimulation in PBMCs and livers. But in spleen, only TNF-α mRNA level in LPS group was significantly higher 120 min after LPS stimulation, compared with that in control group.CONCLUSION: An endotoxic shock model of Macaque mulatta was successfully established. Both antibodies for ELISA and PCR primers based on human cytokine assays were successfully applied to detect macaque cytokines. In the model, inflammatory cytokines, such as TNF-α, IL-1 β,IL-12 and IL-18 as well as anti-inflammation cytokine IL-10,were released at very early phase of

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

    OpenAIRE

    2002-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2011-01-26

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

  2. Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques.

    Science.gov (United States)

    McCracken, Michael K; Gromowski, Gregory D; Friberg, Heather L; Lin, Xiaoxu; Abbink, Peter; De La Barrera, Rafael; Eckles, Kenneth H; Garver, Lindsey S; Boyd, Michael; Jetton, David; Barouch, Dan H; Wise, Matthew C; Lewis, Bridget S; Currier, Jeffrey R; Modjarrad, Kayvon; Milazzo, Mark; Liu, Michelle; Mullins, Anna B; Putnak, J Robert; Michael, Nelson L; Jarman, Richard G; Thomas, Stephen J

    2017-08-01

    Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.

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

    Science.gov (United States)

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

    2012-08-01

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

  4. Troop Takeover and Reproductive Success of Wild Male Japanese Macaques on Yakushima Island (Macaca fuscata yakui

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    Sachiko Hayakawa

    2011-01-01

    Full Text Available Troop takeover is common in one-male primate groups, but there are few reports in multimale groups. Japanese macaques (Macaca fuscata form multimale groups and males commonly join troops at the bottom rank. On Yakushima island, however, where group size is relatively small, entrance into groups at the alpha position is also observed. This paper reports on the general features of troop takeover, on the predictors of takeover events, and on the reproductive success of takeover males. Troop takeovers occurred only in the mating season; nontroop males (NTMs did not cooperate with each other; former alpha males were rarely expelled from the troop; new alpha males did not commit infanticide; new alpha male tenure in the group was usually less than two years. Logistic regression analysis showed that the number of NTMs associating with a troop predicted the occurrence of troop takeover. Paternity discrimination revealed that 33.3% (3/9 of takeover males succeeded in siring offspring. Contrary to this low success rate, binary logistic regression analysis revealed that the takeover males can expect higher reproductive success compared to troop males. Entering a troop and out-competing the alpha male is one of many available strategies to attain reproductive success in male Japanese macaques.

  5. The effect of solicitations on grooming exchanges among female Japanese macaques at Katsuyama.

    Science.gov (United States)

    Ueno, Masataka; Yamada, Kazunori; Nakamichi, Masayuki

    2014-01-01

    In group-living primates, individuals often exchange grooming with not only kin but also non-kin. We investigated the effect of soliciting behaviors on grooming exchanges in a free-ranging Japanese macaque (Macaca fuscata) group at Katsuyama. In this study, we used a focal animal sampling method, targeting 14 females. Data were collected for 15.75 ± 2.67 (mean ± SD) hours per focal female. We classified female-female pairs into three pair types: kin pairs, affiliated non-kin pairs, and unaffiliated non-kin pairs. Females received grooming more frequently when they solicited after grooming their partners than when they did not solicit in all pair types. In addition, females received grooming less frequently when they did not groom their unaffiliated non-kin partners before soliciting; prior grooming was not needed to receive grooming from kin or affiliated non-kin partners. The degree of grooming reciprocity did not differ according to the frequency with which females in kin or affiliated non-kin pairs solicited after grooming. On the other hand, grooming reciprocity between unaffiliated non-kin females was more balanced when they solicited frequently after grooming, as compared with when they did not. In conclusion, our study suggests that soliciting behaviors promote grooming exchanges in female Japanese macaques.

  6. Electroretinogram analysis of relative spectral sensitivity in genetically identified dichromatic macaques.

    Science.gov (United States)

    Hanazawa, A; Mikami, A; Sulistyo Angelika, P; Takenaka, O; Goto, S; Onishi, A; Koike, S; Yamamori, T; Kato, K; Kondo, A; Suryobroto, B; Farajallah, A; Komatsu, H

    2001-07-03

    The retinas of macaque monkeys usually contain three types of photopigment, providing them with trichromatic color vision homologous to that of humans. However, we recently used molecular genetic analysis to identify several macaques with a dichromatic genotype. The affected X chromosome of these animals contains a hybrid gene of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) photopigments instead of separate genes encoding L and M photopigments. The product of the hybrid gene exhibits a spectral sensitivity close to that of M photopigment; consequently, male monkeys carrying the hybrid gene are genetic protanopes, effectively lacking L photopigment. In the present study, we assessed retinal expression of L photopigment in monkeys carrying the hybrid gene. The relative sensitivities to middle-wavelength (green) and long-wavelength (red) light were measured by electroretinogram flicker photometry. We found the sensitivity to red light to be extremely low in protanopic male monkeys compared with monkeys with the normal genotype. In female heterozygotes, sensitivity to red light was intermediate between the genetic protanopes and normal monkeys. Decreased sensitivity to long wavelengths was thus consistent with genetic loss of L photopigment.

  7. Male mate choice in Tibetan macaques Macaca thibetana at Mt. Huangshan, China

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    Min ZHANG, Jinhua LI, Yong ZHU, Xi WANG, Su WANG

    2010-04-01

    Full Text Available Though females are generally more selective in mate choice, males may also benefit from mate choice if male reproductive success is limited by factors other than simply the number of female mates, and if females differ in short-term reproductive potential. We studied male mate choice in a free-ranging troop of Tibetan macaques Macaca thibetana at Mt. Huangshan, China, from August 2007 to April 2008. We employed focal animal sampling and all occurrence sampling to record sexual related behaviors. Eight adult females were divided into three female quality categories according to the females’ age, rank and parity. Using male mating effort as a proxy for male mate choice, we found that males do distinguish female quality and show time-variant mating strategies. Specifically, females with dominant rank, high fecundity, and middle age attracted significantly more males. Our results suggest that female short-term reproductive potential appears to be an important variable in determining male mating effort. Male Tibetan macaques do exercise mate choice for higher quality females as well as reduce useless reproductive cost, which is consistent with the direct benefits theory of mate choice [Current Zoology 56 (2: 213–221, 2010].

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

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

    2016-09-30

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

  9. FACIAL ASYMMETRY IS NEGATIVELY RELATED TO CONDITION IN FEMALE MACAQUE MONKEYS.

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    Little, Anthony C; Paukner, Annika; Woodward, Ruth A; Suomi, Stephen J

    2012-09-01

    The face is an important visual trait in social communication across many species. In evolutionary terms there are large and obvious selective advantages in detecting healthy partners, both in terms of avoiding individuals with poor health to minimise contagion and in mating with individuals with high health to help ensure healthy offspring. Many models of sexual selection suggest that an individual's phenotype provides cues to their quality. Fluctuating asymmetry is a trait that is proposed to be an honest indicator of quality and previous studies have demonstrated that rhesus monkeys gaze longer at symmetric faces, suggesting preferences for such faces. The current study examined the relationship between measured facial symmetry and measures of health in a captive population of female rhesus macaque monkeys. We measured asymmetry from landmarks marked on front-on facial photographs and computed measures of health based on veterinary health and condition ratings, number of minor and major wounds sustained, and gain in weight over the first four years of life. Analysis revealed that facial asymmetry was negatively related to condition related health measures, with symmetric individuals being healthier than more asymmetric individuals. Facial asymmetry appears to be an honest indicator of health in rhesus macaques and asymmetry may then be used by conspecifics in mate-choice situations. More broadly, our data support the notion that faces are valuable sources of information in non-human primates and that sexual selection based on facial information is potentially important across the primate lineage.

  10. Social modulation of cognition: Lessons from rhesus macaques relevant to education.

    Science.gov (United States)

    Monfardini, Elisabetta; Reynaud, Amélie J; Prado, Jérôme; Meunier, Martine

    2016-12-05

    Any animal, human or non-human, lives in a world where there are others like itself. Individuals' behaviors are thus inevitably influenced by others, and cognition is no exception. Long acknowledged in psychology, social modulations of cognition have been neglected in cognitive neuroscience. Yet, infusing this classic topic in psychology with brain science methodologies could yield valuable educational insights. In recent studies, we used a non-human primate model, the rhesus macaque, to identify social influences representing ancient biases rooted in evolution, and neuroimaging to shed light on underlying mechanisms. The behavioral and neural data garnered in humans and macaques are summarized, with a focus on two findings relevant to human education. First, peers' mistakes stand out as exceptional professors and seem to have devoted areas and neurons in the primates' brain. Second, peers' mere presence suffices to enhance performance in well-learned tasks, possibly by boosting activity in the brain network involved in the task at hand. These findings could be translated into concrete pedagogical interventions in the classroom. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Nutritional Composition of Fruits Selected by Long-Tailed Macaques (Macaca fascicularis) in Kuala Selangor, Malaysia.

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    Kassim, Norazila; Hambali, Kamarul; Amir, Aainaa

    2017-01-01

    Proximate analysis of twelve species of fruits commonly consumed by long-tailed macaques (Macaca fascicularis), i.e., Arenga pinnata, Areca catechu, Terminalia catappa, Elaeis guineensis, Lagerstroemia tomentosa, Mangifera indica, Cascabela thevetia, Muntingia calabura, Musa sp., Artocarpus heterophyllus, Ficus tinctoria ssp. gibbosa and Ficus microcarpa, was conducted with the specific objective to determine the nutritional composition of the foodstuffs of long-tailed macaques. The results showed the following order of nutrients: fibre, protein, fat and ash. Based on the results of the chemical analysis, the highest percentage of fibre content (52.7%), protein (9.9%), fat (77.2%) and ash (8.5%) were found in A. catechu, T. catappa, E. guineensis and C. thevetia, respectively. The nutrient composition of these twelve fruit species was found to differ (ANOVA test: crude protein, F (11,24) = 87.978, p < 0.05; crude fibre, F (11,24) = 28.886, p < 0.05; crude fat, F (11,24) = 2081.396, p < 0.05 and ash, F (11,24) = 41.011, p < 0.05). Fibre was found in the highest amount among the four types of nutrients studied. Here, A. catechu had the highest relative fibre content of all tested fruits, E. guineensis had the highest fat content, T. catappa had the highest protein content, and the total mineral content was highest in C. thevetia.

  12. Grasping-related functional MRI brain responses in the macaque monkey

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    Nelissen, Koen; Vanduffel, Wim

    2011-01-01

    Research in recent decades has suggested the existence of a dedicated brain network devoted to the organization and execution of grasping, one of the most important and skilled movements of primates. Grasping an object requires the transformation of intrinsic object properties such as size, orientation and shape into an appropriate motor scheme shaping the hand. While electrophysiological recordings in the monkey model have proven invaluable for gaining insights into the neuronal substrate underlying this complex behavior, knowledge concerning the existence and organization of a similar system in the human brain is derived mainly from imaging studies. Here we present for the first time functional magnetic resonance imaging (fMRI) of brain activity while macaque monkeys performed reaching and grasping movements in a 3 Tesla MR scanner. Grasping-in-the-dark (compared to reaching) yielded significant activations in anterior intraparietal area (AIP) and ventral premotor area F5, in addition to area PFG in the rostral inferior parietal lobule, somatosensory areas (SI, SII, area 5) and the hand field of F1. Whole-brain macaque fMRI motor studies will be instrumental in establishing possible homologies concerning grasping organization in the human and monkey brains, bridging the gap between human imaging and monkey electrophysiology. PMID:21632943

  13. Social power, conflict policing, and the role of subordination signals in rhesus macaque society.

    Science.gov (United States)

    Beisner, Brianne A; Hannibal, Darcy L; Finn, Kelly R; Fushing, Hsieh; McCowan, Brenda

    2016-05-01

    Policing is a conflict-limiting mechanism observed in many primate species. It is thought to require a skewed distribution of social power for some individuals to have sufficiently high social power to stop others' fights, yet social power has not been examined in most species with policing behavior. We examined networks of subordination signals as a source of social power that permits policing behavior in rhesus macaques. For each of seven captive groups of rhesus macaques, we (a) examined the structure of subordination signal networks and used GLMs to examine the relationship between (b) pairwise dominance certainty and subordination network pathways and (c) policing frequency and social power (group-level convergence in subordination signaling pathways). Networks of subordination signals had perfect linear transitivity, and pairs connected by both direct and indirect pathways of signals had more certain dominance relationships than pairs with no such network connection. Social power calculated using both direct and indirect network pathways showed a heavy-tailed distribution and positively predicted conflict policing. Our results empirically substantiate that subordination signaling is associated with greater dominance relationship certainty and further show that pairs who signal rarely (or not at all) may use information from others' signaling interactions to infer or reaffirm the relative certainty of their own relationships. We argue that the network of formal dominance relationships is central to societal stability because it is important for relationship stability and also supports the additional stabilizing mechanism of policing. © 2016 Wiley Periodicals, Inc.

  14. Experimental transmission of bovine spongiform encephalopathy (BSE) to cynomolgus macaques, a non-human primate.

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    Ono, Fumiko; Terao, Keiji; Tase, Naomi; Hiyaoka, Akio; Ohyama, Atsushi; Tezuka, Yukio; Wada, Naomi; Kurosawa, Asuka; Sato, Yuko; Tobiume, Minoru; Hagiwara, Ken'ichi; Yamakawa, Yoshio; Sata, Tetsutaro

    2011-01-01

    Bovine spongiform encephalopathy (BSE) was transmitted to three macaques by intracerebral inoculation of a brain homogenate from affected cattle detected in Japan. All monkeys developed abnormal behavioral signs, such as intermittent anorexia and hyperekplexia, around 24 months after inoculation. Neuronal symptoms, such as tremor, myoclonic jerking, and paralysis, appeared 27-44 months after inoculation. These symptoms worsened and total paralysis ensued within a year after onset. The disease duration was approximately 8-12 months. Both the incubation period and the duration of disease were shortened in the secondary transmission experiment to macaques. Heavy accumulation of disease-causing conformer(s) of prion protein (PrP(Sc)), with a similar glycoform profile to the PrP(Sc) contained in the inoculum, and severe spongiform changes in the histology of the brain, confirmed the successful transmission of BSE to monkeys. Florid plaques, a characteristic histological hallmark of variant Creutzfeldt-Jakob disease, were prominent in the cerebral cortex, in which a prion antigen was detected by immunohistochemistry (IHC). PrP(Sc) was mostly confined to the central nervous system, although small amounts of PrP(Sc) accumulated in the peripheral nerves of monkeys, as detected by Western blotting (WB). Neither IHC nor WB detected PrP(Sc) in the lymphatic organs/tissues, such as the tonsils, spleen, and appendix.

  15. Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin

    Science.gov (United States)

    Pincus, Seth H.; Bhaskaran, Manoj; Brey, Robert N.; Didier, Peter J.; Doyle-Meyers, Lara A.; Roy, Chad J.

    2015-01-01

    Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands) developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN). Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome. PMID:26067369

  16. Processing of Egomotion-Consistent Optic Flow in the Rhesus Macaque Cortex.

    Science.gov (United States)

    Cottereau, Benoit R; Smith, Andrew T; Rima, Samy; Fize, Denis; Héjja-Brichard, Yseult; Renaud, Luc; Lejards, Camille; Vayssière, Nathalie; Trotter, Yves; Durand, Jean-Baptiste

    2017-01-01

    The cortical network that processes visual cues to self-motion was characterized with functional magnetic resonance imaging in 3 awake behaving macaques. The experimental protocol was similar to previous human studies in which the responses to a single large optic flow patch were contrasted with responses to an array of 9 similar flow patches. This distinguishes cortical regions where neurons respond to flow in their receptive fields regardless of surrounding motion from those that are sensitive to whether the overall image arises from self-motion. In all 3 animals, significant selectivity for egomotion-consistent flow was found in several areas previously associated with optic flow processing, and notably dorsal middle superior temporal area, ventral intra-parietal area, and VPS. It was also seen in areas 7a (Opt), STPm, FEFsem, FEFsac and in a region of the cingulate sulcus that may be homologous with human area CSv. Selectivity for egomotion-compatible flow was never total but was particularly strong in VPS and putative macaque CSv. Direct comparison of results with the equivalent human studies reveals several commonalities but also some differences.

  17. Linking macroscale graph analytical organization to microscale neuroarchitectonics in the macaque connectome.

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    Scholtens, Lianne H; Schmidt, Ruben; de Reus, Marcel A; van den Heuvel, Martijn P

    2014-09-03

    Macroscale connectivity of the mammalian brain has been shown to display several characteristics of an efficient communication network architecture. In parallel, at the microscopic scale, histological studies have extensively revealed large interregional variation in cortical neural architectonics. However, how these two "scales" of cerebrum organization are linked remains an open question. Collating and combining data across multiple studies on the cortical cytoarchitecture of the macaque cortex with information on macroscale anatomical wiring derived from tract tracing studies, this study focuses on examining the interplay between macroscale organization of the macaque connectome and microscale cortical neuronal architecture. Our findings show that both macroscale degree as well as the topological role in the overall network are related to the level of neuronal complexity of cortical regions at the microscale, showing (among several effects) a positive overall association between macroscale degree and metrics of microscale pyramidal complexity. Macroscale hub regions, together forming a densely interconnected "rich club," are noted to display a high level of neuronal complexity, findings supportive of a high level of integrative neuronal processes to occur in these regions. Together, we report on cross-scale observations that jointly suggest that a region's microscale neuronal architecture is tuned to its role in the global brain network. Copyright © 2014 the authors 0270-6474/14/3412192-14$15.00/0.

  18. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human.

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    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel

    2014-06-01

    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  19. Exploring the components, asymmetry and distribution of relationship quality in wild Barbary macaques (Macaca sylvanus.

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    Richard McFarland

    Full Text Available Social relationships between group members are a key feature of many animal societies. The quality of social relationships has been described by three main components: value, compatibility and security, based on the benefits, tenure and stability of social exchanges. We aimed to analyse whether this three component structure could be used to describe the quality of social relationships in wild Barbary macaques (Macaca sylvanus. Moreover, we examined whether relationship quality was affected by the sex, age and rank differences between social partners, and investigated the asymmetric nature of social relationships. We collected over 1,900 hours of focal data on seven behavioural variables measuring relationship quality, and used principal component analysis to investigate how these variables clustered together. We found that relationship quality in wild Barbary macaques can be described by a three component structure that represents the value, compatibility and security of a relationship. Female-female dyads had more valuable relationships and same-age dyads more compatible relationships than any other dyad. Rank difference had no effect on the quality of a social relationship. Finally, we found a high degree of asymmetry in how members of a dyad exchange social behaviour. We argue that the asymmetry of social relationships should be taken into account when exploring the pattern and function of social behaviour in animal societies.

  20. Assessing the Effects of Tourist Provisioning on the Health of Wild Barbary Macaques in Morocco.

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    Laëtitia Maréchal

    Full Text Available Feeding wildlife is a very popular tourist activity, largely because it facilitates the close observation of animals in their natural habitat. Such provisioning may benefit animals by improving their survival and reproductive success, especially during periods of natural food shortage. However, provisioning by tourists may also have negative impacts on the health of the animals involved; to date such impacts are poorly understood. Here, we investigated the effects of tourist provisioning on the health of wild adult Barbary macaques, Macaca sylvanus, in Morocco. We compared health measures between a heavily provisioned group and a group that received negligible food from tourists and, in the former group, we also assessed health measures in relation to the intensity of provisioning. We used a broad range of non-invasive health measures relating to birth rate and survival, disease and injury risk, body size and condition, and physiological stress. Our findings indicate that feeding by tourists may overall have negative impacts on the health of Barbary macaques, being linked in particular to larger body size, elevated stress levels and more alopecia. Finally, we propose a framework to help consider the potential costs and benefits of provisioning, which may facilitate future research and management decisions on whether-and how much-provisioning is acceptable.

  1. The impact of Helicobacter pylori infection on the gastric microbiota of the rhesus macaque.

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    Miriam E Martin

    Full Text Available Helicobacter pylori colonization is highly prevalent among humans and causes significant gastric disease in a subset of those infected. When present, this bacterium dominates the gastric microbiota of humans and induces antimicrobial responses in the host. Since the microbial context of H. pylori colonization influences the disease outcome in a mouse model, we sought to assess the impact of H. pylori challenge upon the pre-existing gastric microbial community members in the rhesus macaque model. Deep sequencing of the bacterial 16S rRNA gene identified a community profile of 221 phylotypes that was distinct from that of the rhesus macaque distal gut and mouth, although there were taxa in common. High proportions of both H. pylori and H. suis were observed in the post-challenge libraries, but at a given time, only one Helicobacter species was dominant. However, the relative abundance of non-Helicobacter taxa was not significantly different before and after challenge with H. pylori. These results suggest that while different gastric species may show competitive exclusion in the gastric niche, the rhesus gastric microbial community is largely stable despite immune and physiological changes due to H. pylori infection.

  2. Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

    Science.gov (United States)

    Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

    2012-06-01

    Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

  3. Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin

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    Seth H. Pincus

    2015-06-01

    Full Text Available Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN. Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome.

  4. Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

    Science.gov (United States)

    Gazzaley, A. H.; Thakker, M. M.; Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.

  5. Alcohol Response and Consumption in Adolescent Rhesus Macaques: Life History and Genetic Influences

    Science.gov (United States)

    Schwandt, Melanie L.; Lindell, Stephen G.; Chen, Scott; Higley, J. Dee; Suomi, Stephen J.; Heilig, Markus; Barr, Christina S.

    2009-01-01

    The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Due to their extended period of adolescence, rhesus macaques are especially well-suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence. PMID:20113875

  6. Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques.

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    Michael K McCracken

    2017-08-01

    Full Text Available Studies have demonstrated cross-reactivity of anti-dengue virus (DENV antibodies in human sera against Zika virus (ZIKV, promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.

  7. An effort to use human-based exome capture methods to analyze chimpanzee and macaque exomes.

    Directory of Open Access Journals (Sweden)

    Xin Jin

    Full Text Available Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger-based resequencing validated 85.4% of 41 randomly selected SNPs. Among the short indels identified, a majority (54.6%-77.3% of the variants resulted in a change of 3 base pairs, consistent with expectations for a selection against frame shift mutations. Taken together, these findings indicate that use of a human design exon-capture array can provide efficient enrichment of non-human primate gene regions. Accordingly, use of the human exon-capture methods provides an attractive, cost-effective approach for the comparative analysis of non-human primate genomes, including gene-based DNA variant discovery.

  8. Representation of dynamic interaural phase difference in auditory cortex of awake rhesus macaques.

    Science.gov (United States)

    Scott, Brian H; Malone, Brian J; Semple, Malcolm N

    2009-04-01

    Neurons in auditory cortex of awake primates are selective for the spatial location of a sound source, yet the neural representation of the binaural cues that underlie this tuning remains undefined. We examined this representation in 283 single neurons across the low-frequency auditory core in alert macaques, trained to discriminate binaural cues for sound azimuth. In response to binaural beat stimuli, which mimic acoustic motion by modulating the relative phase of a tone at the two ears, these neurons robustly modulate their discharge rate in response to this directional cue. In accordance with prior studies, the preferred interaural phase difference (IPD) of these neurons typically corresponds to azimuthal locations contralateral to the recorded hemisphere. Whereas binaural beats evoke only transient discharges in anesthetized cortex, neurons in awake cortex respond throughout the IPD cycle. In this regard, responses are consistent with observations at earlier stations of the auditory pathway. Discharge rate is a band-pass function of the frequency of IPD modulation in most neurons (73%), but both discharge rate and temporal synchrony are independent of the direction of phase modulation. When subjected to a receiver operator characteristic analysis, the responses of individual neurons are insufficient to account for the perceptual acuity of these macaques in an IPD discrimination task, suggesting the need for neural pooling at the cortical level.

  9. Lipsmacking imitation skill in newborn macaques is predictive of social partner discrimination.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Simpson

    Full Text Available Newborn rhesus macaques imitate facial gestures even after a delay, revealing the flexible nature of their early communicative exchanges. In the present study we examined whether newborn macaques are also sensitive to the identities of the social partners with whom they are interacting. We measured infant monkeys' (n = 90 lipsmacking and tongue protrusion gestures in a face-to-face interaction task with a human experimenter in the first week of life. After a one-minute delay, the same person who previously presented gestures or a different person returned and presented a still face to infants. We had two primary predictions: (1 infants would demonstrate higher rates of overall gesturing, and especially lipsmacking--an affiliative gesture--to a familiar person, compared to a novel person, and (2 infants' imitative skills would positively correlate with gestures to familiar, but not unfamiliar, social partners, as both abilities may reflect a strong general social interest. We found that overall infants did not produce more gestures or more lipsmacking when approached by a familiar person compared to a novel person; however, we did find individual differences in infants' social responsiveness: lipsmacking imitation was positively correlated with lipsmacking during the return period when the person was the same (p = .025, but not when the person was novel (p = .44. These findings are consistent with the notion that imitative skill is reflective of infants' more general interest in social interactions.

  10. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  11. A non-invasive study of alopecia in Japanese macaques Macaca fuscata

    Institute of Scientific and Technical Information of China (English)

    Peng ZHANG

    2011-01-01

    This article provides information on the phenomenon of alopecia in Japanese macaques, Macaca fuscata, in various environments and proposes a 3-step scoring system for a quantitative assessment of hair loss. Results suggest that alopecia is commonly observed in Japanese macaques, with 20.5% of individuals showing head alopecia and 4.7% showing back alopecia across eight study groups. Alopecia was more commonly observed in adult females (30.8% individuals showing head alopecia and 15.3% showing back alopecia) than in other age-sex classes. Seasonal variation of back alopecia was noted, in particular, individuals with patchy back hair were more frequently observed in winter than in summer. Seasonal variation was not observed in head hair. The distribution of alopecia was also different among study groups. The wild population generally had better hair condition than provisioned populations and captive populations. The present study used a non-invasive alopecia scoring system which can be a useful, rapid and non-invasive tool to monitor animal health and well-being at a population level.

  12. Comparative anatomy of the arterial system of the foot in primates. 1. Macaque.

    Science.gov (United States)

    Matsumoto, S; Ikeda, A

    1990-01-01

    Using stereoscopic angiography, the entire arterial system of the foot of the macaque was analyzed. The arteria saphena, instead of the a. tibialis anterior, reaches the dorsum of the foot, and its branches supply most of the foot. The dorsal arteries are dominant as far as the metatarsal spaces of the lateral four toes. The a. metatarsea dorsalis II showed a tendency to be the single dominant artery and to give rise to even the a. digitalis communis plantaris IV through the catella plantaris distalis. This tendency was observed more clearly in other macaques species than the Japanese monkey. The perforating branch at the second proximal metatarsal space forms the arcus plantaris profundus, which is accompanied by the deep branch of the nervus plantaris lateralis. Beneath the arch, the catella plantaris proximalis is formed on the metatarsal bones among the perforating branches of the aa. metatarseae dorsales. The a. tibialis posterior forms the arcus plantaris superficialis, whose thin branches commonly enter the aa. digitales communes plantares.

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

    Science.gov (United States)

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

    2010-08-01

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

  14. Nutritional Composition of Fruits Selected by Long-Tailed Macaques (Macaca fascicularis) in Kuala Selangor, Malaysia

    Science.gov (United States)

    Kassim, Norazila; Hambali, Kamarul; Amir, Aainaa

    2017-01-01

    Proximate analysis of twelve species of fruits commonly consumed by long-tailed macaques (Macaca fascicularis), i.e., Arenga pinnata, Areca catechu, Terminalia catappa, Elaeis guineensis, Lagerstroemia tomentosa, Mangifera indica, Cascabela thevetia, Muntingia calabura, Musa sp., Artocarpus heterophyllus, Ficus tinctoria ssp. gibbosa and Ficus microcarpa, was conducted with the specific objective to determine the nutritional composition of the foodstuffs of long-tailed macaques. The results showed the following order of nutrients: fibre, protein, fat and ash. Based on the results of the chemical analysis, the highest percentage of fibre content (52.7%), protein (9.9%), fat (77.2%) and ash (8.5%) were found in A. catechu, T. catappa, E. guineensis and C. thevetia, respectively. The nutrient composition of these twelve fruit species was found to differ (ANOVA test: crude protein, F (11,24) = 87.978, p < 0.05; crude fibre, F (11,24) = 28.886, p < 0.05; crude fat, F (11,24) = 2081.396, p < 0.05 and ash, F (11,24) = 41.011, p < 0.05). Fibre was found in the highest amount among the four types of nutrients studied. Here, A. catechu had the highest relative fibre content of all tested fruits, E. guineensis had the highest fat content, T. catappa had the highest protein content, and the total mineral content was highest in C. thevetia. PMID:28228918

  15. Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation.

    Science.gov (United States)

    Ueno, Masataka; Nakamichi, Masayuki

    2016-08-01

    It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation.

  16. Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis) infected with group A Streptococcus.

    Science.gov (United States)

    Olsen, Randall J; Ashraf, Madiha; Gonulal, Vedia E; Ayeras, Ara A; Cantu, Concepcion; Shea, Patrick R; Carroll, Ronan K; Humbird, Tammy; Greaver, Jamieson L; Swain, Jody L; Chang, Ellen; Ragasa, Willie; Jenkins, Leslie; Lally, Kevin P; Blasdel, Terry; Cagle, Philip; Musser, James M

    2010-12-01

    Group A Streptococcus (GAS), a human-specific pathogen, is best known for causing pharyngitis ("strep-throat") and necrotizing fasciitis ("flesh-eating disease"). However, the organism is also an uncommon but important cause of community-acquired bronchopneumonia, an infection with an exceptionally high mortality rate. Inasmuch as little is known about the molecular pathogenesis of GAS lower respiratory tract infection, we sought to develop a relevant human infection model. Nine cynomolgus macaques were infected by intra-bronchial instillation of either sterile saline or GAS (10(5) or 10(7) CFU). Animals were continuously monitored and sacrificed at five days post-inoculation. Serial bronchial alveolar lavage specimens and tissues collected at necropsy were used for histologic and immunohistochemical examination, quantitative microbial culture, lung and blood biomarker analysis, and in vivo GAS gene expression studies. The lower respiratory tract disease observed in cynomolgus macaques mimicked the clinical and pathological features of severe GAS bronchopneumonia in humans. This new monkey model will be useful for testing hypotheses bearing on the molecular pathogenesis of GAS in the lower respiratory tract.

  17. The role of Branhamella catarrhalis in the "bloody-nose syndrome" of cynomolgus macaques.

    Science.gov (United States)

    VandeWoude, S J; Luzarraga, M B

    1991-10-01

    During a 15-month period, 25 cynomolgus macaques (Macaca fascicularis) at the Johns Hopkins University were observed to have nasal discharge. Fifteen (60%) of these animals had positive nasal cultures for Branhamella catarrhalis. Clinical signs associated with infection by this bacterium were sneezing, epistaxis, and mucohemorrhagic nasal discharge. Treatment with antibiotics resulted in prompt resolution of clinical signs. Post-therapeutic nasal cultures were negative for B. catarrhalis. Two groups of clinically normal, culture-negative, cynomolgus macaques were inoculated with natural isolates of B. catarrhalis which had been passaged in culture for various amounts of time. Five of the eight animals inoculated became culture-positive and had mild nasal discharge. Presence of blood on nasal swabs was indicative of infection with B. catarrhalis. Three of the inoculated animals had post-swabbing epistaxis. This report documents the role of B. catarrhalis as an upper respiratory pathogen in the cynomolgus monkey which causes mild self-limiting disease reminiscent of the so-called "Bloody-Nose Syndrome." In addition to the obvious clinical significance of this finding to primate clinicians, development of an animal model for human disease caused by this organism may be possible.

  18. A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex

    Science.gov (United States)

    Markov, N. T.; Ercsey-Ravasz, M. M.; Ribeiro Gomes, A. R.; Lamy, C.; Magrou, L.; Vezoli, J.; Misery, P.; Falchier, A.; Quilodran, R.; Gariel, M. A.; Sallet, J.; Gamanut, R.; Huissoud, C.; Clavagnier, S.; Giroud, P.; Sappey-Marinier, D.; Barone, P.; Dehay, C.; Toroczkai, Z.; Knoblauch, K.; Van Essen, D. C.; Kennedy, H.

    2014-01-01

    Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks. PMID:23010748

  19. Assessing the Effects of Tourist Provisioning on the Health of Wild Barbary Macaques in Morocco.

    Science.gov (United States)

    Maréchal, Laëtitia; Semple, Stuart; Majolo, Bonaventura; MacLarnon, Ann

    2016-01-01

    Feeding wildlife is a very popular tourist activity, largely because it facilitates the close observation of animals in their natural habitat. Such provisioning may benefit animals by improving their survival and reproductive success, especially during periods of natural food shortage. However, provisioning by tourists may also have negative impacts on the health of the animals involved; to date such impacts are poorly understood. Here, we investigated the effects of tourist provisioning on the health of wild adult Barbary macaques, Macaca sylvanus, in Morocco. We compared health measures between a heavily provisioned group and a group that received negligible food from tourists and, in the former group, we also assessed health measures in relation to the intensity of provisioning. We used a broad range of non-invasive health measures relating to birth rate and survival, disease and injury risk, body size and condition, and physiological stress. Our findings indicate that feeding by tourists may overall have negative impacts on the health of Barbary macaques, being linked in particular to larger body size, elevated stress levels and more alopecia. Finally, we propose a framework to help consider the potential costs and benefits of provisioning, which may facilitate future research and management decisions on whether-and how much-provisioning is acceptable.

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

    Science.gov (United States)

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

    2008-12-01

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

  1. The rhesus macaque CCR3 chemokine receptor is a cell entry cofactor for HIV-2, but not for HIV-1.

    Science.gov (United States)

    Sol, N; Tréboute, C; Gomas, E; Ferchal, F; Shacklett, B; Alizon, M

    1998-01-20

    The eotaxin receptor (CCR3) is a CD4-associated coreceptor for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). By comparison with other chemokine receptors, such as CCR5 and CXCR4, the primary sequences of human CCR3 and its rhesus macaque homolog were markedly different in their extracellular domains. Human CD4+ cells expressing CCR3 from either human or macaque origin could be infected by HIV-2, with apparently similar efficiency, but only cells expressing human CCR3 could be infected by HIV-1. It suggests that HIV-1 and HIV-2 envelope proteins interact differently with the CCR3 coreceptor HIV-1 could infect cells expressing chimeric human/macaque CCR3 bearing either the first and second, or the third and fourth extracellular domains of human CCR3. As previously observed for CCR5, there seems to be a certain functional redundancy between domains supporting the coreceptor activity of CCR3. In spite of their close genetic relationship to HIV-2, two macaque simian immunodeficiency virus strains were apparently unable to use the CCR3 coreceptor from either human or simian origin.

  2. A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques.

    Science.gov (United States)

    Safronetz, David; Strong, James E; Feldmann, Friederike; Haddock, Elaine; Sogoba, Nafomon; Brining, Douglas; Geisbert, Thomas W; Scott, Dana P; Feldmann, Heinz

    2013-04-15

    The virulence of Soromba-R, a Lassa virus strain recently isolated from southern Mali, was assessed in 2 animal models of Lassa fever: inbred strain 13 guinea pigs and cynomolgus macaques. In both models, the Malian isolate demonstrated tissue tropism and viral titers similar to those of historical Lassa virus isolates from Sierra Leone (Josiah) and Liberia (Z-132); however, the Soromba-R isolate was found to be less pathogenic, as determined by decreased mortality and prolonged time to euthanasia in macaques. Interestingly, in addition to the classic indicators of Lassa fever, Soromba-R infection presented with moderate to severe pulmonary manifestations in the macaque model. Analysis of host responses demonstrated increased immune activation in Soromba-R-infected macaques, particularly in neutrophil-activating or -potentiating proinflammatory cytokines or growth factors, including tumor necrosis factor α, macrophage inflammatory protein 1α, interleukin 1β, and granulocyte colony-stimulating factor, as well as interleukin 5, which may be responsible for the decreased lethality and uncharacteristic clinical presentation. These results suggest that the strain of Lassa virus circulating in Mali might be less pathogenic than strains circulating in the historical region of endemicity and may result in an atypical presentation for Lassa fever, which could complicate clinical diagnosis.

  3. Construction of an integrated welfare assessment system (MacWel) for Macaques (Macaca spp.) in human husbandry

    DEFF Research Database (Denmark)

    Kirchner, Marlene; Bakker, Jaco

    2015-01-01

    The paper describes the construction procedure of an assessment protocol for Macaques (Macaca spp.). The authors have chosen an integrative approach, currently frequently used for the construction of such protocols with a clear preference for animal-based parameters to assess the welfare states o...

  4. Long-Term Clinical Outcomes in Diabetic Rhesus Macaques (Macaca mulatta) Treated with Medroxyprogesterone Acetate for Endometriosis.

    Science.gov (United States)

    Connolly, Meghan A; Trentalange, Mark; Zeiss, Caroline J

    2016-01-01

    Depot medroxyprogesterone acetate (DMPA) is a common medical treatment for endometriosis in NHP. Because DMPA reportedly impairs glucoregulatory function in humans and rhesus macaques, as well as predisposes humans to diabetes mellitus (DM), we performed a retrospective study to further investigate its potential long-term clinical effects in animals with and without DM. Using a cohort of 29 rhesus macaques, we explored the hypotheses that DMPA treatment accelerates the onset of DM and that its use in rhesus macaques with endometriosis worsens clinical outcome measures (lifespan, body weight and body condition score). For both body weight and body condition score, a declining and statistically significant trend in mean values was evident as macaques developed either DM, or endometriosis or both. The addition of DMPA did not significantly alter this pattern. The presence of DM, endometriosis, or DMPA treatment statistically but not clinically significantly increased risk of death. Similarly, the presence of the 2 highly correlated variables endometriosis and DMPA treatment statistically but not clinically significantly increased the risk of incident DM. These results indicate that DMPA treatment was associated with worsening trends in lifespan and incident DM, however these trends did not achieve clinical significance in this cohort.

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

    Science.gov (United States)

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

    2011-12-01

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

  6. Infection of lymphoid tissues in the macaque upper respiratory tract contributes to the emergence of transmissible measles virus

    NARCIS (Netherlands)

    M. Ludlow (Martin); R. de Vries (René); K. Lemon (Ken); S. McQuaid (Stephen); E.L. Millar (Emma); G. van Amerongen (Geert); S. Yüksel (Selma); R.J. Verbugh (Joyce); A.D.M.E. Osterhaus (Albert); R.L. de Swart (Rik); W.P. Duprex (Paul)

    2013-01-01

    textabstractMeasles virus (MV), a member of the family Paramyxoviridae, remains a major cause of morbidity and mortality in the developing world. MV is spread by aerosols but the mechanism(s) responsible for the high transmissibility of MV are largely unknown. We previously infected macaques with en

  7. Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

    Science.gov (United States)

    Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

    2015-01-01

    The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2013-04-01

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

  10. Park Rangers' Behaviors and Their Effects on Tourists and Tibetan Macaques (Macaca thibetana) at Mt. Huangshan, China.

    Science.gov (United States)

    Usui, Rie; Sheeran, Lori K; Li, Jin-Hua; Sun, Lixing; Wang, Xi; Pritchard, Alexander J; DuVall-Lash, Alexander S; Wagner, R Steve

    2014-09-15

    Previous studies have reported the negative impacts of tourism on nonhuman primates (NHPs) and tourists and advocated the improvement of tourism management, yet what constitutes good quality management remains unclear. We explored whether rates of macaque aggression and self-directed behaviors (SDBs) differed under the supervision of two park ranger teams at the Valley of the Wild Monkeys (VWM) in Mt. Huangshan, Anhui Province, China. The two ranger teams provisioned and managed a group of macaques on an alternating monthly basis. Monkey, tourist and ranger behaviors were collected from August 16-September 30, 2012. Macaque aggression and SDB rates did not differ significantly under the management of the two teams. Overall, there was little intervention in tourist-macaque interactions by park rangers, and even when rangers discouraged tourists' undesirable behaviors, tourist interactions with monkeys persisted. Furthermore, only one or sometimes two park rangers managed monkeys and tourists, and rangers established dominance over the monkeys to control them. In order to effectively manage tourists and monkeys by a single park ranger, we recommend that rangers: (1) prohibit tourists from feeding; (2) move around the viewing platform more frequently; and (3) limit the number of tourists each visiting session.

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

    Science.gov (United States)

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

    2011-03-01

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

  12. Evolution of SIV toward RANTES resistance in macaques rapidly progressing to AIDS upon coinfection with HHV-6A

    Directory of Open Access Journals (Sweden)

    Gallo Robert C

    2009-07-01

    Full Text Available Abstract Background Progression to AIDS is often associated with the evolution of HIV-1 toward increased virulence and/or pathogenicity. Evidence suggests that a virulence factor for HIV-1 is resistance to CCR5-binding chemokines, most notably RANTES, which are believed to play a role in HIV-1 control in vivo. HIV-1 can achieve RANTES resistance either by phenotypic switching from an exclusive CCR5 usage to an expanded coreceptor specificity, or by the acquisition of alternative modalities of CCR5 usage. An infectious agent that might promote the evolution of HIV-1 toward RANTES resistance is human herpesvirus 6A (HHV-6A, which is frequently reactivated in HIV-1-infected patients and is a potent RANTES inducer in lymphoid tissue. Results SIV isolates obtained from pig-tailed macaques (M. nemestrina after approximately one year of single infection with SIVsmE660 or dual infection with SIVsmE660 and HHV-6AGS were characterized for their growth capacity and sensitivity to HHV-6A- and RANTES-mediated inhibition in human or macaque lymphoid tissues ex vivo. Four out of 4 HHV-6A-coinfected macaques, all of which progressed to full-blown AIDS within 2 years of infection, were found to harbor SIV variants with a reduced sensitivity to both HHV-6A and RANTES, despite maintaining an exclusive CCR5 coreceptor specificity; viruses derived from two of these animals replicated even more vigorously in the presence of exogenous HHV-6A or RANTES. The SIV variants that emerged in HHV-6A-coinfected macaques showed an overall reduced ex vivo replication capacity that was partially reversed upon addition of exogenous RANTES, associated with suppressed IL-2 and enhanced IFN-γ production. In contrast, SIV isolates obtained from two singly-infected macaques, none of which progressed to AIDS, maintained HHV-6A/RANTES sensitivity, whereas the only AIDS progressor among singly-infected macaques developed an SIV variant with partial HHV-6A/RANTES resistance and increased

  13. Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

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    Marx Preston

    2006-12-01

    Full Text Available Abstract Background Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1 is a major obstacle to successful antiretroviral therapy (ART in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can be explored in non-human primates infected with simian immunodeficiency virus (SIV. Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific immune responses but remain viremic, often at low levels, for periods of months to years, thus providing a model in which to evaluate the contribution of antiviral immunity to drug efficacy. To investigate the extent to which SIV-specific immune responses augment suppression of drug-resistant SIV, rhesus macaques infected with live, attenuated SIVmac239Δnef were treated with the reverse transcriptase (RT inhibitor tenofovir, and then challenged with pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir. Results Replication of SIVmac055 was detected in untreated macaques infected with SIVmac239Δnef, and in tenofovir-treated, naïve control macaques. The majority of macaques infected with SIVmac055 experienced high levels of plasma viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison, macaques infected with SIVmac239Δnef and treated with tenofovir showed no evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals remained clinically healthy with stable CD4+ T cell counts during three years of follow-up. Both the tenofovir-treated and untreated macaques infected with SIVmac239Δnef had antibody responses to SIV gp130 and p27 antigens and SIV-specific CD8+ T cell responses prior to SIVmac055 challenge, but only those animals receiving concurrent treatment with tenofovir resisted infection with SIVmac055. Conclusion

  14. Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

    Science.gov (United States)

    Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

    2017-09-01

    Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4(+) T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU(+)] CD163(+)), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants.IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model

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

    Science.gov (United States)

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

    2015-11-17

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

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

    Directory of Open Access Journals (Sweden)

    Juan D Rodas

    2009-07-01

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

  17. Evaluation of a rapamycin-regulated serotype 2 adeno-associated viral vector in macaque parotid glands

    Science.gov (United States)

    Zheng, Changyu; Voutetakis, Antonis; Metzger, Mark; Wainer, Sandra; Cotrim, Ana P.; Eckhaus, Michael A.; Rivera, Victor M.; Clackson, Tim; Chiorini, John A.; Donahue, Robert E.; Dunbar, Cynthia E.; Baum, Bruce J.

    2009-01-01

    OBJECTIVES Salivary glands are useful target organs for local and systemic gene therapeutics. For such applications, the regulation of transgene expression is important. Previous studies by us in murine submandibular glands showed that a rapamycin transcriptional regulation system in a single serotype 2, adeno-associated viral (AAV2) vector was effective for this purpose. The present study evaluated if such a vector was similarly useful in rhesus macaque parotid glands. METHODS A recombinant AAV2 vector (AAV-TF-RhEpo-2.3w), encoding rhesus erythropoietin (RhEpo) and a rapamycin-inducible promoter, was constructed. The vector was administered to macaques at either of two doses (1.5×1011 [low dose] or 1.5×1012 [high dose] vector genomes) via cannulation of Stensen’s duct. Animals were followed for 12–14 weeks and treated at intervals with rapamycin (0.1 or 0.5 mg/kg) to induce gene expression. Serum chemistry, hematology and RhEpo levels were measured at interval. RESULTS AAV-TF-RhEpo-2.3w administration led to low levels of rapamycin-inducible RhEpo expression in the serum of most macaques. In five animals no significant changes were seen in serum chemistry and hematology values over the study. One macaque, however, developed pneumonia, became anemic and subsequently required euthanasia. After the onset of anemia, a single administration of rapamycin led to significant RhEpo production in this animal. CONCLUSION Administration of AAV-TF-RhEpo-2.3w to macaque parotid glands was generally safe, but led only to low levels of serum RhEpo in healthy animals following rapamycin treatment. PMID:20374510

  18. Does the macaque monkey provide a good model for studying human executive control? A comparative behavioral study of task switching.

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    Luana Caselli

    Full Text Available The ability to swiftly and smoothly switch from one task set to another is central to intelligent behavior, because it allows an organism to flexibly adapt to ever changing environmental conditions and internal needs. For this reason, researchers interested in executive control processes have often relied on task-switching paradigms as powerful tools to uncover the underlying cognitive and brain architecture. In order to gather fundamental information at the single-cell level, it would be greatly helpful to demonstrate that non-human primates, especially the macaque monkey, share with us similar behavioral manifestations of task-switching and therefore, in all likelihood, similar underlying brain mechanisms. Unfortunately, prior attempts have provided negative results (e.g., Stoet & Snyder, 2003b, in that it was reported that macaques do not show the typical signature of task-switching operations at the behavioral level, represented by switch costs. If confirmed, this would indicate that the macaque cannot be used as a model approach to explore human executive control mechanisms by means of task-switching paradigms. We have therefore decided to re-explore this issue, by conducting a comparative experiment on a group of human participants and two macaque monkeys, whereby we measured and compared performance costs linked to task switching and resistance to interference across the two species. Contrary to what previously reported, we found that both species display robust task switching costs, thus supporting the claim that macaque monkeys provide an exquisitely suitable model to study the brain mechanisms responsible for maintaining and switching task sets.

  19. Does the macaque monkey provide a good model for studying human executive control? A comparative behavioral study of task switching.

    Science.gov (United States)

    Caselli, Luana; Chelazzi, Leonardo

    2011-01-01

    The ability to swiftly and smoothly switch from one task set to another is central to intelligent behavior, because it allows an organism to flexibly adapt to ever changing environmental conditions and internal needs. For this reason, researchers interested in executive control processes have often relied on task-switching paradigms as powerful tools to uncover the underlying cognitive and brain architecture. In order to gather fundamental information at the single-cell level, it would be greatly helpful to demonstrate that non-human primates, especially the macaque monkey, share with us similar behavioral manifestations of task-switching and therefore, in all likelihood, similar underlying brain mechanisms. Unfortunately, prior attempts have provided negative results (e.g., Stoet & Snyder, 2003b), in that it was reported that macaques do not show the typical signature of task-switching operations at the behavioral level, represented by switch costs. If confirmed, this would indicate that the macaque cannot be used as a model approach to explore human executive control mechanisms by means of task-switching paradigms. We have therefore decided to re-explore this issue, by conducting a comparative experiment on a group of human participants and two macaque monkeys, whereby we measured and compared performance costs linked to task switching and resistance to interference across the two species. Contrary to what previously reported, we found that both species display robust task switching costs, thus supporting the claim that macaque monkeys provide an exquisitely suitable model to study the brain mechanisms responsible for maintaining and switching task sets.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-04

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

  1. Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis

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    Montag Judith

    2011-06-01

    Full Text Available Abstract Background Prion diseases such as bovine spongiform encephalopathies (BSE are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results Cynomolgus macaques (Macaca fasicularis were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2 RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2 Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.

  2. Improved xenobiotic metabolism and reduced susceptibility to cancer in gluten-sensitive macaques upon introduction of a gluten-free diet

    National Research Council Canada - National Science Library

    Sestak, Karol; Conroy, Lauren; Aye, Pyone P; Mehra, Smriti; Doxiadis, Gaby G; Kaushal, Deepak

    2011-01-01

    A non-human primate (NHP) model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta...

  3. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Science.gov (United States)

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  4. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Directory of Open Access Journals (Sweden)

    Julie Nemecek

    Full Text Available Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA to amplify abnormal prion protein (PrP(TSE from highly diluted variant Creutzfeldt-Jakob disease (vCJD-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE in tissues and blood. Macaque vCJD PrP(TSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA. Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV, a close relative of the bank vole, seeded with macaque vCJD PrP(TSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N. We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE. Meadow vole brain (170N/N PrP genotype was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE was more permissive than human PrP(TSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE from brains of humans and macaques with vCJD. PrP(TSE signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect Pr

  5. Proteomic Basis of the Antibody Response to Monkeypox Virus Infection Examined in Cynomolgus Macaques and a Comparison to Human Smallpox Vaccination

    Science.gov (United States)

    2010-12-30

    from small - pox , was first observed in macaques no earlier than 6 days after initial infection. We first examined the antibody response during the...I, Jezek Z, Ladnyi ID (1988) Human monkeypox and other poxvirus infections of man In: Fenner F, ed. Small - pox and its Eradication. Geneva: World...virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with

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

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    Sandrine MJ Camus

    2014-02-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  8. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques.

    Science.gov (United States)

    Schwartz, Jennifer A; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K; Gallo, Robert C; DeVico, Anthony L; Fouts, Timothy R

    2016-07-01

    A promising concept for human immunodeficiency virus (HIV) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the HIV glycoprotein gp120 binds to its receptor, CD4. We are developing chimeric antigens (full-length single chain, or FLSC) in which gp120 and CD4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (A. DeVico et al., Proc Natl Acad Sci U S A 104:17477-17482, 2007, doi:10.1073/pnas.0707399104; T. R. Fouts et al., J Virol 74:11427-11436, 2000, doi:10.1128/JVI.74.24.11427-11436.2000). Proof of concept studies with nonhuman primates show that FLSC elicited heterologous protection against simian-human immunodeficiency virus (SHIV)/simian immunodeficiency virus (SIV) (T. R. Fouts et al., Proc Natl Acad Sci U S A 112:E992-E999, 2016, doi:10.1073/pnas.1423669112), which correlated with antibodies against transition state gp120 epitopes. Nevertheless, advancement of any vaccine that comprises gp120-CD4 complexes must consider whether the CD4 component breaks tolerance and becomes immunogenic in the autologous host. To address this, we performed an immunotoxicology study with cynomolgus macaques vaccinated with either FLSC or a rhesus variant of FLSC containing macaque CD4 sequences (rhFLSC). Enzyme-linked immunosorbent assay (ELISA) binding titers, primary CD3(+) T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4(+) T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures

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

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    Fresh Lynn

    2004-07-01

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

  10. Whole-genome sequencing of six Mauritian Cynomolgus macaques (Macaca fascicularis) reveals a genome-wide pattern of polymorphisms under extreme population bottleneck.

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    Osada, Naoki; Hettiarachchi, Nilmini; Adeyemi Babarinde, Isaac; Saitou, Naruya; Blancher, Antoine

    2015-03-23

    Cynomolgus macaques (Macaca fascicularis) were introduced to the island of Mauritius by humans around the 16th century. The unique demographic history of the Mauritian cynomolgus macaques provides the opportunity to not only examine the genetic background of well-established nonhuman primates for biomedical research but also understand the effect of an extreme population bottleneck on the pattern of polymorphisms in genomes. We sequenced the whole genomes of six Mauritian cynomolgus macaques and obtained an average of 20-fold coverage of the genome sequences for each individual. The overall level of nucleotide diversity was 23% smaller than that of the Malaysian cynomolgus macaques, and a reduction of low-frequency polymorphisms was observed. In addition, we also confirmed that the Mauritian cynomolgus macaques were genetically closer to a representative of the Malaysian population than to a representative of the Indochinese population. Excess of nonsynonymous polymorphisms in low frequency, which has been observed in many other species, was not very strong in the Mauritian samples, and the proportion of heterozygous nonsynonymous polymorphisms relative to synonymous polymorphisms is higher within individuals in Mauritian than Malaysian cynomolgus macaques. Those patterns indicate that the extreme population bottleneck made purifying selection overwhelmed by the power of genetic drift in the population. Finally, we estimated the number of founding individuals by using the genome-wide site frequency spectrum of the six samples. Assuming a simple demographic scenario with a single bottleneck followed by exponential growth, the estimated number of founders (∼20 individuals) is largely consistent with previous estimates.

  11. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges

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    John M. Dye

    2016-04-01

    Full Text Available Marburg virus (MARV was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs containing the glycoprotein (GP, matrix protein VP40 and nucleoprotein (NP generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.

  12. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges).

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    Dye, John M; Warfield, Kelly L; Wells, Jay B; Unfer, Robert C; Shulenin, Sergey; Vu, Hong; Nichols, Donald K; Aman, M Javad; Bavari, Sina

    2016-04-08

    Marburg virus (MARV) was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs) containing the glycoprotein (GP), matrix protein VP40 and nucleoprotein (NP) generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ) challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.

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

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

    2006-01-01

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

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

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    Amanda Vinson

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

  15. Infection of rhesus macaques with a pool of simian immunodeficiency virus with the envelope genes from acute HIV-1 infections.

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    Krebs, Kendall C; Tian, Meijuan; Asmal, Mohammed; Ling, Binhua; Nelson, Kenneth; Henry, Kenneth; Gibson, Richard; Li, Yuejin; Han, Weining; Shattock, Robin J; Veazey, Ronald S; Letvin, Norman; Arts, Eric J; Gao, Yong

    2016-11-25

    New simian-human immunodeficiency chimeric viruses with an HIV-1 env (SHIVenv) are critical for studies on HIV pathogenesis, vaccine development, and microbicide testing. Macaques are typically exposed to single CCR5-using SHIVenv which in most instances does not reflect the conditions during acute/early HIV infection (AHI) in humans. Instead of individual and serial testing new SHIV constructs, a pool of SHIVenv_B derived from 16 acute HIV-1 infections were constructed using a novel yeast-based SHIV cloning approach and then used to infect macaques. Even though none of the 16 SHIVenvs contained the recently reported mutations in env genes that could significantly enhance their binding affinity to RhCD4, one SHIVenv (i.e. SHIVenv_B3-PRB926) established infection in macaques exposed to this pool. AHI SHIVenv_B viruses as well as their HIVenv_B counterparts were analyzed for viral protein content, function, and fitness to identify possible difference between SHIVenv_B3-PRB926 and the other 15 SHIVenvs in the pool. All of the constructs produced SHIV or HIV chimeric with wild type levels of capsid (p27 and p24) content, reverse transcriptase (RT) activity, and expressed envelope glycoproteins that could bind to cell receptors CD4/CCR5 and mediate virus entry. HIV-1env_B chimeric viruses were propagated in susceptible cell lines but the 16 SHIVenv_B variants showed only limited replication in macaque peripheral blood mononuclear cells (PBMCs) and 174×CEM.CCR5 cell line. AHI chimeric viruses including HIVenv_B3 showed only minor variations in cell entry efficiency and kinetics as well as replicative fitness in human PBMCs. Reduced number of N-link glycosylation sites and slightly greater CCR5 affinity/avidity was the only distinguishing feature of env_B3 versus other AHI env's in the pool, a feature also observed in the HIV establishing new infections in humans. Despite the inability to propagate in primary cells and cell lines, a pool of 16 SHIVenv viruses could

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

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    Siddappa N Byrareddy

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

  17. Recruitment and monitoring behaviors by leaders predict following in wild Barbary macaques (Macaca sylvanus

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    A. Seltmann

    2016-07-01

    collective movements in a group of wild Barbary macaques (Macaca sylvanus in the Middle Atlas, Morocco. The number of individuals displaying pre-departure behavior predicted the success of an initiation of a collective movement. Pauses of the first departing individual after departure enhanced following behavior and might have served as recruitment signal. However, the opposite was the case for back-glancing, which functions as a monitoring signal in other species. Because in our study frequently back-glancing individuals were also less socially integrated, back glances may better be interpreted as indicators of hesitation and insecurity. To successfully initiate a collective movement, it seemed to be sufficient for a socially integrated group member to take action when other group members signal their willingness prior to departure and to occasionally wait for the group while moving.

  18. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.

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    Smith, Lauren M; Hensley, Lisa E; Geisbert, Thomas W; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene; Young, Howard A; Rubins, Kathleen H; Karp, Christopher L

    2013-07-15

    There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-β production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-β therapy in filovirus infection. Here we show that early postexposure treatment with IFN-β significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-β also significantly increased survival time after Marburg virus infection. IFN-β may have promise as an adjunctive postexposure therapy in filovirus infection.

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

    Science.gov (United States)

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

    2011-11-01

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

  20. Functional MRI of the vocalization-processing network in the macaque brain

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    Michael eOrtiz-Rios

    2015-04-01

    Full Text Available Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC, medial geniculate nucleus (MGN, auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG and sulcus (STS. Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls (scrambled calls also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt.

  1. Face Detection and the Development of Own-Species Bias in Infant Macaques.

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    Simpson, Elizabeth A; Jakobsen, Krisztina V; Damon, Fabrice; Suomi, Stephen J; Ferrari, Pier F; Paukner, Annika

    2017-01-01

    In visually complex environments, numerous items compete for attention. Infants may exhibit attentional efficiency-privileged detection, attention capture, and holding-for face-like stimuli. However, it remains unknown when these biases develop and what role, if any, experience plays in this emerging skill. Here, nursery-reared infant macaques' (Macaca mulatta; n = 10) attention to faces in 10-item arrays of nonfaces was measured using eye tracking. With limited face experience, 3-week-old monkeys were more likely to detect faces and looked longer at faces compared to nonfaces, suggesting a robust face detection system. By 3 months, after peer exposure, infants looked faster to conspecific faces but not heterospecific faces, suggesting an own-species bias in face attention capture, consistent with perceptual attunement. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

  2. Evolved psychology in a novel environment : Male macaques and the "seniority rule".

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    Manson, J H

    1998-06-01

    The human "environment of evolutionary adaptedness" can only be inferred indirectly. In contrast, the behavior of some nonhuman animals can be compared among "natural" and various altered environments. As an example, male immigration tactics in unprovisioned versus provisioned macaque (Macaca) populations are compared using Tooby and Cosmides's (1992) framework for evolutionary functional analysis. In unprovisioned populations, social groups contain few males, and immigrant male takeovers of alpha rank occur frequently. In provisioned populations, groups contain many males, and males almost invariably enter social groups at very low rank and rise in rank only as more dominant males emigrate or die. Male conformity to the "seniority rule" is hypothesized to represent the behavioral output of an evolved decision-making algorithm (psychological mechanism) that takes into account (1) the net payoff of each rank in the dominance hierarchy and (2) the power of male group size as a predictor of the likelihood of successful immigrant takeover.

  3. Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain.

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    Marzi, Andrea; Feldmann, Friederike; Hanley, Patrick W; Scott, Dana P; Günther, Stephan; Feldmann, Heinz

    2015-10-01

    In late 2013, the largest documented outbreak of Ebola hemorrhagic fever started in Guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. In March 2014, Ebola virus (EBOV) was identified as the causative agent. This study compares the pathogenesis of a new EBOV strain, Makona, which was isolated in Guinea in 2014 with the prototype strain from the 1976 EBOV outbreak in the former Zaire. Both strains cause lethal disease in cynomolgus macaques with similar pathologic changes and hallmark features of Ebola hemorrhagic fever. However, disease progression was delayed in EBOV-Makona-infected animals, suggesting decreased rather than increased virulence of this most recent EBOV strain.

  4. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

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    Sara C Johnston

    Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

  5. Image statistics underlying natural texture selectivity of neurons in macaque V4

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    Okazawa, Gouki; Tajima, Satohiro; Komatsu, Hidehiko

    2015-01-01

    Our daily visual experiences are inevitably linked to recognizing the rich variety of textures. However, how the brain encodes and differentiates a plethora of natural textures remains poorly understood. Here, we show that many neurons in macaque V4 selectively encode sparse combinations of higher-order image statistics to represent natural textures. We systematically explored neural selectivity in a high-dimensional texture space by combining texture synthesis and efficient-sampling techniques. This yielded parameterized models for individual texture-selective neurons. The models provided parsimonious but powerful predictors for each neuron’s preferred textures using a sparse combination of image statistics. As a whole population, the neuronal tuning was distributed in a way suitable for categorizing textures and quantitatively predicts human ability to discriminate textures. Together, we suggest that the collective representation of visual image statistics in V4 plays a key role in organizing the natural texture perception. PMID:25535362

  6. Live-social-video reward maintains joystick task performance in bonnet macaques.

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    Andrews, M W; Rosenblum, L A

    1993-12-01

    A number of studies have now indicated that monkeys of several species will perform hundreds of food-rewarded joystick tasks on a daily basis. Our goal in this study was to identify the level of joystick task performance that could be maintained by 10 sec. of live, color video of a conspecific social group contingent upon the completion of a joystick task. The subjects were five individually housed bonnet macaques that were highly experienced on joystick tasks. Performance with social-video reward was compared to that maintained by a 190-mg banana-flavored pellet reward and to a nonreward condition. Comparable levels of task activity were maintained by both video and pellet reward, whereas task activity nearly ceased in the absence of reward. Four of the five monkeys increased their levels of task activity between the first and second weeks of social-video reward.

  7. Quantitative analysis of postnatal neurogenesis and neuron number in the macaque monkey dentate gyrus

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    Jabès, Adeline; Lavenex, Pamela Banta; Amaral, David G.; Lavenex, Pierre

    2010-01-01

    The dentate gyrus is one of only two regions of the mammalian brain where substantial neurogenesis occurs postnatally. However, detailed quantitative information about the postnatal structural maturation of the primate dentate gyrus is meager. We performed design-based, stereological studies of neuron number and size, and volume of the dentate gyrus layers in rhesus macaque monkeys (Macaca mulatta) of different postnatal ages. We found that about 40% of the total number of granule cells observed in mature 5–10-year-old macaque monkeys are added to the granule cell layer postnatally; 25% of these neurons are added within the first three postnatal months. Accordingly, cell proliferation and neurogenesis within the dentate gyrus peak within the first three months after birth and remain at an intermediate level between three months and at least one year of age. Although granule cell bodies undergo their largest increase in size during the first year of life, cell size and the volume of the three layers of the dentate gyrus (i.e., the molecular, granule cell and polymorphic layers) continue to increase beyond one year of age. Moreover, the different layers of the dentate gyrus exhibit distinct volumetric changes during postnatal development. Finally, we observe significant levels of cell proliferation, neurogenesis and cell death in the context of an overall stable number of granule cells in mature 5–10-year-old monkeys. These data identify an extended developmental period during which neurogenesis might be modulated to significantly impact the structure and function of the dentate gyrus in adulthood. PMID:20074220

  8. MicroRNA expression and regulation in human, chimpanzee, and macaque brains.

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    Hai Yang Hu

    2011-10-01

    Full Text Available Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA in the regulation of gene expression divergence among adult humans, chimpanzees, and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using a combination of high-throughput sequencing, miRNA microarrays, and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2%-4% of mRNA and 4%-6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA-driven regulation on the human evolutionary lineage, was further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions.

  9. Whom to groom and for what? Patterns of grooming in female Barbary macaques (Macaca sylvanus).

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    Roubová, Veronika; Konečná, Martina; Šmilauer, Petr; Wallner, Bernard

    2015-01-01

    Grooming is one of the most conspicuous social interactions among nonhuman primates. The selection of grooming partners can provide important clues about factors relevant for the distribution of grooming within a social group. We analyzed grooming behavior among 17 semi-free ranging female Barbary macaques (Macaca sylvanus). We tested whether grooming is related to kinship, rank and friendship. Furthermore, we tested whether grooming is reciprocated or exchanged for rank related benefits (i.e. lower aggression and increased tolerance whilst feeding). We found that in general grooming was reciprocally exchanged, directed up the hierarchy and at the same time affected by friendship and kinship. Grooming was more frequent among individuals with higher friendship values as well as amongst related individuals. We also divided our data set on the basis of rank difference and tested if different power asymmetries between individuals affected the tendency to exchange grooming for rank related benefits and grooming reciprocation. In support of our initial hypothesis our results show that the reciprocation of grooming was a significant predictor of grooming interactions between individuals of similar rank, but not between those individuals more distantly separated in the social hierarchy. However, we did not find any evidence for grooming being exchanged for rank related benefits in either data set. Our results, together with previously published studies, illustrate the behavioral flexibility of macaques. It is clear that multiple studies of the same species are necessary to gather the data required for the solid comparative studies needed to shed light on patterns of grooming behavior in primates.

  10. Feeding behavior and aggression in wild Siberut macaques (Macaca siberu) living under low predation risk.

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    Richter, Christin; Gras, Pierre; Hodges, Keith; Ostner, Julia; Schülke, Oliver

    2015-07-01

    Investigating which factors influence feeding competition is crucial for our understanding of the diversity of social relationships. Socio-ecological models differ in their predictions whether predation risk directly influences feeding competition and which factors exactly predict contest competition. We investigated feeding competition in Siberut macaques (Macaca siberu), a species endemic to Siberut Island (West Sumatra, Indonesia). Siberut macaques experience low predation risk, as major predators (felids, raptors) are absent. They are therefore appropriate subjects to test the prediction that low predation risk reduces feeding competition. To estimate contest potential, we quantified size, spatial distribution and density of food plants, and the availability of alternative resources. We recorded behavior in food patches using a modified focal tree method. Food patches, sorted by decreasing average feeding group size, included large trees (40% of focal plant observations), lianas/strangler (16%), medium trees (9%), small (palm) trees (20%), and rattan (15%). Most food patches were clumped but occurred at low densities relative to the area of average group spread. Thus, availability of alternative food patches was low. Although food patch characteristics indicate high contest potential, the observed aggression rate (0.13 bouts between adults/h) was low relative to other primates. Average feeding group size was small relative to total group size, and feeding group size matched crown volume. Perceived predation risk was low, based on spatial and feeding behavior of juveniles. Together, these results suggest that predation risk may influence feeding competition. Social and temporal factors (patch feeding time), but not ecological factors (fruit abundance in patch and forest, alternative resources) predicted aggression frequency in food patches. Overall, comparative data are still relatively scarce, and researchers should collect more data on group spread, sub

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

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

    2013-11-01

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

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

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    Gregory Spear

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

  13. Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis.

    Directory of Open Access Journals (Sweden)

    Justin B Schaal

    Full Text Available Theta-defensins (θ-defensins are macrocyclic antimicrobial peptides expressed in leukocytes of Old World monkeys. The peptides are broad spectrum microbicides in vitro and numerous θ-defensin isoforms have been identified in granulocytes of rhesus macaques and Olive baboons. Several mammalian α- and β-defensins, genetically related to θ-defensins, have proinflammatory and immune-activating properties that bridge innate and acquired immunity. In the current study we analyzed the immunoregulatory properties of rhesus θ-defensins 1-5 (RTDs 1-5. RTD-1, the most abundant θ-defensin in macaques, reduced the levels of TNF, IL-1α, IL-1β, IL-6, and IL-8 secreted by blood leukocytes stimulated by several TLR agonists. RTDs 1-5 suppressed levels of soluble TNF released by bacteria- or LPS-stimulated blood leukocytes and THP-1 monocytes. Despite their highly conserved conformation and amino acid sequences, the anti-TNF activities of RTDs 1-5 varied by as much as 10-fold. Systemically administered RTD-1 was non-toxic for BALB/c mice, and escalating intravenous doses were well tolerated and non-immunogenic in adult chimpanzees. The peptide was highly stable in serum and plasma. Single dose administration of RTD-1 at 5 mg/kg significantly improved survival of BALB/c mice with E. coli peritonitis and cecal ligation-and-puncture induced polymicrobial sepsis. Peptide treatment reduced serum levels of several inflammatory cytokines/chemokines in bacteremic animals. Collectively, these results indicate that the anti-inflammatory properties of θ-defensins in vitro and in vivo are mediated by the suppression of numerous proinflammatory cytokines and blockade of TNF release may be a primary effect.

  14. Phylogeography of Barbary macaques (Macaca sylvanus) and the origin of the Gibraltar colony.

    Science.gov (United States)

    Modolo, Lara; Salzburger, Walter; Martin, Robert D

    2005-05-17

    The Barbary macaque (Macaca sylvanus) is the earliest offshoot of the genus Macaca and the only extant African representative, all other species being Asiatic. Once distributed throughout North Africa, M. sylvanus is now restricted to isolated forest fragments in Algeria and Morocco. The species is threatened; the maximum total wild population size is estimated at 10,000 individuals. Relationships among surviving wild subpopulations in Algeria (96 samples) and Morocco (116 samples) were examined by using 468-bp sequences from hypervariable region I of the mitochondrial DNA control region. Twenty-four different haplotypes were identified, differing by 1-26 mutational steps (0.2-5.6%) and 1 insertion. With one exception (attributable to secondary introduction in coastal Morocco), Algerian and Moroccan haplotypes are clearly distinct. However, whereas Moroccan subpopulations show little divergence in hypervariable region I sequences and little correspondence with geographical distribution, there is a deep division between two main subpopulations in Algeria and one marked secondary division, with haplotypes generally matching geographical distribution. Accepting an origin of the genus Macaca of 5.5 million years ago, the Moroccan population and the two main Algerian subpopulations diverged approximately 1.6 million years ago. Distinction between Moroccan and Algerian haplotypes permitted analysis of the origin of the Gibraltar colony of Barbary macaques (68 samples; 30% of the population). It is generally held that the present Gibraltar population descended from a dozen individuals imported during World War II. However, the Gibraltar sample was found to include Algerian and Moroccan haplotypes separated by at least 16 mutational steps, revealing a dual origin of the founding females.

  15. Effect of feature-selective attention on neuronal responses in macaque area MT.

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    Chen, X; Hoffmann, K-P; Albright, T D; Thiele, A

    2012-03-01

    Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).

  16. Development of sexual behavior in free-ranging female Japanese macaques.

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

    2014-09-01

    We studied the development of sexual behaviors in female Japanese macaques (Macaca fuscata) living at Arashiyama, Japan, in a group where adult females routinely exhibit sexual interactions with both males and females. Our cross-sectional data on juvenile, adolescent, and adult females supported most of our predictions related to the learning hypothesis, which holds that adolescence serves to provide females with a period in which to practice adult female-like sexual behavioral patterns, including sexual solicitations, sexual mounts, and spatio-temporal coordination during consortships. We found evidence for a gradual acquisition of adult-like behavioral patterns (e.g., more frequent solicitations with body contact, more frequent complete mounts, more diverse solicitation patterns and complete mounting postures, and longer consortships involving prolonged inter-mount grasping behavior between partners), and a gradual disappearance of less effective immature behavioral patterns (e.g., less frequent non-contact solicitations, ambiguous mounting initiations, and incomplete mounts). We distinguished between three major categories of sexual behavioral patterns based on their speed of development, ranging from fast (e.g., diversity in mounting postures and genital stimulation during mounting) to slow (e.g., contact solicitations and grasping behavior between consortship partners), with some being intermediate (e.g., range of solicitation patterns and expression of complete mounts). This study showed that the emergence of both conceptive and non-conceptive adult sexual behaviors can be traced back to immature behavioral patterns in adolescent female Japanese macaques, with a major threshold occurring at the age of 4 years.

  17. Model-observer similarity, error modeling and social learning in rhesus macaques.

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    Monfardini, Elisabetta; Hadj-Bouziane, Fadila; Meunier, Martine

    2014-01-01

    Monkeys readily learn to discriminate between rewarded and unrewarded items or actions by observing their conspecifics. However, they do not systematically learn from humans. Understanding what makes human-to-monkey transmission of knowledge work or fail could help identify mediators and moderators of social learning that operate regardless of language or culture, and transcend inter-species differences. Do monkeys fail to learn when human models show a behavior too dissimilar from the animals' own, or when they show a faultless performance devoid of error? To address this question, six rhesus macaques trained to find which object within a pair concealed a food reward were successively tested with three models: a familiar conspecific, a 'stimulus-enhancing' human actively drawing the animal's attention to one object of the pair without actually performing the task, and a 'monkey-like' human performing the task in the same way as the monkey model did. Reward was manipulated to ensure that all models showed equal proportions of errors and successes. The 'monkey-like' human model improved the animals' subsequent object discrimination learning as much as a conspecific did, whereas the 'stimulus-enhancing' human model tended on the contrary to retard learning. Modeling errors rather than successes optimized learning from the monkey and 'monkey-like' models, while exacerbating the adverse effect of the 'stimulus-enhancing' model. These findings identify error modeling as a moderator of social learning in monkeys that amplifies the models' influence, whether beneficial or detrimental. By contrast, model-observer similarity in behavior emerged as a mediator of social learning, that is, a prerequisite for a model to work in the first place. The latter finding suggests that, as preverbal infants, macaques need to perceive the model as 'like-me' and that, once this condition is fulfilled, any agent can become an effective model.

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

    Science.gov (United States)

    Beisner, Brianne A; Isbell, Lynne A

    2011-11-01

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

  19. When dispersal fails: unexpected genetic separation in Gibraltar macaques (Macaca sylvanus).

    Science.gov (United States)

    Modolo, Lara; Martin, Robert D; van Schaik, Carel P; van Noordwijk, Maria A; Krũtzen, Michael

    2008-09-01

    Barbary macaques (Macaca sylvanus), now restricted in the wild to a few isolated forested areas of Morocco and Algeria, are present in a free-ranging colony on Gibraltar. For many decades, the Gibraltar colony was exposed to multiple bottlenecks due to highly nonrandom removal of animals, followed by repeated introductions of animals from North Africa. Moreover, because of complete isolation, Gibraltar's several social groups of macaques provide an ideal system to study the genetic consequences of dispersal in cercopithecines in situ. Predictions of genetic consequences due to male-biased dispersal in cercopithecines will be different for autosomal and maternally inherited genetic markers, such as the control region of the mitochondrial DNA. We used a panel of 14 highly polymorphic microsatellite loci and part of the hypervariable region I of the mitochondrial control region to estimate genetic structure between five social groups in Gibraltar. Surprisingly, for autosomal markers, both classical summary statistics and an individual-based method using a Bayesian framework detected significant genetic structure between social groups in Gibraltar, despite much closer proximity than wild Algerian and Moroccan populations. Mitochondrial data support this finding, as a very substantial portion of the total genetic variation (70.2%) was found between social groups. Using two Bayesian approaches, we likewise identified not only a small number of male first-generation immigrants (albeit less than expected for cercopithecines) but also unexpectedly a few females. We hypothesize that the culling of males that are more likely to disperse might slow down genetic homogenization among neighbouring groups, but may also and more perversely produce selection on certain behavioural traits. This may have important repercussions for conservation, as it could lead to evolutionary changes that are not due to inbreeding or genetic drift.

  20. Patterns of infant handling and relatedness in Barbary macaques (Macaca sylvanus) on Gibraltar.

    Science.gov (United States)

    Kümmerli, Rolf; Martin, Robert D

    2008-10-01

    Among papionin primates, the Barbary macaque (Macaca sylvanus) shows the most extensive interactions between infants and group members other than the mother. Two different types of interactions occur: (1) long-lasting dyadic interactions between a handler and an infant, and (2) brief triadic interactions between two handlers involving an infant. Previous investigations showed that infant handling by males is best explained as use of infants to manage relationships with other males. In contrast, no adaptive explanation for infant handling by females emerged. Here, we compared the infant-handling pattern between subadult/adult males and subadult/adult females in a free-ranging group of 46 Barbary macaques on Gibraltar to test whether the relationship management hypothesis also applies to female handlers. We further investigated the infant-handling pattern of juveniles and used microsatellite markers to estimate relatedness between infant handlers and the infant's mother. We found that males, females and juveniles all participated extensively in triadic interactions using infants of above-average related females. In contrast, only males and juveniles were highly involved in dyadic interactions with infants of related females, while females rarely handled infants other than their own. The pattern of infant handling was entirely compatible with the predictions of the relationship management hypothesis for males and mostly so for females. Moreover, our genetic analysis revealed that males and females differ in their partner choice: while females preferred to interact with related females, males had no significant preference to interact with related males. We further discuss the observed above-average relatedness values between infant handlers and the infant's mother in the light of kin-selection theory.

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

    Science.gov (United States)

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

    2014-02-01

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

  2. Pharmacokinetics and immunogenicity of broadly neutralizing HIV monoclonal antibodies in macaques.

    Science.gov (United States)

    Rosenberg, Yvonne; Sack, Markus; Montefiori, David; Labranche, Celia; Lewis, Mark; Urban, Lori; Mao, Lingjun; Fischer, Rainer; Jiang, Xiaoming

    2015-01-01

    The identification of highly potent broadly neutralizing antibodies (bnAbs) against HIV-1, and success in preventing SHIV infection following their passive administration, have increased the likelihood that immunotherapeutic strategies can be adopted to prevent and treat HIV-1 infection. However, while broad and potent neutralizing activity is an essential prerequisite, in vivo properties such as good circulatory stability and non-immunogenicity are equally critical for developing a human treatment. In the present study, glycoforms of the bnAbs 10-1074, NIH45-46G54W, 10E8, PGT121, PGT128, PGT145, PGT135, PG9, PG16, VRC01 and b12 were produced by Agrobacterium-mediated transient transfection of Nicotiana benthamiana and assessed following administration in rhesus macaques. The results indicate that (i) N-glycans within the VL domain impair plasma stability of plant-derived bnAbs and (ii) while PGT121 and b12 exhibit no immunogenicity in rhesus macaques after multiple injections, VRC01, 10-1074 and NIH45-46G54W elicit high titer anti-idiotypic antibodies following a second injection. These anti-idiotypic antibodies specifically bind the administered bnAb or a close family member, and inhibit the bnAb in neutralization assays. These findings suggest that specific mutations in certain bnAbs contribute to their immunogenicity and call attention to the prospect that these mutated bnAbs will be immunogenic in humans, potentially compromising their value for prophylaxis and therapy of HIV-1.

  3. Effects of modified chromophores on the spectral sensitivity of salamander, squirrel and macaque cones.

    Science.gov (United States)

    Makino, C L; Kraft, T W; Mathies, R A; Lugtenburg, J; Miley, M E; van der Steen, R; Baylor, D A

    1990-05-01

    1. Chemically modified retinal chromophores were used to investigate the mechanisms that produce the characteristic spectral absorptions of cone pigments. Spectral sensitivities of single cones from the salamander, squirrel and macaque retina were determined by electrical recording. The chromophore was then replaced by bleaching the pigment and regenerating it with a retinal analogue. 2. Exposing a bleached cone to 9-cis-retinal for a brief period (less than 20 min) caused its flash sensitivity to recover to about 0.2 of the pre-bleach value. Similar exposure to a locked 6-s-cis, 9-cis analogue gave a recovery to about 0.03 of the pre-bleach value. 3. Unlike the flash sensitivity, the saturating photocurrent amplitude often recovered completely after bleaching and regenerating the pigment. 4. When the 3-dehydroretinal chromophore in the salamander long-wavelength-sensitive (red) cone was replaced with 11-cis-retinal, shortening the conjugated chain in the chromophore, the spectral sensitivity underwent a blue shift of 67 nm. 5. Pigments containing the planar-locked 6-s-cis.9-cis-retinal analogue absorbed at substantially longer wavelength than those containing unmodified 9-cis-retinal. The opsin shift, a measure of the protein's ability to modify the chromophore's absorption was larger for the locked analogue than for 9-cis-retinal. This suggests that the native chromophore assumes a twisted 6-s-cis conformation