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Sample records for normal macaques revealed

  1. Attention and normalization circuits in macaque V1

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    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

  2. 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. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Economic choices reveal probability distortion in macaque monkeys.

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    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.

  4. Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

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    Vickers Mark H

    2011-10-01

    Full Text Available Abstract Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile to those of lower birth weight (5-25th centile and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk.

  5. Use-Wear Patterns on Wild Macaque Stone Tools Reveal Their Behavioural History

    OpenAIRE

    Haslam, Michael; Gumert, Michael D.; Biro, Dora; Carvalho, Susana; Malaivijitnond, Suchinda

    2013-01-01

    Burmese long-tailed macaques (Macaca fascicularis aurea) are one of a limited number of wild animal species to use stone tools, with their tool use focused on pounding shelled marine invertebrates foraged from intertidal habitats. These monkeys exhibit two main styles of tool use: axe hammering of oysters, and pound hammering of unattached encased foods. In this study, we examined macroscopic use-wear patterns on a sample of 60 wild macaque stone tools from Piak Nam Yai Island, Thailand, that...

  6. Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2.

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    Zarella, Mark D; Ts'o, Daniel Y

    2017-01-01

    Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure-ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure-ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure-ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization.

  7. Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2

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    Zarella MD

    2017-04-01

    Full Text Available Mark D Zarella, Daniel Y Ts’o Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, NY, USA Abstract: Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure–ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure–ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure–ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization. Keywords: striate, extrastriate, segmentation, figure–ground, functional organization

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

    DEFF Research Database (Denmark)

    Southwood, Scott; Solomon, Christopher; Hoof, Ilka

    2011-01-01

    The Simian immunodeficiency virus (SIV)-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection and AIDS-related research, despite the potential that macaques of Chinese origin is a more relevant model. Ongoing efforts to further characterize the Chinese...... populations. In this study, we have characterized two additional alleles expressed with high frequency in Chinese rhesus macaques, Mamu-A1*02601 and Mamu-B*08301. Upon the development of MHC–peptide-binding assays and definition of their associated motifs, we reveal that these Mamu alleles share peptide...

  9. Longitudinal analysis reveals characteristically high proportions of bacterial vaginosis-associated bacteria and temporal variability of vaginal microbiota in northern pig-tailed macaques (Macaca leonina).

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    Zhu, Lin; Lei, Ai-Hua; Zheng, Hong-Yi; Lyu, Long-Bao; Zhang, Zhi-Gang; Zheng, Yong-Tang

    2015-09-18

    The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques (Macaca leonina) are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.

  10. Mitochondrial DNA analyses and ecological niche modeling reveal post-LGM expansion of the Assam macaque (Macaca assamensis) in the foothills of Nepal Himalaya.

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    Khanal, Laxman; Chalise, Mukesh K; He, Kai; Acharya, Bipin K; Kawamoto, Yoshi; Jiang, Xuelong

    2018-03-01

    Genetic diversity of a species is influenced by multiple factors, including the Quaternary glacial-interglacial cycles and geophysical barriers. Such factors are not yet well documented for fauna from the southern border of the Himalayan region. This study used mitochondrial DNA (mtDNA) sequences and ecological niche modeling (ENM) to explore how the late Pleistocene climatic fluctuations and complex geography of the Himalayan region have shaped genetic diversity, population genetic structure, and demographic history of the Nepalese population of Assam macaques (Macaca assamensis) in the Himalayan foothills. A total of 277 fecal samples were collected from 39 wild troops over almost the entire distribution of the species in Nepal. The mtDNA fragment encompassing the complete control region (1121 bp) was recovered from 208 samples, thus defining 54 haplotypes. Results showed low nucleotide diversity (0.0075 ± SD 0.0001) but high haplotype diversity (0.965 ± SD 0.004). The mtDNA sequences revealed a shallow population genetic structure with a moderate but statistically significant effect of isolation by distance. Demographic history analyses using mtDNA sequences suggested a post-pleistocene population expansion. Paleodistribution reconstruction projected that the potential habitat of the Assam macaque was confined to the lower elevations of central Nepal during the Last Glacial Maximum. With the onset of the Holocene climatic optimum, the glacial refugia population experienced eastward range expansion to higher elevations. We conclude that the low genetic diversity and shallow population genetic structure of the Assam macaque population in the Nepal Himalaya region are the consequence of recent demographic and spatial expansion. © 2018 Wiley Periodicals, Inc.

  11. In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain

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    Joo Chan-Gyu

    2009-06-01

    Full Text Available Abstract Background In vivo proton magnetic resonance spectroscopy (1H-MRS studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection. Results Changes in the N-acetylaspartate (NAA, choline (Cho, myo-inositol (MI, creatine (Cr and glutamine/glutamate (Glx resonances were quantified both in absolute terms and relative to the creatine resonance. Most abnormalities were observed at the time of peak viremia, 2 weeks post infection (wpi. At that time point, significant decreases in NAA and NAA/Cr, reflecting neuronal injury, were observed only in the frontal cortex. Cr was significantly elevated only in the white matter. Changes in Cho and Cho/Cr were similar across the brain regions, increasing at 2 wpi, and falling below baseline levels at 4 wpi. MI and MI/Cr levels were increased across all brain regions. Conclusion These data best support the hypothesis that different brain regions have variable intrinsic vulnerabilities to neuronal injury caused by the AIDS virus.

  12. Early monocular defocus disrupts the normal development of receptive-field structure in V2 neurons of macaque monkeys.

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    Tao, Xiaofeng; Zhang, Bin; Shen, Guofu; Wensveen, Janice; Smith, Earl L; Nishimoto, Shinji; Ohzawa, Izumi; Chino, Yuzo M

    2014-10-08

    Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion. Copyright © 2014 the authors 0270-6474/14/3413840-15$15.00/0.

  13. Longitudinal analysis reveals characteristically high proportions of bacterial vaginosis-associated bacteria and temporal variability of vaginal microbiota in northern pig-tailed macaques (Macaca leonina)

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    ZHU, Lin; LEI, Ai-Hua; ZHENG, Hong-Yi; LYU, Long-Bao; ZHANG, Zhi-Gang; ZHENG, Yong-Tang

    2015-01-01

    The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques (Macaca leonina) are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, littl...

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

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    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.

  15. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

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    Bin Jia

    Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.

  16. Personality structure and social style in macaques.

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

    2015-08-01

    Why regularities in personality can be described with particular dimensions is a basic question in differential psychology. Nonhuman primates can also be characterized in terms of personality structure. Comparative approaches can help reveal phylogenetic constraints and social and ecological patterns associated with the presence or absence of specific personality dimensions. We sought to determine how different personality structures are related to interspecific variation in social style. Specifically, we examined this question in 6 different species of macaques, because macaque social style is well characterized and can be categorized on a spectrum of despotic (Grade 1) versus tolerant (Grade 4) social styles. We derived personality structures from adjectival ratings of Japanese (Macaca fuscata; Grade 1), Assamese (M. assamensis; Grade 2), Barbary (M. sylvanus; Grade 3), Tonkean (M. tonkeana; Grade 4), and crested (M. nigra; Grade 4) macaques and compared these species with rhesus macaques (M. mulatta; Grade 1) whose personality was previously characterized. Using a nonparametric method, fuzzy set analysis, to identify commonalities in personality dimensions across species, we found that all but 1 species exhibited consistently defined Friendliness and Openness dimensions, but that similarities in personality dimensions capturing aggression and social competence reflect similarities in social styles. These findings suggest that social and phylogenetic relationships contribute to the origin, maintenance, and diversification of personality. (c) 2015 APA, all rights reserved.

  17. Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal.

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    Kyes, Randall C; Jones-Engel, Lisa; Chalise, Mukesh K; Engel, Gregory; Heidrich, John; Grant, Richard; Bajimaya, Shyam S; McDonough, John; Smith, David Glenn; Ferguson, Betsy

    2006-05-01

    Indian-origin rhesus macaques (Macaca mulatta) have long served as an animal model for the study of human disease and behavior. Given the current shortage of Indian-origin rhesus, many researchers have turned to rhesus macaques from China as a substitute. However, a number of studies have identified marked genetic differences between the Chinese and Indian animals. We investigated the genetic characteristics of a third rhesus population, the rhesus macaques of Nepal. Twenty-one rhesus macaques at the Swoyambhu Temple in Kathmandu, Nepal, were compared with more than 300 Indian- and Chinese-origin rhesus macaques. The sequence analyses of two mitochondrial DNA (mtDNA) loci, from the HVS I and 12 S rRNA regions, showed that the Nepali animals were more similar to Indian-origin than to Chinese-origin animals. The distribution of alleles at 24 short tandem repeat (STR) loci distributed across 17 chromosomes also showed greater similarity between the Nepali and Indian-origin animals. Finally, an analysis of seven major histocompatibility complex (MHC) alleles showed that the Nepali animals expressed Class I alleles that are common to Indian-origin animals, including Mamu-A*01. All of these analyses also revealed a low level of genetic diversity within this Nepali rhesus sample. We conclude that the rhesus macaques of Nepal more closely resemble rhesus macaques of Indian origin than those of Chinese origin. As such, the Nepali rhesus may offer an additional resource option for researchers who wish to maintain research protocols with animals that possess key genetic features characteristic of Indian-origin rhesus macaques. 2005 Wiley-Liss, Inc.

  18. Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM.

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    Li, Wan; Yang, Chunlan; Shi, Feng; Wang, Qun; Wu, Shuicai; Lu, Wangsheng; Li, Shaowu; Nie, Yingnan; Zhang, Xin

    2018-04-16

    Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.

  19. In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging.

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    Cao, Xu; Wang, Haiqiong; Wang, Zhao; Wang, Qingyao; Zhang, Shuang; Deng, Yuanping; Fang, Yanshan

    2017-10-01

    Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons. However, lack of Pink1 or Parkin did not lead to the accumulation of axonal mitochondria or axonal degeneration. Further, unlike in in vitro cultured neurons, we found that mitophagy rarely occurred in intact axons in vivo, even in aged animals. Furthermore, blocking overall mitophagy by knockdown of the core autophagy genes Atg12 or Atg17 had little effect on the turnover of axonal mitochondria or axonal integrity, suggesting that mitophagy is not required for axonal maintenance; this is regardless of whether the mitophagy is PINK1-Parkin dependent or independent. In contrast, downregulation of mitochondrial fission-fusion genes caused age-dependent axonal degeneration. Moreover, Opa1 expression in the fly head was significantly decreased with age, which may underlie the accumulation of fragmented mitochondria in aged axons. Finally, we showed that adult-onset, neuronal downregulation of the fission-fusion, but not mitophagy genes, dramatically accelerated features of aging. We propose that axonal mitochondria are maintained independently of mitophagy and that mitophagy-independent mechanisms such as fission-fusion may be central to the maintenance of axonal mitochondria and neural integrity during normal aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. Rotational displacement skills in rhesus macaques (Macaca mulatta).

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    Hughes, Kelly D; Santos, Laurie R

    2012-11-01

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

  1. 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

  2. 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.

  3. Improved xenobiotic metabolism and reduced susceptibility to cancer in gluten-sensitive macaques upon introduction of a gluten-free diet.

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    Karol Sestak

    2011-04-01

    Full Text Available 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.Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD and gluten-containing (GD diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies,targeting expression of over 20,000 genes.When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories--cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function--this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function and actin-collagen-matrix metalloproteinases (MMP genes.A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research.

  4. Improved Xenobiotic Metabolism and Reduced Susceptibility to Cancer in Gluten-Sensitive Macaques upon Introduction of a Gluten-Free Diet

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    Sestak, Karol; Conroy, Lauren; Aye, Pyone P.; Mehra, Smriti; Doxiadis, Gaby G.; Kaushal, Deepak

    2011-01-01

    Background A non-human primate (NHP) model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta). Methodology Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD) and gluten-containing (GD) diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies),targeting expression of over 20,000 genes. Principal Findings When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories - cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function - this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function) and actin-collagen-matrix metalloproteinases (MMP) genes. Conclusions/Significance A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research. PMID:21533263

  5. Varying acoustic-phonemic ambiguity reveals that talker normalization is obligatory in speech processing.

    Science.gov (United States)

    Choi, Ja Young; Hu, Elly R; Perrachione, Tyler K

    2018-04-01

    The nondeterministic relationship between speech acoustics and abstract phonemic representations imposes a challenge for listeners to maintain perceptual constancy despite the highly variable acoustic realization of speech. Talker normalization facilitates speech processing by reducing the degrees of freedom for mapping between encountered speech and phonemic representations. While this process has been proposed to facilitate the perception of ambiguous speech sounds, it is currently unknown whether talker normalization is affected by the degree of potential ambiguity in acoustic-phonemic mapping. We explored the effects of talker normalization on speech processing in a series of speeded classification paradigms, parametrically manipulating the potential for inconsistent acoustic-phonemic relationships across talkers for both consonants and vowels. Listeners identified words with varying potential acoustic-phonemic ambiguity across talkers (e.g., beet/boat vs. boot/boat) spoken by single or mixed talkers. Auditory categorization of words was always slower when listening to mixed talkers compared to a single talker, even when there was no potential acoustic ambiguity between target sounds. Moreover, the processing cost imposed by mixed talkers was greatest when words had the most potential acoustic-phonemic overlap across talkers. Models of acoustic dissimilarity between target speech sounds did not account for the pattern of results. These results suggest (a) that talker normalization incurs the greatest processing cost when disambiguating highly confusable sounds and (b) that talker normalization appears to be an obligatory component of speech perception, taking place even when the acoustic-phonemic relationships across sounds are unambiguous.

  6. Quantitative ChIP-Seq Normalization Reveals Global Modulation of the Epigenome

    Directory of Open Access Journals (Sweden)

    David A. Orlando

    2014-11-01

    Full Text Available Epigenomic profiling by chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq is a prevailing methodology used to investigate chromatin-based regulation in biological systems such as human disease, but the lack of an empirical methodology to enable normalization among experiments has limited the precision and usefulness of this technique. Here, we describe a method called ChIP with reference exogenous genome (ChIP-Rx that allows one to perform genome-wide quantitative comparisons of histone modification status across cell populations using defined quantities of a reference epigenome. ChIP-Rx enables the discovery and quantification of dynamic epigenomic profiles across mammalian cells that would otherwise remain hidden using traditional normalization methods. We demonstrate the utility of this method for measuring epigenomic changes following chemical perturbations and show how reference normalization of ChIP-seq experiments enables the discovery of disease-relevant changes in histone modification occupancy.

  7. Estimation of Shear Wave Speed in the Rhesus Macaques Uterine Cervix

    Science.gov (United States)

    Huang, Bin; Drehfal, Lindsey C.; Rosado-Mendez, Ivan M.; Guerrero, Quinton W.; Palmeri, Mark L.; Simmons, Heather A.; Feltovich, Helen; Hall, Timothy J.

    2016-01-01

    Cervical softness is a critical parameter in pregnancy. Clinically, preterm birth is associated with premature cervical softening and post-dates birth is associated with delayed cervical softening. In practice, the assessment of softness is subjective, based on digital examination. Fortunately, objective, quantitative techniques to assess softness and other parameters associated with microstructural cervical change are emerging. One of these is shear wave speed (SWS) estimation. In principle, this allows objective characterization of stiffness because waves travel more slowly in softer tissue. We are studying SWS in humans and rhesus macaques, the latter in order to accelerate translation from bench to bedside. For the current study, we estimated SWS in ex vivo cervices of rhesus macaques, n=24 nulliparous (never given birth) and n=9 multiparous (delivered at least 1 baby). Misoprostol (a prostaglandin used to soften human cervices prior to gynecological procedures) was administered to 13 macaques prior to necropsy (nulliparous: 7, multiparous: 6). SWS measurements were made at predetermined locations from the distal to proximal end of the cervix on both the anterior and posterior cervix, with 5 repeat measures at each location. The intent was to explore macaque cervical microstructure, including biological and spatial variability, to elucidate the similarities and differences between the macaque and the human cervix in order to facilitate future in vivo studies. We found that SWS is dependent on location in the normal nonpregnant macaque cervix, as in the human cervix. Unlike the human cervix, we detected no difference between ripened and unripened rhesus macaque cervix samples, nor nulliparous versus multiparous samples, although we observed a trend toward stiffer tissue in nulliparous samples. We found rhesus macaque cervix to be much stiffer than human, which is important for technique refinement. These findings are useful for guiding study of cervical

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Radiographic changes in rhesus macaques affected by scurvy

    International Nuclear Information System (INIS)

    Morgan, J.P.; Eisele, P.H.

    1992-01-01

    Spontaneous vitamin C deficiency, or scurvy, was recognized in juvenile rhesus monkeys maintained in a research center as a result of being fed a commercial diet for 2 to 3 months with low levels of vitamin C. Most severely affected animals (13) were radiographed repeatedly up to day 300 following detection of the disease. Early radiographic changes consisted of widened, lucent metaphyses with lateral flaring and radiopaque metaphyseal lines at the junction of the metaphyses and physes. Physeal slippage was noted commonly. Following institution of vitamin C therapy, calcification of subperiosteal hemorrhage occurred in the metaphyseal regions. Metaphyses and physes returned to normal radiographic appearance within 15 to 30 days. Initially, the subperiosteal hemorrhage progressed and a longer time was required for solution of the calcified hematomas. The macaques improved clinically and were released from the hospital when fractures were stable at 4-5 weeks after admission. Of the 13 macaques studied, all but one returned as normal members of the colony

  10. Illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, Daan|info:eu-repo/dai/nl/380477025

    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. BMI and breast cancer prognosis benefit: mammography screening reveals differences between normal weight and overweight women.

    Science.gov (United States)

    Crispo, Anna; Grimaldi, Maria; D'Aiuto, Massimiliano; Rinaldo, Massimo; Capasso, Immacolata; Amore, Alfonso; D'Aiuto, Giuseppe; Giudice, Aldo; Ciliberto, Gennaro; Montella, Maurizio

    2015-02-01

    Few studies are available on the potential impact of body weight on breast cancer prognosis in screen-detected patients. Moreover, it is not known whether body mass index (BMI) could have a different prognostic impact in screen-detected versus symptomatic breast cancer patients. To investigate these unsolved issues, we carried out a retrospective study evaluating the effect of BMI on breast cancer prognosis in screen-detected vs symptomatic breast cancer patients. We conducted a follow-up study on 448 women diagnosed with incident, histologically-confirmed breast cancer. Patients were categorized according to their BMI as normal weight, overweight and obese. Disease free survival (DFS), overall survival (OS), and BMI curves were compared according to mode of cancer detection. Among screen-detected patients, higher BMI was associated with a significant lower DFS, whereas no significant difference was observed among symptomatic patients. OS showed similar results. In the multivariate analysis adjusting for age, education, tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR) and menopausal status, the risk for high level of BMI among screen-detected patients did not reach the statistical significance for either recurrence or survival. Our study highlights the potential impact of high bodyweight in breast cancer prognosis, the findings confirm that obesity plays a role in women breast cancer prognosis independently from diagnosis mode. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. On the Physiology of Normal Swallowing as Revealed by Magnetic Resonance Imaging in Real Time

    Directory of Open Access Journals (Sweden)

    Arno Olthoff

    2014-01-01

    Full Text Available The aim of this study was to assess the physiology of normal swallowing using recent advances in real-time magnetic resonance imaging (MRI. Therefore ten young healthy subjects underwent real-time MRI and flexible endoscopic evaluations of swallowing (FEES with thickened pineapple juice as oral contrast bolus. MRI movies were recorded in sagittal, coronal, and axial orientations during successive swallows at about 25 frames per second. Intermeasurement variation was analyzed and comparisons between real-time MRI and FEES were performed. Twelve distinct swallowing events could be quantified by real-time MRI (start time, end time, and duration. These included five valve functions: oro-velar opening, velo-pharyngeal closure, glottal closure, epiglottic retroflexion, and esophageal opening; three bolus transports: oro-velar transit, pharyngeal delay, pharyngeal transit; and four additional events: laryngeal ascent, laryngeal descent, vallecular, and piriform sinus filling and pharyngeal constriction. Repetitive measurements confirmed the general reliability of the MRI method with only two significant differences for the start times of the velo-pharyngeal closure (t(8=-2.4, P≤0.046 and laryngeal ascent (t(8=-2.6, P≤0.031. The duration of the velo-pharyngeal closure was significantly longer in real-time MRI compared to FEES (t(8=-3.3, P≤0.011. Real-time MRI emerges as a simple, robust, and reliable tool for obtaining comprehensive functional and anatomical information about the swallowing process.

  13. Internal structure of normal maize starch granules revealed by chemical surface gelatinization.

    Science.gov (United States)

    Pan, D D; Jane, J I

    2000-01-01

    Normal maize starch was fractionated into two sizes: large granules with diameters more than 5 microns and small granules with diameters less than 5 microns. The large granules were surface gelatinized by treating them with an aqueous LiCl solution (13 M) at 22-23 degrees C. Surface-gelatinized remaining granules were obtained by mechanical blending, and gelatinized surface starch was obtained by grinding with a mortar and a pestle. Starches of different granular sizes and radial locations, obtained after different degrees of surface gelatinization, were subjected to scanning electron microscopy, iodine potentiometric titration, gel-permeation chromatography, and amylopectin branch chain length analysis. Results showed that the remaining granules had a rough surface with a lamella structure. Amylose was more concentrated at the periphery than at the core of the granule. Amylopectin had longer long B-chains at the core than at the periphery of the granule. Greater proportions of the long B-chains were present at the core than at the periphery of the granule.

  14. Mycobacterium kansasii Isolated from Tuberculinpositive Rhesus Macaques (Macaca mulatta) in the Absence of Disease.

    Science.gov (United States)

    Shipley, Steven T; Johnson, David K; Roodgar, Morteza; Smith, David Glenn; Montgomery, Charles A; Lloyd, Steven M; Higgins, James A; Kriel, Edwin H; Klein, Hilton J; Porter, William P; Nazareno, Jerome B; Houghton, Paul W; Panda, Aruna; DeTolla, Louis J

    2017-08-01

    Mycobacterial infections are of primary health concern in NHP colonies in biomedical research. NHP are constantly monitored and screened for Mycobacterium spp. We report 6 Chinese-origin rhesus macaques infected with Mycobacterium kansasii that exhibited positive tuberculin skin tests in the absence of disease. Two of these macaques were being used for research purposes; the remaining 4 macaques were residing at the contract quarantine company. Histopathology and acid-fast staining of fixed tissues from all macaques showed that all were free of disease. Thoracic radiographs were negative for any signs of disease or infection. Samples from bronchial lavage and tissues including lung, spleen, hilar and mesenteric lymph nodes tested negative by PCR assay for Mycobacterium spp. One of the research macaques tested culture-positive for M. kansasii and a poorly characterized M. avium complex organism. One macaque from the contract quarantine facility tested culture positive for M. kansasii. Genomic testing and target gene RNA expression analysis of the 2 M. kansasii isolates were performed to evaluate possible kinship and affected genes that might contribute to susceptibility to mycobacterial infection. Genotyping of the 2 isolates revealed 2 genetically distinct strains (strains 1 and 4). The presence of positive tuberculin skin tests in the absence of disease raises serious concerns regarding diagnostic methods used for infected NHP.

  15. 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.

  16. Gene expression analysis of skin grafts and cultured keratinocytes using synthetic RNA normalization reveals insights into differentiation and growth control.

    Science.gov (United States)

    Katayama, Shintaro; Skoog, Tiina; Jouhilahti, Eeva-Mari; Siitonen, H Annika; Nuutila, Kristo; Tervaniemi, Mari H; Vuola, Jyrki; Johnsson, Anna; Lönnerberg, Peter; Linnarsson, Sten; Elomaa, Outi; Kankuri, Esko; Kere, Juha

    2015-06-25

    Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.

  17. 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

  18. Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences.

    Science.gov (United States)

    Love, Tanzy M T; Thurston, Sally W; Keefer, Michael C; Dewhurst, Stephen; Lee, Ha Youn

    2010-06-01

    The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

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

    Science.gov (United States)

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

    2014-11-01

    While studies of rhesus macaques (Macaca mulatta) in the eastern (e.g., China) and western (e.g., India) parts of their geographic range have revealed major genetic differences that warrant the recognition of two different subspecies, little is known about genetic characteristics of rhesus macaques in the transitional zone extending from eastern India and Bangladesh through the northern part of Indo-China, the probable original homeland of the species. We analyzed genetic variation of 762 base pairs of mitochondrial DNA from 86 fecal swab samples and 19 blood samples from 25 local populations of rhesus macaque in Bangladesh collected from January 2010 to August 2012. These sequences were compared with those of rhesus macaques from India, China, and Myanmar. Forty-six haplotypes defined by 200 (26%) polymorphic nucleotide sites were detected. Estimates of gene diversity, expected heterozygosity, and nucleotide diversity for the total population were 0.9599 ± 0.0097, 0.0193 ± 0.0582, and 0.0196 ± 0.0098, respectively. A mismatch distribution of paired nucleotide differences yielded a statistically significantly negative value of Tajima's D, reflecting a population that rapidly expanded after the terminal Pleistocene. Most haplotypes throughout regions of Bangladesh, including an isolated region in the southwestern area (Sundarbans), clustered with haplotypes assigned to the minor haplogroup Ind-2 from India reflecting an east to west dispersal of rhesus macaques to India. Haplotypes from the southeast region of Bangladesh formed a cluster with those from Myanmar, and represent the oldest rhesus macaque haplotypes of Bangladesh. These results are consistent with the hypothesis that rhesus macaques first entered Bangladesh from the southeast, probably from Indo-China, then dispersed westward throughout eastern and central India. © 2014 Wiley Periodicals, Inc.

  20. Cyto- and receptor architecture of area 32 in human and macaque brains.

    Science.gov (United States)

    Palomero-Gallagher, Nicola; Zilles, Karl; Schleicher, Axel; Vogt, Brent A

    2013-10-01

    Human area 32 plays crucial roles in emotion and memory consolidation. It has subgenual (s32), pregenual (p32), dorsal, and midcingulate components. We seek to determine whether macaque area 32 has subgenual and pregenual subdivisions and the extent to which they are comparable to those in humans by means of NeuN immunohistochemistry and multireceptor analysis of laminar profiles. The macaque has areas s32 and p32. In s32, layer IIIa/b neurons are larger than those of layer IIIc. This relationship is reversed in p32. Layer Va is thicker and Vb thinner in s32. Area p32 contains higher kainate, benzodiazepine (BZ), and serotonin (5-HT)1A but lower N-methyl-D-aspartate (NMDA) and α2 receptor densities. Most differences were found in layers I, II, and VI. Together, these differences support the dual nature of macaque area 32. Comparative analysis of human and macaque s32 and p32 supports equivalences in cyto- and receptor architecture. Although there are differences in mean areal receptor densities, there are considerable similarities at the layer level. Laminar receptor distribution patterns in each area are comparable in the two species in layers III-Va for kainate, NMDA, γ-aminobutyric acid (GABA)B , BZ, and 5-HT1A receptors. Multivariate statistical analysis of laminar receptor densities revealed that human s32 is more similar to macaque s32 and p32 than to human p32. Thus, macaque 32 is more complex than hitherto known. Our data suggest a homologous neural architecture in anterior cingulate s32 and p32 in human and macaque brains. © 2013 Wiley Periodicals, Inc.

  1. Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes.

    Science.gov (United States)

    Clark, David J; Fondrie, William E; Yang, Austin; Mao, Li

    2016-02-05

    Exosomes are 30-100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals

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

    Directory of Open Access Journals (Sweden)

    Laura M J Ylinen

    2010-08-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys.

    Science.gov (United States)

    Shooner, Christopher; Hallum, Luke E; Kumbhani, Romesh D; García-Marín, Virginia; Kelly, Jenna G; Majaj, Najib J; Movshon, J Anthony; Kiorpes, Lynne

    2017-09-06

    In amblyopia, abnormal visual experience leads to an extreme form of eye dominance, in which vision through the nondominant eye is degraded. A key aspect of this disorder is perceptual suppression: the image seen by the stronger eye often dominates during binocular viewing, blocking the image of the weaker eye from reaching awareness. Interocular suppression is the focus of ongoing work aimed at understanding and treating amblyopia, yet its physiological basis remains unknown. We measured binocular interactions in visual cortex of anesthetized amblyopic monkeys (female Macaca nemestrina ), using 96-channel "Utah" arrays to record from populations of neurons in V1 and V2. In an experiment reported recently (Hallum et al., 2017), we found that reduced excitatory input from the amblyopic eye (AE) revealed a form of balanced binocular suppression that is unaltered in amblyopia. Here, we report on the modulation of the gain of excitatory signals from the AE by signals from its dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE responses to grating stimuli were attenuated by the presentation of a noise mask to the FE, as in a normal control animal. Responses to FE stimuli, by contrast, could not be masked from the AE. We conclude that a weakened ability of the amblyopic eye to modulate cortical response gain creates an imbalance of suppression that favors the dominant eye. SIGNIFICANCE STATEMENT In amblyopia, vision in one eye is impaired as a result of abnormal early visual experience. Behavioral observations in humans with amblyopia suggest that much of their visual loss is due to active suppression of their amblyopic eye. Here we describe experiments in which we studied binocular interactions in macaques with experimentally induced amblyopia. In normal monkeys, the gain of neuronal response to stimulation of one eye is modulated by contrast in the other eye, but in monkeys with amblyopia the balance of gain modulation is altered so that

  5. Monkey business : the illegal trade in Barbary macaques

    NARCIS (Netherlands)

    van Uhm, D.P.|info:eu-repo/dai/nl/380477025

    2016-01-01

    This article focuses on the organization, modus operandi and trade route of the illegal trade in Barbary macaques. The Barbary macaque is the most seized CITES mammal in the EU, accounting for almost 25% of live mammalrelated seizures. It is estimated that as few as 5,000-6,000 Barbary macaques

  6. 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. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  7. Immunohistochemical and morphological features of a small bowel leiomyoma in a black crested macaque (Macaca nigra

    Directory of Open Access Journals (Sweden)

    Aristizabal-Arbelaez Mónica

    2012-06-01

    Full Text Available Abstract Background Spontaneous gastrointestinal neoplasms in non-human primates are commonly seen in aged individuals. Due to genetic similarities between human and non-human primates, scientists have shown increasing interest in terms of comparative oncology studies. Case presentation The present study is related to a case of an intestinal leiomyoma in a black crested macaque (Macaca nigra, kept on captivity by Matecaña Zoo, Pereira City, Colombia. The animal had abdominal distension, anorexia, vomiting, diarrhea and behavioral changes. Clinical examination showed an increased volume in the upper right abdominal quadrant caused by a neoplastic mass. The patient died during the surgical procedure. Necropsy revealed several small nodules in the peritoneum with adhesion to different portions of the small and large intestines, liver, stomach and diaphragm. Tissue samples were collected, routinely processed and stained by H&E. Microscopic examination revealed a mesenchymal tumor limited to tunica muscularis, resembling normal smooth muscle cells. Neoplastic cells were positive for alpha-smooth muscle actin and vimentin, and negative for cytokeratin AE1/AE3 by immunohistochemistry. Those morphological and immunohistochemical findings allowed to diagnose the intestinal leiomyoma referred above. Conclusion Neoplastic diseases in primates have multifaceted causes. Their manifestations are understudied, leading to a greater difficulty in detection and measurement of the real impact provides by this disease.

  8. Ambiguity aversion in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Benjamin eHayden

    2010-09-01

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

  9. Analysis of the variability of human normal urine by 2D-GE reveals a "public" and a "private" proteome.

    Science.gov (United States)

    Molina, Laurence; Salvetat, Nicolas; Ameur, Randa Ben; Peres, Sabine; Sommerer, Nicolas; Jarraya, Fayçal; Ayadi, Hammadi; Molina, Franck; Granier, Claude

    2011-12-10

    The characterization of the normal urinary proteome is steadily progressing and represents a major interest in the assessment of clinical urinary biomarkers. To estimate quantitatively the variability of the normal urinary proteome, urines of 20 healthy people were collected. We first evaluated the impact of the sample conservation temperature on urine proteome integrity. Keeping the urine sample at RT or at +4°C until storage at -80°C seems the best way for long-term storage of samples for 2D-GE analysis. The quantitative variability of the normal urinary proteome was estimated on the 20 urines mapped by 2D-GE. The occurrence of the 910 identified spots was analysed throughout the gels and represented in a virtual 2D gel. Sixteen percent of the spots were found to occur in all samples and 23% occurred in at least 90% of urines. About 13% of the protein spots were present only in 10% or less of the samples, thus representing the most variable part of the normal urinary proteome. Twenty proteins corresponding to a fraction of the fully conserved spots were identified by mass spectrometry. In conclusion, a "public" urinary proteome, common to healthy individuals, seems to coexist with a "private" urinary proteome, which is more specific to each individual. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Occipital Proton Magnetic Resonance Spectroscopy ((1)H-MRS) Reveals Normal Metabolite Concentrations in Retinal Visual Field Defects

    NARCIS (Netherlands)

    Boucard, Christine C.; Hoogduin, Johannes M.; van der Grond, Jeroen; Cornelissen, Frans W.

    2007-01-01

    Background. Progressive visual field defects, such as age-related macular degeneration and glaucoma, prevent normal stimulation of visual cortex. We investigated whether in the case of visual field defects, concentrations of metabolites such as N-acetylaspartate (NAA), a marker for degenerative

  11. Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

    Science.gov (United States)

    Noguchi, Kevin K; Johnson, Stephen A; Manzella, Francesca M; Masuoka, Kobe L; Williams, Sasha L; Martin, Lauren D; Dissen, Gregory A; Ikonomidou, Chrysanthy; Schenning, Katie J; Olney, John W; Brambrink, Ansgar M

    2018-03-28

    Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.

  12. Isotropic 3D nuclear morphometry of normal, fibrocystic and malignant breast epithelial cells reveals new structural alterations.

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    Vivek Nandakumar

    Full Text Available Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the

  13. Isotropic 3D nuclear morphometry of normal, fibrocystic and malignant breast epithelial cells reveals new structural alterations.

    Science.gov (United States)

    Nandakumar, Vivek; Kelbauskas, Laimonas; Hernandez, Kathryn F; Lintecum, Kelly M; Senechal, Patti; Bussey, Kimberly J; Davies, Paul C W; Johnson, Roger H; Meldrum, Deirdre R

    2012-01-01

    Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria. We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure. We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At pfibrocystic from the metastatic cell populations. Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.

  14. Altered Balance of Receptive Field Excitation and Suppression in Visual Cortex of Amblyopic Macaque Monkeys.

    Science.gov (United States)

    Hallum, Luke E; Shooner, Christopher; Kumbhani, Romesh D; Kelly, Jenna G; García-Marín, Virginia; Majaj, Najib J; Movshon, J Anthony; Kiorpes, Lynne

    2017-08-23

    In amblyopia, a visual disorder caused by abnormal visual experience during development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted by interocular suppression. We used 96-electrode arrays to record neurons and neuronal groups in areas V1 and V2 of six female macaque monkeys ( Macaca nemestrina ) made amblyopic by artificial strabismus or anisometropia in early life, as well as two visually normal female controls. To measure suppressive binocular interactions directly, we recorded neuronal responses to dichoptic stimulation. We stimulated both eyes simultaneously with large sinusoidal gratings, controlling their contrast independently with raised-cosine modulators of different orientations and spatial frequencies. We modeled each eye's receptive field at each cortical site using a difference of Gaussian envelopes and derived estimates of the strength of central excitation and surround suppression. We used these estimates to calculate ocular dominance separately for excitation and suppression. Excitatory drive from the FE dominated amblyopic visual cortex, especially in more severe amblyopes, but suppression from both the FE and AEs was prevalent in all animals. This imbalance created strong interocular suppression in deep amblyopes: increasing contrast in the AE decreased responses at binocular cortical sites. These response patterns reveal mechanisms that likely contribute to the interocular suppression that disrupts vision in amblyopes. SIGNIFICANCE STATEMENT Amblyopia is a developmental visual disorder that alters both monocular vision and binocular interaction. Using microelectrode arrays, we examined binocular interaction in primary visual cortex and V2 of six amblyopic macaque monkeys ( Macaca nemestrina ) and two visually normal controls. By stimulating the eyes dichoptically, we showed that, in amblyopic cortex, the binocular combination of signals is

  15. Gene targeting in adult rhesus macaque fibroblasts

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    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.

  16. Project Lifescape - The Macaques of India

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 9. Project Lifescape - The Macaques of India. Anindya Sinha. Classroom Volume 6 Issue 9 September 2001 pp 94-105. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/006/09/0094-0105 ...

  17. Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells.

    Science.gov (United States)

    Cereser, Biancastella; Jansen, Marnix; Austin, Emily; Elia, George; McFarlane, Taneisha; van Deurzen, Carolien Hm; Sieuwerts, Anieta M; Daidone, Maria G; Tadrous, Paul J; Wright, Nicholas A; Jones, Louise; McDonald, Stuart Ac

    2018-01-01

    It is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell; however, demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and premalignant mammary epithelium or its cellular hierarchy. Here, we use deficiency in the mitochondrial enzyme cytochrome c oxidase (CCO), typically caused by somatic mutations in the mitochondrial genome, as a means to perform lineage tracing in the human mammary epithelium. PCR sequencing of laser-capture microdissected cells in combination with immunohistochemistry for markers of lineage differentiation was performed to determine the clonal nature of the mammary epithelium. We have shown that in the normal human breast, clonal expansions (defined here by areas of CCO deficiency) are typically uncommon and of limited size, but can occur at any site within the adult mammary epithelium. The presence of a stem cell population was shown by demonstrating multi-lineage differentiation within CCO-deficient areas. Interestingly, we observed infrequent CCO deficiency that was restricted to luminal cells, suggesting that niche succession, and by inference stem cell location, is located within the luminal layer. CCO-deficient areas appeared large within areas of ductal carcinoma in situ, suggesting that the rate of clonal expansion was altered in the premalignant lesion. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  18. 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

  19. 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

  20. Cultivation Versus Molecular Analysis of Banana (Musa sp.) Shoot-Tip Tissue Reveals Enormous Diversity of Normally Uncultivable Endophytic Bacteria.

    Science.gov (United States)

    Thomas, Pious; Sekhar, Aparna Chandra

    2017-05-01

    The interior of plants constitutes a unique environment for microorganisms with various organisms inhabiting as endophytes. Unlike subterranean plant parts, aboveground parts are relatively less explored for endophytic microbial diversity. We employed a combination of cultivation and molecular approaches to study the endophytic bacterial diversity in banana shoot-tips. Cultivable bacteria from 20 sucker shoot-tips of cv. Grand Naine included 37 strains under 16 genera and three phyla (Proteobacteria, Actinobacteria, Firmicutes). 16S rRNA gene-ribotyping approach on 799f and 1492r PCR-amplicons to avoid plant organelle sequences was ineffective showing limited bacterial diversity. 16S rRNA metagene profiling targeting the V3-V4 hypervariable region after filtering out the chloroplast (74.2 %), mitochondrial (22.9 %), and unknown sequences (1.1 %) revealed enormous bacterial diversity. Proteobacteria formed the predominant phylum (64 %) succeeded by Firmicutes (12.1 %), Actinobacteria (9.5 %), Bacteroidetes (6.4 %), Planctomycetes, Cyanobacteria, and minor shares (banana shoot-tips (20 phyla, 46 classes) with about 2.6 % of the deciphered 269 genera and 1.5 % of the 656 observed species from the same source of shoot-tips attained through cultivation. The predominant genera included several agriculturally important bacteria. The study reveals an immense ecosystem of endophytic bacteria in banana shoot tissues endorsing the earlier documentation of intracellular "Cytobacts" and "Peribacts" with possible roles in plant holobiome and hologenome.

  1. Extensive structural variations between mitochondrial genomes of CMS and normal peppers (Capsicum annuum L.) revealed by complete nucleotide sequencing.

    Science.gov (United States)

    Jo, Yeong Deuk; Choi, Yoomi; Kim, Dong-Hwan; Kim, Byung-Dong; Kang, Byoung-Cheorl

    2014-07-04

    Cytoplasmic male sterility (CMS) is an inability to produce functional pollen that is caused by mutation of the mitochondrial genome. Comparative analyses of mitochondrial genomes of lines with and without CMS in several species have revealed structural differences between genomes, including extensive rearrangements caused by recombination. However, the mitochondrial genome structure and the DNA rearrangements that may be related to CMS have not been characterized in Capsicum spp. We obtained the complete mitochondrial genome sequences of the pepper CMS line FS4401 (507,452 bp) and the fertile line Jeju (511,530 bp). Comparative analysis between mitochondrial genomes of peppers and tobacco that are included in Solanaceae revealed extensive DNA rearrangements and poor conservation in non-coding DNA. In comparison between pepper lines, FS4401 and Jeju mitochondrial DNAs contained the same complement of protein coding genes except for one additional copy of an atp6 gene (ψatp6-2) in FS4401. In terms of genome structure, we found eighteen syntenic blocks in the two mitochondrial genomes, which have been rearranged in each genome. By contrast, sequences between syntenic blocks, which were specific to each line, accounted for 30,380 and 17,847 bp in FS4401 and Jeju, respectively. The previously-reported CMS candidate genes, orf507 and ψatp6-2, were located on the edges of the largest sequence segments that were specific to FS4401. In this region, large number of small sequence segments which were absent or found on different locations in Jeju mitochondrial genome were combined together. The incorporation of repeats and overlapping of connected sequence segments by a few nucleotides implied that extensive rearrangements by homologous recombination might be involved in evolution of this region. Further analysis using mtDNA pairs from other plant species revealed common features of DNA regions around CMS-associated genes. Although large portion of sequence context was

  2. All-atom normal-mode analysis reveals an RNA-induced allostery in a bacteriophage coat protein.

    Science.gov (United States)

    Dykeman, Eric C; Twarock, Reidun

    2010-03-01

    Assembly of the T=3 bacteriophage MS2 is initiated by the binding of a 19 nucleotide RNA stem loop from within the phage genome to a symmetric coat protein dimer. This binding event effects a folding of the FG loop in one of the protein subunits of the dimer and results in the formation of an asymmetric dimer. Since both the symmetric and asymmetric forms of the dimer are needed for the assembly of the protein container, this allosteric switch plays an important role in the life cycle of the phage. We provide here details of an all-atom normal-mode analysis of this allosteric effect. The results suggest that asymmetric contacts between the A -duplex RNA phosphodiester backbone of the stem loop with the EF loop in one coat protein subunit results in an increased dynamic behavior of its FG loop. The four lowest-frequency modes, which encompass motions predominantly on the FG loops, account for over 90% of the increased dynamic behavior due to a localization of the vibrational pattern on a single FG loop. Finally, we show that an analysis of the allosteric effect using an elastic network model fails to predict this localization effect, highlighting the importance of using an all-atom full force field method for this problem.

  3. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

    Science.gov (United States)

    Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

    2016-03-29

    Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

  4. 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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    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.

  7. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    International Nuclear Information System (INIS)

    Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

    2014-01-01

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  8. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  9. Seismic Supercycles of Normal Faults in Central Italy over Various Time Scales Revealed by 36Cl Cosmogenic Dating

    Science.gov (United States)

    Benedetti, L. C.; Tesson, J.; Perouse, E.; Puliti, I.; Fleury, J.; Rizza, M.; Billant, J.; Pace, B.

    2017-12-01

    The use of 36Cl cosmogenic nuclide as a paleoseismological tool for normal faults in the Mediterranean has revolutionized our understanding of their seismic cycle (Gran Mitchell et al. 2001, Benedetti et al. 2002). Here we synthetized results obtained on 13 faults in Central Italy. Those records cover a period of 8 to 45 ka. The mean recurrence time of retrieved seismic events is 5.5 ±6 ka, with a mean slip per event of 2.5 ± 1.8 m and a mean slip-rate from 0.1 to 2.4 mm/yr. Most retrieved events correspond to single events according to scaling relationships. This is also supported by the 2 m-high co-seismic slip observed on the Mt Vettore fault after the October 30, 2016 M6.5 earthquake in Central Italy (EMERGEO working group). Our results suggest that all faults have experienced one or several periods of slip acceleration with bursts of seismic activity, associated with very high slip-rate of 1.7-9 mm/yr, corresponding to 2-20 times their long-term slip-rate. The duration of those bursts is variable from a fault to another (from recurrence time. This might suggest that the seismic activity of those faults could be controlled by their intrinsic properties (e.g. long-term slip-rate, fault-length, state of structural maturity). Our results also show events clustering with several faults rupturing in less than 500 yrs on adjacent or distant faults within the studied area. The Norcia-Amatrice seismic sequence, ≈ 50 km north of our study area, also evidenced this clustering behaviour, with over the last 20 yrs several successive events of Mw 5 to 6.5 (from north to south: Colfiorito 1997 Mw6.0, Norcia 2016 Mw6.5, L'Aquila 2009 Mw6.3), rupturing various fault systems, over a total length of ≈100 km. This sequence will allow to better understand earthquake kinematics and spatiotemporal slip distribution during those seismic bursts.

  10. Chromosome-wide mapping of DNA methylation patterns in normal and malignant prostate cells reveals pervasive methylation of gene-associated and conserved intergenic sequences

    Directory of Open Access Journals (Sweden)

    De Marzo Angelo M

    2011-06-01

    Full Text Available Abstract Background DNA methylation has been linked to genome regulation and dysregulation in health and disease respectively, and methods for characterizing genomic DNA methylation patterns are rapidly emerging. We have developed/refined methods for enrichment of methylated genomic fragments using the methyl-binding domain of the human MBD2 protein (MBD2-MBD followed by analysis with high-density tiling microarrays. This MBD-chip approach was used to characterize DNA methylation patterns across all non-repetitive sequences of human chromosomes 21 and 22 at high-resolution in normal and malignant prostate cells. Results Examining this data using computational methods that were designed specifically for DNA methylation tiling array data revealed widespread methylation of both gene promoter and non-promoter regions in cancer and normal cells. In addition to identifying several novel cancer hypermethylated 5' gene upstream regions that mediated epigenetic gene silencing, we also found several hypermethylated 3' gene downstream, intragenic and intergenic regions. The hypermethylated intragenic regions were highly enriched for overlap with intron-exon boundaries, suggesting a possible role in regulation of alternative transcriptional start sites, exon usage and/or splicing. The hypermethylated intergenic regions showed significant enrichment for conservation across vertebrate species. A sampling of these newly identified promoter (ADAMTS1 and SCARF2 genes and non-promoter (downstream or within DSCR9, C21orf57 and HLCS genes hypermethylated regions were effective in distinguishing malignant from normal prostate tissues and/or cell lines. Conclusions Comparison of chromosome-wide DNA methylation patterns in normal and malignant prostate cells revealed significant methylation of gene-proximal and conserved intergenic sequences. Such analyses can be easily extended for genome-wide methylation analysis in health and disease.

  11. 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

  12. Comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.

    Science.gov (United States)

    Daggett, Gregory J; Zhao, Chunxia; Connor-Stroud, Fawn; Oviedo-Moreno, Patricia; Moon, Hojin; Cho, Michael W; Moench, Thomas; Anderson, Deborah J; Villinger, Francois

    2017-10-01

    Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study. We tested the vaginal environment of rhesus and cynomolgus macaques longitudinally to characterize the normal microflora based on Nugent scores and pH. This evaluation was extended after colonization of the vaginal space with Lactobacilli in an effort to recreate NHP models representing the healthy human vaginal environment. Nugent scores and pH differed significantly between species, although data from both species were suggestive of stable bacterial vaginosis. Colonization with Lactobacilli was successful in both species leading to lower Nugent score and pH, although rhesus macaques appeared better able to sustain Lactobacillus spp over time. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Shimada, Masaki

    2006-10-01

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

  14. Dynamic Interaction of Enterovirus 71 and Dendritic Cells in Infected Neonatal Rhesus Macaques.

    Science.gov (United States)

    Zhao, Ting; Zhang, Zhixiao; Zhang, Ying; Feng, Min; Fan, Shengtao; Wang, Lichun; Liu, Longding; Wang, Xi; Wang, Qinglin; Zhang, Xiaolong; Wang, Jingjing; Liao, Yun; He, Zhanlong; Lu, Shuaiyao; Yang, Huai; Li, Qihan

    2017-01-01

    Enterovirus 71 (EV71) is one of the main pathogens responsible for hand, foot, and mouth disease (HFMD). Infection with EV71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. Based on the previous pathological study of EV71 infections in neonatal rhesus macaques, our work using this animal model and an EV71 chimera that expresses enhanced green fluorescent protein (EGFP-EV71) primarily explored where EV71 localizes and proliferates, and the subsequent initiation of the pathological process. The chimeric EGFP-EV71 we constructed was similar to the wild-type EV71 (WT-EV71) virus in its biological characteristics. Similar clinical manifestations and histo-pathologic features were equally displayed in neonatal rhesus macaques infected with either WT-EV71 or EGFP-EV71 via the respiratory route. Fluorescent signal tracing in tissues from the animals infected with EGFP-EV71 showed that EV71 proliferated primarily in the respiratory tract epithelium and the associated lymphoid tissues. Immunofluorescence and flow cytometry analyses revealed that EV71 was able to enter a pre-conventional dendritic cell (DC) population at the infection sites. The viremia identified in the macaques infected by WT-EV71 or EGFP-EV71 was present even in the artificial presence of a specific antibody against the virus. Our results suggest that EV71 primarily proliferates in the respiratory tract epithelium followed by subsequent entry into a pre-cDC population of DCs. These cells are then hijacked by the virus and they can potentially transmit the virus from local sites to other organs through the blood circulation during the infection process. Our results suggest that the EV71 infection process in this DC population does not interfere with the induction of an independent immune response against the EV71 infection in the neonatal macaques.

  15. Use of ultrasound imaging for the diagnosis of abnormal uterine bleeding in the bonnet macaque ( Macaca radiata).

    Science.gov (United States)

    Chaudhari, Uddhav K; Imran, M; Manjramkar, Dhananjay D; Metkari, Siddhanath M; Sable, Nilesh P; Gavhane, Dnyaneshwar S; Katkam, Rajendra R; Sachdeva, Geetanjali; Thakur, Meenakshi H; Kholkute, Sanjeeva D

    2017-02-01

    Ultrasound is a powerful, low-cost, non-invasive medical tool used by laboratory animal veterinarians for diagnostic imaging. Sonohysterography and transvaginal ultrasound are frequently used to assess uterine anomalies in women presenting with abnormal uterine bleeding (AUB). In the present study, we have evaluated the abdominal ultrasound of bonnet monkeys ( n = 8) showing spontaneous ovulatory ( n = 5) and anovulatory ( n = 3) AUB. The ovulatory ( n = 5) macaques showed cyclic AUB for 7-8 days. The anovulatory ( n = 3) macaques had irregular AUB with menstrual cycles of 40-45 days. The B-mode abdominal, colour Doppler and 3D ultrasound scans were performed during the proliferative phase of the menstrual cycle. Ultrasound examination revealed endometrial polyps in five macaques and endometrial hyperplasia in three animals. The width and length of endometrial polyps was around 0.5-1 cm (average 0.51 ± 0.23 cm × 0.96 ± 0.16 cm) with significant increase in endometrial thickness ( P uterine cavity and colour Doppler ultrasound showed increased vascularity in the endometrial polyps. Endometrial hyperplasia characteristically appeared as a thickened echogenic endometrium ( P < 0.0002). This study demonstrates the use of non-invasive ultrasound techniques in the diagnosis of AUB in macaques.

  16. 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. © 2013 Wiley Periodicals, Inc.

  17. Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

    Science.gov (United States)

    Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

    2010-11-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

  18. Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

    International Nuclear Information System (INIS)

    Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

    2010-01-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

  19. A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal123

    Science.gov (United States)

    Schwander, Flurina; Kopf-Bolanz, Katrin A.; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G.; Piya, Milan K.; Gijs, Martin A. M.; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

    2014-01-01

    A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20–25 kg/m2) and 18 obese (BMI: >30 kg/m2) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. PMID:24812072

  20. A dose-response strategy reveals differences between normal-weight and obese men in their metabolic and inflammatory responses to a high-fat meal.

    Science.gov (United States)

    Schwander, Flurina; Kopf-Bolanz, Katrin A; Buri, Caroline; Portmann, Reto; Egger, Lotti; Chollet, Magali; McTernan, Philip G; Piya, Milan K; Gijs, Martin A M; Vionnet, Nathalie; Pralong, François; Laederach, Kurt; Vergères, Guy

    2014-10-01

    A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068. © 2014 American Society for Nutrition.

  1. Effect of Chronic Social Stress on Prenatal Transfer of Antitetanus Immunity in Captive Breeding Rhesus Macaques (Macaca mulatta).

    Science.gov (United States)

    Stammen, Rachelle L; Cohen, Joyce K; Meeker, Tracy L; Crane, Maria M; Amara, Rama R; Hicks, Sakeenah L; Meyer, Jerrold S; Ethun, Kelly F

    2018-05-15

    Because tetanus can cause significant morbidity and mortality in NHP, colonywide vaccination with tetanus toxoid is recommendedfor outdoor breeding colonies of rhesus macaques, with primary immunizations commonly given to infants at 6 mo of age followed by booster vaccines every 10 y. Maternal antibodies are thought to offer protective immunity to infants younger than 6 mo. However, historical colony data from the Yerkes National Primate Research Center show a higher incidence of tetanus among infants (≤ 6 mo old) born to subordinate dams. Whether this higher incidence of infantile tetanus is due to a higher incidence of trauma among subordinate animals or is a stress-induced impairment of maternal antibody protection is unknown. Studies in other NHP species suggest that chronic exposure to social stressors interferes with the receptor-mediated transplacental transfer of IgG. Therefore, the primary aim of this study was to determine whether chronic stress associated with social subordination impairs prenatal transfer of antitetanus immunity in breeding female rhesus macaques. Subjects included 26 high- and 26 low-ranking adult female rhesus macaques that were nearly 5 or 10 y after their initial immunization and their nonimmunized infants. We hypothesized that infants born to subordinate dams that were nearly 10 y after immunization would have the lowest infant-to-dam antibody ratios and thus would be at greatest risk for infection. Results revealed no significant intergroup differences in infant antitetanus IgG levels. However, infant-to-dam IgG ratios against tetanus were significantly lower among subordinate animals compared with dominant macaques, after accounting for the number of years since the dam's initial vaccination. In addition, higher maternal hair cortisol levels predicted lower infant-to-dam tetanus toxoid IgG ratios. Together, these findings suggest that chronic social stress in female rhesus macaques may hamper the prenatal transfer of

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Of the two rhesus macaque subspecies used for AIDS studies, the Simian immunodeficiency virus-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection, providing both insight into pathogenesis and a system for testing novel vaccines. Despite the Chinese rhesus.......3%) of the sequences identified were novel. From all MHC alleles detected, we prioritized Mamu-A1*02201 for functional characterization based on its higher frequency of expression. Upon the development of MHC/peptide binding assays and definition of its associated motif, we revealed that this allele shares peptide...

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

    Science.gov (United States)

    Regaiolli, Barbara; Spiezio, Caterina; Vallortigara, Giorgio

    2016-01-01

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

  4. Tracing the phylogeographic history of Southeast Asian long-tailed macaques through mitogenomes of museum specimens.

    Science.gov (United States)

    Yao, Lu; Li, Hongjie; Martin, Robert D; Moreau, Corrie S; Malhi, Ripan S

    2017-11-01

    The biogeographical history of Southeast Asia is complicated due to the continuous emergences and disappearances of land bridges throughout the Pleistocene. Here, we use long-tailed macaques (Macaca fascicularis), which are widely distributed throughout the mainland and islands of Southeast Asia, asa model for better understanding the biogeographical patterns of diversification in this geographically complex region. A reliable intraspecific phylogeny including individuals from localities on oceanic islands, continental islands, and the mainland is needed to trace relatedness along with the pattern and timing of colonization in this region. We used high-throughput sequencing techniques to sequence mitochondrial genomes (mitogenomes) from 95 Southeast Asian M. fascicularis specimens housed at natural history museums around the world. To achieve a comprehensive picture, we more than tripled the mitogenome sample size for M. fascicularis from previous studies, and for the first time included documented samples from the Philippines and several small Indonesian islands. Confirming the result from a previous, recent intraspecific phylogeny for M. fascicularis, the newly reconstructed phylogeny of 135 specimens divides the samples into two major clades: Clade A includes haplotypes from the mainland and some from northern Sumatra, while Clade B includes all insular haplotypes along with lineages from southern Sumatra. This study resolves a previous disparity by revealing a disjunction in the origin of Sumatran macaques, with separate lineages originating within the two major clades, suggesting that at least two major migrations to Sumatra occurred. However, our dated phylogeny reveals that the two major clades split ∼1.88Ma, which is earlier than in previously published phylogenies. Our new data reveal that most Philippine macaque lineages diverged from the Borneo stock within the last ∼0.06-0.43Ma. Finally, our study provides insight into successful sequencing of DNA

  5. The presence of the casein kinase II phosphorylation sites of Vpu enhances the CD4+ T cell loss caused by the simian-human immunodeficiency virus SHIVKU-lbMC33 in pig-tailed macaques

    International Nuclear Information System (INIS)

    Singh, Dinesh K.; Griffin, Darcy M.; Pacyniak, Erik; Jackson, Mollie; Werle, Michael J.; Wisdom, Bo; Sun, Francis; Hout, David R.; Pinson, David M.; Gunderson, Robert S.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

    2003-01-01

    The simian-human immunodeficiency virus (SHIV)/ macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of Vpu in lentivirus pathogenesis. In this report, we have mutated the two phosphorylated serine residues of the HIV-1 Vpu to glycine residues and have reconstructed a SHIV expressing this nonphosphorylated Vpu (SHIV S52,56G ). Expression studies revealed that this protein was localized to the same intracellular compartment as wild-type Vpu. To determine if this virus was pathogenic, four pig-tailed macaques were inoculated with SHIV S52,56G and virus burdens and circulating CD4 + T cells monitored up to 1 year. Our results indicate that SHIV S52,56G caused rapid loss in the circulating CD4 + T cells within 3 weeks of inoculation in one macaque (CC8X), while the other three macaques developed no or gradual numbers of CD4 + T cells and a wasting syndrome. Histological examination of tissues revealed that macaque CC8X had lesions in lymphoid tissues (spleen, lymph nodes, and thymus) that were typical for macaques inoculated with pathogenic parental SHIV KU-1bMC33 and had no lesions within the CNS. To rule out that macaque CC8X had selected for a virus in which there was reversion of the glycine residues at positions 52 and 56 to serine residues and/or compensating mutations occurred in other genes associated with CD4 down-regulation, sequence analysis was performed on amplified vpu sequences isolated from PBMC and from several lymphoid tissues at necropsy. Sequence analysis revealed a reversion of the glycine residues back to serine residues in this macaque. The other macaques maintained low virus burdens, with one macaque (P003) developing a wasting syndrome between months 9 and 11. Histological examination of tissues from this macaque revealed a thymus with severe atrophy that was similar to that of a previously reported macaque inoculated with a SHIV lacking vpu (Virology 293, 2002, 252). Sequence analysis revealed no

  6. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2007-10-01

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

  9. Ancestry, Plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (Macaca fascicularis) bred for export in Chinese breeding farms.

    Science.gov (United States)

    Zhang, Xinjun; Meng, Yuhuan; Houghton, Paul; Liu, Mingyu; Kanthaswamy, Sreetharan; Oldt, Robert; Ng, Jillian; Trask, Jessica Satkoski; Huang, Ren; Singh, Balbir; Du, Hongli; Smith, David Glenn

    2017-04-01

    Most cynomolgus macaques (Macaca fascicularis) used in the United States as animal models are imported from Chinese breeding farms without documented ancestry. Cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model. DNA of 400 cynomolgus macaques from 10 Chinese breeding farms was genotyped to characterize their regional origin and rhesus ancestry proportion. A nested PCR assay was used to detect Plasmodium cynomolgi infection in sampled individuals. All populations exhibited high levels of genetic heterogeneity and low levels of inbreeding and genetic subdivision. Almost all individuals exhibited an Indochinese origin and a rhesus ancestry proportion of 5%-48%. The incidence of P. cynomolgi infection in cynomolgus macaques is strongly associated with proportion of rhesus ancestry. The varying amount of rhesus ancestry in cynomolgus macaques underscores the importance of monitoring their genetic similarity in malaria research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Mahesh Mohan

    2016-10-01

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

  11. Radiographic measurement of the cardiothoracic ratio in a feral population of long-tailed macaques (Macaca fascicularis)

    Energy Technology Data Exchange (ETDEWEB)

    Schillaci, Michael A. [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada)], E-mail: schillaci@utsc.utoronto.ca; Lischka, Andrea R.; Karamitsos, Anisah A. [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada); Engel, Gregory A. [Swedish/Cherry Hill Family Medicine Residency, 550 16th Avenue, Seattle, WA 98122 (United States); Washington National Primate Research Center, University of Washington, Seattle, WA 98195 (United States); Paul, Narinder [Division of Cardiothoracic Imaging, University Health Network, University of Toronto, Toronto, Ontario M5G 2N2 (Canada); Ramoul, Rima [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada); Rompis, Aida; Putra, Arta; Wandia, I. Nengah [Fakultas Kedokteran Hewan, Udayana University, Denpasar, Bali 80361 (Indonesia); Jones-Engel, Lisa [Washington National Primate Research Center, University of Washington, Seattle, WA 98195 (United States)

    2010-05-15

    The cardiothoracic ratio is often used as a proxy measure of cardiovascular pathophysiology in humans but less frequently in nonhuman primates, for whom little published data are available to establish normal values. The present study is the first to examine relative cardiac size in a feral population of primates. This report presents estimates of the cardiothoracic ratio in long-tailed macaques (Macaca fascicularis) from Bali, Indonesia. The mean cardiothoracic ratio for the study sample was 0.55, above the commonly used threshold of 0.50 for identifying an enlarged heart in human medicine. Future research on wild populations of macaques is needed and should include multiple assessments of cardiac function including both radiography and echocardiography.

  12. Radiographic measurement of the cardiothoracic ratio in a feral population of long-tailed macaques (Macaca fascicularis)

    International Nuclear Information System (INIS)

    Schillaci, Michael A.; Lischka, Andrea R.; Karamitsos, Anisah A.; Engel, Gregory A.; Paul, Narinder; Ramoul, Rima; Rompis, Aida; Putra, Arta; Wandia, I. Nengah; Jones-Engel, Lisa

    2010-01-01

    The cardiothoracic ratio is often used as a proxy measure of cardiovascular pathophysiology in humans but less frequently in nonhuman primates, for whom little published data are available to establish normal values. The present study is the first to examine relative cardiac size in a feral population of primates. This report presents estimates of the cardiothoracic ratio in long-tailed macaques (Macaca fascicularis) from Bali, Indonesia. The mean cardiothoracic ratio for the study sample was 0.55, above the commonly used threshold of 0.50 for identifying an enlarged heart in human medicine. Future research on wild populations of macaques is needed and should include multiple assessments of cardiac function including both radiography and echocardiography.

  13. Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

    Science.gov (United States)

    Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

    2013-01-01

    Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Donald K. Nichols

    2012-10-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  17. Analysis of carboxylesterase 2 transcript variants in cynomolgus macaque liver.

    Science.gov (United States)

    Uno, Yasuhiro; Igawa, Yoshiyuki; Tanaka, Maori; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

    2018-04-27

    Carboxylesterase (CES) is important for the detoxification of a wide range of drugs and xenobiotics. In this study, the hepatic level of CES2 mRNA was examined in cynomolgus macaques used widely in preclinical studies for drug metabolism. Three CES2 mRNAs were present in cynomolgus macaque liver. The mRNA level was highest for cynomolgus CES2A (formerly CES2v3), much lower for cynomolgus CES2B (formerly CES2v1) and extremely low for cynomolgus CES2C (formerly CES2v2). Most various transcript variants produced from cynomolgus CES2B gene did not contain a complete coding region. Thus, CES2A is the major CES2 enzyme in cynomolgus liver. A new transcript variant of CES2A, CES2Av2, was identified. CES2Av2 contained exon 3 region different from wild-type (CES2Av1). In cynomolgus macaques expressing only CES2Av2 transcript, CES2A contained the sequence of CES2B in exon 3 and vicinity, probably due to gene conversion. On genotyping, this CES2Av2 allele was prevalent in Indochinese cynomolgus macaques, but not in Indonesian cynomolgus or rhesus macaques. CES2Av2 recombinant protein showed similar activity to CES2Av1 protein for several substrates. It is concluded that CES2A is the major cynomolgus hepatic CES2, and new transcript variant, CES2Av2, has similar functions to CES2Av1.

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

    Directory of Open Access Journals (Sweden)

    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

  19. MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

    Science.gov (United States)

    Brammer, David W; Gillespie, Patrick J; Tian, Mei; Young, Daniel; Raveendran, Muthuswamy; Williams, Lawrence E; Gagea, Mihai; Benavides, Fernando J; Perez, Carlos J; Broaddus, Russell R; Bernacky, Bruce J; Barnhart, Kirstin F; Alauddin, Mian M; Bhutani, Manoop S; Gibbs, Richard A; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih; Rogers, Jeffrey; Abee, Christian R; Gelovani, Juri G

    2018-03-13

    Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoroacetate ([ 18 F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [ 18 F]fluorothymidine ([ 18 F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1 -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans. Copyright © 2018 the Author(s). Published by PNAS.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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. © 2015 Wiley Periodicals, Inc.

  2. Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex

    Science.gov (United States)

    Smiley, John F.; Schroeder, Charles E.

    2017-01-01

    Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is

  3. Tuned Normalization Explains the Size of Attention Modulations

    OpenAIRE

    Ni, Amy M.; Ray, Supratim; Maunsell, John H.R.

    2012-01-01

    The effect of attention on firing rates varies considerably within a single cortical area. The firing rate of some neurons is greatly modulated by attention while others are hardly affected. The reason for this variability across neurons is unknown. We found that the variability in attention modulation across neurons in area MT of macaques can be well explained by variability in the strength of tuned normalization across neurons. The presence of tuned normalization also explains a striking as...

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

    Science.gov (United States)

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

    2016-10-01

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

  5. Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

    Directory of Open Access Journals (Sweden)

    John K. Maxi

    2016-11-01

    Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

  6. Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Roman A Siddiqui

    Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.

  7. Detection thresholds of macaque otolith afferents.

    Science.gov (United States)

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

    2012-06-13

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

  8. 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.

  9. The influence of age on wild rhesus macaques' affiliative social interactions.

    Science.gov (United States)

    Liao, Zhijie; Sosa, Sebastian; Wu, Chengfeng; Zhang, Peng

    2018-02-01

    The social relationships that individuals experience at different life stages have a non-negligible influence on their lives, and this is particularly true for group living animals. The long lifespan of many primates makes it likely that these animals have various tactics of social interaction to adapt to complex changes in environmental or physical conditions. The different strategies used in social interaction by individuals at different life stages, and whether the position (central or peripheral) or role (initiator or recipient) of an individual in the group social network changes with age, are intriguing questions that remain to be investigated. We used social network analysis to examine age-related differences in social interaction patterns, social roles, and social positions in three affiliative social networks (approach, allogrooming, and social play) in a group of wild rhesus macaques (Macaca mulatta). Our results showed that social interaction patterns of rhesus macaques differ between age classes in the following ways: i) young individuals tend to allocate social time to a high number of groupmates, older individuals prefer to focus on fewer, specific partners; ii) as they grow older, individuals tend to be recipients in approach interactions and initiators in grooming interactions; and iii) regardless of the different social interaction strategies, individuals of all ages occupy a central position in the group. These results reveal a possible key role played by immature individuals in group social communication, a little-explored issue which deserves closer investigation in future research. © 2017 Wiley Periodicals, Inc.

  10. Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

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    Wei Zhao

    2008-01-01

    Full Text Available A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6 CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P[8] and G9P[8] of human rotaviruses. Infection accompanied by G1P[8] shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA in plasma. To measure the interferon gamma (IFN-γ and tumor necrosis factor (TNF anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6 161–395 region revealed reactivity of CD4+ T cells with the VP6 281–331 domain. A VP6 301–315 region was identified as the epitope responsible for IFN-γ production while a broader VP6 293–327 domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.

  11. Stepping toward a Macaque Model of HIV-1 Induced AIDS

    Directory of Open Access Journals (Sweden)

    Jason T. Kimata

    2014-09-01

    Full Text Available HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina, but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.

  12. 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...

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

    NARCIS (Netherlands)

    Cooper, M.A.; Bernstein, I.S.; Hemelrijk, C.K.

    A consistent conclusion in reconciliation research is that animals that reconcile are likely to have strong social bonds. This has led to the hypothesis that reconciliation occurs most often between valuable social partners. We tested this hypothesis in a group of Assamese macaques (Macaca

  14. Molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Mahadhi, Hassan M D; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

    2018-06-01

    Butyrylcholinesterase (BChE), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. BChE polymorphisms partly account for variable BChE activities among individuals in humans, but have not been investigated in cynomolgus macaques. Molecular characterization was carried out by analyzing primary sequence, gene, tissue expression, and genetic variants. In cynomolgus and human BChE, phylogenetically closely related, amino acid residues important for enzyme function were conserved, and gene and genomic structure were similar. Cynomolgus BChE mRNA was most abundantly expressed in liver among the 10 tissue types analyzed. Re-sequencing found 26 non-synonymous genetic variants in 121 cynomolgus and 23 rhesus macaques, indicating that macaque BChE is polymorphic, although none of these variants corresponded to the null or defective alleles of human BChE. These results suggest molecular similarities of cynomolgus and human BChE. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Expression of cytochrome P450 regulators in cynomolgus macaque.

    Science.gov (United States)

    Uno, Yasuhiro; Yamazaki, Hiroshi

    2017-09-11

    1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed 17 P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of 17 P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered in a phylogenetic tree, with the human orthologs. 3. Many of the P450 regulator mRNAs were preferentially expressed in the liver, kidney, and/or jejunum. Among the P450 regulator mRNAs, PXR was most abundant in the liver and jejunum, and HNF4α in the kidney. In the liver, the expression of most P450 regulator mRNAs did not show significant differential expression (>2.5-fold) between cynomolgus macaques bred in Cambodia, China, and Indonesia, or rhesus macaques. 4. By correlation analysis, most of the P450 regulators were significantly (p < 0.05) correlated to other P450 regulators, and many of them were also significantly (p < 0.05) correlated with P450s. 5. These results suggest that 17 P450 regulators of cynomolgus macaques had similar molecular characteristics to the human orthologs.

  16. Occipital White Matter Tracts in Human and Macaque.

    Science.gov (United States)

    Takemura, Hiromasa; Pestilli, Franco; Weiner, Kevin S; Keliris, Georgios A; Landi, Sofia M; Sliwa, Julia; Ye, Frank Q; Barnett, Michael A; Leopold, David A; Freiwald, Winrich A; Logothetis, Nikos K; Wandell, Brian A

    2017-06-01

    We compare several major white-matter tracts in human and macaque occipital lobe using diffusion magnetic resonance imaging. The comparison suggests similarities but also significant differences in the tracts. There are several apparently homologous tracts in the 2 species, including the vertical occipital fasciculus (VOF), optic radiation, forceps major, and inferior longitudinal fasciculus (ILF). There is one large human tract, the inferior fronto-occipital fasciculus, with no corresponding fasciculus in macaque. We could identify the macaque VOF (mVOF), which has been little studied. Its position is consistent with classical invasive anatomical studies by Wernicke. VOF homology is supported by similarity of the endpoints in V3A and ventral V4 across species. The mVOF fibers intertwine with the dorsal segment of the ILF, but the human VOF appears to be lateral to the ILF. These similarities and differences between the occipital lobe tracts will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Social network community structure and the contact-mediated sharing of commensal E. coli among captive rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Balasubramaniam, Krishna; Beisner, Brianne; Guan, Jiahui; Vandeleest, Jessica; Fushing, Hsieh; Atwill, Edward; McCowan, Brenda

    2018-01-01

    In group-living animals, heterogeneity in individuals' social connections may mediate the sharing of microbial infectious agents. In this regard, the genetic relatedness of individuals' commensal gut bacterium Escherichia coli may be ideal to assess the potential for pathogen transmission through animal social networks. Here we use microbial phylogenetics and population genetics approaches, as well as host social network reconstruction, to assess evidence for the contact-mediated sharing of E. coli among three groups of captively housed rhesus macaques ( Macaca mulatta ), at multiple organizational scales. For each group, behavioral data on grooming, huddling, and aggressive interactions collected for a six-week period were used to reconstruct social network communities via the Data Cloud Geometry (DCG) clustering algorithm. Further, an E. coli isolate was biochemically confirmed and genotypically fingerprinted from fecal swabs collected from each macaque. Population genetics approaches revealed that Group Membership, in comparison to intrinsic attributes like age, sex, and/or matriline membership of individuals, accounted for the highest proportion of variance in E. coli genotypic similarity. Social network approaches revealed that such sharing was evident at the community-level rather than the dyadic level. Specifically, although we found no links between dyadic E. coli similarity and social contact frequencies, similarity was significantly greater among macaques within the same social network communities compared to those across different communities. Moreover, tests for one of our study-groups confirmed that E. coli isolated from macaque rectal swabs were more genotypically similar to each other than they were to isolates from environmentally deposited feces. In summary, our results suggest that among frequently interacting, spatially constrained macaques with complex social relationships, microbial sharing via fecal-oral, social contact-mediated routes may

  18. Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up.

    Science.gov (United States)

    Berg, Jan; Kottwitz, Jan; Baltensperger, Nora; Kissel, Christine K; Lovrinovic, Marina; Mehra, Tarun; Scherff, Frank; Schmied, Christian; Templin, Christian; Lüscher, Thomas F; Heidecker, Bettina; Manka, Robert

    2017-11-01

    There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. © 2017 American Heart Association, Inc.

  19. The nucleus pararaphales in the human, chimpanzee, and macaque monkey.

    Science.gov (United States)

    Baizer, Joan S; Weinstock, Nadav; Witelson, Sandra F; Sherwood, Chet C; Hof, Patrick R

    2013-03-01

    The human cerebral cortex and cerebellum are greatly expanded compared to those of other mammals, including the great apes. This expansion is reflected in differences in the size and organization of precerebellar brainstem structures, such as the inferior olive. In addition, there are cell groups unique to the human brainstem. One such group may be the nucleus pararaphales (PRa); however, there is disagreement among authors about the size and location of this nucleus in the human brainstem. The name "pararaphales" has also been used for neurons in the medulla shown to project to the flocculus in the macaque monkey. We have re-examined the existence and status of the PRa in eight humans, three chimpanzees, and four macaque monkeys using Nissl-stained sections as well as immunohistochemistry. In the human we found a cell group along the midline of the medulla in all cases; it had the form of interrupted cell columns and was variable among cases in rostrocaudal and dorsoventral extent. Cells and processes were highly immunoreactive for non-phosphorylated neurofilament protein (NPNFP); somata were immunoreactive to the synthetic enzyme for nitric oxide, nitric oxide synthase, and for calretinin. In macaque monkey, there was a much smaller oval cell group with NPNFP immunoreactivity. In the chimpanzee, we found a region of NPNFP-immunoreactive cells and fibers similar to what was observed in macaques. These results suggest that the "PRa" in the human may not be the same structure as the flocculus-projecting cell group described in the macaque. The PRa, like the arcuate nucleus, therefore may be unique to humans.

  20. Geomorphological evolution of landslides near an active normal fault in northern Taiwan, as revealed by lidar and unmanned aircraft system data

    Science.gov (United States)

    Chang, Kuo-Jen; Chan, Yu-Chang; Chen, Rou-Fei; Hsieh, Yu-Chung

    2018-03-01

    Several remote sensing techniques, namely traditional aerial photographs, an unmanned aircraft system (UAS), and airborne lidar, were used in this study to decipher the morphological features of obscure landslides in volcanic regions and how the observed features may be used for understanding landslide occurrence and potential hazard. A morphological reconstruction method was proposed to assess landslide morphology based on the dome-shaped topography of the volcanic edifice and the nature of its morphological evolution. Two large-scale landslides in the Tatun volcano group in northern Taiwan were targeted to more accurately characterize the landslide morphology through airborne lidar and UAS-derived digital terrain models and images. With the proposed reconstruction method, the depleted volume of the two landslides was estimated to be at least 820 ± 20 × 106 m3. Normal faulting in the region likely played a role in triggering the two landslides, because there are extensive geological and historical records of an active normal fault in this region. The subsequent geomorphological evolution of the two landslides is thus inferred to account for the observed morphological and tectonic features that are indicative of resulting in large and life-threatening landslides, as characterized using the recent remote sensing techniques.

  1. A Normalization-Free and Nonparametric Method Sharpens Large-Scale Transcriptome Analysis and Reveals Common Gene Alteration Patterns in Cancers.

    Science.gov (United States)

    Li, Qi-Gang; He, Yong-Han; Wu, Huan; Yang, Cui-Ping; Pu, Shao-Yan; Fan, Song-Qing; Jiang, Li-Ping; Shen, Qiu-Shuo; Wang, Xiao-Xiong; Chen, Xiao-Qiong; Yu, Qin; Li, Ying; Sun, Chang; Wang, Xiangting; Zhou, Jumin; Li, Hai-Peng; Chen, Yong-Bin; Kong, Qing-Peng

    2017-01-01

    Heterogeneity in transcriptional data hampers the identification of differentially expressed genes (DEGs) and understanding of cancer, essentially because current methods rely on cross-sample normalization and/or distribution assumption-both sensitive to heterogeneous values. Here, we developed a new method, Cross-Value Association Analysis (CVAA), which overcomes the limitation and is more robust to heterogeneous data than the other methods. Applying CVAA to a more complex pan-cancer dataset containing 5,540 transcriptomes discovered numerous new DEGs and many previously rarely explored pathways/processes; some of them were validated, both in vitro and in vivo , to be crucial in tumorigenesis, e.g., alcohol metabolism ( ADH1B ), chromosome remodeling ( NCAPH ) and complement system ( Adipsin ). Together, we present a sharper tool to navigate large-scale expression data and gain new mechanistic insights into tumorigenesis.

  2. Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75 NTR in malignancy.

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    Dalley, Andrew J; AbdulMajeed, Ahmad A; Upton, Zee; Farah, Camile S

    2013-01-01

    Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75(NTR), CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75(NTR) was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75(NTR), CD24 antigens and ALDH activity (ALDEFLUOR(®) assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells. © 2012 John Wiley & Sons A/S.

  3. Proteomics reveals novel oxidative and glycolytic mechanisms in type 1 diabetic patients' skin which are normalized by kidney-pancreas transplantation.

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    Franco Folli

    2010-03-01

    Full Text Available In type 1 diabetes (T1D vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold.We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease. We therefore examined pathways that may be normalized by restoration of normoglycemia with kidney-pancreas (KP transplantation. Using proteomic and ultrastructural approaches, multiple alterations in the expression of proteins involved in oxidative stress (catalase, superoxide dismutase 1, Hsp27, Hsp60, ATP synthase delta chain, and flavin reductase, aerobic and anaerobic glycolysis (ACBP, pyruvate kinase muscle isozyme, and phosphoglycerate kinase 1, and intracellular signaling (stratifin-14-3-3, S100-calcyclin, cathepsin, and PPI rotamase as well as endothelial vascular abnormalities were identified in T1D and T1D+ESRD patients. These abnormalities were reversed after KP transplant. Increased plasma levels of malondialdehyde were observed in T1D and T1D+ESRD patients, confirming increased oxidative stress which was normalized after KP transplant.Our data suggests persistent cellular changes of anti-oxidative machinery and of aerobic/anaerobic glycolysis are present in T1D and T1D+ESRD patients, and these abnormalities may play a key role in the pathogenesis of hyperglycemia-related vascular complications. Restoration of normoglycemia and removal of uremia with KP transplant can correct these abnormalities. Some of these identified pathways may become potential therapeutic targets for a new generation of drugs.

  4. Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes

    International Nuclear Information System (INIS)

    Pascal, Laura E; Liu, Alvin Y; Vêncio, Ricardo ZN; Page, Laura S; Liebeskind, Emily S; Shadle, Christina P; Troisch, Pamela; Marzolf, Bruz; True, Lawrence D; Hood, Leroy E

    2009-01-01

    Prostate cancer cells in primary tumors have been typed CD10 - /CD13 - /CD24 hi /CD26 + /CD38 lo /CD44 - /CD104 - . This CD phenotype suggests a lineage relationship between cancer cells and luminal cells. The Gleason grade of tumors is a descriptive of tumor glandular differentiation. Higher Gleason scores are associated with treatment failure. CD26 + cancer cells were isolated from Gleason 3+3 (G3) and Gleason 4+4 (G4) tumors by cell sorting, and their gene expression or transcriptome was determined by Affymetrix DNA array analysis. Dataset analysis was used to determine gene expression similarities and differences between G3 and G4 as well as to prostate cancer cell lines and histologically normal prostate luminal cells. The G3 and G4 transcriptomes were compared to those of prostatic cell types of non-cancer, which included luminal, basal, stromal fibromuscular, and endothelial. A principal components analysis of the various transcriptome datasets indicated a closer relationship between luminal and G3 than luminal and G4. Dataset comparison also showed that the cancer transcriptomes differed substantially from those of prostate cancer cell lines. Genes differentially expressed in cancer are potential biomarkers for cancer detection, and those differentially expressed between G3 and G4 are potential biomarkers for disease stratification given that G4 cancer is associated with poor outcomes. Differentially expressed genes likely contribute to the prostate cancer phenotype and constitute the signatures of these particular cancer cell types

  5. Network-directed cis-mediator analysis of normal prostate tissue expression profiles reveals downstream regulatory associations of prostate cancer susceptibility loci.

    Science.gov (United States)

    Larson, Nicholas B; McDonnell, Shannon K; Fogarty, Zach; Larson, Melissa C; Cheville, John; Riska, Shaun; Baheti, Saurabh; Weber, Alexandra M; Nair, Asha A; Wang, Liang; O'Brien, Daniel; Davila, Jaime; Schaid, Daniel J; Thibodeau, Stephen N

    2017-10-17

    Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis -acting associations due to study limitations. While trans -eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans -eQTL associations are mediated by cis -regulated genes, such as transcription factors. Leveraging a data-driven gene co-expression network, we conducted a comprehensive cis -mediator analysis using RNA-Seq data from 471 normal prostate tissue samples to identify downstream regulatory associations of previously identified prostate cancer risk variants. We discovered multiple trans -eQTL associations that were significantly mediated by cis -regulated transcripts, four of which involved risk locus 17q12, proximal transcription factor HNF1B , and target trans -genes with known HNF response elements ( MIA2 , SRC , SEMA6A , KIF12 ). We additionally identified evidence of cis -acting down-regulation of MSMB via rs10993994 corresponding to reduced co-expression of NDRG1 . The majority of these cis -mediator relationships demonstrated trans -eQTL replicability in 87 prostate tissue samples from the Gene-Tissue Expression Project. These findings provide further biological context to known risk loci and outline new hypotheses for investigation into the etiology of prostate cancer.

  6. Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques

    Science.gov (United States)

    Campbell, Kevin J.; Detmer, Ann M.; Karl, Julie A.; Wiseman, Roger W.; Blasky, Alex J.; Hughes, Austin L.; Bimber, Benjamin N.; O’Connor, Shelby L.; O’Connor, David H.

    2009-01-01

    Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for infectious disease research. Several geographically distinct populations of these macaques from Southeast Asia and the Indian Ocean island of Mauritius are available for pathogenesis studies. Though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. In this study we identified 47 full-length MHC class I nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority of MHC class I sequences characterized (39 of 47) were unique to this regional population. However, we discovered eight sequences with perfect identity and six sequences with close similarity to previously defined MHC class I sequences from other macaque populations. We identified two ancestral MHC haplotypes that appear to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B haplotype that has previously been shown to protect Mauritian cynomolgus macaques against challenge with a simian/human immunodeficiency virus, SHIV89.6P. We also identified a Filipino cynomolgus macaque MHC class I sequence for which the predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is important because Mamu-B*17 is strongly associated with protection against simian immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols. PMID:19107381

  7. Identification and characterization of short tandem repeats in the Tibetan macaque genome based on resequencing data.

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    Liu, San-Xu; Hou, Wei; Zhang, Xue-Yan; Peng, Chang-Jun; Yue, Bi-Song; Fan, Zhen-Xin; Li, Jing

    2018-07-18

    The Tibetan macaque, which is endemic to China, is currently listed as a Near Endangered primate species by the International Union for Conservation of Nature (IUCN). Short tandem repeats (STRs) refer to repetitive elements of genome sequence that range in length from 1-6 bp. They are found in many organisms and are widely applied in population genetic studies. To clarify the distribution characteristics of genome-wide STRs and understand their variation among Tibetan macaques, we conducted a genome-wide survey of STRs with next-generation sequencing of five macaque samples. A total of 1 077 790 perfect STRs were mined from our assembly, with an N50 of 4 966 bp. Mono-nucleotide repeats were the most abundant, followed by tetra- and di-nucleotide repeats. Analysis of GC content and repeats showed consistent results with other macaques. Furthermore, using STR analysis software (lobSTR), we found that the proportion of base pair deletions in the STRs was greater than that of insertions in the five Tibetan macaque individuals (Pgenome showed good amplification efficiency and could be used to study population genetics in Tibetan macaques. The neighbor-joining tree classified the five macaques into two different branches according to their geographical origin, indicating high genetic differentiation between the Huangshan and Sichuan populations. We elucidated the distribution characteristics of STRs in the Tibetan macaque genome and provided an effective method for screening polymorphic STRs. Our results also lay a foundation for future genetic variation studies of macaques.

  8. The Tectonic Boundary Between Eastern Subbaisin and South-West Subbasin of the South China Sea Revealed from the Normalized Magnetic Source Strength

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    Guo, L.; Meng, X.

    2014-12-01

    The South China Sea (SCS), surrounded by the Eurasia, Pacific and India-Australia plates, is one of the largest marginal seas in the Western Pacific. It was formed by the interaction of the three plates and the seafloor spreading during Late Oligocene time to Early Miocene time. The boundary between Eastern Subbaisin and South-west Subbasin of the SCS has long been debated in the literature. Refining the boundary is one of the crucial tasks for correctly understanding the seafloor spreading model of the SCS. Due to few drills on the deep ocean basin of the SCS, magnetic data become important information for refining the boundary. However, the interpretation of magnetic data in the SCS suffers from the remanent magnetization of ocean crust as well as igneous rock and seamounts. The conventional reduction-to-pole anomalies at low latitudes usually neglect the remanent magnetization, making the interpretation incorrect. Here, we assembled high-resolution total magnetic intensity (TMI) data around the ocean basin of the SCS, and then did a special transformation of the TMI anomalies with a varying magnetic inclinations algorithm to obtain the normalized source strength (NSS). The NSS has advantage of insensitivity to remanent magnetization, benefitting correct interpretation. The NSS presents discriminative features from east to west in the ocean basin. The boundary of the discriminative features is clear and just ranges from the northeastern edge of the Zhongsha Islands running in the southeast direction to the northeastern edge of the Reed Bank. These imply that magnetic structure and tectonic features in the crust are discriminative between both sides of this boundary. It can be deduced that this boundary is the tectonic boundary between Eastern Subbaisin and South-west Subbasin. We acknowledge the financial support of the National Natural Science Foundation of China (41374093) and the SinoProbe-01-05 project.

  9. Fibered Confocal Fluorescence Microscopy for the Noninvasive Imaging of Langerhans Cells in Macaques.

    Science.gov (United States)

    Todorova, Biliana; Salabert, Nina; Tricot, Sabine; Boisgard, Raphaël; Rathaux, Mélanie; Le Grand, Roger; Chapon, Catherine

    2017-01-01

    We developed a new approach to visualize skin Langerhans cells by in vivo fluorescence imaging in nonhuman primates. Macaques were intradermally injected with a monoclonal, fluorescently labeled antibody against HLA-DR molecule and were imaged for up to 5 days by fibered confocal microscopy (FCFM). The network of skin Langerhans cells was visualized by in vivo fibered confocal fluorescence microscopy. Quantification of Langerhans cells revealed no changes to cell density with time. Ex vivo experiments confirmed that injected fluorescent HLA-DR antibody specifically targeted Langerhans cells in the epidermis. This study demonstrates the feasibility of single-cell, in vivo imaging as a noninvasive technique to track Langerhans cells in nontransgenic animals.

  10. Effects of obesogenic diet and estradiol on dorsal raphe gene expression in old female macaques.

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    Cynthia L Bethea

    Full Text Available The beneficial effects of bioidentical ovarian steroid hormone therapy (HT during the perimenopause are gaining recognition. However, the positive effects of estrogen (E plus or minus progesterone (P administration to ovariectomized (Ovx lab animals were recognized in multiple systems for years before clinical trials could adequately duplicate the results. Moreover, very large numbers of women are often needed to find statistically significant results in clinical trials of HT; and there are still opposing results being published, especially in neural and cardiovascular systems. One of the obvious differences between human and animal studies is diet. Laboratory animals are fed a diet that is low in fat and refined sugar, but high in micronutrients. In the US, a large portion of the population eats what is known as a "western style diet" or WSD that provides calories from 36% fat, 44% carbohydrates (includes 18.5% sugars and 18% protein. Unfortunately, obesity and diabetes have reached epidemic proportions and the percentage of obese women in clinical trials may be overlooked. We questioned whether WSD and obesity could decrease the positive neural effects of estradiol (E in the serotonin system of old macaques that were surgically menopausal. Old ovo-hysterectomized female monkeys were fed WSD for 2.5 years, and treated with placebo, Immediate E (ImE or Delayed E (DE. Compared to old Ovx macaques on primate chow and treated with placebo or E, the WSD-fed monkeys exhibited greater individual variance and blunted responses to E-treatment in the expression of genes related to serotonin neurotransmission, CRH components in the midbrain, synapse assembly, DNA repair, protein folding, ubiquitylation, transport and neurodegeneration. For many of the genes examined, transcript abundance was lower in WSD-fed than chow-fed monkeys. In summary, an obesogenic diet for 2.5 years in old surgically menopausal macaques blunted or increased variability in E

  11. Cochlear pathology following reimplantation of a multichannel scala tympani electrode array in the macaque.

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    Shepherd, R K; Clark, G M; Xu, S A; Pyman, B C

    1995-03-01

    The histopathologic consequence of removing and reimplanting intracochlear electrode arrays on residual auditory nerve fibers is an important issue when evaluating the safety of cochlear prostheses. The authors have examined this issue by implanting multichannel intracochlear electrodes in macaque monkeys. Macaques were selected because of the similarity of the surgical technique used to insert electrodes into the cochlea compared to that in humans, in particular the ability to insert the arrays into the upper basal turn. Five macaques were bilaterally implanted with the Melbourne/Cochlear banded electrode array. Following a minimum implant period of 5 months, the electrode array on one side of each animal was removed and another immediately implanted. The animals were sacrificed a minimum of 5 months following the reinsertion procedure, and the cochleas prepared for histopathologic analysis. Long-term implantation of the electrode resulted in a relatively mild tissue response within the cochlea. Results also showed that inner and outer hair cell survival, although significantly reduced adjacent to the array, was normal in 8 of the 10 cochleas apicalward. Moreover, the electrode reinsertion procedure did not appear to adversely affect this apical hair cell population. Significant new bone formation was frequently observed in both control and reimplanted cochleas close to the electrode fenestration site and was associated with trauma to the endosteum and/or the introduction of bone chips into the cochlea at the time of surgery. Electrode insertion trauma, involving the osseous spiral lamina or basilar membrane, was more commonly observed in reimplanted cochleas. This damage was usually restricted to the lower basal turn and resulted in a more extensive ganglion cell loss. Finally, in a number of cochleas part of the electrode array was located within the scala media or scala vestibuli. These electrodes did not appear to evoke a more extensive tissue response or

  12. Lethal influenza virus infection in macaques is associated with early dysregulation of inflammatory related genes.

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    Cristian Cillóniz

    2009-10-01

    Full Text Available The enormous toll on human life during the 1918-1919 Spanish influenza pandemic is a constant reminder of the potential lethality of influenza viruses. With the declaration by the World Health Organization of a new H1N1 influenza virus pandemic, and with continued human cases of highly pathogenic H5N1 avian influenza virus infection, a better understanding of the host response to highly pathogenic influenza viruses is essential. To this end, we compared pathology and global gene expression profiles in bronchial tissue from macaques infected with either the reconstructed 1918 pandemic virus or the highly pathogenic avian H5N1 virus A/Vietnam/1203/04. Severe pathology was observed in respiratory tissues from 1918 virus-infected animals as early as 12 hours after infection, and pathology steadily increased at later time points. Although tissues from animals infected with A/Vietnam/1203/04 also showed clear signs of pathology early on, less pathology was observed at later time points, and there was evidence of tissue repair. Global transcriptional profiles revealed that specific groups of genes associated with inflammation and cell death were up-regulated in bronchial tissues from animals infected with the 1918 virus but down-regulated in animals infected with A/Vietnam/1203/04. Importantly, the 1918 virus up-regulated key components of the inflammasome, NLRP3 and IL-1beta, whereas these genes were down-regulated by A/Vietnam/1203/04 early after infection. TUNEL assays revealed that both viruses elicited an apoptotic response in lungs and bronchi, although the response occurred earlier during 1918 virus infection. Our findings suggest that the severity of disease in 1918 virus-infected macaques is a consequence of the early up-regulation of cell death and inflammatory related genes, in which additive or synergistic effects likely dictate the severity of tissue damage.

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

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    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.

  14. Molecular and functional aspects of menstruation in the macaque.

    Science.gov (United States)

    Brenner, Robert M; Slayden, Ov D

    2012-12-01

    Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

  15. Astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

    2013-01-01

    Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  16. Raman dispersion spectroscopy on the highly saddled nickel(II)-octaethyltetraphenylporphyrin reveals the symmetry of nonplanar distortions and the vibronic coupling strength of normal modes

    International Nuclear Information System (INIS)

    Schweitzer-Stenner, R.; Stichternath, A.; Dreybrodt, W.; Jentzen, W.; Song, X.; Shelnutt, J.A.; Nielsen, O.F.; Medforth, C.J.; Smith, K.M.

    1997-01-01

    We have measured the polarized Raman cross sections and depolarization ratios of 16 fundamental modes of nickel octaethyltetraphenylporphyrin in a CS 2 solution for 16 fundamental modes, i.e., the A 1g -type vibrations ν 1 , ν 2 , ν 3 , ν 4 , ν 5 , and φ 8 , the B 1g vibrations ν 11 and ν 14 , the B 2g vibrations ν 28 , ν 29 , and ν 30 and the antisymmetric A 2g modes ν 19 , ν 20 , ν 22 , and ν 23 as function of the excitation wavelength. The data cover the entire resonant regions of the Q- and B-bands. They were analyzed by use of a theory which describes intra- and intermolecular coupling in terms of a time-independent nonadiabatic perturbation theory [E. Unger, U. Bobinger, W. Dreybrodt, and R. Schweitzer-Stenner, J. Phys. Chem. 97, 9956 (1993)]. This approach explicitly accounts in a self-consistent way for multimode mixing with all Raman modes investigated. The vibronic coupling parameters obtained from this procedure were then used to successfully fit the vibronic side bands of the absorption spectrum and to calculate the resonance excitation profiles in absolute units. Our results show that the porphyrin macrocycle is subject to B 2u -(saddling) and B 1u -(ruffling) distortions which lower its symmetry to S 4 . Thus, evidence is provided that the porphyrin molecule maintains the nonplanar structure of its crystal phase in an organic solvent. The vibronic coupling parameters indicate a breakdown of the four-orbital model. This notion is corroborated by (ZINDO/S) calculations which reveal that significant configurational interaction occurs between the electronic transitions into |Q right-angle- and |1B right-angle-states and various porphyrin→porphyrin, metal→porphyrin, and porphyrin→metal transitions. (Abstract Truncated)

  17. Spontaneous extracutaneous systemic mastocytosis in a cynomolgus macaque ()

    OpenAIRE

    Martina , Z. Zöller; Joachim , Kaspareit

    2010-01-01

    Abstract A uniform cell population of proliferating mast cells with poor cytoplasmic granularity and few eosinophilic infiltrates was observed in hepatic portal tracts and the cecal submucosa of an adult male cynomolgus macaque (Macaca fascicularis) that was part of a drug safety assessment toxicity study. The proliferating mast cells were positive for Giemsa and toluidine blue staining and had strong immunoreactivity for mast cell tryptase and CD68. Considering size, morphology, i...

  18. Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.

    Science.gov (United States)

    Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J; Bateman, John F; Wilson, Richard

    2013-05-10

    Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Matrilin-4, collagen XII, thrombospondin-4, fibronectin, βig-h3, and epiphycan are components of the in vivo collagen IX interactome. We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage. The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level

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

    Science.gov (United States)

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

    2015-12-01

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

  20. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Martin Cranage

    2008-08-01

    modified virus outcomes (n = 2, while all untreated macaques and three of four macaques given placebo gel were infected, as were two of three animals receiving tenofovir gel after challenge. Moreover, analysis of lymphoid tissues post mortem failed to reveal sequestration of SIV in the protected animals. We found a strong positive association between the concentration of tenofovir in the plasma 15 min after rectal application of gel and the degree of protection in the six animals challenged with virus at this time point. Moreover, colorectal explants from non-SIV challenged tenofovir-treated macaques were resistant to infection ex vivo, whereas no inhibition was seen in explants from the small intestine. Tissue-specific inhibition of infection was associated with the intracellular detection of tenofovir. Intriguingly, in the absence of seroconversion, Gag-specific gamma interferon (IFN-gamma-secreting T cells were detected in the blood of four of seven protected animals tested, with frequencies ranging from 144 spot forming cells (SFC/10(6 PBMC to 261 spot forming cells (SFC/10(6 PBMC.These results indicate that colorectal pretreatment with ARV drugs, such as tenofovir, has potential as a clinically relevant strategy for the prevention of HIV transmission. We conclude that plasma tenofovir concentration measured 15 min after rectal administration may serve as a surrogate indicator of protective efficacy. This may prove to be useful in the design of clinical studies. Furthermore, in vitro intestinal explants served as a model for drug distribution in vivo and susceptibility to virus infection. The finding of T cell priming following exposure to virus in the absence of overt infection is provocative. Further studies would reveal if a combined modality microbicide and vaccination strategy is feasible by determining the full extent of local immune responses induced and their protective potential.

  1. 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.

  2. 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…

  3. Correction of refractive errors in rhesus macaques (Macaca mulatta) involved in visual research.

    Science.gov (United States)

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

    2014-08-01

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

  4. 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...

  5. Distribution of cortical neurons projecting to the superior colliculus in macaque monkeys

    Directory of Open Access Journals (Sweden)

    Cerkevich CM

    2014-09-01

    Full Text Available Christina M Cerkevich,1 David C Lyon,2 Pooja Balaram,3 Jon H Kaas3 1Department of Neurobiology, University of Pittsburgh School of Medicine, Systems Neuroscience Institute, Pittsburgh, PA, USA; 2Department of Anatomy and Neurobiology, University of California, Irvine, CA, USA; 3Department of Psychology, Vanderbilt University, Nashville, TN, USA Abstract: To better reveal the pattern of corticotectal projections to the superficial layers of the superior colliculus (SC, we made a total of ten retrograde tracer injections into the SC of three macaque monkeys (Macaca mulatta. The majority of these injections were in the superficial layers of the SC, which process visual information. To isolate inputs to the purely visual layers in the superficial SC from those inputs to the motor and multisensory layers deeper in the SC, two injections were placed to include the intermediate and deep layers of the SC. In another case, an injection was placed in the medial pulvinar, a nucleus not known to be strongly connected with visual cortex, to identify possible projections from tracer spread past the lateral boundary of the SC. Four conclusions are supported by the results: 1 all early visual areas of cortex, including V1, V2, V3, and the middle temporal area, project to the superficial layers of the SC; 2 with the possible exception of the frontal eye field, few areas of cortex outside of the early visual areas project to the superficial SC, although many do, however, project to the intermediate and deep layers of the SC; 3 roughly matching retinotopy is conserved in the projections of visual areas to the SC; and 4 the projections from different visual areas are similarly dense, although projections from early visual areas appear somewhat denser than those of higher order visual areas in macaque cortex. Keywords: visual cortex, superior colliculus, frontal eye field, posterior parietal cortex, visual system

  6. Comparison of energy balance between two different-sized groups of Japanese macaques (Macaca fuscata yakui).

    Science.gov (United States)

    Kurihara, Yosuke; Hanya, Goro

    2017-07-01

    Quantifying the energy balance is essential for testing socio-ecological models. To reveal costs and benefits of group living in Japanese macaques from the perspective of feeding competition, Kurihara and Hanya (Am J Primatol 77:986-1000, 2015) previously compared feeding behavior between two different-sized groups of macaques (larger group 30-35 individuals; smaller group 13-15 individuals) in the coastal forest of Yakushima, Japan. The results suggested that the larger group exhibited greater feeding effort because of intragroup scramble competition and that the smaller group suffered from higher travel costs, possibly owing to intergroup contest competition. However, it remained unclear whether the behavioral differences affected their energy budgets. The present study examined energetic consequences of the different feeding behaviors in the two groups. Using behavioral data from 10 to 13 adult females and nutritional composition of food items, we compared ingestion rates, energetic/nutritional content of diet, and energy budgets between the two groups. Ingestion rates and energetic/nutritional content of diet did not differ between the two groups. Despite the higher feeding effort of the larger group, energy intake did not differ between the two groups. Energy expenditure did not differ between the two groups because higher travel costs were negated by lower feeding effort in the smaller group. Consequently, the energy balance did not differ between the two groups. We demonstrated that the behavioral measures of feeding competition were not translated into their energetic condition; moreover, our findings re-emphasize the importance of quantifying behavioral and fitness measures for interpreting variation in feeding behavior properly.

  7. Sex Differences in the Development of Social Relationships in Rhesus Macaques (Macaca mulatta)

    Science.gov (United States)

    Amici, Federica; Langos, Doreen; Widdig, Anja

    2015-01-01

    Several studies have documented the importance of social bonding for the enhancement of individual fitness. However, little is known about how social relationships develop through ontogeny, and whether their development follows the same trajectory in males and females. Here we analyzed affiliative interactions (proximity, social grooming, play) combined with demographic and genetic data in semi-free-ranging rhesus macaques (Macaca mulatta) on Cayo Santiago over their first 4 yr of life (from birth to sexual maturation) to understand how these interactions change through development in both sexes. Generalized linear mixed models revealed that social behaviors mostly followed different developmental trajectories in males and females and were highly dependent on the social context. In particular, sex differences in social behavior varied through development depending on the partner’s sex and age. Females engaged in more social interactions than males, especially with other females, and were more involved in grooming around the time of maturation. In contrast, males interacted more with males and age peers, especially around maturation. Sex differences in social behavior varied through development, but also depended on rank, partner’s rank, and kin line, although not consistently. High-ranking individuals, especially older females, were generally preferred as social partners. Moreover, both male and female individuals interacted mostly with maternal kin, although males also preferred paternal kin over nonkin. Importantly, most developmental changes in sociality happened when individuals were ca. 2 yr old, suggesting that this might be a milestone in the development of sociality in rhesus macaques. The only notable exception to this pattern was play, which was more pronounced in males from the beginning of their lives. We propose that play might serve as a trigger of sex differences in social behavior, with sex differences emerging early in development and

  8. Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

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    James V Lawler

    2006-05-01

    Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

  9. Sex Differences in the Development of Social Relationships in Rhesus Macaques (Macaca mulatta).

    Science.gov (United States)

    Kulik, Lars; Amici, Federica; Langos, Doreen; Widdig, Anja

    2015-04-01

    Several studies have documented the importance of social bonding for the enhancement of individual fitness. However, little is known about how social relationships develop through ontogeny, and whether their development follows the same trajectory in males and females. Here we analyzed affiliative interactions (proximity, social grooming, play) combined with demographic and genetic data in semi-free-ranging rhesus macaques ( Macaca mulatta ) on Cayo Santiago over their first 4 yr of life (from birth to sexual maturation) to understand how these interactions change through development in both sexes. Generalized linear mixed models revealed that social behaviors mostly followed different developmental trajectories in males and females and were highly dependent on the social context. In particular, sex differences in social behavior varied through development depending on the partner's sex and age. Females engaged in more social interactions than males, especially with other females, and were more involved in grooming around the time of maturation. In contrast, males interacted more with males and age peers, especially around maturation. Sex differences in social behavior varied through development, but also depended on rank, partner's rank, and kin line, although not consistently. High-ranking individuals, especially older females, were generally preferred as social partners. Moreover, both male and female individuals interacted mostly with maternal kin, although males also preferred paternal kin over nonkin. Importantly, most developmental changes in sociality happened when individuals were ca . 2 yr old, suggesting that this might be a milestone in the development of sociality in rhesus macaques. The only notable exception to this pattern was play, which was more pronounced in males from the beginning of their lives. We propose that play might serve as a trigger of sex differences in social behavior, with sex differences emerging early in development and increasing

  10. 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

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

    Science.gov (United States)

    Haddow, Andrew D; 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

    2017-08-01

    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.

  12. Evaluation of a therapy for Idiopathic Chronic Enterocolitis in rhesus macaques (Macaca mulatta and linked microbial community correlates

    Directory of Open Access Journals (Sweden)

    Joshua M. Taylor

    2018-04-01

    Full Text Available Idiopathic chronic enterocolitis (ICE is one of the most commonly encountered and difficult to manage diseases of captive rhesus macaques (Macaca mulatta. The etiology is not well understood, but perturbations in gut microbial communities have been implicated. Here we evaluated the effects of a 14-day course of vancomycin, neomycin, and fluconazole on animals affected with ICE, comparing treated, untreated, and healthy animals. We performed microbiome analysis on duodenal and colonic mucosal samples and feces in order to probe bacterial and/or fungal taxa potentially associated with ICE. All treated animals showed a significant and long-lasting improvement in stool consistency over time when compared to untreated and healthy controls. Microbiome analysis revealed trends associating bacterial community composition with ICE, particularly lineages of the Lactobacillaceae family. Sequencing of DNA from macaque food biscuits revealed that fungal sequences recovered from stool were dominated by yeast-derived food additives; in contrast, bacteria in stool appeared to be authentic gut residents. In conclusion, while validation in larger cohorts is needed, the treatment described here was associated with significantly improved clinical signs; results suggested possible correlates of microbiome structure with disease, though no strong associations were detected between single microbes and ICE.

  13. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Anna de Lang

    2007-08-01

    Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

  14. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Directory of Open Access Journals (Sweden)

    Alan D Curtis

    Full Text Available Atypical models of experimental autoimmune encephalomyelitis (EAE are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS. Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG in complete Freund's adjuvant (CFA followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA. The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in

  15. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    Science.gov (United States)

    Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

    2014-01-01

    Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and

  16. Relationship of Estimated SHIV Acquisition Time Points During the Menstrual Cycle and Thinning of Vaginal Epithelial Layers in Pigtail Macaques.

    Science.gov (United States)

    Kersh, Ellen N; Ritter, Jana; Butler, Katherine; Ostergaard, Sharon Dietz; Hanson, Debra; Ellis, Shanon; Zaki, Sherif; McNicholl, Janet M

    2015-12-01

    HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P layer thinning (Pearson r = 0.6, P = 0.15). These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.

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

    Directory of Open Access Journals (Sweden)

    Krishna Balasubramaniam

    2016-10-01

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

  18. New radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Hodgen, G.D.; Wilks, J.W.; Vaitukaitis, J.L.; Chen, H.C.; Papkoff, H.; Ross, G.

    1976-07-01

    A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75 percent macaque luteinizing hormone (mLH) and 1 percent mFSH, was used to demonstrate the specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone.

  19. Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

    Science.gov (United States)

    Bell, T M; Shaia, C I; Bunton, T E; Robinson, C G; Wilkinson, E R; Hensley, L E; Cashman, K A

    2015-01-01

    Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection. © The Author(s) 2014.

  20. 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.

  1. Developmental Anatomy of Cerebellum of Long-Tailed Macaque (Macaca fascicularis at the First Trimester of Gestation

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    Tri Wahyu Pangestiningsih

    2014-11-01

    Full Text Available Long tailed macaque was one of animal models in biomedical research because it has  many similarities with humans, both anatomical and physiological properties. There were many research about cerebellum associated with its role in the coordination of muscle activity. Understanding of normal development of cerebellum long tailed macaque may help to understand about the development in human cerebellum and its abnormalities. Embryonic and fetal brain samples were obtained through caesarean section and were  then made for histological preparation stained with cresyl violet. Staining results were observed using a microscope with a digital camera. Images obtained are processed by graphics software Adobe Photoshop CS 8.0. Cerebellum Macaca fascicularis Ed40 showed the isthmus and rhombic lip that were composed of ventricular layer, mantle layer, and marginal layer. Cerebellum Macaca fascicularis Fd55 showed future lobes and future  fissures, but the cortex and medulla are not bounded clear. The cortex consisted of the external granular layer, neuroblast basket, and neuroblast stellate, while the  medulla consisted of neuroblast deep cerebellar nuclei. From this research, we concluded that neurons were on stage of proliferation and migration in the embryo aged 40 days, then differentiated and migrated to form cortex  cerebellum and deep cerebellar nuclei at the age of 55 days, but the development of the cerebellum was not fully completed yet.

  2. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  3. Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques.

    Science.gov (United States)

    Staheli, Jeannette P; Dyen, Michael R; Deutsch, Gail H; Basom, Ryan S; Fitzgibbon, Matthew P; Lewis, Patrick; Barcy, Serge

    2016-08-01

    Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally

  4. A critical period of progesterone withdrawal precedes menstruation in macaques

    Science.gov (United States)

    Slayden, Ov D; Brenner, Robert M

    2006-01-01

    Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

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

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    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.

  6. Early-life stress and the development of obesity and insulin resistance in juvenile bonnet macaques.

    Science.gov (United States)

    Kaufman, Daniel; Banerji, Mary Ann; Shorman, Igor; Smith, Eric L P; Coplan, Jeremy D; Rosenblum, Leonard A; Kral, John G

    2007-05-01

    Stress is a risk factor for chronic illnesses such as obesity, type 2 diabetes, and hypertension and has been postulated to cause the metabolic syndrome via perturbation of the hypothalamo-pituitary-adrenal (HPA) axis. In our model of early-life stress (variable foraging demand [VFD]), food insecurity is imposed on monkey mothers for 16 weeks beginning when their nursing offspring are 3-5 months of age. Under VFD, food availability is never restricted, and the infant's growth is unaffected. VFD rearing does, however, cause a range of neurobiological abnormalities, including dysregulation of the HPA axis, manifested in abnormal cerebrospinal fluid cortisol and corticotropin-releasing factor levels. We previously reported spontaneous occurrence of metabolic syndrome in 14% of normally reared peripubertal bonnet macaques given ad libitum access to standard monkey chow. Here, we show that compared with normally reared monkeys, peripubertal VFD juveniles exhibit greater weight, BMI, abdominal circumference, and glucagon-like peptide-1 and decreased glucose disposal rates during hyperinsulinemic-euglycemic clamps. Our data suggest that early-life stress during a critical period of neuro development can result in the peripubertal emergence of obesity and insulin resistance.

  7. Seroconversion to HCoV-NL63 in Rhesus Macaques

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    Lia van der Hoek

    2009-10-01

    Full Text Available HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63.

  8. The Lion-tailed Macaque Macaca silenus (Primates: Cercopithecidae: conservation history and status of a flagship species of the tropical rainforests of the Western Ghats, India

    Directory of Open Access Journals (Sweden)

    M. Singh

    2009-03-01

    Full Text Available The Lion-tailed Macaque (Macaca silenus is a threatened species inhabiting the rainforests of the Western Ghats mountain range in southern India. Once assessed to be less than a thousand individuals remaining in the wild habitats, the population is now estimated to be between 3000 and 3500 individuals. However, the rainforest habitats of the species are highly fragmented. During the past three decades or less, the population of this species has severely declined due to habitat degradation and illegal hunting in several areas of its occurrence. In situ conservation programs included notification of certain areas as Lion-tailed Macaque conservation regions. Several captive breeding programs have been initiated in order to have a viable captive population of the species. However, the analysis reveals that both in situ and ex situ conservation programs have not achieved the desired success and the species is even more endangered than it was a few decades ago. In this article, we discuss these conservation programs and suggest further measures for effective conservation of Lion-tailed Macaques.

  9. Expression and localization of p-glycoprotein, multidrug resistance protein 4, and breast cancer resistance protein in the female lower genital tract of human and pigtailed macaque.

    Science.gov (United States)

    Zhou, Tian; Hu, Minlu; Pearlman, Andrew; Patton, Dorothy; Rohan, Lisa

    2014-11-01

    Antiretroviral drug absorption and disposition in cervicovaginal tissue is important for the effectiveness of vaginally or orally administered drug products in preexposure prophylaxis (PrEP) of HIV-1 sexual transmission to women. Therefore, it is imperative to understand critical determinants of cervicovaginal tissue pharmacokinetics. This study aimed to examine the mRNA expression and protein localization of three efflux transporters, P-glycoprotein (P-gp), multidrug resistance-associated protein 4 (MRP4), and breast cancer resistance protein (BCRP), in the lower genital tract of premenopausal women and pigtailed macaques. Along the human lower genital tract, the three transporters were moderately to highly expressed compared to colorectal tissue and liver, as revealed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). In a given genital tract segment, the transporter with the highest expression level was either BCRP or P-gp, while MRP4 was always expressed at the lowest level among the three transporters tested. The immunohistochemical staining showed that P-gp and MRP4 were localized in multiple cell types including epithelial cells and vascular endothelial cells. BCRP was predominantly localized in the vascular endothelial cells. Differences in transporter mRNA level and localization were observed among endocervix, ectocervix, and vagina. Compared to human tissues, the macaque cervicovaginal tissues displayed comparable expression and localization patterns of the three transporters, although subtle differences were observed between the two species. The role of these cervicovaginal transporters in drug absorption and disposition warrants further studies. The resemblance between human and pigtailed macaque in transporter expression and localization suggests the utility of the macaque model in the studies of human cervicovaginal transporters.

  10. ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

    Science.gov (United States)

    Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

    2017-11-01

    A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Differential sequence diversity at merozoite surface protein-1 locus of Plasmodium knowlesi from humans and macaques in Thailand.

    Science.gov (United States)

    Putaporntip, Chaturong; Thongaree, Siriporn; Jongwutiwes, Somchai

    2013-08-01

    To determine the genetic diversity and potential transmission routes of Plasmodium knowlesi, we analyzed the complete nucleotide sequence of the gene encoding the merozoite surface protein-1 of this simian malaria (Pkmsp-1), an asexual blood-stage vaccine candidate, from naturally infected humans and macaques in Thailand. Analysis of Pkmsp-1 sequences from humans (n=12) and monkeys (n=12) reveals five conserved and four variable domains. Most nucleotide substitutions in conserved domains were dimorphic whereas three of four variable domains contained complex repeats with extensive sequence and size variation. Besides purifying selection in conserved domains, evidence of intragenic recombination scattering across Pkmsp-1 was detected. The number of haplotypes, haplotype diversity, nucleotide diversity and recombination sites of human-derived sequences exceeded that of monkey-derived sequences. Phylogenetic networks based on concatenated conserved sequences of Pkmsp-1 displayed a character pattern that could have arisen from sampling process or the presence of two independent routes of P. knowlesi transmission, i.e. from macaques to human and from human to humans in Thailand. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Scrambling of the amino acids within the transmembrane domain of Vpu results in a simian-human immunodeficiency virus (SHIVTM) that is less pathogenic for pig-tailed macaques

    International Nuclear Information System (INIS)

    Hout, David R.; Gomez, Melissa L.; Pacyniak, Erik; Gomez, Lisa M.; Inbody, Sarah H.; Mulcahy, Ellyn R.; Culley, Nathan; Pinson, David M.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

    2005-01-01

    Previous studies have shown that the transmembrane (TM) domain of the subtype B Vpu enhances virion release from cells and some studies have shown that this domain may form an oligomeric structure with properties of an ion channel. To date, no studies have been performed to assess the role of this domain in virus pathogenesis in a macaque model of disease. Using a pathogenic molecular clone of simian human immunodeficiency virus (SHIV KU-1bMC33 ), we have generated a novel virus in which the transmembrane domain of the Vpu protein was scrambled but maintained hydrophobic in nature (SHIV TM ), which presumably would disrupt any ion channel TM properties of this protein. Vectors expressing the Vpu as a fusion protein with the enhanced green fluorescent protein (Vpu TM EGFP) indicate that it was transported to the same intracellular compartment as the unmodified Vpu protein but did not down-regulate cell surface expression of CD4. To assess the pathogenicity of SHIV TM , three pig-tailed macaques were inoculated with the SHIV TM and monitored for 6-8 months for CD4 + T cell levels, viral loads and the stability of the sequence of the vpu gene. Our results indicated that unlike the parental SHIV KU-1bMC33 , inoculation of macaques with SHIV TM did not cause a severe CD4 + T cell loss over the course of their infections. Sequence analysis of the vpu gene analyzed from sequential PBMC samples derived from macaques revealed that the scrambled TM was stable during the course of infection. At necropsy, examination of tissues revealed low viral loads and none of the pathology commonly observed in lymphoid and non-lymphoid tissues following inoculation with the pathogenic parental SHIV KU-1bMC33 virus. Thus, these results show for the first time that the TM domain of Vpu contributes to the pathogenicity of SHIV KU-1bMC33 in pig-tailed macaques

  13. Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

    Science.gov (United States)

    Daza-Vamenta, Riza; Glusman, Gustavo; Rowen, Lee; Guthrie, Brandon; Geraghty, Daniel E.

    2004-01-01

    The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque. PMID:15289473

  14. Risk Factors for Dystocia in Pigtailed Macaques (Macaca nemestrina)

    Science.gov (United States)

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

    2011-01-01

    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. PMID:21535929

  15. Astrocyte atrophy and immune dysfunction in self-harming macaques.

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    Kim M Lee

    Full Text Available BACKGROUND: Self-injurious behavior (SIB is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. METHODS: We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP and Toll-like receptor 2 (TLR2. Morphologic features of astrocytes were determined using computer-assisted camera lucida. RESULTS: There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. CONCLUSIONS: These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

  16. Grooming reciprocity in female tibetan macaques macaca thibetana.

    Science.gov (United States)

    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. © 2012 Wiley Periodicals, Inc.

  17. Macaques can predict social outcomes from facial expressions.

    Science.gov (United States)

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

    2016-09-01

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

  18. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for

  19. Strength of Gamma Rhythm Depends on Normalization

    Science.gov (United States)

    Ray, Supratim; Ni, Amy M.; Maunsell, John H. R.

    2013-01-01

    Neuronal assemblies often exhibit stimulus-induced rhythmic activity in the gamma range (30–80 Hz), whose magnitude depends on the attentional load. This has led to the suggestion that gamma rhythms form dynamic communication channels across cortical areas processing the features of behaviorally relevant stimuli. Recently, attention has been linked to a normalization mechanism, in which the response of a neuron is suppressed (normalized) by the overall activity of a large pool of neighboring neurons. In this model, attention increases the excitatory drive received by the neuron, which in turn also increases the strength of normalization, thereby changing the balance of excitation and inhibition. Recent studies have shown that gamma power also depends on such excitatory–inhibitory interactions. Could modulation in gamma power during an attention task be a reflection of the changes in the underlying excitation–inhibition interactions? By manipulating the normalization strength independent of attentional load in macaque monkeys, we show that gamma power increases with increasing normalization, even when the attentional load is fixed. Further, manipulations of attention that increase normalization increase gamma power, even when they decrease the firing rate. Thus, gamma rhythms could be a reflection of changes in the relative strengths of excitation and normalization rather than playing a functional role in communication or control. PMID:23393427

  20. A case of polymicrogyria in macaque monkey: impact on anatomy and function of the motor system

    Directory of Open Access Journals (Sweden)

    Rouiller Eric M

    2009-12-01

    Full Text Available Abstract Background Polymicrogyria is a malformation of the cerebral cortex often resulting in epilepsy or mental retardation. It remains unclear whether this pathology affects the structure and function of the corticospinal (CS system. The anatomy and histology of the brain of one macaque monkey exhibiting a spontaneous polymicrogyria (PMG monkey were examined and compared to the brain of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA unilaterally in a region where low intensity electrical microstimulation elicited contralateral hand movements (presumably the primary motor cortex in the PMG monkey. Results The examination of the brain showed a large number of microgyri at macro- and microscopic levels, covering mainly the frontoparietal regions. The layered cortical organization was locally disrupted and the number of SMI-32 stained pyramidal neurons in the cortical layer III of the presumed motor cortex was reduced. We compared the distribution of labelled CS axons in the PMG monkey at spinal cervical level C5. The cumulated length of CS axon arbors in the spinal grey matter was not significantly different in the PMG monkey. In the red nucleus, numerous neurons presented large vesicles. We also assessed its motor performances by comparing its capacity to execute a complex reach and grasp behavioral task. The PMG monkey exhibited an increase of reaction time without any modification of other motor parameters, an observation in line with a normal CS tract organisation. Conclusion In spite of substantial cortical malformations in the frontal and parietal lobes, the PMG monkey exhibits surprisingly normal structure and function of the corticospinal system.

  1. No effects of dioxin singly on limb malformations in macaque monkeys through epidemiological and treated studies

    Energy Technology Data Exchange (ETDEWEB)

    Asaoka, Kazuo; Iida, Hiroko [Kyoto Univ. (Japan). Primate Research Insitute, Dept. of Molecular and Cellular Biochemistry; Watanabe, Kunio [Kyoto Univ. (Japan). Primate Research Institute, Field Research Center; Goda, Hiroshi [Towa Kagaku Co., Ltd. (Japan); Ihara, Toshio; Nagata, Ryoichi [Shin Nippon Biomedical Laboratories, Ltd. (Japan). Safety Research Facility; Yasuda, Mineo [Hiroshima International Univ. (Japan). Fac. of Health Sciences, Dept. of Clinical Engineering; Kubata, Shunichiro [Tokyo Univ. (Japan). Dept. of Life Science, Graduate School of Arts and Sciences

    2004-09-15

    Human populations exposed with highly dioxin were suspected to be caused immunological dysfunctions, carcinogenesis, and developmental and reproductive dysfunctions. Because of species resemblances, the dioxin effects have been investigating using monkeys as a model for assessment of dioxin exposure on human health. Since 1957 the limb malformations of monkeys in Japan have been reported. The higher frequency of them was found in provisional groups of monkeys who were given the same kind of food for human. The chromosomal abnormalities are excluded from the factor for the congenital limb malformations that are still producing in Japan. In this study, the relations between dioxin and the limb malformations of macaque monkeys were estimated by the epidemiological and administered researches. The dioxin levels in monkeys were measured at two districts that one has the provisional groups including monkeys with limb malformations and the other has breeding groups never seeing the malformations for a long time. TEQ was calculated by the levels of dioxin isomers in the monkeys and the values show no difference between the two places and between the individuals with and without the limb malformations. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered via subcutaneous to pregnant rhesus monkeys from the day 20 of gestation to the day 90 after birth. The exposed babies, including the offspring and died in neonatal, had observed normal limbs in the range of 30-300 ng TCDD /kg of body weight.

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

    Science.gov (United States)

    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

  3. Function and Innervation of the Locus Ceruleus in a Macaque Model of Functional Hypothalamic Amenorrhea

    OpenAIRE

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

    2012-01-01

    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. Afte...

  4. Social management of laboratory rhesus macaques housed in large groups using a network approach: A review.

    Science.gov (United States)

    McCowan, Brenda; Beisner, Brianne; Hannibal, Darcy

    2017-12-07

    Biomedical facilities across the nation and worldwide aim to develop cost-effective methods for the reproductive management of macaque breeding groups, typically by housing macaques in large, multi-male multi-female social groups that provide monkey subjects for research as well as appropriate socialization for their psychological well-being. One of the most difficult problems in managing socially housed macaques is their propensity for deleterious aggression. From a management perspective, deleterious aggression (as opposed to less intense aggression that serves to regulate social relationships) is undoubtedly the most problematic behavior observed in group-housed macaques, which can readily escalate to the degree that it causes social instability, increases serious physical trauma leading to group dissolution, and reduces psychological well-being. Thus for both welfare and other management reasons, aggression among rhesus macaques at primate centers and facilities needs to be addressed with a more proactive approach.Management strategies need to be instituted that maximize social housing while also reducing problematic social aggression due to instability using efficacious methods for detection and prevention in the most cost effective manner. Herein we review a new proactive approach using social network analysis to assess and predict deleterious aggression in macaque groups. We discovered three major pathways leading to instability, such as unusually high rates and severity of trauma and social relocations.These pathways are linked either directly or indirectly to network structure in rhesus macaque societies. We define these pathways according to the key intrinsic and extrinsic variables (e.g., demographic, genetic or social factors) that influence network and behavioral measures of stability (see Fig. 1). They are: (1) presence of natal males, (2) matrilineal genetic fragmentation, and (3) the power structure and conflict policing behavior supported by this

  5. The ORF59 DNA polymerase processivity factor homologs of Old World primate RV2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques

    Directory of Open Access Journals (Sweden)

    Burnside Kellie L

    2009-11-01

    Full Text Available Abstract Background ORF59 DNA polymerase processivity factor of the human rhadinovirus, Kaposi's sarcoma-associated herpesvirus (KSHV, is required for efficient copying of the genome during virus replication. KSHV ORF59 is antigenic in the infected host and is used as a marker for virus activation and replication. Results We cloned, sequenced and expressed the genes encoding related ORF59 proteins from the RV1 rhadinovirus homologs of KSHV from chimpanzee (PtrRV1 and three species of macaques (RFHVMm, RFHVMn and RFHVMf, and have compared them with ORF59 proteins obtained from members of the more distantly-related RV2 rhadinovirus lineage infecting the same non-human primate species (PtrRV2, RRV, MneRV2, and MfaRV2, respectively. We found that ORF59 homologs of the RV1 and RV2 Old World primate rhadinoviruses are highly conserved with distinct phylogenetic clustering of the two rhadinovirus lineages. RV1 and RV2 ORF59 C-terminal domains exhibit a strong lineage-specific conservation. Rabbit antiserum was developed against a C-terminal polypeptide that is highly conserved between the macaque RV2 ORF59 sequences. This anti-serum showed strong reactivity towards ORF59 encoded by the macaque RV2 rhadinoviruses, RRV (rhesus and MneRV2 (pig-tail, with no cross reaction to human or macaque RV1 ORF59 proteins. Using this antiserum and RT-qPCR, we determined that RRV ORF59 is expressed early after permissive infection of both rhesus primary fetal fibroblasts and African green monkey kidney epithelial cells (Vero in vitro. RRV- and MneRV2-infected foci showed strong nuclear expression of ORF59 that correlated with production of infectious progeny virus. Immunohistochemical studies of an MneRV2-infected macaque revealed strong nuclear expression of ORF59 in infected cells within the differentiating layer of epidermis corroborating previous observations that differentiated epithelial cells are permissive for replication of KSHV-like rhadinoviruses

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

    Science.gov (United States)

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

    2016-07-01

    How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging. The present study analyzed changes in glial morphology and density through the entire lifespan of rhesus macaques, which are physiologically and anatomically similar to humans. We observed apparent increases in gray matter astrocytic process length and process complexity as rhesus macaques matured from juveniles through adulthood. These changes were not attributed to cell enlargement because they were not accompanied by proportional changes in soma or process volume. There was a decrease in white matter microglial process length as rhesus macaques aged. Aging was shown to have a significant effect on gray matter microglial density, with a significant increase in aged macaques compared with adults. Overall, we observed significant changes in glial morphology as macaques age indicative of astrocytic activation with subsequent increase in microglial density in aged macaques. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2.

    OpenAIRE

    Tsai, C C; Follis, K E; Yarnall, M; Blakley, G A

    1989-01-01

    Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV...

  8. 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

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

    Reproductive synchrony and the consequent clustering of births are hypothesized to be regulated by seasonal changes in rainfall and food availability. Such climate-related seasonality is, however, questionable in tropical populations occupying temporally invariant habitats year round. Using the long-term data of the Cayo Santiago rhesus macaques from 1973 to 2013, this study distinguishes synchrony (a greater than chance clustering of births) from seasonality (a cluster of births during a period of the year when abiotic conditions are favorable) and shows that females are highly synchronized (>72% of births in a 3-month period) but the effects of environmental zeitgebers on reproduction are overridden by biological factors. Specifically, biotic and abiotic factors including (i) loss of immature offspring; (ii) population density; (iii) age at delivery; (iv) rainfall; and (v) changes in colony management were modeled in relation to the annual onset of births and the median birth date. Females experiencing loss of immature offspring had an interbirth interval of trend in both the onset of births and the median date of birth is documented and the model predicts that the median birth date will advance across all calendar-based seasons by 2050. The secular trend in reproduction appears to be triggered by changes in the age at delivery of females, the absence of physiological constraints from maternal investment due to offspring loss, shorter interbirth interval, and a higher degree of coordination due to increasing population density. This study challenges the reproductive phenology previously described for rhesus macaques highlighting the importance of long-term studies in addressing the ultimate causes of reproductive synchrony. © 2015 Wiley Periodicals, Inc.

  11. Acoustic characteristics used by Japanese macaques for individual discrimination.

    Science.gov (United States)

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

    2017-10-01

    The vocalizations of primates contain information about speaker individuality. Many primates, including humans, are able to distinguish conspecifics based solely on vocalizations. The purpose of this study was to investigate the acoustic characteristics used by Japanese macaques in individual vocal discrimination. Furthermore, we tested human subjects using monkey vocalizations to evaluate species specificity with respect to such discriminations. Two monkeys and five humans were trained to discriminate the coo calls of two unfamiliar monkeys. We created a stimulus continuum between the vocalizations of the two monkeys as a set of probe stimuli (whole morph). We also created two sets of continua in which only one acoustic parameter, fundamental frequency ( f 0 ) or vocal tract characteristic (VTC), was changed from the coo call of one monkey to that of another while the other acoustic feature remained the same ( f 0 morph and VTC morph, respectively). According to the results, the reaction times both of monkeys and humans were correlated with the morph proportion under the whole morph and f 0 morph conditions. The reaction time to the VTC morph was correlated with the morph proportion in both monkeys, whereas the reaction time in humans, on average, was not correlated with morph proportion. Japanese monkeys relied more consistently on VTC than did humans for discriminating monkey vocalizations. Our results support the idea that the auditory system of primates is specialized for processing conspecific vocalizations and suggest that VTC is a significant acoustic feature used by Japanese macaques to discriminate conspecific vocalizations. © 2017. Published by The Company of Biologists Ltd.

  12. 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.

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

    Science.gov (United States)

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

  14. Predictors of insubordinate aggression among captive female rhesus macaques.

    Science.gov (United States)

    Seil, Shannon K; Hannibal, Darcy L; Beisner, Brianne A; McCowan, Brenda

    2017-11-01

    Cercopithicine primates tend to have nepotistic hierarchies characterized by predictable, kinship-based dominance. Although aggression is typically directed down the hierarchy, insubordinate aggression does occur. Insubordination is important to understand because it can precipitate social upheaval and undermine group stability; however, the factors underlying it are not well understood. We test whether key social and demographic variables predict insubordination among captive female rhesus macaques. To identify factors influencing insubordination, multivariate analyses of 10,821 dyadic conflicts among rhesus macaque females were conducted, using data from six captive groups. A segmented regression analysis was used to identify dyads with insubordination. Negative binomial regression analyses and an information theoretic approach were used to assess predictors of insubordination among dyads. In the best models, weight difference (w = 1.0; IRR = 0.930), age (dominant: w = 1.0, IRR = 0.681; subordinate: w = 1.0, IRR = 1.069), the subordinate's total number of allies (w = 0.727, IRR = 1.060) or non-kin allies (w = 0.273, IRR = 1.165), the interaction of the dominant's kin allies and weight difference (w = 0.938, IRR = 1.046), violation of youngest ascendancy (w = 1.0; IRR = 2.727), and the subordinate's maternal support (w = 1.0; IRR = 2.928), are important predictors of insubordination. These results show that both intrinsic and social factors influence insubordinate behavior. This adds to evidence of the importance of intrinsic factors and flexibility in a social structure thought to be rigid and predetermined by external factors. Further, because insubordination can precipitate social overthrow, determining predictors of insubordination will shed light on mechanisms underlying stability in nepotistic societies. © 2017 Wiley Periodicals, Inc.

  15. 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. (c) 2015 APA, all rights reserved).

  16. A study of Huntington disease-like syndromes in black South African patients reveals a single SCA2 mutation and a unique distribution of normal alleles across five repeat loci.

    Science.gov (United States)

    Baine, Fiona K; Peerbhai, Nabeelah; Krause, Amanda

    2018-07-15

    Huntington disease (HD) is a progressive neurodegenerative disease, characterised by a triad of movement disorder, emotional and behavioural disturbances and cognitive impairment. The underlying cause is an expanded CAG repeat in the huntingtin gene. For a small proportion of patients presenting with HD-like symptoms, the mutation in this gene is not identified and they are said to have a HD "phenocopy". South Africa has the highest number of recorded cases of an African-specific phenocopy, Huntington disease-like 2 (HDL2), caused by a repeat expansion in the junctophilin-3 gene. However, a significant proportion of black patients with clinical symptoms suggestive of HD still test negative for HD and HDL2. This study thus aimed to investigate five other loci associated with HD phenocopy syndromes - ATN1, ATXN2, ATXN7, TBP and C9orf72. In a sample of patients in whom HD and HDL2 had been excluded, a single expansion was identified in the ATXN2 gene, confirming a diagnosis of Spinocerebellar ataxia 2. The results indicate that common repeat expansion disorders do not contribute significantly to the HD-like phenotype in black South African patients. Importantly, allele sizing reveals unique distributions of normal repeat lengths across the associated loci in the African population studied. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Visual Memories Bypass Normalization.

    Science.gov (United States)

    Bloem, Ilona M; Watanabe, Yurika L; Kibbe, Melissa M; Ling, Sam

    2018-05-01

    How distinct are visual memory representations from visual perception? Although evidence suggests that briefly remembered stimuli are represented within early visual cortices, the degree to which these memory traces resemble true visual representations remains something of a mystery. Here, we tested whether both visual memory and perception succumb to a seemingly ubiquitous neural computation: normalization. Observers were asked to remember the contrast of visual stimuli, which were pitted against each other to promote normalization either in perception or in visual memory. Our results revealed robust normalization between visual representations in perception, yet no signature of normalization occurring between working memory stores-neither between representations in memory nor between memory representations and visual inputs. These results provide unique insight into the nature of visual memory representations, illustrating that visual memory representations follow a different set of computational rules, bypassing normalization, a canonical visual computation.

  18. Ex-vivo α-galactosylceramide activation of NKT cells in humans and macaques.

    Science.gov (United States)

    Fernandez, Caroline S; Cameron, Garth; Godfrey, Dale I; Kent, Stephen J

    2012-08-31

    NKT cells are key mediators of antiviral and anticancer immunity. Experiments in mice have demonstrated that activation of NKT cells in vivo induces the expression of multiple effector molecules critical to successful immunity. Human clinical trials have shown similar responses, although in vivo activation of NKT cells in humans or primate models are far more limited in number and scope. Measuring ex vivo activation of NKT cells by the CD1d-restricted glycolipid ligand α-Galactosylceramide (α-GalCer) through cytokine expression profiles is a useful marker of NKT cell function, but for reasons that are unclear, this approach does not appear to work as well in humans and non-human primate macaque models in comparison to mice. We performed a series of experiments on human and macaque (Macaca nemestrina) fresh whole blood samples to define optimal conditions to detect NKT cell cytokine (TNF, IFNγ, IL-2) and degranulation marker (CD107a) expression by flow cytometry. We found that conditions previously described for mouse splenocyte NKT cell activation were suboptimal on human or macaque blood NKT cells. In contrast, a 6h incubation with brefeldin A added for the last 4h, in a 96-well plate based assay, and using an α-GalCer concentration of 1 μg/ml were optimal methods to stimulate NKT cells in fresh blood from both humans and macaques. Unexpectedly, we noted that blood NKT cells from macaques infected with SIV were more readily activated by α-GalCer than NKT cells from uninfected macaques, suggesting that SIV infection may have primed the NKT cells. In conclusion, we describe optimized methods for the ex vivo antigen-specific activation of human and macaque blood NKT cells. These assays should be useful in monitoring NKT cells in disease and in immunotherapy studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Malware Normalization

    OpenAIRE

    Christodorescu, Mihai; Kinder, Johannes; Jha, Somesh; Katzenbeisser, Stefan; Veith, Helmut

    2005-01-01

    Malware is code designed for a malicious purpose, such as obtaining root privilege on a host. A malware detector identifies malware and thus prevents it from adversely affecting a host. In order to evade detection by malware detectors, malware writers use various obfuscation techniques to transform their malware. There is strong evidence that commercial malware detectors are susceptible to these evasion tactics. In this paper, we describe the design and implementation of a malware normalizer ...

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

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    2015-03-01

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

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

    Science.gov (United States)

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

    2015-03-06

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

  2. Anti-angiogenic mechanism of cordycepin on rhesus macaque choroid-retinal endothelial cell line cultured in high glucose condition

    Directory of Open Access Journals (Sweden)

    Xiao-Li Zhu*

    2016-07-01

    Full Text Available AIM: To investigate the angiogenesis effect and protective mechanism of cordycepin on rhesus macaque choroid-retinal endothelial(RF/6Acell line cultured in high glucose condition. METHODS: Cultured RF/6A cells were divided into normal control group, high glucose group and high glucose(HG+ different concentration cordycepin groups(HG+10μg/mL group, HG+50μg/mL group, HG+100μg/mL group. The cell proliferation was assessed using cholecystokinin octapeptide dye after treated for 48h. The cell migration was investigated by a Transwell assay. The tube formation was measured on Matrigel. Furthermore, the impact of cordycepin on high glucose-induced activation of VEGF and VEGF receptor 2(VEGFR-2was tested by Western blot analysis. RESULTS: Compared with normal control group, cell viability markedly increased in high glucose group(PPPPPPvs normal control group, oppositely gradually decreased with the increase of cordycepin concentrations, and had a statistically significant difference vs high glucose group(PCONCLUSION: Cordycepin can suppress the proliferation, migration and tubu formation of RF/6A in high glucose condition, might via inhibiting expression of VEGF and VEGFR-2.

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

    Directory of Open Access Journals (Sweden)

    J Gerardo García-Lerma

    2008-02-01

    Full Text Available 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.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.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 PrEP modalities.

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

    Science.gov (United States)

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

    2017-06-15

    There are substantial differences across species in the organization 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 Kv3.1b expression 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 labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and 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. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  5. Normal accidents

    International Nuclear Information System (INIS)

    Perrow, C.

    1989-01-01

    The author has chosen numerous concrete examples to illustrate the hazardousness inherent in high-risk technologies. Starting with the TMI reactor accident in 1979, he shows that it is not only the nuclear energy sector that bears the risk of 'normal accidents', but also quite a number of other technologies and industrial sectors, or research fields. The author refers to the petrochemical industry, shipping, air traffic, large dams, mining activities, and genetic engineering, showing that due to the complexity of the systems and their manifold, rapidly interacting processes, accidents happen that cannot be thoroughly calculated, and hence are unavoidable. (orig./HP) [de

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

    Directory of Open Access Journals (Sweden)

    Karli K Watson

    Full Text Available 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.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.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.

  7. 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.

  8. The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

    Science.gov (United States)

    Kanthaswamy, S; Ng, J; Satkoski Trask, J; George, D A; Kou, A J; Hoffman, L N; Doherty, T B; Houghton, P; Smith, D G

    2013-06-01

    The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Primate-specific spliced PMCHL RNAs are non-protein coding in human and macaque tissues

    Directory of Open Access Journals (Sweden)

    Delerue-Audegond Audrey

    2008-12-01

    Full Text Available Abstract Background Brain-expressed genes that were created in primate lineage represent obvious candidates to investigate molecular mechanisms that contributed to neural reorganization and emergence of new behavioural functions in Homo sapiens. PMCHL1 arose from retroposition of a pro-melanin-concentrating hormone (PMCH antisense mRNA on the ancestral human chromosome 5p14 when platyrrhines and catarrhines diverged. Mutations before divergence of hylobatidae led to creation of new exons and finally PMCHL1 duplicated in an ancestor of hominids to generate PMCHL2 at the human chromosome 5q13. A complex pattern of spliced and unspliced PMCHL RNAs were found in human brain and testis. Results Several novel spliced PMCHL transcripts have been characterized in human testis and fetal brain, identifying an additional exon and novel splice sites. Sequencing of PMCHL genes in several non-human primates allowed to carry out phylogenetic analyses revealing that the initial retroposition event took place within an intron of the brain cadherin (CDH12 gene, soon after platyrrhine/catarrhine divergence, i.e. 30–35 Mya, and was concomitant with the insertion of an AluSg element. Sequence analysis of the spliced PMCHL transcripts identified only short ORFs of less than 300 bp, with low (VMCH-p8 and protein variants or no evolutionary conservation. Western blot analyses of human and macaque tissues expressing PMCHL RNA failed to reveal any protein corresponding to VMCH-p8 and protein variants encoded by spliced transcripts. Conclusion Our present results improve our knowledge of the gene structure and the evolutionary history of the primate-specific chimeric PMCHL genes. These genes produce multiple spliced transcripts, bearing short, non-conserved and apparently non-translated ORFs that may function as mRNA-like non-coding RNAs.

  10. Dynamically Allocated Hub in Task-Evoked Network Predicts the Vulnerable Prefrontal Locus for Contextual Memory Retrieval in Macaques.

    Directory of Open Access Journals (Sweden)

    Takahiro Osada

    2015-06-01

    Full Text Available Neuroimaging and neurophysiology have revealed that multiple areas in the prefrontal cortex (PFC are activated in a specific memory task, but severity of impairment after PFC lesions is largely different depending on which activated area is damaged. The critical relationship between lesion sites and impairments has not yet been given a clear mechanistic explanation. Although recent works proposed that a whole-brain network contains hubs that play integrative roles in cortical information processing, this framework relying on an anatomy-based structural network cannot account for the vulnerable locus for a specific task, lesioning of which would bring impairment. Here, we hypothesized that (i activated PFC areas dynamically form an ordered network centered at a task-specific "functional hub" and (ii the lesion-effective site corresponds to the "functional hub," but not to a task-invariant "structural hub." To test these hypotheses, we conducted functional magnetic resonance imaging experiments in macaques performing a temporal contextual memory task. We found that the activated areas formed a hierarchical hub-centric network based on task-evoked directed connectivity, differently from the anatomical network reflecting axonal projection patterns. Using a novel simulated-lesion method based on support vector machine, we estimated severity of impairment after lesioning of each area, which accorded well with a known dissociation in contextual memory impairment in macaques (impairment after lesioning in area 9/46d, but not in area 8Ad. The predicted severity of impairment was proportional to the network "hubness" of the virtually lesioned area in the task-evoked directed connectivity network, rather than in the anatomical network known from tracer studies. Our results suggest that PFC areas dynamically and cooperatively shape a functional hub-centric network to reallocate the lesion-effective site depending on the cognitive processes, apart from

  11. Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Li

    Full Text Available Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes.We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function.Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets.

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

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  13. 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.

  14. Reconstructing Normality

    DEFF Research Database (Denmark)

    Gildberg, Frederik Alkier; Bradley, Stephen K.; Fristed, Peter Billeskov

    2012-01-01

    Forensic psychiatry is an area of priority for the Danish Government. As the field expands, this calls for increased knowledge about mental health nursing practice, as this is part of the forensic psychiatry treatment offered. However, only sparse research exists in this area. The aim of this study...... was to investigate the characteristics of forensic mental health nursing staff interaction with forensic mental health inpatients and to explore how staff give meaning to these interactions. The project included 32 forensic mental health staff members, with over 307 hours of participant observations, 48 informal....... The intention is to establish a trusting relationship to form behaviour and perceptual-corrective care, which is characterized by staff's endeavours to change, halt, or support the patient's behaviour or perception in relation to staff's perception of normality. The intention is to support and teach the patient...

  15. Pursuing Normality

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Handberg, Charlotte

    2018-01-01

    implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease......BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study...... was to understand the reflections on cancer survivorship care of lymphoma survivors to aid the future planning of cancer survivorship care and overcome barriers to participation. METHODS: Data were generated in a hematological ward during 4 months of ethnographic fieldwork, including participant observation and 46...

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

    Science.gov (United States)

    Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

    2016-06-01

    In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kevin R McCarthy

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

  20. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. A 52-week safety study in cynomolgus macaques for genetically modified rice expressing Cry1Ab/1Ac protein.

    Science.gov (United States)

    Mao, Jie; Sun, Xing; Cheng, Jian-Hua; Shi, Yong-Jie; Wang, Xin-Zheng; Qin, Jun-Jie; Sang, Zhi-Hong; He, Kun; Xia, Qing

    2016-09-01

    A 52-week feeding study in cynomolgus macaques was carried out to evaluate the safety of Bt rice Huahui 1 (HH1), a transgenic rice line expressing Cry1Ab/1Ac protein. Monkeys were fed a diet with 20% or 60% HH1 rice, 20% or 60% parental rice (Minghui 63, MH63), normal diet, normal diet spiked with purified recombinant Cry1Ab/1Ac fusion protein or bovine serum albumin (BSA) respectively. During the feeding trail, clinical observations were conducted daily, and multiple parameters, including body weight, body temperature, electrocardiogram, hematology, blood biochemistry, serum metabolome and gut microbiome were examined at regular intervals. Upon sacrifice, the organs were weighted, and the macroscopic, microscopic and electron microscopic examinations were performed. The results show no adverse or toxic effects of Bt rice HH1 or Cry1Ab/1Ac fusion protein on monkeys. Therefore, the present 52-week primate feeding study suggests that the transgenic rice containing Cry 1Ab/1Ac is equivalent to its parental rice line MH63. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

    Science.gov (United States)

    Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

    2017-05-01

    We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

  3. Hair cortisol predicts object permanence performance in infant rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Dettmer, Amanda M; Novak, Matthew F S X; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2009-12-01

    Although high circulating levels of glucocorticoids are associated with impaired cognitive performance in adults, less is known about this relationship in infancy. Furthermore, because studies have relied on acute cortisol measures in blood plasma or saliva, interpretation of the results may be difficult as acute measures may in part reflect emotional responses to testing procedures. In this study we examined whether hair cortisol, an integrated measure of hypothalamic-pituitary-adrenal (HPA) axis functioning, predicted performance of nursery-reared (NR) infant rhesus monkeys (n = 32) on Piagetian object permanence tasks. Testing of NR infants began at 19.8 +/- 2.2 (mean +/- SE) days of age and continued for the next several months. Hair cortisol concentrations from the 32 NR monkeys were compared to those of 20 mother-peer-reared (MPR) infants. Hair was shaved at Day 14, allowed to regrow, and obtained again at month 6, thus representing integrated cortisol over a 5.5-month period of time. NR and MPR infants did not differ in month 6 hair cortisol values (t((50)) = 0.02, p = 0.98). Linear regression revealed that hair cortisol predicted object permanence performance in the NR infants. Infants with higher hair cortisol reached criterion at later ages on the well (p < 0.01), screen (p < 0.05), and A-not-B (p < 0.05) tasks and required more test sessions to complete the well (p < 0.01) and screen tasks (p < 0.05). These data are the first to implicate hair cortisol as a reliable predictor of early cognitive performance in infant macaque monkeys.

  4. Phylogenetic relationships of Malaysia's long-tailed macaques, Macaca fascicularis, based on cytochrome b sequences.

    Science.gov (United States)

    Abdul-Latiff, Muhammad Abu Bakar; Ruslin, Farhani; Fui, Vun Vui; Abu, Mohd-Hashim; Rovie-Ryan, Jeffrine Japning; Abdul-Patah, Pazil; Lakim, Maklarin; Roos, Christian; Yaakop, Salmah; Md-Zain, Badrul Munir

    2014-01-01

    Phylogenetic relationships among Malaysia's long-tailed macaques have yet to be established, despite abundant genetic studies of the species worldwide. The aims of this study are to examine the phylogenetic relationships of Macaca fascicularis in Malaysia and to test its classification as a morphological subspecies. A total of 25 genetic samples of M. fascicularis yielding 383 bp of Cytochrome b (Cyt b) sequences were used in phylogenetic analysis along with one sample each of M. nemestrina and M. arctoides used as outgroups. Sequence character analysis reveals that Cyt b locus is a highly conserved region with only 23% parsimony informative character detected among ingroups. Further analysis indicates a clear separation between populations originating from different regions; the Malay Peninsula versus Borneo Insular, the East Coast versus West Coast of the Malay Peninsula, and the island versus mainland Malay Peninsula populations. Phylogenetic trees (NJ, MP and Bayesian) portray a consistent clustering paradigm as Borneo's population was distinguished from Peninsula's population (99% and 100% bootstrap value in NJ and MP respectively and 1.00 posterior probability in Bayesian trees). The East coast population was separated from other Peninsula populations (64% in NJ, 66% in MP and 0.53 posterior probability in Bayesian). West coast populations were divided into 2 clades: the North-South (47%/54% in NJ, 26/26% in MP and 1.00/0.80 posterior probability in Bayesian) and Island-Mainland (93% in NJ, 90% in MP and 1.00 posterior probability in Bayesian). The results confirm the previous morphological assignment of 2 subspecies, M. f. fascicularis and M. f. argentimembris, in the Malay Peninsula. These populations should be treated as separate genetic entities in order to conserve the genetic diversity of Malaysia's M. fascicularis. These findings are crucial in aiding the conservation management and translocation process of M. fascicularis populations in Malaysia.

  5. Low-ranking female Japanese macaques make efforts for social grooming.

    Science.gov (United States)

    Kurihara, Yosuke

    2016-04-01

    Grooming is essential to build social relationships in primates. Its importance is universal among animals from different ranks; however, rank-related differences in feeding patterns can lead to conflicts between feeding and grooming in low-ranking animals. Unifying the effects of dominance rank on feeding and grooming behaviors contributes to revealing the importance of grooming. Here, I tested whether the grooming behavior of low-ranking females were similar to that of high-ranking females despite differences in their feeding patterns. I followed 9 Japanese macaques Macaca fuscata fuscata adult females from the Arashiyama group, and analyzed the feeding patterns and grooming behaviors of low- and high-ranking females. Low-ranking females fed on natural foods away from the provisioning site, whereas high-ranking females obtained more provisioned food at the site. Due to these differences in feeding patterns, low-ranking females spent less time grooming than high-ranking females. However, both low- and high-ranking females performed grooming around the provisioning site, which was linked to the number of neighboring individuals for low-ranking females and feeding on provisioned foods at the site for high-ranking females. The similarity in grooming area led to a range and diversity of grooming partners that did not differ with rank. Thus, low-ranking females can obtain small amounts of provisioned foods and perform grooming with as many partners around the provisioning site as high-ranking females. These results highlight the efforts made by low-ranking females to perform grooming and suggest the importance of grooming behavior in group-living primates.

  6. Altered regional homogeneity of brain spontaneous signals in SIV infected rhesus macaque model.

    Science.gov (United States)

    Zhao, Jing; Jing, Bin; Chen, Feng; Liu, Jiaojiao; Wang, Yuanyuan; Li, Hongjun

    2017-04-01

    Regional homogeneity (ReHo), a measurement from resting-state functional magnetic imaging (rs-fMRI) to reflect local synchronization of brain activities, has been widely explored in previous studies of neurological diseases. SIV infected model for detecting the neurological changes with progression was studied. In the study, six rhesus macaques infected by simian immunodeficiency virus (SIV) were scanned by resting-state fMRI at the following time points: before SIV inoculation (baseline), 12weeks and 24weeks post inoculation (12wpi, 24wpi). Meanwhile, the immunological parameters including serum percentage of CD4+ T cell, CD4/CD8 ratio and absolute CD4+ T cell number were measured and analyzed. In comparison of baseline, significant decreased ReHo was found in the left superior frontal gyrus, left superior temporal gyrus, left hippocampus, right precuneus, left angular gyrus, and bilateral occipital gyrus; in contrast increased ReHo in putamen at 12wpi. Moreover, at the time of 24wpi, decreased ReHo was observed in the right postcentral gyrus, left precentral gyrus, posterior cingulated gyrus and thalamus, while ReHo was increased in the left putamen, hippocampus, left anterior cingulated cortex and precentral cortex. The correlation analysis revealed that ReHo in the superior frontal gyrus showed negative association with CD4/CD8 ratio and positive with absolute CD4+ T cell number. The correlation analysis showed that percentage of CD4+ was correlated with the ReHo values in right middle frontal gyrus, bilateral thalamus and amygdala positively; negative relationship with left putamen, left superior frontal gyrus, left superior and middle temporal gyrus. The study first indicates that hippocampus, putamen, frontal and occipital lobe were impaired by using rs-fMRI and correlated with immunological parameters. Thus, ReHo value can be utilized as a noninvasive biomarker of spontaneous brain activity changes caused by the progression of neurological impairments

  7. Low-ranking female Japanese macaques make efforts for social grooming

    Science.gov (United States)

    Kurihara, Yosuke

    2016-01-01

    Abstract Grooming is essential to build social relationships in primates. Its importance is universal among animals from different ranks; however, rank-related differences in feeding patterns can lead to conflicts between feeding and grooming in low-ranking animals. Unifying the effects of dominance rank on feeding and grooming behaviors contributes to revealing the importance of grooming. Here, I tested whether the grooming behavior of low-ranking females were similar to that of high-ranking females despite differences in their feeding patterns. I followed 9 Japanese macaques Macaca fuscata fuscata adult females from the Arashiyama group, and analyzed the feeding patterns and grooming behaviors of low- and high-ranking females. Low-ranking females fed on natural foods away from the provisioning site, whereas high-ranking females obtained more provisioned food at the site. Due to these differences in feeding patterns, low-ranking females spent less time grooming than high-ranking females. However, both low- and high-ranking females performed grooming around the provisioning site, which was linked to the number of neighboring individuals for low-ranking females and feeding on provisioned foods at the site for high-ranking females. The similarity in grooming area led to a range and diversity of grooming partners that did not differ with rank. Thus, low-ranking females can obtain small amounts of provisioned foods and perform grooming with as many partners around the provisioning site as high-ranking females. These results highlight the efforts made by low-ranking females to perform grooming and suggest the importance of grooming behavior in group-living primates. PMID:29491896

  8. 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.

  9. Functional organization of area V2 in the alert macaque.

    Science.gov (United States)

    Peterhans, E; von der Heydt, R

    1993-05-01

    We studied the relation between anatomical structure and functional properties of cells in area V2 of the macaque. Visual function was assessed in the alert animal during fixation of gaze. Recording sites were reconstructed with respect to cortical lamination and the cytochrome oxidase pattern. We measured orientation and direction selectivity, end-stopping, sensitivity to binocular disparity and ocular dominance, and determined more complex functions like sensitivity to anomalous contours and lines defined by coherent motion. Orientation selectivity was found in all parts of area V2, with high frequencies in the pale and thick stripes of the cytochrome oxidase pattern, and with lower frequency in the thin stripes. Representations of anomalous contours were found in the pale and thick stripes with similar frequencies, but generally not in the thin stripes, which have been thought to process colour. Lines defined by coherent motion were most frequently represented in the thick stripes; they were less frequent in the pale stripes, and (as with anomalous contours) were not found in the thin stripes. Sensitivity to binocular disparity was found in all types of stripes, but more frequently in the thick stripes, where the exclusively binocular neurons were also concentrated. By contrast, no segregation was found for direction selectivity and end-stopping. All neuronal properties were distributed evenly across cortical laminae. We conclude that mechanisms for figure-ground segregation involve the pale and the thick stripes of the cytochrome oxidase pattern, perhaps with greater emphasis on 'shape from motion' and 'stereoscopic depth' in the thick stripes, while more elementary neuronal properties are distributed almost evenly across the stripe pattern.

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

    Science.gov (United States)

    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

    2014-09-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. A Neural Circuit Covarying with Social Hierarchy in Macaques

    Science.gov (United States)

    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

    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. PMID:25180883

  13. Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

    2018-02-22

    Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2014-02-01

    Spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (Macaca fascicularis), concentrating them in areas in close proximity to humans. In this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestinal parasites to understand if age, education level, or occupation are significant determinants of exposure behaviors. These exposure risk behaviors and attitudes include fear of macaques, direct contact with macaques, owning pet macaques, hunting and eating macaques, and overlapping water uses. We find that willingness to participate in exposure risk behaviors are correlated with an individual's occupation, age, and/or education level. We also found that because the actual risk of infection varies across populations, activities such as direct macaque contact and pet ownership, could be putting individuals at real risk in certain contexts. Thus, we show that human demographics and social structure can influence willingness to participate in behaviors putting them at increased risk for exposure to parasites. © 2013 Wiley Periodicals, Inc.

  15. Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques

    International Nuclear Information System (INIS)

    Stevceva, Liljana; Moniuszko, Marcin; Alvarez, Xavier; Lackner, Andrew A.; Franchini, Genoveffa

    2004-01-01

    The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251. Of the 15 Mamu-A*01-positive macaques studied here, eight were chronically infected with either SIVmac251 or simian-human immunodeficiency virus (SHIV) KU2 and the remaining seven were exposed mucosally to SIVmac251 and sacrificed within 48 h to assess the local immune response. Gag-specific CD8+ T-cells were found in separated IELs from the rectum, colon, jejunum, and vagina of most infected animals. Direct staining of tetramers also revealed their presence in intact tissue. These Gag-specific IELs expressed the activation marker CD69 and produced IFN-γ, suggesting an active immune response in this locale

  16. Population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space.

    Science.gov (United States)

    Feng, Lei; Jeon, Tina; Yu, Qiaowen; Ouyang, Minhui; Peng, Qinmu; Mishra, Virendra; Pletikos, Mihovil; Sestan, Nenad; Miller, Michael I; Mori, Susumu; Hsiao, Steven; Liu, Shuwei; Huang, Hao

    2017-12-01

    Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

  17. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

    Science.gov (United States)

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

    2015-01-14

    Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

  18. No costly prosociality among related long-tailed macaques (Macaca fascicularis).

    Science.gov (United States)

    Sterck, Elisabeth H M; Olesen, Caroline U; Massen, Jorg J M

    2015-08-01

    Altruism, benefiting another at a cost to the donor, may be achieved through prosocial behavior. Studies of nonhuman animals typically investigate prosocial behavior with paradigms in which the donor can choose to give a recipient a food item, and the choice does not affect the donor's reward (which is either present or absent). In such tasks, long-tailed macaques (Macaca fascicularis) show prosocial behavior, especially toward kin. Here, we tested captive long-tailed macaques with related recipients in an alternative task, in which the donor had to give up a preferred reward to benefit the recipient; that is, they had to choose a lower valued reward for themselves to provide food to their kin. Overall, the macaques did not provide their kin with food. The task forced the donor to balance its prosocial behavior with its selfish choice for a higher value reward, a balance that turned out to favor selfish motives. Consequently, our study shows that a prosocial tendency is not sufficient to elicit costly prosocial behavior in long-tailed macaques. Subsequently, we feel that tasks in which the donor must choose a lower value reward to benefit another individual may allow the titration of the strength of prosocial behavior, and thus provides interesting possibilities for future comparative studies. (c) 2015 APA, all rights reserved).

  19. Hair loss and hair-pulling in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Lutz, Corrine K; Coleman, Kristine; Worlein, Julie; Novak, Melinda A

    2013-07-01

    Alopecia is a common problem in rhesus macaque colonies. A possible cause of this condition is hair-pulling; however the true relationship between hair-pulling and alopecia is unknown. The purpose of this study was to examine the relationship between hair loss and hair-pulling in 1258 rhesus macaques housed in 4 primate colonies across the United States. Alopecia levels ranged from 34.3% to 86.5% (mean, 49.3%) at the primate facilities. At facilities reporting a sex-associated difference, more female macaques were reported to exhibit alopecia than were males. In contrast, more males were reported to hair-pull. Animals reported to hair-pull were significantly more likely to have some amount of alopecia, but rates of hair-pulling were substantially lower than rates of alopecia, ranging from 0.6% to 20.5% (mean, 7.7%) of the populations. These results further demonstrate that hair-pulling plays only a small role in alopecia in rhesus macaques.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Enari, Hiroto; Sakamaki-Enari, Haruka

    2013-07-01

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

  3. A single gp120 residue can affect HIV-1 tropism in macaques.

    Directory of Open Access Journals (Sweden)

    Gregory Q Del Prete

    2017-09-01

    Full Text Available Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env glycoproteins, (SHIVs and simian-tropic HIV-1 (stHIV strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

  4. Temporary hindlimb paresis following dystocia due to foetal macrosomia in a Celebes crested macaque (Macaca nigra).

    Science.gov (United States)

    Debenham, John James; Bettembourg, Vanessa; Østevik, Liv; Modig, Michaela; Jâderlund, Karin Hultin; Lervik, Andreas

    2017-04-01

    A multiparous Celebes crested macaque presented with dystocia due to foetal macrosomia, causing foetal mortality and hindlimb paresis. After emergency caesarean section, recovery of motor function took 1 month before hindlimbs were weight bearing and 2 months before re-integration with the troop. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. 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.

  6. Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo

    Directory of Open Access Journals (Sweden)

    Ting Xu

    2018-04-01

    Full Text Available Summary: Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing, though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols. : Noninvasive fMRI in macaques is an essential tool in translation research. Xu et al. establish the individual functional parcellation of the macaque cortex and demonstrate that brain organization is unique, reproducible, and valid, serving as a fingerprint for an individual macaque. Keywords: macaque, parcellation, cortical areas, gradient, functional connectivity

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

    Science.gov (United States)

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

    2009-01-01

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

  8. An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

    2018-04-01

    Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

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

    Directory of Open Access Journals (Sweden)

    Hsieh Fushing

    2011-03-01

    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.

  10. Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999–2012

    Science.gov (United States)

    Klegarth, Amy R.; Ezeonwu, Chigozie A.; Rompis, Aida; Lee, Benjamin P.Y.-H.; Aggimarangsee, Nantiya; Chalise, Mukesh; Cortes, John; Feeroz, M.; Molini, Barbara J.; Godornes, Bess C.; Marks, Michael; Schillaci, Michael; Engel, Gregory; Knauf, Sascha; Lukehart, Sheila A.

    2017-01-01

    Survey results showed treponemal infection among pet macaques in Southeast Asia, a region with a high prevalence of human yaws. This finding, along with studies showing treponemal infection in nonhuman primates in Africa, should encourage a One Health approach to yaws eradication and surveillance activities, possibly including monitoring of nonhuman primates in yaws-endemic regions. PMID:28418297

  11. 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].

  12. Young macaques (Macaca fascicularis) preferentially bias attention towards closer, older, and better tool users.

    Science.gov (United States)

    Tan, Amanda W Y; Hemelrijk, Charlotte K; Malaivijitnond, Suchinda; Gumert, Michael D

    2018-05-12

    Examining how animals direct social learning during skill acquisition under natural conditions, generates data for examining hypotheses regarding how transmission biases influence cultural change in animal populations. We studied a population of macaques on Koram Island, Thailand, and examined model-based biases during interactions by unskilled individuals with tool-using group members. We first compared the prevalence of interactions (watching, obtaining food, object exploration) and proximity to tool users during interactions, in developing individuals (infants, juveniles) versus mature non-learners (adolescents, adults), to provide evidence that developing individuals are actively seeking information about tool use from social partners. All infants and juveniles, but only 49% of mature individuals carried out interacted with tool users. Macaques predominantly obtained food by scrounging or stealing, suggesting maximizing scrounging opportunities motivates interactions with tool users. However, while interactions by adults was limited to obtaining food, young macaques and particularly infants also watched tool users and explored objects, indicating additional interest in tool use itself. We then ran matrix correlations to identify interaction biases, and what attributes of tool users influenced these. Biases correlated with social affiliation, but macaques also preferentially targeted tool users that potentially increase scrounging and learning opportunities. Results suggest that social structure may constrain social learning, but the motivation to bias interactions towards tool users to maximize feeding opportunities may also socially modulate learning by facilitating close proximity to better tool users, and further interest in tool-use actions and materials, especially during development.

  13. 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.

  14. Beneficial effect of hot spring bathing on stress levels in Japanese macaques.

    Science.gov (United States)

    Takeshita, Rafaela S C; Bercovitch, Fred B; Kinoshita, Kodzue; Huffman, Michael A

    2018-05-01

    The ability of animals to survive dramatic climates depends on their physiology, morphology and behaviour, but is often influenced by the configuration of their habitat. Along with autonomic responses, thermoregulatory behaviours, including postural adjustments, social aggregation, and use of trees for shelter, help individuals maintain homeostasis across climate variations. Japanese macaques (Macaca fuscata) are the world's most northerly species of nonhuman primates and have adapted to extremely cold environments. Given that thermoregulatory stress can increase glucocorticoid concentrations in primates, we hypothesized that by using an available hot spring, Japanese macaques could gain protection against weather-induced cold stress during winter. We studied 12 adult female Japanese macaques living in Jigokudani Monkey Park, Japan, during the spring birth season (April to June) and winter mating season (October to December). We collected faecal samples for determination of faecal glucocorticoid (fGC) metabolite concentrations by enzyme immunoassay, as well as behavioural data to determine time spent in the hot springs, dominance rank, aggression rates, and affiliative behaviours. We used nonparametric statistics to examine seasonal changes in hot spring bathing, and the relationship between rank and air temperature on hot spring bathing. We used general linear mixed-effect models to examine factors impacting hormone concentrations. We found that Japanese macaques use hot spring bathing for thermoregulation during the winter. In the studied troop, the single hot spring is a restricted resource favoured by dominant females. High social rank had both costs and benefits: dominant females sustained high fGC levels, which were associated with high aggression rates in winter, but benefited by priority of access to the hot spring, which was associated with low fGC concentrations and therefore might help reduce energy expenditure and subsequent body heat loss. This unique

  15. A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

    Science.gov (United States)

    Barnable, Patrick; Calenda, Giulia; Ouattara, Louise; Gettie, Agegnehu; Blanchard, James; Jean-Pierre, Ninochka; Kizima, Larisa; Rodríguez, Aixa; Abraham, Ciby; Menon, Radhika; Seidor, Samantha; Cooney, Michael L; Roberts, Kevin D; Sperling, Rhoda; Piatak, Michael; Lifson, Jeffrey D; Fernandez-Romero, Jose A; Zydowsky, Thomas M; Robbiani, Melissa; Teleshova, Natalia

    2014-01-01

    To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

  16. 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.

  17. Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

    Science.gov (United States)

    Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

    2017-02-20

    We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

  18. A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

    Directory of Open Access Journals (Sweden)

    Patrick Barnable

    Full Text Available To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M and zinc acetate dihydrate (ZA in carrageenan (CG (MZC inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100 and MC (1∶30, the only dilution tested, but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines of vaginal (but not cervical mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74% did not significantly differ from CG (32-45%, it was within the range of protection (∼75% against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

  19. Corticocortical feedback increases the spatial extent of normalization.

    Science.gov (United States)

    Nassi, Jonathan J; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T

    2014-01-01

    Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a "normalization pool." Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing.

  20. Corticocortical feedback increases the spatial extent of normalization

    Science.gov (United States)

    Nassi, Jonathan J.; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T.

    2014-01-01

    Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a “normalization pool.” Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing. PMID:24910596

  1. Tuned Normalization Explains the Size of Attention Modulations

    Science.gov (United States)

    Ni, Amy M.; Ray, Supratim; Maunsell, John H. R.

    2012-01-01

    SUMMARY The effect of attention on firing rates varies considerably within a single cortical area. The firing rate of some neurons is greatly modulated by attention while others are hardly affected. The reason for this variability across neurons is unknown. We found that the variability in attention modulation across neurons in area MT of macaques can be well explained by variability in the strength of tuned normalization across neurons. The presence of tuned normalization also explains a striking asymmetry in attention effects within neurons: when two stimuli are in a neuron’s receptive field, directing attention to the preferred stimulus modulates firing rates more than directing attention to the non-preferred stimulus. These findings show that much of the neuron-to-neuron variability in modulation of responses by attention depends on variability in the way the neurons process multiple stimuli, rather than differences in the influence of top-down signals related to attention. PMID:22365552

  2. Tuned normalization explains the size of attention modulations.

    Science.gov (United States)

    Ni, Amy M; Ray, Supratim; Maunsell, John H R

    2012-02-23

    The effect of attention on firing rates varies considerably within a single cortical area. The firing rate of some neurons is greatly modulated by attention while others are hardly affected. The reason for this variability across neurons is unknown. We found that the variability in attention modulation across neurons in area MT of macaques can be well explained by variability in the strength of tuned normalization across neurons. The presence of tuned normalization also explains a striking asymmetry in attention effects within neurons: when two stimuli are in a neuron's receptive field, directing attention to the preferred stimulus modulates firing rates more than directing attention to the nonpreferred stimulus. These findings show that much of the neuron-to-neuron variability in modulation of responses by attention depends on variability in the way the neurons process multiple stimuli, rather than differences in the influence of top-down signals related to attention. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Conformational variability of the stationary phase survival protein E from Xylella fastidiosa revealed by X-ray crystallography, small-angle X-ray scattering studies, and normal mode analysis.

    Science.gov (United States)

    Machado, Agnes Thiane Pereira; Fonseca, Emanuella Maria Barreto; Reis, Marcelo Augusto Dos; Saraiva, Antonio Marcos; Santos, Clelton Aparecido Dos; de Toledo, Marcelo Augusto Szymanski; Polikarpov, Igor; de Souza, Anete Pereira; Aparicio, Ricardo; Iulek, Jorge

    2017-10-01

    Xylella fastidiosa is a xylem-limited bacterium that infects a wide variety of plants. Stationary phase survival protein E is classified as a nucleotidase, which is expressed when bacterial cells are in the stationary growth phase and subjected to environmental stresses. Here, we report four refined X-ray structures of this protein from X. fastidiosa in four different crystal forms in the presence and/or absence of the substrate 3'-AMP. In all chains, the conserved loop verified in family members assumes a closed conformation in either condition. Therefore, the enzymatic mechanism for the target protein might be different of its homologs. Two crystal forms exhibit two monomers whereas the other two show four monomers in the asymmetric unit. While the biological unit has been characterized as a tetramer, differences of their sizes and symmetry are remarkable. Four conformers identified by Small-Angle X-ray Scattering (SAXS) in a ligand-free solution are related to the low frequency normal modes of the crystallographic structures associated with rigid body-like protomer arrangements responsible for the longitudinal and symmetric adjustments between tetramers. When the substrate is present in solution, only two conformers are selected. The most prominent conformer for each case is associated to a normal mode able to elongate the protein by moving apart two dimers. To our knowledge, this work was the first investigation based on the normal modes that analyzed the quaternary structure variability for an enzyme of the SurE family followed by crystallography and SAXS validation. The combined results raise new directions to study allosteric features of XfSurE protein. © 2017 Wiley Periodicals, Inc.

  4. Pair housing for female longtailed and rhesus macaques in the laboratory: behavior in protected contact versus full contact.

    Science.gov (United States)

    Baker, Kate C; Crockett, Carolyn M; Lee, Grace H; Oettinger, Brooke C; Schoof, Valérie; Thom, Jinhee P

    2012-01-01

    Pair housing for caged macaques in the laboratory generally allows unrestricted tactile contact but, less commonly, may involve limited contact via grooming-contact bars or perforated panels. The purpose of using this protected contact housing, which prevents entry into pair-mates' cages, typically is to accommodate research and management requirements. The study used behavioral data collected on 12 pairs of female longtailed macaques (Macaca fascicularis) at the Washington National Primate Research Center and 7 pairs of female rhesus macaques (Macaca mulatta) housed at the Tulane National Primate Research Center to assess the relative benefits of protected versus full protected contact. The study collected data in stable pairs housed first in protected contact followed by full contact. Species combined, the study found the presence of the panel was associated with lower levels of social grooming and higher levels of self-grooming, abnormal behavior, and tension-related behavior. Within species, only the protected- versus full-contact contrasts for abnormal and tension were statistically significant-and only for rhesus macaques. Results suggest that for female rhesus macaques, potential disadvantages or inconveniences of full contact should be balanced against the improved behavioral profile in comparison to protected contact. The use of protected contact among female longtailed macaques does not appear to require the same cost-benefit analysis. Copyright © Taylor & Francis Group, LLC

  5. Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay Reach-to-Grasp Task.

    Science.gov (United States)

    Torre, Emiliano; Quaglio, Pietro; Denker, Michael; Brochier, Thomas; Riehle, Alexa; Grün, Sonja

    2016-08-10

    a method to extend this type of investigation to larger data. Here, we apply it to simultaneous recordings of hundreds of neurons from the motor cortex of macaque monkeys performing a motor task. Our analysis reveals groups of neurons selectively synchronizing their activity in relation to behavior, which sheds new light on the role of synchrony in information processing in the cerebral cortex. Copyright © 2016 Torre, et al.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-15

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

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

    Science.gov (United States)

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

    2014-09-01

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

  8. Visual artificial grammar learning by rhesus macaques (Macaca mulatta): exploring the role of grammar complexity and sequence length.

    Science.gov (United States)

    Heimbauer, Lisa A; Conway, Christopher M; Christiansen, Morten H; Beran, Michael J; Owren, Michael J

    2018-03-01

    Humans and nonhuman primates can learn about the organization of stimuli in the environment using implicit sequential pattern learning capabilities. However, most previous artificial grammar learning studies with nonhuman primates have involved relatively simple grammars and short input sequences. The goal in the current experiments was to assess the learning capabilities of monkeys on an artificial grammar-learning task that was more complex than most others previously used with nonhumans. Three experiments were conducted using a joystick-based, symmetrical-response serial reaction time task in which two monkeys were exposed to grammar-generated sequences at sequence lengths of four in Experiment 1, six in Experiment 2, and eight in Experiment 3. Over time, the monkeys came to respond faster to the sequences generated from the artificial grammar compared to random versions. In a subsequent generalization phase, subjects generalized their knowledge to novel sequences, responding significantly faster to novel instances of sequences produced using the familiar grammar compared to those constructed using an unfamiliar grammar. These results reveal that rhesus monkeys can learn and generalize the statistical structure inherent in an artificial grammar that is as complex as some used with humans, for sequences up to eight items long. These findings are discussed in relation to whether or not rhesus macaques and other primate species possess implicit sequence learning abilities that are similar to those that humans draw upon to learn natural language grammar.

  9. Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography

    Science.gov (United States)

    Koller, Kristin; Bultitude, Janet H.; Mullins, Paul; Ward, Robert; Mitchell, Anna S.; Bell, Andrew H.

    2015-01-01

    It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species. PMID:26224780

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

    International Nuclear Information System (INIS)

    Schoultz, Bent W.; Hjornevik, Trine; Willoch, Frode; Marton, Janos; Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro; Aarstad, Erik; Drzezga, Alexander; Matsunari, Ichiro; Henriksen, Gjermund

    2010-01-01

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

  11. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  12. 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

  13. An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques.

    Science.gov (United States)

    Singer, Rachel; Mawson, Paul; Derby, Nina; Rodriguez, Aixa; Kizima, Larisa; Menon, Radhika; Goldman, Daniel; Kenney, Jessica; Aravantinou, Meropi; Seidor, Samantha; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Robbiani, Melissa; Zydowsky, Thomas M

    2012-09-05

    Microbicides may prevent HIV and sexually transmitted infections (STIs) in women; however, determining the optimal means of delivery of active pharmaceutical ingredients remains a major challenge. We previously demonstrated that a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150 partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase) infection, and the addition of zinc acetate rendered the gel significantly protective. We test the activity of MIV-150 without the addition of zinc acetate when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal rings (IVRs). MIV-150 was successfully delivered, because it was detected in vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies. Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our results demonstrate that MIV-150-containing IVRs have the potential to prevent HIV infection and highlight the possible use of IVRs for delivering drugs that block HIV and other STIs.

  14. 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.

  15. Do infant Japanese macaques ( Macaca fuscata) categorize objects without specific training?

    Science.gov (United States)

    Murai, Chizuko; Tomonaga, Masaki; Kamegai, Kimi; Terazawa, Naoko; Yamaguchi, Masami K

    2004-01-01

    In the present study, we examined whether infant Japanese macaques categorize objects without any training, using a similar technique also used with human infants (the paired-preference method). During the familiarization phase, subjects were presented twice with two pairs of different objects from one global-level category. During the test phase, they were presented twice with a pair consisting of a novel familiar-category object and a novel global-level category object. The subjects were tested with three global-level categories (animal, furniture, and vehicle). It was found that they showed significant novelty preferences as a whole, indicating that they processed similarities between familiarization objects and novel familiar-category objects. These results suggest that subjects responded distinctively to objects without training, indicating the possibility that infant macaques possess the capacity for categorization.

  16. Temporal Lobe Lesions and Perception of Species-Specific Vocalizations by Macaques

    Science.gov (United States)

    Heffner, Henry E.; Heffner, Rickye S.

    1984-10-01

    Japanese macaques were trained to discriminate two forms of their coo vocalization before and after unilateral and bilateral ablation of the temporal cortex. Unilateral ablation of the left superior temporal gyrus, including auditory cortex, resulted in an initial impairment in the discrimination, but similar unilateral ablation of the right superior temporal gyrus had no effect. Bilateral temporal lesions including auditory cortex completely abolished the ability of the animals to discriminate their coos. Neither unilateral nor bilateral ablation of cortex dorsal to and sparing the auditory cortex had any effect on the discrimination. The perception of species-specific vocalizations by Japanese macaques seems to be mediated by the temporal cortex, with the left hemisphere playing a predominant role.

  17. 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.

  18. Vocal tract length and formant frequency dispersion correlate with body size in rhesus macaques.

    Science.gov (United States)

    Fitch, W T

    1997-08-01

    Body weight, length, and vocal tract length were measured for 23 rhesus macaques (Macaca mulatta) of various sizes using radiographs and computer graphic techniques. linear predictive coding analysis of tape-recorded threat vocalizations were used to determine vocal tract resonance frequencies ("formants") for the same animals. A new acoustic variable is proposed, "formant dispersion," which should theoretically depend upon vocal tract length. Formant dispersion is the averaged difference between successive formant frequencies, and was found to be closely tied to both vocal tract length and body size. Despite the common claim that voice fundamental frequency (F0) provides an acoustic indication of body size, repeated investigations have failed to support such a relationship in many vertebrate species including humans. Formant dispersion, unlike voice pitch, is proposed to be a reliable predictor of body size in macaques, and probably many other species.

  19. 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; Van Rompay, Koen K A

    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.

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

    Directory of Open Access Journals (Sweden)

    Lark L Coffey

    Full Text Available 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.

  1. Radiographic measurement of the cardiothoracic ratio in pet macaques from Sulawesi, Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Schillaci, Michael A. [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada)], E-mail: schillaci@utsc.utoronto.ca; Parish, Stephanie [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada); Jones-Engel, Lisa [National Primate Research Center, University of Washington, 1705 N.E. Pacific Street, Seattle, WA 98195 (United States)

    2009-11-15

    The relative size of the heart, as measured by the cardiothoracic ratio, is often used as an index of ventricular hypertrophy-an important measure of myocardial pathophysiology in human primates. Despite its widespread use in human medicine, use of the cardiothoracic ratio in nonhuman primate veterinary medicine has been poorly documented. This report describes the results of our radiographic study of the cardiothoracic ratio in a sample of pet monkeys from Sulawesi, Indonesia. We assessed the effects of age and sex on cardiothoracic ratios, and compared our estimates with those presented in the literature for the Formosan macaque (Macaca cyclopis). Our results indicated a significant difference between the Sulawesi macaque species groupings in cardiothoracic ratios. Sex and age-related differences were not significant. Comparisons of cardiothoracic ratios with published ratios indicated similarity between M. cyclopis and Macaca nigra, but not between M. cyclopis and Macaca tonkeana.

  2. Radiographic measurement of the cardiothoracic ratio in pet macaques from Sulawesi, Indonesia

    International Nuclear Information System (INIS)

    Schillaci, Michael A.; Parish, Stephanie; Jones-Engel, Lisa

    2009-01-01

    The relative size of the heart, as measured by the cardiothoracic ratio, is often used as an index of ventricular hypertrophy-an important measure of myocardial pathophysiology in human primates. Despite its widespread use in human medicine, use of the cardiothoracic ratio in nonhuman primate veterinary medicine has been poorly documented. This report describes the results of our radiographic study of the cardiothoracic ratio in a sample of pet monkeys from Sulawesi, Indonesia. We assessed the effects of age and sex on cardiothoracic ratios, and compared our estimates with those presented in the literature for the Formosan macaque (Macaca cyclopis). Our results indicated a significant difference between the Sulawesi macaque species groupings in cardiothoracic ratios. Sex and age-related differences were not significant. Comparisons of cardiothoracic ratios with published ratios indicated similarity between M. cyclopis and Macaca nigra, but not between M. cyclopis and Macaca tonkeana.

  3. Effects of Vitrectomy and Lensectomy on Older Rhesus Macaques: Oxygen Distribution, Antioxidant Status, and Aqueous Humor Dynamics.

    Science.gov (United States)

    Siegfried, Carla J; Shui, Ying-Bo; Tian, Baohe; Nork, T Michael; Heatley, Gregg A; Kaufman, Paul L

    2017-08-01

    The purpose of this study is to evaluate effects of vitrectomy (PPV) and lens extraction with intraocular lens implantation (PE/IOL) on molecular oxygen (pO2) distribution, aqueous humor antioxidant-oxidant balance, aqueous humor dynamics, and histopathologic changes in the trabecular meshwork (TM) in the older macaque monkey. Six rhesus monkeys underwent PPV followed by PE/IOL. pO2, outflow facility, and intraocular pressure (IOP) were measured. Aqueous and vitreous humor specimens were analyzed for antioxidant status and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage. TM specimens were obtained for immunohistochemical and quantitative PCR analysis. pO2 at baseline revealed steep gradients in the anterior chamber and low levels in the posterior chamber (PC) and around the lens. Following PPV and PE/IOL, pO2 significantly increased in the PC, around the IOL, and angle. IOP increased following both surgical interventions, with no change in outflow facility. Histopathologic analysis did not show changes in TM cell quantification, but there was an increase in 8-OHdG. Quantitative PCR did not reveal significant differences in glaucoma-related gene expression. Aqueous and vitreous humor analysis revealed decreased ascorbate and total reactive antioxidant potential and increased 8-OHdG in the aqueous humor only in the surgical eyes. Oxygen distribution in the older rhesus monkey is similar to humans at baseline and following surgical interventions. Our findings of histopathologic changes of TM oxidative damage and alterations in the oxidant-antioxidant balance suggest a potential correlation of increased oxygen exposure with oxidative stress/damage and the development of open angle glaucoma.

  4. Prior Exposure to Zika Virus Significantly Enhances Peak Dengue-2 Viremia in Rhesus Macaques

    OpenAIRE

    George, Jeffy; Valiant, William G.; Mattapallil, Mary J.; Walker, Michelle; Huang, Yan-Jang S.; Vanlandingham, Dana L.; Misamore, John; Greenhouse, Jack; Weiss, Deborah E.; Verthelyi, Daniela; Higgs, Stephen; Andersen, Hanne; Lewis, Mark G.; Mattapallil, Joseph J.

    2017-01-01

    Structural and functional homologies between the Zika and Dengue viruses? envelope proteins raise the possibility that cross-reactive antibodies induced following Zika virus infection might enhance subsequent Dengue infection. Using the rhesus macaque model we show that prior infection with Zika virus leads to a significant enhancement of Dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammat...

  5. 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.

  6. Plasmid-Mediated Quinolone Resistance in Shigella flexneri Isolated From Macaques

    Directory of Open Access Journals (Sweden)

    Anthony J. Mannion

    2018-03-01

    Full Text Available Non-human primates (NHPs for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae. In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques. Antibiotic susceptibility testing confirmed resistance or decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, cephalosporins, gentamicin, tetracycline, ciprofloxacin, enrofloxacin, levofloxacin, and nalidixic acid. S. flexneri isolates were susceptible to trimethoprim-sulfamethoxazole, and this drug was used to eradicate infection in two of the macaques. Plasmid DNA from all isolates was positive for the plasmid-encoded quinolone resistance gene qnrS, but not qnrA and qnrB. Conjugation and transformation of plasmid DNA from several S. flexneri isolates into antibiotic-susceptible Escherichia coli strains conferred the recipients with resistance or decreased susceptibility to quinolones and beta-lactams. Genome sequencing of two representative S. flexneri isolates identified the qnrS gene on a plasmid-like contig. These contigs showed >99% homology to plasmid sequences previously characterized from quinolone-resistant Shigella flexneri 2a and Salmonella enterica strains. Other antibiotic resistance genes and virulence factor genes were also identified in chromosome and plasmid sequences in these genomes. The findings from this study indicate macaques harbor pathogenic S. flexneri strains with chromosomally- and plasmid-encoded antibiotic resistance genes. To our knowledge, this is the first report of plasmid-mediated quinolone resistance in S. flexneri isolated from NHPs and warrants

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

    OpenAIRE

    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

    2015-01-01

    Objectives: 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...

  8. Vocalizations during post-conflict affiliations from victims toward aggressors based on uncertainty in Japanese macaques.

    Science.gov (United States)

    Katsu, Noriko; Yamada, Kazunori; Nakamichi, Masayuki

    2017-01-01

    We investigated the use of vocalizations called "grunts," "girneys," and "coos" accompanied by post-conflict affiliative interaction between former opponents (reconciliation) in Japanese macaques (Macaca fuscata). Although reconciliation functions to repair bonds, such interactions sometimes entail risks of receiving further aggression. Vocalizations can be used at a distance from the former opponent; thus, we predict that vocalizations are used particularly by victims of a conflict, and are frequently used in situations of uncertainty when it is difficult for them to estimate whether the former opponent will resume aggression. In addition, we predict that vocalizations are effective in preventing further aggression. To test these hypotheses, we conducted observations of post-conflict and matched-control situations in female Japanese macaques living in a free-ranging group. We found that former opponents tended to be attracted to each other within the first minute following a conflict, thus demonstrating reconciliation behavior. Vocalizations were more frequently used by the victims in post-conflict interactions than under control situations; however, this tendency was not found in aggressors. When affiliation with the former opponent occurred, victims were more likely to use vocalizations towards less familiar opponents. These findings suggest that Japanese macaques used vocalizations more often when interacting with less predictable former opponents. Victims were more likely to receive aggression from former aggressors when engaged in affiliations with them than under no such affiliations. No significant differences were found in the probability of the victims receiving aggression, regardless of whether they used vocalizations; thus, whether the victim benefits from using vocalizations in these contexts remains unclear. Japanese macaques form despotic societies and therefore, further aggression was inevitable, to some degree, after a conflict. The use of

  9. Vocalizations during post-conflict affiliations from victims toward aggressors based on uncertainty in Japanese macaques.

    Directory of Open Access Journals (Sweden)

    Noriko Katsu

    Full Text Available We investigated the use of vocalizations called "grunts," "girneys," and "coos" accompanied by post-conflict affiliative interaction between former opponents (reconciliation in Japanese macaques (Macaca fuscata. Although reconciliation functions to repair bonds, such interactions sometimes entail risks of receiving further aggression. Vocalizations can be used at a distance from the former opponent; thus, we predict that vocalizations are used particularly by victims of a conflict, and are frequently used in situations of uncertainty when it is difficult for them to estimate whether the former opponent will resume aggression. In addition, we predict that vocalizations are effective in preventing further aggression. To test these hypotheses, we conducted observations of post-conflict and matched-control situations in female Japanese macaques living in a free-ranging group. We found that former opponents tended to be attracted to each other within the first minute following a conflict, thus demonstrating reconciliation behavior. Vocalizations were more frequently used by the victims in post-conflict interactions than under control situations; however, this tendency was not found in aggressors. When affiliation with the former opponent occurred, victims were more likely to use vocalizations towards less familiar opponents. These findings suggest that Japanese macaques used vocalizations more often when interacting with less predictable former opponents. Victims were more likely to receive aggression from former aggressors when engaged in affiliations with them than under no such affiliations. No significant differences were found in the probability of the victims receiving aggression, regardless of whether they used vocalizations; thus, whether the victim benefits from using vocalizations in these contexts remains unclear. Japanese macaques form despotic societies and therefore, further aggression was inevitable, to some degree, after a conflict

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

    Science.gov (United States)

    Ito, T; Inoue, K; Takada, M

    2015-12-03

    Macaque monkeys use complex communication calls and are regarded as a model for studying the coding and decoding of complex sound in the auditory system. However, little is known about the distribution of excitatory and inhibitory neurons in the auditory system of macaque monkeys. In this study, we examined the overall distribution of cell bodies that expressed mRNAs for VGLUT1, and VGLUT2 (markers for glutamatergic neurons), GAD67 (a marker for GABAergic neurons), and GLYT2 (a marker for glycinergic neurons) in the auditory system of the Japanese macaque. In addition, we performed immunohistochemistry for VGLUT1, VGLUT2, and GAD67 in order to compare the distribution of proteins and mRNAs. We found that most of the excitatory neurons in the auditory brainstem expressed VGLUT2. In contrast, the expression of VGLUT1 mRNA was restricted to the auditory cortex (AC), periolivary nuclei, and cochlear nuclei (CN). The co-expression of GAD67 and GLYT2 mRNAs was common in the ventral nucleus of the lateral lemniscus (VNLL), CN, and superior olivary complex except for the medial nucleus of the trapezoid body, which expressed GLYT2 alone. In contrast, the dorsal nucleus of the lateral lemniscus, inferior colliculus, thalamus, and AC expressed GAD67 alone. The absence of co-expression of VGLUT1 and VGLUT2 in the medial geniculate, medial superior olive, and VNLL suggests that synaptic responses in the target neurons of these nuclei may be different between rodents and macaque monkeys. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Speech-like orofacial oscillations in stump-tailed macaque (Macaca arctoides) facial and vocal signals.

    Science.gov (United States)

    Toyoda, Aru; Maruhashi, Tamaki; Malaivijitnond, Suchinda; Koda, Hiroki

    2017-10-01

    Speech is unique to humans and characterized by facial actions of ∼5 Hz oscillations of lip, mouth or jaw movements. Lip-smacking, a facial display of primates characterized by oscillatory actions involving the vertical opening and closing of the jaw and lips, exhibits stable 5-Hz oscillation patterns, matching that of speech, suggesting that lip-smacking is a precursor of speech. We tested if facial or vocal actions exhibiting the same rate of oscillation are found in wide forms of facial or vocal displays in various social contexts, exhibiting diversity among species. We observed facial and vocal actions of wild stump-tailed macaques (Macaca arctoides), and selected video clips including facial displays (teeth chattering; TC), panting calls, and feeding. Ten open-to-open mouth durations during TC and feeding and five amplitude peak-to-peak durations in panting were analyzed. Facial display (TC) and vocalization (panting) oscillated within 5.74 ± 1.19 and 6.71 ± 2.91 Hz, respectively, similar to the reported lip-smacking of long-tailed macaques and the speech of humans. These results indicated a common mechanism for the central pattern generator underlying orofacial movements, which would evolve to speech. Similar oscillations in panting, which evolved from different muscular control than the orofacial action, suggested the sensory foundations for perceptual saliency particular to 5-Hz rhythms in macaques. This supports the pre-adaptation hypothesis of speech evolution, which states a central pattern generator for 5-Hz facial oscillation and perceptual background tuned to 5-Hz actions existed in common ancestors of macaques and humans, before the emergence of speech. © 2017 Wiley Periodicals, Inc.

  12. Intergroup variation in robbing and bartering by long-tailed macaques at Uluwatu Temple (Bali, Indonesia).

    Science.gov (United States)

    Brotcorne, Fany; Giraud, Gwennan; Gunst, Noëlle; Fuentes, Agustín; Wandia, I Nengah; Beudels-Jamar, Roseline C; Poncin, Pascal; Huynen, Marie-Claude; Leca, Jean-Baptiste

    2017-10-01

    Robbing and bartering (RB) is a behavioral practice anecdotally reported in free-ranging commensal macaques. It usually occurs in two steps: after taking inedible objects (e.g., glasses) from humans, the macaques appear to use them as tokens, returning them to humans in exchange for food. While extensively studied in captivity, our research is the first to investigate the object/food exchange between humans and primates in a natural setting. During a 4-month study in 2010, we used both focal and event sampling to record 201 RB events in a population of long-tailed macaques (Macaca fascicularis), including four neighboring groups ranging freely around Uluwatu Temple, Bali (Indonesia). In each group, we documented the RB frequency, prevalence and outcome, and tested the underpinning anthropogenic and demographic determinants. In line with the environmental opportunity hypothesis, we found a positive qualitative relation at the group level between time spent in tourist zones and RB frequency or prevalence. For two of the four groups, RB events were significantly more frequent when humans were more present in the environment. We also found qualitative partial support for the male-biased sex ratio hypothesis [i.e., RB was more frequent and prevalent in groups with higher ratios of (sub)adult males], whereas the group density hypothesis was not supported. This preliminary study showed that RB is a spontaneous, customary (in some groups), and enduring population-specific practice characterized by intergroup variation in Balinese macaques. As such, RB is a candidate for a new behavioral tradition in this species.

  13. 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

  14. 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.

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

    Science.gov (United States)

    Chang, W L William; 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.

  16. Fading Perceptual Resemblance: A Path for Rhesus Macaques (Macaca mulatta) to Conceptual Matching?

    Science.gov (United States)

    Smith, J. David; Flemming, Timothy M.; Boomer, Joseph; Beran, Michael J.; Church, Barbara A.

    2013-01-01

    Cognitive, comparative, and developmental psychologists have long been intrigued by humans’ and animals’ capacity to respond to abstract relations like sameness and difference, because this capacity may underlie crucial aspects of cognition like analogical reasoning. Recently, this capacity has been explored in higher-order, relational matching-to-sample (RMTS) tasks in which humans and animals try to complete analogies of sameness and difference between disparate groups of items. The authors introduced a new paradigm to this area, by yoking the relational-matching cue to a perceptual-matching cue. Then, using established algorithms for shape distortion, the perceptual cue was weakened and eliminated. Humans’ RMTS performance easily transcended the elimination of perceptual support. In contrast, RMTS performance by six macaques faltered as they were weaned from perceptual support. No macaque showed evidence of mature RMTS performance, even given more than 260,000 training trials during which we tried to coax a relational-matching performance from them. It is an important species difference that macaques show so hesitant a response to conceptual relations when humans respond to them so effortlessly. It raises theoretical questions about the emergence of this crucial capacity during humans’ cognitive evolution and during humans’ cognitive development. PMID:24076537

  17. A comparative study of middle cerebral pressure in dogs and macaques

    Science.gov (United States)

    Symon, Lindsay

    1967-01-01

    1. A comparison has been made of the pressures recorded from pial branches of the middle cerebral artery in dogs and macaques. This pressure has been shown to be between 88 and 95% of femoral arterial pressure in dogs under chloralose anaesthesia, and between 80 and 90% of femoral arterial pressure in macaques similarly anaesthetized. 2. The effect of occlusion of the main vessels in the neck is shown to differ considerably in the two species. Blood pressure within the forebrain of the dog is shown to be largely dependent upon the integrity of the external carotid artery, whereas in the monkey the external carotid artery is without effect in the maintenance of forebrain blood pressure. Occlusion of the four major arteries in the neck is shown to produce a greater effect in the macaque and to be accompanied by signs of medullary ischaemia in this species. 3. After occlusion of the main middle cerebral artery, arterial pressure measured distal to the occlusion depends upon the integrity of collateral vessels from the other cerebral arteries. When only a branch of the middle cerebral artery is occluded, the greater part of the residual blood pressure depends upon anastomoses from other branches of the middle cerebral artery itself. ImagesFig. 1 PMID:4963869

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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 species....... Reference intervals established were as follows: SAA, 29.5–87.7 mg/L; CRP, 0–17.5 mg/L; haptoglobin, 354.3–2,414.7 mg/L; albumin, 36.1–53.0 g/L; and iron, 13.3–40.2 lmol/L. Furthermore, changes in the acute-phase reactants were studied in two additional groups of animals: eight rhesus macaques suffering...... from acute traumatic injuries and nine rhesus macaques experimentally infected with Mycobacterium tuberculosis reflecting a chronic active inflammation. In animals with inflammation, SAA and haptoglobin concentrations were moderately increased, while CRP increased more than 200-fold. In addition, marked...

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  1. 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 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.

  2. Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

    Directory of Open Access Journals (Sweden)

    Hongzhao Li

    Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

  3. Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

    Science.gov (United States)

    Stewart, Laurel M.; Koenig, Michelle; Semler, Matthew; Breitbach, Meghan E.; Zeng, Xiankun; Weiler, Andrea M.; Barry, Gabrielle L.; Thoong, Troy H.; Wiepz, Gregory J.; Dudley, Dawn M.; Simmons, Heather A.; Mejia, Andres; Morgan, Terry K.; Salamat, M. Shahriar; Kohn, Sarah; Antony, Kathleen M.; Mohns, Mariel S.; Hayes, Jennifer M.; Schultz-Darken, Nancy; Schotzko, Michele L.; Peterson, Eric; Capuano, Saverio; Osorio, Jorge E.; O’Connor, Shelby L.; O’Connor, David H.; Golos, Thaddeus G.

    2018-01-01

    Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection. PMID:29381706

  4. Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.

    Science.gov (United States)

    Magnani, Diogo M; Rogers, Thomas F; Maness, Nicholas J; Grubaugh, Nathan D; Beutler, Nathan; Bailey, Varian K; Gonzalez-Nieto, Lucas; Gutman, Martin J; Pedreño-Lopez, Núria; Kwal, Jaclyn M; Ricciardi, Michael J; Myers, Tereance A; Julander, Justin G; Bohm, Rudolf P; Gilbert, Margaret H; Schiro, Faith; Aye, Pyone P; Blair, Robert V; Martins, Mauricio A; Falkenstein, Kathrine P; Kaur, Amitinder; Curry, Christine L; Kallas, Esper G; Desrosiers, Ronald C; Goldschmidt-Clermont, Pascal J; Whitehead, Stephen S; Andersen, Kristian G; Bonaldo, Myrna C; Lackner, Andrew A; Panganiban, Antonito T; Burton, Dennis R; Watkins, David I

    2018-04-24

    Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

  5. Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Tingfu Du

    2017-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ- induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.

  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. Hierarchical ordering with partial pairwise hierarchical relationships on the macaque brain data sets.

    Directory of Open Access Journals (Sweden)

    Woosang Lim

    Full Text Available Hierarchical organizations of information processing in the brain networks have been known to exist and widely studied. To find proper hierarchical structures in the macaque brain, the traditional methods need the entire pairwise hierarchical relationships between cortical areas. In this paper, we present a new method that discovers hierarchical structures of macaque brain networks by using partial information of pairwise hierarchical relationships. Our method uses a graph-based manifold learning to exploit inherent relationship, and computes pseudo distances of hierarchical levels for every pair of cortical areas. Then, we compute hierarchy levels of all cortical areas by minimizing the sum of squared hierarchical distance errors with the hierarchical information of few cortical areas. We evaluate our method on the macaque brain data sets whose true hierarchical levels are known as the FV91 model. The experimental results show that hierarchy levels computed by our method are similar to the FV91 model, and its errors are much smaller than the errors of hierarchical clustering approaches.

  8. Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

    Science.gov (United States)

    Makarova, Natalia; Henning, Tara; Taylor, Andrew; Dinh, Chuong; Lipscomb, Jonathan; Aubert, Rachael; Hanson, Debra; Phillips, Christi; Papp, John; Mitchell, James; McNicholl, Janet; Garcia-Lerma, Gerardo J; Heneine, Walid; Kersh, Ellen; Dobard, Charles

    2017-03-27

    Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.

  9. Alcohol and illicit drugs in drivers involved in road traffic crashes in the Milan area. A comparison with normal traffic reveals the possible inadequacy of current cut-off limits.

    Science.gov (United States)

    Ferrari, Davide; Manca, Monica; Banfi, Giuseppe; Locatelli, Massimo

    2018-01-01

    Driving under the influence of alcohol and/or illicit drugs in Italy is regulated by the articles 186 and 187 of the National Street Code. Epidemiological studies on drivers involved in road traffic crashes (RTC) provide useful information about the use/abuse of these substances in the general population. Comparison with case control studies may reveal important information like the cut-off limits adequacy. Data from 1587 blood tests for alcohol and 1258 blood tests for illicit drugs on drivers involved in RTC around Milan between 2012 and 2016, were analyzed and compared with a published random survey (DRUID) from the European Community. Our data from RTC-involved drivers show that alcohol abuse is not age-related whereas illicit drugs are more common in young people. Cannabinoids are frequent among younger drivers (median age 27) whereas cocaine is more often detected in adults (median age 34). The calculated odds ratio after comparison with the DRUID survey shows that a blood alcohol concentration below the legal limit does not represent a risk factor in having a car accident whereas concentrations of cocaine and cannabinoids within the legal limits are associated with being involved in a car accident. Despite authority efforts, the abuse of alcohol and illicit drugs is still common in young drivers. We suspect that the cut-off limits for cannabinoids and cocaine and/or the pre-analytical procedures for these substances are inadequate. We suggest a better standardization of the procedure by shortening the time interval between the request for investigation and blood collection and propose the adoption of more stringent cut-off limits. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Normalization: A Preprocessing Stage

    OpenAIRE

    Patro, S. Gopal Krishna; Sahu, Kishore Kumar

    2015-01-01

    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  11. The effects of huperzine A and IDRA 21 on visual recognition memory in young macaques

    Science.gov (United States)

    Malkova, Ludise; Kozikowski, Alan P.; Gale, Karen

    2011-01-01

    Nootropic agents or cognitive enhancers are purported to improve mental functions such as cognition, memory, or attention. The aim of our study was to determine the effects of two possible cognitive enhancers, huperzine A and IDRA 21, in normal young adult monkeys performing a visual memory task of varying degrees of difficulty. Huperzine A is a reversible acetylcholinesterase (AChE) inhibitor, its administration results in regionally specific increases in acetylcholine levels in the brain. In human clinical trials, Huperzine A resulted in cognitive improvement in patients with mild to moderate form of Alzheimer's disease (AD) showing its potential as a palliative agent in the treatment of AD. IDRA 21 is a positive allosteric modulator of glutamate AMPA receptors. It increases excitatory synaptic strength by attenuating rapid desensitization of AMPA receptors and may thus have beneficial therapeutic effects to ameliorate memory deficits in patients with cognitive impairments, including AD. The present study evaluated the effects of the two drugs in normal, intact, young adult monkeys to determine whether they can result in cognitive enhancement in a system that is presumably functioning optimally. Six young pigtail macaques (Macaca nemestrina) were trained on delayed non-matching-to-sample task, a measure of visual recognition memory, up to criterion of 90% correct responses on each of the four delays (10s, 30s, 60s, and 90s). They were then tested on two versions of the task: Task 1 included the four delays intermixed within a session and the monkeys performed it with the accuracy of 90%. Task 2 included, in each of 24 trials, a list of six objects presented in succession. Two objects from the list were then presented for choice paired with novel objects and following two of the four delays intermixed within a session. This task with a higher mnemonic demand yielded an average performance of 64% correct. Oral administration of huperzine A did not significantly

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

    Science.gov (United States)

    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. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8αα homodimer

    International Nuclear Information System (INIS)

    Zong, Lili; Chen, Yong; Yan, Jinghua; Zhang, Jianhua

    2010-01-01

    CD8α exodomain protein, a crucial immune-system factor in rhesus macaque (M. mulatta), one of the best animal models for vaccine design, was assembled and crystallized. The full structure data will contribute to future studies of immune responses in rhesus macaques. As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) αα homodimer was obtained and rCD8α exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4 Å. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 46.52, b = 56.28, c = 82.40 Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque

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

    Science.gov (United States)

    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.

  15. Local and systemic changes associated with long-term, percutaneous, static implantation with titanium alloys in rhesus macaques (Macaca mulatta)

    Energy Technology Data Exchange (ETDEWEB)

    Frydman, Galit F.; Marini, Robert P.; Bakthavatchalu, Vasudevan; Biddle, Kathleen; Muthupalani, Sureshkumar; Vanderburg, Charles R.; Lai, Barry; Bendapudi, Pavan K.; Tompkins, Ronald G.; Fox, James G.

    2017-04-01

    Metal alloys are frequently used as implant materials in veterinary medicine. Recent studies suggest that many types of metal alloys may induce both local and systemic inflammatory responses. In this study, 37 rhesus macaques with long-term skull-anchored percutaneous titanium alloy implants (0-14 years duration) were evaluated for changes in their hematology, coagulation and serum chemistry profiles. Negative controls (n=28) did not have implants. All of the implanted animals were on IACUC-approved protocols and were not implanted for the purpose of this study. Animals with implants had significantly higher plasma D-dimer and lower antithrombin III concentrations compared with nonimplanted animals (p-values < 0.05). Additionally, animals with implants had significantly higher globulin, and lower albumin and calcium concentrations compared with nonimplanted animals (p-values < 0.05). Many of these changes were positively correlated with duration of implantation as well as the number of implants. Chronic bacterial infection was observed on the skin around many of the implant sites, and within deeper tissues. Representative histopathology around the implant site of two implanted animals revealed chronic suppurative to pyogranulomatous inflammation extending from the skin to the dura mater. X-ray fluorescence microscopy of tissue biopsies from the implant site of the same two animals revealed significant increases in free metal ions within the tissue, including titanium and iron. Free metal ions persisted in the tissues up to 6 months postexplant. These results suggest that long-term skull-anchored percutaneous titanium alloy implants results in localized inflammation, chronic infection, and leaching of metal ions into local tissues.

  16. Supplementation of Reduced Gluten Barley Diet with Oral Prolyl Endopeptidase Effectively Abrogates Enteropathy-Associated Changes in Gluten-Sensitive Macaques

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    2016-06-01

    Full Text Available Celiac disease (CD is an autoimmune disorder that affects approximately three million people in the United States. Furthermore, non-celiac gluten sensitivity (NCGS affects an estimated additional 6% of the population, e.g., 20 million in the U.S. The only effective treatment of CD and NCGS requires complete removal of gluten sources from the diet. While required adherence to a gluten-free diet (GFD is extremely difficult to accomplish, efforts to develop additional supportive treatments are needed. To facilitate these efforts, we developed a gluten-sensitive (GS rhesus macaque model to study the effects of novel therapies. Recently reported results from phase one of this project suggest that partial improvement—but not remission—of gluten-induced disease can be accomplished by 100-fold reduction of dietary gluten, i.e., 200 ppm—by replacement of conventional dietary sources of gluten with a mutant, reduced gluten (RG barley (lys3a-derived source. The main focus of this (phase two study was to determine if the inflammatory effects of the residual gluten in lys3a mutant barley grain could be further reduced by oral supplementation with a prolylendopeptidase (PE. Results reveal that PE supplementation of RG barley diet induces more complete immunological, histopathological and clinical remission than RG barley diet alone. The combined effects of RG barley diet and PE supplementation resulted in a further decrease of inflammatory mediators IFN-γ and TNF secretion by peripheral lymphocytes, as well as decreased plasma anti-gliadin and anti-intestinal tissue transglutaminase (TG2 antibodies, diminished active caspase production in small intestinal mucosa, and eliminated clinical diarrhea—all comparable with a gluten-free diet induced remission. In summary, the beneficial results of a combined RG barley and PE administration in GS macaques may warrant the investigation of similar synergistic approaches.

  17. Background and stimulus-induced patterns of high metabolic activity in the visual cortex (area 17) of the squirrel and macaque monkey

    International Nuclear Information System (INIS)

    Humphrey, A.L.; Hendrickson, A.E.

    1983-01-01

    We have used 2-deoxy-D-[ 14 C]glucose (2-DG) autoradiography and cytochrome oxidase histochemistry to examine background and stimulus-induced patterns of metabolic activity in monkey striate cortex. In squirrel monkeys (Saimiri sciureus) that binocularly or monocularly viewed diffuse white light or binocularly viewed bars of many orientations and spatial frequencies, 2-DG consumption was not uniform across the cortex but consisted of regularly spaced radial zones of high uptake. The zones extended through all laminae except IVc beta and, when viewed tangentially, formed separate patches 500 microns apart. The cytochrome oxidase stain in these animals also revealed patches of high metabolism which coincided with the 2-DG patches. Squirrel monkeys binocularly viewing vertical stripes showed parallel bands of increased 2-DG uptake in the cortex, while the cytochrome label in these animals remained patchy. When monkeys were kept in the dark during 2-DG exposure, 2-DG-labeled patches were not seen but cytochrome oxidase-positive patches remained. In macaque (Macaca nemestrina) monkeys, binocular stimulation with many orientations and spatial frequencies produced radial zones of high 2-DG uptake in layers I to IVa and VI. When viewed tangentially, these zones formed a dots-in-rows pattern with a spacing of 350 X 500 microns; cytochrome oxidase staining produced an identical pattern. Macaca differed from Saimiri in that monocular stimulation labeled alternate rows. These results indicate that there are radial zones of high background metabolism across squirrel and macaque monkey striate cortex. In Saimiri these zones do not appear to be related to an eye dominance system, while in Macaca they do. The presence of these zones of high metabolism may complicate the interpretation of 2-DG autoradiographs that result from specific visual stimuli

  18. Evidence of direct reciprocity, but not of indirect and generalized reciprocity, in the grooming exchanges of wild Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Molesti, Sandra; Majolo, Bonaventura

    2017-09-01

    Reciprocity is one of the mechanisms that have been proposed to explain the exchange of social behaviors, such as grooming, in animals. Reciprocity assumes that individuals act as the donor and recipient of grooming and switch roles over time to balance the benefits and costs of this behavior. Three main patterns of reciprocity may follow a grooming given: (i) direct reciprocity, where the former recipient returns the grooming to the former donor; (ii) indirect reciprocity, where another individual returns the grooming to the former donor; and (iii) generalized reciprocity, where the former recipient returns the grooming to another individual. While there is evidence that direct reciprocity plays an important role in various species of animals, the role of indirect and generalized reciprocity is less clear and has been rarely analyzed. We tested the role of direct, indirect, and generalized reciprocity in explaining grooming exchanges of wild Barbary macaques, by analyzing the temporal contingency between giving and receiving grooming. We collected the occurrence and latency of the three types of grooming reciprocation during 1 hr long focal sessions run simultaneously on two partners who just stopped grooming (post-grooming session) or who were in proximity (i.e., within 1.5 m) without grooming each other (control session). We ran the analyses on 284 post-grooming and 63 control sessions. The results revealed a temporal contingency of grooming interactions exchanged according to direct reciprocity but not according to indirect or generalized reciprocity. Our results indicate that grooming distribution in Barbary macaques is partner-specific. We discuss the possible role of cognition and emotions in explaining direct reciprocity in animals. © 2017 Wiley Periodicals, Inc.

  19. A Neural Signature of Divisive Normalization at the Level of Multisensory Integration in Primate Cortex.

    Science.gov (United States)

    Ohshiro, Tomokazu; Angelaki, Dora E; DeAngelis, Gregory C

    2017-07-19

    Studies of multisensory integration by single neurons have traditionally emphasized empirical principles that describe nonlinear interactions between inputs from two sensory modalities. We previously proposed that many of these empirical principles could be explained by a divisive normalization mechanism operating in brain regions where multisensory integration occurs. This normalization model makes a critical diagnostic prediction: a non-preferred sensory input from one modality, which activates the neuron on its own, should suppress the response to a preferred input from another modality. We tested this prediction by recording from neurons in macaque area MSTd that integrate visual and vestibular cues regarding self-motion. We show that many MSTd neurons exhibit the diagnostic form of cross-modal suppression, whereas unisensory neurons in area MT do not. The normalization model also fits population responses better than a model based on subtractive inhibition. These findings provide strong support for a divisive normalization mechanism in multisensory integration. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India.

    Science.gov (United States)

    Velankar, Avadhoot D; Kumara, Honnavalli N; Pal, Arijit; Mishra, Partha Sarathi; Singh, Mewa

    2016-01-01

    Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species.

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

    Science.gov (United States)

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

    2016-08-01

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

  2. Food resources, distribution and seasonal variations in ranging in lion-tailed macaques, Macaca silenus in the Western Ghats, India.

    Science.gov (United States)

    Erinjery, Joseph J; Kavana, T S; Singh, Mewa

    2015-01-01

    The distribution and availability of food was examined to see how it influenced ranging patterns and sleeping site selection in a group of lion-tailed macaques. The home range and core area were 130.48 ha (95% kernel) and 26.68 ha (50% kernel) respectively. The lion-tailed macaques had a longer day range, had a greater number of sleeping sites and used more core areas in the summer as compared to the monsoon and the post-monsoon seasons. The ranging patterns and sleeping site use were influenced by the major food resources used in a particular season. The ranging was mainly influenced by Artocarpus heterophyllus in monsoon, Cullenia exarillata and Toona ciliata in post- monsoon, and Artocarpus heterophyllus and Ficus amplissima in summer. The distribution of these four plant species is, therefore, critical to ranging, and thus to conservation of the lion-tailed macaque.

  3. L-Arginine ethylester enhances in vitro amplification of PrP(Sc) in macaques with atypical L-type bovine spongiform encephalopathy and enables presymptomatic detection of PrP(Sc) in the bodily fluids.

    Science.gov (United States)

    Murayama, Y; Ono, F; Shimozaki, N; Shibata, H

    2016-02-12

    Protease-resistant, misfolded isoforms (PrP(Sc)) of a normal cellular prion protein (PrP(C)) in the bodily fluids, including blood, urine, and saliva, are expected to be useful diagnostic markers of prion diseases, and nonhuman primate models are suited for performing valid diagnostic tests for human Creutzfeldt-Jakob disease (CJD). We developed an effective amplification method for PrP(Sc) derived from macaques infected with the atypical L-type bovine spongiform encephalopathy (L-BSE) prion by using mouse brain homogenate as a substrate in the presence of polyanions and L-arginine ethylester. This method was highly sensitive and detected PrP(Sc) in infected brain homogenate diluted up to 10(10) by sequential amplification. This method in combination with PrP(Sc) precipitation by sodium phosphotungstic acid is capable of amplifying very small amounts of PrP(Sc) contained in the cerebrospinal fluid (CSF), saliva, urine, and plasma of macaques that have been intracerebrally inoculated with the L-BSE prion. Furthermore, PrP(Sc) was detectable in the saliva or urine samples as well as CSF samples obtained at the preclinical phases of the disease. Thus, our novel method may be useful for furthering the understanding of bodily fluid leakage of PrP(Sc) in nonhuman primate models. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  5. Comparison of feeding behavior between two different-sized groups of Japanese macaques (Macaca fuscata yakui).

    Science.gov (United States)

    Kurihara, Yosuke; Hanya, Goro

    2015-05-13

    Group-living animals face intragroup scramble and intergroup contest competitions. Many studies have shown that larger groups bear the costs of intragroup scramble competition, which negatively affects the reproductive success of females. Unlike most primate species, Japanese macaques in the Yakushima coastal forest show increased reproductive success with group size. However, it remains unclear how group size affects the behavior of macaques. The present study examined the effects of group size on the feeding behavior of Japanese macaques in the Yakushima coastal forest. We investigated 9-13 adult females from two different-sized groups via focal animal sampling during October 2012-August 2013. We compared the feeding behavior, including patch use, between the two groups. The larger group had a larger home range and spent more time feeding, especially on mature leaves. This suggests that intragroup feeding competition should be more intense in the larger group than in the smaller group. The feeding of mature leaves might enable the larger group to increase the number of co-feeding individuals. Contrary to the predictions that the larger group travels longer distances and spends more time moving, the smaller group traveled longer distances, and spent more time moving, although the number of visited patches did not differ between the two groups. The immediate consequences of the loss of inter-group encounters could accumulate as daily travel costs, considering that group size is associated with inter-group dominance and that intergroup aggressive encounters occur frequently in the Yakushima coastal forest. This suggests that the smaller group has increased travel costs as a result of intergroup contest competition, which leads to decline in reproductive success. Am. J. Primatol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. Cortico-cortical connections of areas 44 and 45B in the macaque monkey.

    Science.gov (United States)

    Frey, Stephen; Mackey, Scott; Petrides, Michael

    2014-04-01

    In the human brain, areas 44 and 45 constitute Broca's region, the ventrolateral frontal region critical for language production. The homologues of these areas in the macaque monkey brain have been established by direct cytoarchitectonic comparison with the human brain. The cortical areas that project monosynaptically to areas 44 and 45B in the macaque monkey brain require clarification. Fluorescent retrograde tracers were placed in cytoarchitectonic areas 44 and 45B of the macaque monkey, as well as in the anterior part of the inferior parietal lobule and the superior temporal gyrus. The results demonstrate that ipsilateral afferent connections of area 44 arise from local frontal areas, including rostral premotor cortical area 6, from secondary somatosensory cortex, the caudal insula, and the cingulate motor region. Area 44 is strongly linked with the anterior inferior parietal lobule (particularly area PFG and the adjacent anterior intraparietal sulcus). Input from the temporal lobe is limited to the fundus of the superior temporal sulcus extending caudal to the central sulcus. There is also input from the sulcal part of area Tpt in the upper bank of the superior temporal sulcus. Area 45B shares some of the connections of area 44, but can be distinguished from area 44 by input from the caudal inferior parietal lobule (area PG) and significant input from the part of the superior temporal sulcus that extends anterior to the central sulcus. Area 45B also receives input from visual association cortex that is not observed in area 44. The results have provided a clarification of the relative connections of areas 44 and 45B of the ventrolateral frontal region which, in the human brain, subserves certain aspects of language processing. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Social play among juvenile wild Japanese macaques (Macaca fuscata) strengthens their social bonds.

    Science.gov (United States)

    Shimada, Masaki; Sueur, Cédric

    2018-01-01

    Social play and grooming are typical affiliative interactions for many primate species, and are thought to have similar biological functions. However, grooming increases with age, whereas social play decreases. We proposed the hypothesis that both social grooming and social play in juveniles strengthen their social bonds in daily activities. We carried out field research on the social relationships among juvenile wild Japanese macaques in a troop in Kinkazan, Miyagi Prefecture, Japan, from fall 2007 to spring 2008 to investigate this hypothesis. We evaluated three relationships among juveniles, play indices (PI), grooming indices (GI), and 3-m-proximity indices (3mI) of each dyad (i.e., interacting pair), and compared these social networks based on the matrices of the indices. The play and grooming networks were correlated with the association network throughout the two research periods. The multiple network level measurements of the play network, but not the grooming network, resembled those of the association network. Using a causal step approach, we showed that social play and grooming interactions in fall seem to predict associations in the following spring, controlling for the PI and GI matrix in spring, respectively. Social play and grooming for each juvenile were negatively correlated. The results partially support our predictions; therefore, the hypothesis that the biological function of social play among immature Japanese macaques is to strengthen their social bonds in the near future and develop their social life appears to be correct. For juvenile macaques, social play, rather than grooming, functions as an important social mechanism to strengthen affiliative relationships. © 2017 Wiley Periodicals, Inc.

  8. Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).

    Science.gov (United States)

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

    2017-07-01

    In species with a high male reproductive skew, competition between males for the top dominant position is high and escalated fights are common between competitors. As a consequence, challenges incur potentially high costs. Selection should favor males who time an alpha male challenge to maximize chances of a successful outcome minimizing costs. Despite the importance of alpha male replacements for individual males, we know little about the timing of challenges and the condition of the challenger. We investigated the timing and process of alpha male replacements in a species living in multi-male groups with high male reproductive skew, the crested macaque. We studied four wild groups over 6 years in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male replacements occurred. Although unusual for cercopithecines, male crested macaques delayed their natal dispersal until they attained maximum body mass and therefore fighting ability whereupon they emigrated and challenged the alpha male in another group. Accordingly, all observed alpha male replacements were from outside males. Ours is the first report of such a pattern in a primate species living in multi-male groups. Although the majority of alpha male replacements occurred through direct male-male challenges, many also took place opportunistically (i.e., after the alpha male had already been injured or had left the group). Furthermore, alpha male tenures were very short (averaging ca. 12 months). We hypothesize that this unusual pattern of alpha male replacements in crested macaques is related to the species-specific combination of high male reproductive skew with a large number of males per group. Am. J. Primatol. 79:e22448, 2017. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.

  9. Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.

    Science.gov (United States)

    Lee, Kim M; Chiu, Kevin B; Didier, Peter J; Baker, Kate C; MacLean, Andrew G

    2015-11-01

    The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    James Andrew Solyst

    2014-11-01

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

  11. Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

    Science.gov (United States)

    Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

    2017-11-22

    Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Intermittent pair-housing, pair relationship qualities, and HPA activity in adult female rhesus macaques.

    Science.gov (United States)

    Hannibal, Darcy L; Cassidy, Lauren C; Vandeleest, Jessica; Semple, Stuart; Barnard, Allison; Chun, Katie; Winkler, Sasha; McCowan, Brenda

    2018-05-02

    Laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. While both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. In this study, we investigated the effects of overnight separations on the urinary cortisol concentration of 20 differentially paired adult female rhesus macaques (Macaca mulatta) at the California National Primate Research Center. These females were initially kept in either continuous (no overnight separation) or intermittent (with overnight separation) pair-housing and then switched to the alternate pair-housing condition part way through the study. Each study subject was observed for 5 weeks, during which we collected measures of affiliative, aggressive, anxious, abnormal, and activity-state behaviors in both pair-housing conditions. Additionally, up to three urine samples were collected from each subject per week and assayed for urinary free cortisol and creatinine. Lastly, the behavioral observer scored each pair on four relationship quality attributes ("Anxious," "Tense," "Well-meshed," and "Friendly") using a seven-point scale. Data were analyzed using a generalized linear model with gamma distribution and an information theoretic approach to determine the best model set. An interaction between the intermittent pairing condition and tense pair adjective rating was in the top three models of the best model set. Dominance and rates of affiliation were also important for explaining urinary cortisol variation. Our results suggest that to prevent significant changes in HPA-axis activation in rhesus macaque females, which could have unintended effects on research outcomes, pairs with "Tense" relationships and overnight separations preventing tactile contact

  14. Short-term separation from groups by male Japanese macaques: costs and benefits in feeding behavior and social interaction.

    Science.gov (United States)

    Otani, Yosuke; Sawada, Akiko; Hanya, Goro

    2014-04-01

    To expand our understanding of fission-fusion behavior and determine its variability among primates, studies of both individual-based and group-based fission-fusion are necessary. We conducted a parallel tracking study of male and female Japanese macaques (Macaca fuscata yakui) during the non-mating season to clarify the general features of separate ranging by males of this species, an example of fission-fusion behavior, and to reveal its associated costs and benefits. Males frequently engaged in short-term separate ranging, leaving the company of females and ranging on their own for periods averaging 68 min in duration. However, the males did not venture outside the group's home range. When ranging separately from the group, males spent more time feeding, particularly on fruit, stayed longer in each feeding tree, and fed at a lower rate than when ranging with the group. These behavioral changes suggest that males can avoid within-group feeding competition by ranging alone. However, this behavior was also associated with higher traveling costs, and these separated males were more vulnerable to intergroup competition and had fewer opportunities for social interaction. The frequency of separate ranging was lower when highly clumped food plant species were the main food source. Lower-ranked males, who received more aggression when ranging with the group, exhibited a higher frequency of separate ranging. This behavioral flexibility with respect to group cohesion may allow males to reduce the costs of group living without completely losing the benefits. Specifically, by ranging alone, males may acquire sufficient feeding time without being disturbed by other group members. Conversely, when ranging with the group, males can access grooming partners and advantages in intergroup competition. © 2013 Wiley Periodicals, Inc.

  15. Phylogenetic relationships of Malaysia’s long-tailed macaques, Macaca fascicularis, based on cytochrome b sequences

    Science.gov (United States)

    Abdul-Latiff, Muhammad Abu Bakar; Ruslin, Farhani; Fui, Vun Vui; Abu, Mohd-Hashim; Rovie-Ryan, Jeffrine Japning; Abdul-Patah, Pazil; Lakim, Maklarin; Roos, Christian; Yaakop, Salmah; Md-Zain, Badrul Munir

    2014-01-01

    Abstract Phylogenetic relationships among Malaysia’s long-tailed macaques have yet to be established, despite abundant genetic studies of the species worldwide. The aims of this study are to examine the phylogenetic relationships of Macaca fascicularis in Malaysia and to test its classification as a morphological subspecies. A total of 25 genetic samples of M. fascicularis yielding 383 bp of Cytochrome b (Cyt b) sequences were used in phylogenetic analysis along with one sample each of M. nemestrina and M. arctoides used as outgroups. Sequence character analysis reveals that Cyt b locus is a highly conserved region with only 23% parsimony informative character detected among ingroups. Further analysis indicates a clear separation between populations originating from different regions; the Malay Peninsula versus Borneo Insular, the East Coast versus West Coast of the Malay Peninsula, and the island versus mainland Malay Peninsula populations. Phylogenetic trees (NJ, MP and Bayesian) portray a consistent clustering paradigm as Borneo’s population was distinguished from Peninsula’s population (99% and 100% bootstrap value in NJ and MP respectively and 1.00 posterior probability in Bayesian trees). The East coast population was separated from other Peninsula populations (64% in NJ, 66% in MP and 0.53 posterior probability in Bayesian). West coast populations were divided into 2 clades: the North-South (47%/54% in NJ, 26/26% in MP and 1.00/0.80 posterior probability in Bayesian) and Island-Mainland (93% in NJ, 90% in MP and 1.00 posterior probability in Bayesian). The results confirm the previous morphological assignment of 2 subspecies, M. f. fascicularis and M. f. argentimembris, in the Malay Peninsula. These populations should be treated as separate genetic entities in order to conserve the genetic diversity of Malaysia’s M. fascicularis. These findings are crucial in aiding the conservation management and translocation process of M. fascicularis populations

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Higham, James P; Heistermann, Michael; Saggau, Carina; Agil, Muhammad; Perwitasari-Farajallah, Dyah; Engelhardt, Antje

    2012-06-18

    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. 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. 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 circumstances it is in the interest of females to increase

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

    Directory of Open Access Journals (Sweden)

    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

  19. Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex

    OpenAIRE

    Noonan, M. P.; Walton, M. E.; Behrens, T. E. J.; Sallet, J.; Buckley, M. J.; Rushworth, M. F. S.

    2010-01-01

    Uncertainty about the function of orbitofrontal cortex (OFC) in guiding decision-making may be a result of its medial (mOFC) and lateral (lOFC) divisions having distinct functions. Here we test the hypothesis that the mOFC is more concerned with reward-guided decision making, in contrast with the lOFC's role in reward-guided learning. Macaques performed three-armed bandit tasks and the effects of selective mOFC lesions were contrasted against lOFC lesions. First, we present analyses that make...

  20. Shigella flexneri infection in a newly acquired rhesus macaque (Macaca mulatta)

    OpenAIRE

    Lee, Jae-Il; Kim, Sang-Joon; Park, Chung-Gyu

    2011-01-01

    A 3.4 year-old rhesus macaque weighing 4.5 kg, was suffering from anorexia, acute mucous and bloody diarrhea. On physical examination, the monkey showed a loss of activity, hunched posture, abdominal pain, dehydration, mild gingivitis and unclean anus with discharge. Whole blood was collected for the examination of electrolytes, hematology and serum chemistry; fresh stool was also collected for bacterial culture. Blood profiles showed leukocytosis (14.5 K/?L) and neutrophilia (11.0 K/?L) on c...

  1. 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.

  2. Strabismus and the Oculomotor System: Insights from Macaque Models

    Science.gov (United States)

    Das, Vallabh E.

    2017-01-01

    Disrupting binocular vision in infancy leads to strabismus and oftentimes to a variety of associated visual sensory deficits and oculomotor abnormalities. Investigation of this disorder has been aided by the development of various animal models, each of which has advantages and disadvantages. In comparison to studies of binocular visual responses in cortical structures, investigations of neural oculomotor structures that mediate the misalignment and abnormalities of eye movements have been more recent, and these studies have shown that different brain areas are intimately involved in driving several aspects of the strabismic condition, including horizontal misalignment, dissociated deviations, A and V patterns of strabismus, disconjugate eye movements, nystagmus, and fixation switch. The responses of cells in visual and oculomotor areas that potentially drive the sensory deficits and also eye alignment and eye movement abnormalities follow a general theme of disrupted calibration, lower sensitivity, and poorer specificity compared with the normally developed visual oculomotor system. PMID:28532347

  3. Normalized modes at selected points without normalization

    Science.gov (United States)

    Kausel, Eduardo

    2018-04-01

    As every textbook on linear algebra demonstrates, the eigenvectors for the general eigenvalue problem | K - λM | = 0 involving two real, symmetric, positive definite matrices K , M satisfy some well-defined orthogonality conditions. Equally well-known is the fact that those eigenvectors can be normalized so that their modal mass μ =ϕT Mϕ is unity: it suffices to divide each unscaled mode by the square root of the modal mass. Thus, the normalization is the result of an explicit calculation applied to the modes after they were obtained by some means. However, we show herein that the normalized modes are not merely convenient forms of scaling, but that they are actually intrinsic properties of the pair of matrices K , M, that is, the matrices already "know" about normalization even before the modes have been obtained. This means that we can obtain individual components of the normalized modes directly from the eigenvalue problem, and without needing to obtain either all of the modes or for that matter, any one complete mode. These results are achieved by means of the residue theorem of operational calculus, a finding that is rather remarkable inasmuch as the residues themselves do not make use of any orthogonality conditions or normalization in the first place. It appears that this obscure property connecting the general eigenvalue problem of modal analysis with the residue theorem of operational calculus may have been overlooked up until now, but which has in turn interesting theoretical implications.Á

  4. Analysis of nuclear and organellar genomes of Plasmodium knowlesi in humans reveals ancient population structure and recent recombination among host-specific subpopulations

    KAUST Repository

    Diez Benavente, Ernest

    2017-09-18

    The macaque parasite Plasmodium knowlesi is a significant concern in Malaysia where cases of human infection are increasing. Parasites infecting humans originate from genetically distinct subpopulations associated with the long-tailed (Macaca fascicularis (Mf)) or pig-tailed macaques (Macaca nemestrina (Mn)). We used a new high-quality reference genome to re-evaluate previously described subpopulations among human and macaque isolates from Malaysian-Borneo and Peninsular-Malaysia. Nuclear genomes were dimorphic, as expected, but new evidence of chromosomal-segment exchanges between subpopulations was found. A large segment on chromosome 8 originating from the Mn subpopulation and containing genes encoding proteins expressed in mosquito-borne parasite stages, was found in Mf genotypes. By contrast, non-recombining organelle genomes partitioned into 3 deeply branched lineages, unlinked with nuclear genomic dimorphism. Subpopulations which diverged in isolation have re-connected, possibly due to deforestation and disruption of wild macaque habitats. The resulting genomic mosaics reveal traits selected by host-vector-parasite interactions in a setting of ecological transition.

  5. Analysis of nuclear and organellar genomes of Plasmodium knowlesi in humans reveals ancient population structure and recent recombination among host-specific subpopulations

    KAUST Repository

    Diez Benavente, Ernest; Florez de Sessions, Paola; Moon, Robert W.; Holder, Anthony A.; Blackman, Michael J.; Roper, Cally; Drakeley, Christopher J.; Pain, Arnab; Sutherland, Colin J.; Hibberd, Martin L.; Campino, Susana; Clark, Taane G.

    2017-01-01

    The macaque parasite Plasmodium knowlesi is a significant concern in Malaysia where cases of human infection are increasing. Parasites infecting humans originate from genetically distinct subpopulations associated with the long-tailed (Macaca fascicularis (Mf)) or pig-tailed macaques (Macaca nemestrina (Mn)). We used a new high-quality reference genome to re-evaluate previously described subpopulations among human and macaque isolates from Malaysian-Borneo and Peninsular-Malaysia. Nuclear genomes were dimorphic, as expected, but new evidence of chromosomal-segment exchanges between subpopulations was found. A large segment on chromosome 8 originating from the Mn subpopulation and containing genes encoding proteins expressed in mosquito-borne parasite stages, was found in Mf genotypes. By contrast, non-recombining organelle genomes partitioned into 3 deeply branched lineages, unlinked with nuclear genomic dimorphism. Subpopulations which diverged in isolation have re-connected, possibly due to deforestation and disruption of wild macaque habitats. The resulting genomic mosaics reveal traits selected by host-vector-parasite interactions in a setting of ecological transition.

  6. The statistical neuroanatomy of frontal networks in the macaque.

    Directory of Open Access Journals (Sweden)

    Bruno B Averbeck

    2008-04-01

    Full Text Available We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework.

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

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    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. Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

    Science.gov (United States)

    Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

    2015-09-01

    In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. © 2015 British Society for Immunology.

  9. Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

    Science.gov (United States)

    Cabrera-Mora, Monica; Garcia, AnaPatricia; Orkin, Jack; Strobert, Elizabeth; Barnwell, John W.; Galinski, Mary R.

    2013-01-01

    Severe malaria, a leading cause of mortality among children and nonimmune adults, is a multisystemic disorder characterized by complex clinical syndromes that are mechanistically poorly understood. The interplay of various parasite and host factors is critical in the pathophysiology of severe malaria. However, knowledge regarding the pathophysiological mechanisms and pathways leading to the multisystemic disorders of severe malaria in humans is limited. Here, we systematically investigate infections with Plasmodium coatneyi, a simian malaria parasite that closely mimics the biological characteristics of P. falciparum, and develop baseline data and protocols for studying erythrocyte turnover and severe malaria in greater depth. We show that rhesus macaques (Macaca mulatta) experimentally infected with P. coatneyi develop anemia, coagulopathy, and renal and metabolic dysfunction. The clinical course of acute infections required suppressive antimalaria chemotherapy, fluid support, and whole-blood transfusion, mimicking the standard of care for the management of severe malaria cases in humans. Subsequent infections in the same animals progressed with a mild illness in comparison, suggesting that immunity played a role in reducing the severity of the disease. Our results demonstrate that P. coatneyi infection in rhesus macaques can serve as a highly relevant model to investigate the physiological pathways and molecular mechanisms of malaria pathogenesis in naïve and immune individuals. Together with high-throughput postgenomic technologies, such investigations hold promise for the identification of new clinical interventions and adjunctive therapies. PMID:23509137

  10. Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis.

    Science.gov (United States)

    Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo

    2012-05-09

    Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p diversification during early infection might enhance immune control by slowing the selection of escape mutants.

  11. An experimental investigation of referential looking in free-ranging Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    Roberts, Sam G B; McComb, Karen; Ruffman, Ted

    2008-02-01

    The authors examined looking behavior between 15 Barbary macaque (Macaca sylvanus) infants and their mothers in the presence of a rubber snake (experimental period) and in the absence of the snake (control period). Two of the 15 infants looked referentially at their mother in the experimental period. Including both referential and nonreferential looks, the six older infants (aged 5 to 12 months) displayed a higher frequency of looks to mother than nine younger infants (aged 3 to 4.5 months) in the experimental period, but not in the control period. Older infants looked more to the mother in the experimental condition, whereas the younger infants looked more to the mother in the control condition, or looked equally in the two conditions. These results suggest that age is an important factor in determining looking behavior to mother in situations of uncertainty. Compared to hand-reared chimpanzees or human infants tested in standard social referencing paradigms, the infant macaques displayed a low rate of referential looking. Possible explanations for this are discussed. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

  12. An experimental examination of female responses to infant face coloration in rhesus macaques.

    Science.gov (United States)

    Gerald, Melissa S; Waitt, Corri; Maestripieri, Dario

    2006-11-01

    In many primates, infants possess distinctive coloration that changes as a function of age. This colour is thought to serve the purpose of eliciting caretaking behaviour from the mother as well as other conspecifics. The present study investigated the responses of adult female rhesus macaques (Macaca mulatta) to pictures of infant faces in relation to infant age and facial coloration. Study animals were shown digitized images of neonates and 5-6-month-old infants displaying either unaltered facial colour, pink neonatal colour, or novel (green) facial colour. While infant and neonate faces of all colours elicited the attention of adult females, pink neonatal facial coloration did not appear to be especially attractive to subjects in contrast with the findings from an earlier study [Higley, J.D., Hopkins, W.D., Hirsch, R.M. Marra, L.M. Suomi S.J., 1987. Preferences of female rhesus monkeys (Macaca mulatta) for infantile coloration. Dev. Psychobiol. 20, 7-18]. The results suggest that infant facial colour is not particularly important in mediating infant attractiveness to rhesus macaque females as previously suggested or that other infantile facial characteristics might be more important than colour in eliciting caretaking behaviours amongst females.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Identification of a Novel Enterovirus Species in Rhesus Macaque in China.

    Science.gov (United States)

    Ao, Yuan-Yun; Yu, Jie-Mei; Zhang, Cui-Yuan; Xin, Yun-Yun; Li, Li-Li; Duan, Zhao-Jun

    2016-06-22

    Recent studies of Enterovirus (EV) in nonhuman primates (NHPs), which could act as a source of future emerging human viral diseases, have boosted interest in the search for novel EVs. Here, a highly divergent strain of EV, tentatively named SEV-gx, was identified by viral metagenomic analysis from stool samples of rhesus macaques in China. In total, 27 of 280 (9.6%) faecal samples from rhesus macaques were positive for SEV-gx. Its complete genomic sequence is 7,367 nucleotide (nt). Genomic analyses showed that it has a standard genomic organisation for EVs, being more closely related to EV-J strains (approximately 54.0%, 43.0-44.1%, 52.3-55.2%, 61.1-62.7% and 64.0% amino acids identity in polyprotein, P1, P2 and P3 and combined 2C/3CD regions, respectively). It was also shown to have genome characteristics typical of EVs. Phylogenetic analysis of P1, 2C and 3CD aa indicated that SEV-gx can be classified as a distinct cluster in the EVs. All of this evidence demonstrates SEV-gx is a novel species (tentatively named EV-K) in the EV genus, which contributes to our understanding of the genetic diversity and evolution of EVs. Further studies are needed to investigate the potential pathogenicity of SEV-gx in NHPs and humans.

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

    Directory of Open Access Journals (Sweden)

    Brianne A Beisner

    2011-01-01

    Full Text Available 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.

  16. 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.

  17. Responses to social and environmental stress are attenuated by strong male bonds in wild macaques

    Science.gov (United States)

    Young, Christopher; Majolo, Bonaventura; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

    2014-01-01

    In humans and obligatory social animals, individuals with weak social ties experience negative health and fitness consequences. The social buffering hypothesis conceptualizes one possible mediating mechanism: During stressful situations the presence of close social partners buffers against the adverse effects of increased physiological stress levels. We tested this hypothesis using data on social (rate of aggression received) and environmental (low temperatures) stressors in wild male Barbary macaques (Macaca sylvanus) in Morocco. These males form strong, enduring, and equitable affiliative relationships similar to human friendships. We tested the effect of the strength of a male’s top three social bonds on his fecal glucocorticoid metabolite (fGCM) levels as a function of the stressors’ intensity. The attenuating effect of stronger social bonds on physiological stress increased both with increasing rates of aggression received and with decreasing minimum daily temperature. Ruling out thermoregulatory and immediate effects of social interactions on fGCM levels, our results indicate that male Barbary macaques employ a tend-and-befriend coping strategy in the face of increased environmental as well as social day-to-day stressors. This evidence of a stress-ameliorating effect of social bonding among males under natural conditions and beyond the mother–offspring, kin or pair bond broadens the generality of the social buffering hypothesis. PMID:25489097

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

    Science.gov (United States)

    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. © 2015 Wiley Periodicals, Inc.

  19. Decoding Target Distance and Saccade Amplitude from Population Activity in the Macaque Lateral Intraparietal Area (LIP)

    Science.gov (United States)

    Bremmer, Frank; Kaminiarz, Andre; Klingenhoefer, Steffen; Churan, Jan

    2016-01-01

    Primates perform saccadic eye movements in order to bring the image of an interesting target onto the fovea. Compared to stationary targets, saccades toward 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 toward 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. PMID:27630547

  20. Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.

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    Katsuo Kimura

    Full Text Available In neurodegenerative disorders, such as Parkinson's disease (PD, alpha-synuclein (α-syn accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB. This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

  1. 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.

  2. Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques.

    Science.gov (United States)

    Wong, Gary; Qiu, Xiangguo; de La Vega, Marc-Antoine; Fernando, Lisa; Wei, Haiyan; Bello, Alexander; Fausther-Bovendo, Hugues; Audet, Jonathan; Kroeker, Andrea; Kozak, Robert; Tran, Kaylie; He, Shihua; Tierney, Kevin; Soule, Geoff; Moffat, Estella; Günther, Stephan; Gao, George F; Strong, Jim; Embury-Hyatt, Carissa; Kobinger, Gary

    2016-10-15

    Enhanced virulence and/or transmission of West African Ebola virus (EBOV) variants, which are divergent from their Central African counterparts, are suspected to have contributed to the sizable toll of the recent Ebola virus disease (EVD) outbreak. This study evaluated the pathogenicity and shedding in rhesus macaques infected with 1 of 2 West African isolates (EBOV-C05 or EBOV-C07) or a Central African isolate (EBOV-K). All animals infected with EBOV-C05 or EBOV-C07 died of EVD, whereas 2 of 3 EBOV-K-infected animals died. The viremia level was elevated 10-fold in EBOV-C05-infected animals, compared with EBOV-C07- or EBOV-K-infected animals. More-severe lung pathology was observed in 2 of 6 EBOV-C05/C07-infected macaques. This is the first detailed analysis of the recently circulating EBOV-C05/C07 in direct comparison to EBOV-K with 6 animals per group, and it showed that EBOV-C05 but not EBOV-C07 can replicate at higher levels and cause more tissue damage in some animals. Increased virus shedding from individuals who are especially susceptible to EBOV replication is possibly one of the many challenges facing the community of healthcare and policy-making responders since the beginning of the outbreak. © Crown copyright 2016.

  3. The use of preferred social stimuli as rewards for rhesus macaques in behavioural neuroscience.

    Directory of Open Access Journals (Sweden)

    Helen Gray

    Full Text Available Macaques are often motivated to perform in neuroscientific experiments by implementing fluid restriction protocols. Daily access to water is controlled and the monkeys are rewarded with droplets of fluid for performing correct trials in the laboratory. Although these protocols are widely used and highly effective, it is important from a 3Rs perspective to investigate refinements that may help to lessen the severity of the fluid restriction applied. We assessed the use of social stimuli (images of conspecifics as rewards for four rhesus macaques performing simple cognitive tasks. We found that individual preferences for images of male faces, female perinea and control stimuli could be identified in each monkey. However, using preferred images did not translate into effective motivators on a trial-by-trial basis: animals preferred fluid rewards, even when fluid restriction was relaxed. There was no difference in the monkeys' performance of a task when using greyscale versus colour images. Based on our findings, we cannot recommend the use of social stimuli, in this form, as a refinement to current fluid restriction protocols. We discuss the potential alternatives and possibilities for future research.

  4. A population MRI brain template and analysis tools for the macaque.

    Science.gov (United States)

    Seidlitz, Jakob; Sponheim, Caleb; Glen, Daniel; Ye, Frank Q; Saleem, Kadharbatcha S; Leopold, David A; Ungerleider, Leslie; Messinger, Adam

    2018-04-15

    The use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the "National Institute of Mental Health Macaque Template", or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies. Copyright © 2017 ElsevierCompany. All rights reserved.

  5. Information processing architecture of functionally defined clusters in the macaque cortex.

    Science.gov (United States)

    Shen, Kelly; Bezgin, Gleb; Hutchison, R Matthew; Gati, Joseph S; Menon, Ravi S; Everling, Stefan; McIntosh, Anthony R

    2012-11-28

    Computational and empirical neuroimaging studies have suggested that the anatomical connections between brain regions primarily constrain their functional interactions. Given that the large-scale organization of functional networks is determined by the temporal relationships between brain regions, the structural limitations may extend to the global characteristics of functional networks. Here, we explored the extent to which the functional network community structure is determined by the underlying anatomical architecture. We directly compared macaque (Macaca fascicularis) functional connectivity (FC) assessed using spontaneous blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to directed anatomical connectivity derived from macaque axonal tract tracing studies. Consistent with previous reports, FC increased with increasing strength of anatomical connection, and FC was also present between regions that had no direct anatomical connection. We observed moderate similarity between the FC of each region and its anatomical connectivity. Notably, anatomical connectivity patterns, as described by structural motifs, were different within and across functional modules: partitioning of the functional network was supported by dense bidirectional anatomical connections within clusters and unidirectional connections between clusters. Together, our data directly demonstrate that the FC patterns observed in resting-state BOLD-fMRI are dictated by the underlying neuroanatomical architecture. Importantly, we show how this architecture contributes to the global organizational principles of both functional specialization and integration.

  6. Interspecies sexual behaviour between a male Japanese macaque and female sika deer.

    Science.gov (United States)

    Pelé, Marie; Bonnefoy, Alexandre; Shimada, Masaki; Sueur, Cédric

    2017-04-01

    Interspecies sexual behaviour or 'reproductive interference' has been reported across a wide range of animal taxa. However, most of these occurrences were observed in phylogenetically close species and were mainly discussed in terms of their effect on fitness, hybridization and species survival. The few cases of heterospecific mating in distant species occurred between animals that were bred and maintained in captivity. Only one scientific study has reported this phenomenon, describing sexual harassment of king penguins by an Antarctic fur seal. This is the first article to report mating behaviour between a male Japanese macaque (Macaca fuscata yakui) and female sika deer (Cervus nippon yakushimae) on Yakushima Island, Japan. Although Japanese macaques are known to ride deer, this individual showed clearly sexual behaviour towards several female deer, some of which tried to escape whilst others accepted the mount. This male seems to belong to a group of peripheral males. Although this phenomenon may be explained as copulation learning, this is highly unlikely. The most realistic hypothesis would be that of mate deprivation, which states that males with limited access to females are more likely to display this behaviour. Whatever the cause for this event may be, the observation of highly unusual animal behaviour may be a key to understanding the evolution of heterospecific mating behaviour in the animal kingdom.

  7. Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque.

    Science.gov (United States)

    Edens, Chris; Dybdahl-Sissoko, Naomi C; Weldon, William C; Oberste, M Steven; Prausnitz, Mark R

    2015-09-08

    The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Combined Transcriptomics and Metabolomics in a Rhesus Macaque Drug Administration Study

    Directory of Open Access Journals (Sweden)

    Kevin J. Lee

    2014-10-01

    Full Text Available We describe a multi-omic approach to understanding the effects that the anti-malarial drug pyrimethamine has on immune physiology in rhesus macaques (Macaca mulatta. Whole blood and bone marrow RNA-Seq and plasma metabolome profiles (each with over 15,000 features have been generated for five naïve individuals at up to seven time-points before, during and after three rounds of drug administration. Linear modelling and Bayesian network analyses are both considered, alongside investigations of the impact of statistical modeling strategies on biological inference. Individual macaques were found to be a major source of variance for both omic data types, and factoring individuals into subsequent modelling increases power to detect temporal effects. A major component of the whole blood transcriptome follows the bone marrow with a time-delay, while other components of variation are unique to each compartment. We demonstrate that pyrimethamine administration does impact both compartments throughout the experiment, but very limited perturbation of transcript or metabolite abundance following each round of drug exposure is observed. New insights into the mode of action of the drug are presented in the context of pyrimethamine’s predicted effect on suppression of cell division and metabolism in the immune system.

  9. Social modulation of cognition: Lessons from rhesus macaques relevant to education.

    Science.gov (United States)

    Monfardini, Elisabetta; Reynaud, Amélie J; Prado, Jérôme; Meunier, Martine

    2017-11-01

    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.

  10. Rhesus macaques form preferences for brand logos through sex and social status based advertising.

    Science.gov (United States)

    Acikalin, M Yavuz; Watson, Karli K; Fitzsimons, Gavan J; Platt, Michael L

    2018-01-01

    Like humans, monkeys value information about sex and status, inviting the hypothesis that our susceptibility to these factors in advertising arises from shared, ancestral biological mechanisms that prioritize social information. To test this idea, we asked whether rhesus macaques (Macaca mulatta) show choice behavior that is similar to humans in response to sex and social status in advertising. Our results show that monkeys form preferences for brand logos repeatedly paired with images of macaque genitals and high status monkeys. Moreover, monkeys sustain preferences for these brand logos even though choosing them provided no tangible rewards, a finding that cannot be explained by a decision mechanism operating solely on material outcomes. Together, our results endorse the hypothesis that the power of sex and status in advertising emerges from the spontaneous engagement of shared, ancestral neural circuits that prioritize information useful for navigating the social environment. Finally, our results show that simple associative conditioning is sufficient to explain the formation of preferences for brand logos paired with sexual or status-based images.

  11. 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.

  12. 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.

  13. 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.

  14. Use of photogrammetry as a means to assess hybrids of rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques.

    Science.gov (United States)

    Jadejaroen, Janya; Hamada, Yuzuru; Kawamoto, Yoshi; Malaivijitnond, Suchinda

    2015-01-01

    Rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques are the most commonly used non-human primate models for biomedical research, but it is difficult to identify these two species in the hybrid zone (15-20°N). In this work, we used morphological values obtained via photogrammetry to assess hybrids of rhesus and long-tailed macaques at Khao Khieow Open Zoo (KKZ; 13°21'N, 101°06'E), eastern Thailand. Long-tailed and rhesus macaques have species-specific tail lengths and contrasts of their yellowish pelages. The accuracy and precision of the relative tail length (%RTL) and the contrast of the yellow hue (Cb*) of the pelage, as obtained from photographs, were compared with the corresponding direct measurements (morphometrics). The photogrammetric and morphometric measurements of %RTL and Cb* were highly significantly correlated (r = 0.989 and 0.980, p photogrammetry can be utilized to identify macaque species or hybrids when species identification relies mainly on tail length and pelage color.

  15. 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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

    Science.gov (United States)

    Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

    2013-07-19

    HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  17. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

    Directory of Open Access Journals (Sweden)

    Roger Le Grand

    2013-07-01

    Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

  18. Inter-Group Variation in Non-Conceptive Sexual Activity in Female Japanese Macaques: Could it be Cultural?

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Leca

    2014-08-01

    Full Text Available We compared two non-conceptive sexual behavioral patterns (female-male mounting – FMM – and female-female mounting – FFM across four free-ranging groups of Japanese macaques (Macaca fuscata living at three different field sites in Japan (Arashiyama, Minoo, and Jigokudani. We found marked inter-group differences and covariation in the frequency and form of FMM and FFM. This result supports the view that FMM and FFM in Japanese macaques are developmentally and evolutionarily linked. The customary occurrence, high prevalence, and great diversity of FMM and FFM at Arashiyama may be the result of combined favorable socio-demographic conditions, namely few resident males, most of them being old, sexually under-motivated, and less aggressive and controlling than the average male Japanese macaques. We suggest that FMM and FFM may be cultural sexual practices in the Arashiyama-E group. In most other populations, all the aforementioned favorable socio-demographic conditions are not met, and although female mounting may occasionally be expressed by several group members, it does not reach the group-level tradition status. Our cultural interpretation of female mounting in Japanese macaques is consistent with evidence of the social transmission of courtship behaviors and mating preferences in various animal taxa, including nonhuman primates and humans. Our study may have implications for the evolution of non-conceptive sexuality in humans, including sexual fluidity in women.

  19. Normal foot and ankle

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    The foot may be thought of as a bag of bones tied tightly together and functioning as a unit. The bones re expected to maintain their alignment without causing symptomatology to the patient. The author discusses a normal radiograph. The bones must have normal shape and normal alignment. The density of the soft tissues should be normal and there should be no fractures, tumors, or foreign bodies

  20. Revealing Rembrandt

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    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  1. 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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

  3. Magnetic resonance imaging-based cerebral tissue classification reveals distinct spatiotemporal patterns of changes after stroke in non-human primates.

    Science.gov (United States)

    Bouts, Mark J R J; Westmoreland, Susan V; de Crespigny, Alex J; Liu, Yutong; Vangel, Mark; Dijkhuizen, Rick M; Wu, Ona; D'Arceuil, Helen E

    2015-12-15

    Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.

  4. Anomalous normal mode oscillations in semiconductor microcavities

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H. [Univ. of Oregon, Eugene, OR (United States). Dept. of Physics; Hou, H.Q.; Hammons, B.E. [Sandia National Labs., Albuquerque, NM (United States)

    1997-04-01

    Semiconductor microcavities as a composite exciton-cavity system can be characterized by two normal modes. Under an impulsive excitation by a short laser pulse, optical polarizations associated with the two normal modes have a {pi} phase difference. The total induced optical polarization is then expected to exhibit a sin{sup 2}({Omega}t)-like oscillation where 2{Omega} is the normal mode splitting, reflecting a coherent energy exchange between the exciton and cavity. In this paper the authors present experimental studies of normal mode oscillations using three-pulse transient four wave mixing (FWM). The result reveals surprisingly that when the cavity is tuned far below the exciton resonance, normal mode oscillation in the polarization is cos{sup 2}({Omega}t)-like, in contrast to what is expected form the simple normal mode model. This anomalous normal mode oscillation reflects the important role of virtual excitation of electronic states in semiconductor microcavities.

  5. A genetically engineered live-attenuated simian-human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques

    International Nuclear Information System (INIS)

    Shimizu, Yuya; Inaba, Katsuhisa; Kaneyasu, Kentaro; Ibuki, Kentaro; Himeno, Ai; Okoba, Masashi; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi

    2007-01-01

    Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper (Th) type-1 responses against HIV-1. To evaluate the adjuvant effects of RANTES against HIV vaccine candidate in SHIV-macaque models, we genetically engineered a live-attenuated SHIV to express the RANTES gene (SHIV-RANTES) and characterized the virus's properties in vivo. After the vaccination, the plasma viral loads were same in the SHIV-RANTES-inoculated monkeys and the parental nef-deleted SHIV (SHIV-NI)-inoculated monkeys. SHIV-RANTES provided some immunity in monkeys by remarkably increasing the antigen-specific CD4 + Th cell-proliferative response and by inducing an antigen-specific IFN-γ ELISpot response. The magnitude of the immunity in SHIV-RANTES-immunized animals, however, failed to afford greater protection against a heterologous pathogenic SHIV (SHIV-C2/1) challenge compared to control SHIV-NI-immunized animals. SHIV-RANTES immunized monkeys, elicited robust cellular CD4 + Th responses and IFN-γ ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4 + T cell responses

  6. 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

  7. Chemical composition of axillary odorants reflects social and individual attributes in rhesus macaques.

    Science.gov (United States)

    Weiß, Brigitte M; Kücklich, Marlen; Thomsen, Ruth; Henkel, Stefanie; Jänig, Susann; Kulik, Lars; Birkemeyer, Claudia; Widdig, Anja

    2018-01-01

    Scents play an important role in the life of most terrestrial mammals and may transmit valuable information about conspecifics. Olfaction was long considered of low importance in Old World monkeys due to their relative reduction of olfactory structures and low incidence of scent-marking behavior but has been increasingly recognized for mediating social relationships in recent years. Yet, studies investigating the composition of their chemical cues remain scarce. In the present study, we analyzed the potential information content of chemicals present on the skin of rhesus macaques ( Macaca mulatta ). We collected axillary secretions from 60 animals of the semifree-ranging population on Cayo Santiago (Puerto Rico, USA) with precleaned cotton swabs from which the secretions were subsequently extracted and analyzed by gas chromatography-mass spectrometry. Rhesus macaque axillary odorants varied in their overall similarity and composition. This variation was attributable to differences in sex, group membership, and kinship and further appeared to reflect age and rank in parts of our sample. The compounds most strongly associated with this variation primarily comprised larger molecular weight aldehydes and steroids. Such compounds are considered to be perceivable by the primate olfactory system through close-range interactions or through breakdown into smaller molecules by bacterial fermentation. Overall, our results provide additional evidence that odors of Old World monkeys reflect a wealth of potential information about their carrier, which provides the basis for chemical communication via body odors; however, its use by conspecifics needs to be confirmed in bioassays. One prerequisite for olfactory communication is the presence of systematic variation in animal odors that is related to attributes such as age, sex, or kinship. The composition of odors has been examined in numerous mammals but, with the exception of humans, remains poorly understood in Old World

  8. Isolation of a monoclonal antibody from a phage display library binding the rhesus macaque MHC class I allomorph Mamu-A1*001.

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    Nathan Holman

    Full Text Available Monoclonal antibodies that bind to human leukocyte antigen (HLA are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001. We induced Mamu-A1*001-binding antibodies by alloimmunizing a female Mamu-A1*001-negative rhesus macaque with peripheral blood mononuclear cells (PBMC from a male Mamu-A1*001-positive donor. A Fab phage display library was constructed with PBMC from the alloimmunized macaque and panned to isolate an antibody that binds to Mamu-A1*001 but not to other common rhesus macaque MHC class I molecules. The isolated antibody distinguishes PBMC from Mamu-A1*001-positive and -negative macaques. Additionally, the Mamu-A1*001-specific antibody binds the cynomolgus macaque MHC class I ortholog Mafa-A1*001:01 but not variants Mafa-A1*001:02/03, indicating a high degree of binding specificity. The Mamu-A1*001-specific antibody will be useful for identifying Mamu-A1*001-positive rhesus macaques, for detecting Mamu-A1*001-positive cells in populations of Mamu-A1*001-negative cells, and for examining disease processes that alter expression of Mamu-A1*001 on cell surfaces. Moreover, the alloimmunization process we describe will be useful for isolating additional MHC allomorph-specific monoclonal antibodies or antibodies against other polymorphic host proteins which are difficult to isolate with traditional technologies.

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

    International Nuclear Information System (INIS)

    Feng, Youjun; Qi, Jianxun; Zhang, Huimin; Wang, Jinzi; Liu, Jinhua; Jiang, Fan; Gao, Feng

    2005-01-01

    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 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-01-01

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

  11. Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges

    Directory of Open Access Journals (Sweden)

    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. Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

    Science.gov (United States)

    Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa

    2016-12-01

    H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  13. Perturbations de l'homéostasie lymphocytaire T chez le macaque rhésus chinois en phase aiguë d'infection par le SIVmac251

    OpenAIRE

    Ponte, Rosalie

    2014-01-01

    As a model to study type 1 human immunodeficiency virus (HIV-1) pathogenesis, rhesus macaques infected with the simian immunodeficiency virus (SIV) are under extensive investigation. Two subspecies of rhesus macaques have been defined, based on a different geographic origin. Indian rhesus macaques exhibit a rapid disease progression and acute infection is characterized by a massive CD4 T-cell loss in the intestinal mucosa. This was associated to the translocation of bacterial products through...

  14. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

    Science.gov (United States)

    Johnston, Sara C.; Lin, Kenny L.; Twenhafel, Nancy A.; Raymond, Jo Lynne W.; Shamblin, Joshua D.; Wollen, Suzanne E.; Wlazlowski, Carly B.; Wilkinson, Eric R.; Botto, Miriam A.; Goff, Arthur J.

    2015-01-01

    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. PMID:26413900

  15. Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain.

    Science.gov (United States)

    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.

  16. Online Adaptation and Over-Trial Learning in Macaque Visuomotor Control

    Science.gov (United States)

    Braun, Daniel A.; Aertsen, Ad; Paz, Rony; Vaadia, Eilon; Rotter, Stefan; Mehring, Carsten

    2011-01-01

    When faced with unpredictable environments, the human motor system has been shown to develop optimized adaptation strategies that allow for online adaptation during the control process. Such online adaptation is to be contrasted to slower over-trial learning that corresponds to a trial-by-trial update of the movement plan. Here we investigate the interplay of both processes, i.e., online adaptation and over-trial learning, in a visuomotor experiment performed by macaques. We show that simple non-adaptive control schemes fail to perform in this task, but that a previously suggested adaptive optimal feedback control model can explain the observed behavior. We also show that over-trial learning as seen in learning and aftereffect curves can be explained by learning in a radial basis function network. Our results suggest that both the process of over-trial learning and the process of online adaptation are crucial to understand visuomotor learning. PMID:21720526

  17. Applicability of Non-Invasive Sampling in Population Genetic Study of Taiwanese Macaques (Macaca cyclopis

    Directory of Open Access Journals (Sweden)

    Jui-Hua Chu

    2006-12-01

    Full Text Available This paper presents a pilot study conducted to test the applicability of non-invasive sampling approach in population genetic studies of Taiwanese macaques (Macaca cyclopis. Monkey feces were collected in the field and used as non-invasive DNA sources. PCR success rates of both microsatellite and mitochondrial DNA markers were examined. When compared with other studies by non-invasive genetic sampling of different mammal species, success rate of microsatellite PCR amplification is low (42.4%, N = 181 while that of mtDNA PCR amplification is acceptable (66.5%, N = 334. The low PCR success rate and poor PCR repeatability of microsatellite alleles due to allelic dropout and false alleles make it difficult to obtain a reliable microsatellite data set. However, the difficulties may be overcome by new techniques.

  18. Modeling vocalization with ECoG cortical activity recorded during vocal production in the macaque monkey.

    Science.gov (United States)

    Fukushima, Makoto; Saunders, Richard C; Fujii, Naotaka; Averbeck, Bruno B; Mishkin, Mortimer

    2014-01-01

    Vocal production is an example of controlled motor behavior with high temporal precision. Previous studies have decoded auditory evoked cortical activity while monkeys listened to vocalization sounds. On the other hand, there have been few attempts at decoding motor cortical activity during vocal production. Here we recorded cortical activity during vocal production in the macaque with a chronically implanted electrocorticographic (ECoG) electrode array. The array detected robust activity in motor cortex during vocal production. We used a nonlinear dynamical model of the vocal organ to reduce the dimensionality of `Coo' calls produced by the monkey. We then used linear regression to evaluate the information in motor cortical activity for this reduced representation of calls. This simple linear model accounted for circa 65% of the variance in the reduced sound representations, supporting the feasibility of using the dynamical model of the vocal organ for decoding motor cortical activity during vocal production.

  19. Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque.

    Science.gov (United States)

    Fukushima, Makoto; Saunders, Richard C; Leopold, David A; Mishkin, Mortimer; Averbeck, Bruno B

    2012-06-07

    In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. A multidisciplinary view on cultural primatology: behavioral innovations and traditions in Japanese macaques.

    Science.gov (United States)

    Leca, Jean-Baptiste; Gunst, Noëlle; Pelletier, Amanda N; Vasey, Paul L; Nahallage, Charmalie A D; Watanabe, Kunio; Huffman, Michael A

    2016-07-01

    Cultural primatology (i.e., the study of behavioral traditions in nonhuman primates as a window into the evolution of human cultural capacities) was founded in Japan by Kinji Imanishi in the early 1950s. This relatively new research area straddles different disciplines and now benefits from collaborations between Japanese and Western primatologists. In this paper, we return to the cradle of cultural primatology by revisiting our original articles on behavioral innovations and traditions in Japanese macaques. For the past 35 years, our international team of biologists, psychologists and anthropologists from Japan, France, Sri Lanka, the USA and Canada, has been taking an integrative approach to addressing the influence of environmental, sociodemographic, developmental, cognitive and behavioral constraints on the appearance, diffusion, and maintenance of behavioral traditions in Macaca fuscata across various domains; namely, feeding innovation, tool use, object play, and non-conceptive sex.

  1. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

    Directory of Open Access Journals (Sweden)

    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.

  2. Functional MRI of the vocalization-processing network in the macaque brain

    Directory of Open Access Journals (Sweden)

    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.

  3. Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA

    International Nuclear Information System (INIS)

    Buckley, Kathleen A.; Li Peilin; Khimani, Anis H.; Hofmann-Lehmann, Regina; Liska, Vladimir; Anderson, Daniel C.; McClure, Harold M.; Ruprecht, Ruth M.

    2003-01-01

    The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVΔ3 (the live attenuated vaccine strain derived from SIVmac239), or SIVΔ3+ (a pathogenic progeny virus that had evolved from SIVΔ3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVΔ3, and SIVΔ3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression

  4. Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.

    Directory of Open Access Journals (Sweden)

    Chia-Chyi Liu

    Full Text Available Enterovirus 71 (EV71 has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-γ and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.

  5. Baby Poop: What's Normal?

    Science.gov (United States)

    ... I'm breast-feeding my newborn and her bowel movements are yellow and mushy. Is this normal for baby poop? Answers from Jay L. Hoecker, M.D. Yellow, mushy bowel movements are perfectly normal for breast-fed babies. Still, ...

  6. Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

    Science.gov (United States)

    Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

    2009-08-01

    There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

  7. Temporally evolving gain mechanisms of attention in macaque area V4.

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    Sani, Ilaria; Santandrea, Elisa; Morrone, Maria Concetta; Chelazzi, Leonardo

    2017-08-01

    Cognitive attention and perceptual saliency jointly govern our interaction with the environment. Yet, we still lack a universally accepted account of the interplay between attention and luminance contrast, a fundamental dimension of saliency. We measured the attentional modulation of V4 neurons' contrast response functions (CRFs) in awake, behaving macaque monkeys and applied a new approach that emphasizes the temporal dynamics of cell responses. We found that attention modulates CRFs via different gain mechanisms during subsequent epochs of visually driven activity: an early contrast-gain, strongly dependent on prestimulus activity changes (baseline shift); a time-limited stimulus-dependent multiplicative modulation, reaching its maximal expression around 150 ms after stimulus onset; and a late resurgence of contrast-gain modulation. Attention produced comparable time-dependent attentional gain changes on cells heterogeneously coding contrast, supporting the notion that the same circuits mediate attention mechanisms in V4 regardless of the form of contrast selectivity expressed by the given neuron. Surprisingly, attention was also sometimes capable of inducing radical transformations in the shape of CRFs. These findings offer important insights into the mechanisms that underlie contrast coding and attention in primate visual cortex and a new perspective on their interplay, one in which time becomes a fundamental factor. NEW & NOTEWORTHY We offer an innovative perspective on the interplay between attention and luminance contrast in macaque area V4, one in which time becomes a fundamental factor. We place emphasis on the temporal dynamics of attentional effects, pioneering the notion that attention modulates contrast response functions of V4 neurons via the sequential engagement of distinct gain mechanisms. These findings advance understanding of attentional influences on visual processing and help reconcile divergent results in the literature. Copyright © 2017 the

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

    International Nuclear Information System (INIS)

    Herring, M.J.; Putney, L.F.; St George, J.A.; Avdalovic, M.V.; Schelegle, E.S.; Miller, L.A.; Hyde, D.M.

    2015-01-01

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

  9. MIV-150-containing intravaginal rings protect macaque vaginal explants against SHIV-RT infection.

    Science.gov (United States)

    Ouattara, Louise A; Barnable, Patrick; Mawson, Paul; Seidor, Samantha; Zydowsky, Thomas M; Kizima, Larisa; Rodriguez, Aixa; Fernández-Romero, José A; Cooney, Michael L; Roberts, Kevin D; Gettie, Agegnehu; Blanchard, James; Robbiani, Melissa; Teleshova, Natalia

    2014-05-01

    Recent studies demonstrated that intravaginal rings (IVRs) containing 100 mg of the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 significantly protect macaques against a chimeric simian-human immunodeficiency virus that expresses the HIV-1 HxB2 reverse transcriptase (SHIV-RT) when present before and after vaginal challenge. The objectives of this study were to (i) evaluate the pharmacodynamics (PD) of MIV-150 in vaginal fluids (VF) and in ectocervical and vaginal tissues following 100-mg MIV-150 IVR exposure and to (ii) gain more insight whether pharmacokinetics (PK) of MIV-150 can predict PD. MIV-150 in VF collected at 1 day and 14 days post-MIV-150 IVR insertion inhibited ex vivo SHIV-RT infection in vaginal biopsy specimens from untreated animals (not carrying IVRs) in a dose-dependent manner. Previous PK studies demonstrated a significant increase of ectocervical and vaginal tissue MIV-150 concentrations 14 days versus 1 day post-IVR insertion, with the highest increase in vaginal tissue. Therefore, we tested PD of MIV-150 in tissues 14 days post-MIV-150 IVR insertion. Ex vivo SHIV-RT infection of vaginal, but not ectocervical, tissues collected 14 days post-MIV-150 IVR insertion was significantly inhibited compared to infection at the baseline (prior to MIV-150 IVR exposure). No changes in vaginal and ectocervical tissue infection were observed after placebo IVR exposure. Overall, these data underscore the use of the ex vivo macaque explant challenge models to evaluate tissue and VF PK/PD of candidate microbicides before in vivo animal efficacy studies. The data support further development of MIV-150-containing IVRs.

  10. Network stability is a balancing act of personality, power, and conflict dynamics in rhesus macaque societies.

    Science.gov (United States)

    McCowan, Brenda; Beisner, Brianne A; Capitanio, John P; Jackson, Megan E; Cameron, Ashley N; Seil, Shannon; Atwill, Edward R; Fushing, Hsieh

    2011-01-01

    Stability in biological systems requires evolved mechanisms that promote robustness. Cohesive primate social groups represent one example of a stable biological system, which persist in spite of frequent conflict. Multiple sources of stability likely exist for any biological system and such robustness, or lack thereof, should be reflected and thus detectable in the group's network structure, and likely at multiple levels. Here we show how network structure and group stability are linked to the fundamental characteristics of the individual agents in groups and to the environmental and social contexts in which these individuals interact. Both internal factors (e.g., personality, sex) and external factors (e.g., rank dynamics, sex ratio) were considered from the level of the individual to that of the group to examine the effects of network structure on group stability in a nonhuman primate species. The results yielded three main findings. First, successful third-party intervention behavior is a mechanism of group stability in rhesus macaques in that successful interventions resulted in less wounding in social groups. Second, personality is the primary factor that determines which individuals perform the role of key intervener, via its effect on social power and dominance discrepancy. Finally, individuals with high social power are not only key interveners but also key players in grooming networks and receive reconciliations from a higher diversity of individuals. The results from this study provide sound evidence that individual and group characteristics such as personality and sex ratio influence network structures such as patterns of reconciliation, grooming and conflict intervention that are indicators of network robustness and consequent health and well-being in rhesus macaque societies. Utilizing this network approach has provided greater insight into how behavioral and social processes influence social stability in nonhuman primate groups.

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

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    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.

  12. Network stability is a balancing act of personality, power, and conflict dynamics in rhesus macaque societies.

    Directory of Open Access Journals (Sweden)

    Brenda McCowan

    Full Text Available Stability in biological systems requires evolved mechanisms that promote robustness. Cohesive primate social groups represent one example of a stable biological system, which persist in spite of frequent conflict. Multiple sources of stability likely exist for any biological system and such robustness, or lack thereof, should be reflected and thus detectable in the group's network structure, and likely at multiple levels. Here we show how network structure and group stability are linked to the fundamental characteristics of the individual agents in groups and to the environmental and social contexts in which these individuals interact. Both internal factors (e.g., personality, sex and external factors (e.g., rank dynamics, sex ratio were considered from the level of the individual to that of the group to examine the effects of network structure on group stability in a nonhuman primate species. The results yielded three main findings. First, successful third-party intervention behavior is a mechanism of group stability in rhesus macaques in that successful interventions resulted in less wounding in social groups. Second, personality is the primary factor that determines which individuals perform the role of key intervener, via its effect on social power and dominance discrepancy. Finally, individuals with high social power are not only key interveners but also key players in grooming networks and receive reconciliations from a higher diversity of individuals. The results from this study provide sound evidence that individual and group characteristics such as personality and sex ratio influence network structures such as patterns of reconciliation, grooming and conflict intervention that are indicators of network robustness and consequent health and well-being in rhesus macaque societies. Utilizing this network approach has provided greater insight into how behavioral and social processes influence social stability in nonhuman primate groups.

  13. 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. © 2013 Wiley Periodicals, Inc.

  14. 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.

  15. Lutein Is Differentially Deposited across Brain Regions following Formula or Breast Feeding of Infant Rhesus Macaques.

    Science.gov (United States)

    Jeon, Sookyoung; Ranard, Katherine M; Neuringer, Martha; Johnson, Emily E; Renner, Lauren; Kuchan, Matthew J; Pereira, Suzette L; Johnson, Elizabeth J; Erdman, John W

    2018-01-01

    Lutein, a yellow xanthophyll, selectively accumulates in primate retina and brain. Lutein may play a critical role in neural and retinal development, but few studies have investigated the impact of dietary source on its bioaccumulation in infants. We explored the bioaccumulation of lutein in infant rhesus macaques following breastfeeding or formula-feeding. From birth to 6 mo of age, male and female rhesus macaques (Macaca mulatta) were either breastfed (BF) (n = 8), fed a formula supplemented with lutein, zeaxanthin, β-carotene, and lycopene (237, 19.0, 74.2, and 338 nmol/kg, supplemented formula-fed; SF) (n = 8), or fed a formula with low amounts of these carotenoids (38.6, 2.3, 21.5, and 0 nmol/kg, unsupplemented formula-fed; UF) (n = 7). The concentrations of carotenoids in serum and tissues were analyzed by HPLC. At 6 mo of age, the BF group exhibited significantly higher lutein concentrations in serum, all brain regions, macular and peripheral retina, adipose tissue, liver, and other tissues compared to both formula-fed groups (P Lutein concentrations were higher in the SF group than in the UF group in serum and all tissues, with the exception of macular retina. Lutein was differentially distributed across brain areas, with the highest concentrations in the occipital cortex, regardless of the diet. Zeaxanthin was present in all brain regions but only in the BF infants; it was present in both retinal regions in all groups but was significantly enhanced in BF infants compared to either formula group (P lutein concentrations compared to unsupplemented formula, concentrations were still well below those in BF infants. Regardless of diet, occipital cortex showed selectively higher lutein deposition than other brain regions, suggesting lutein's role in visual processing in early life. © 2018 American Society for Nutrition. All rights reserved.

  16. Characterization of Cardiac Time Intervals in Healthy Bonnet Macaques (Macaca radiata) by Using an Electronic Stethoscope

    Science.gov (United States)

    Kamran, Haroon; Salciccioli, Louis; Pushilin, Sergei; Kumar, Paraag; Carter, John; Kuo, John; Novotney, Carol; Lazar, Jason M

    2011-01-01

    Nonhuman primates are used frequently in cardiovascular research. Cardiac time intervals derived by phonocardiography have long been used to assess left ventricular function. Electronic stethoscopes are simple low-cost systems that display heart sound signals. We assessed the use of an electronic stethoscope to measure cardiac time intervals in 48 healthy bonnet macaques (age, 8 ± 5 y) based on recorded heart sounds. Technically adequate recordings were obtained from all animals and required 1.5 ± 1.3 min. The following cardiac time intervals were determined by simultaneously recording acoustic and single-lead electrocardiographic data: electromechanical activation time (QS1), electromechanical systole (QS2), the time interval between the first and second heart sounds (S1S2), and the time interval between the second and first sounds (S2S1). QS2 was correlated with heart rate, mean arterial pressure, diastolic blood pressure, and left ventricular ejection time determined by using echocardiography. S1S2 correlated with heart rate, mean arterial pressure, diastolic blood pressure, left ventricular ejection time, and age. S2S1 correlated with heart rate, mean arterial pressure, diastolic blood pressure, systolic blood pressure, and left ventricular ejection time. QS1 did not correlate with any anthropometric or echocardiographic parameter. The relation S1S2/S2S1 correlated with systolic blood pressure. On multivariate analyses, heart rate was the only independent predictor of QS2, S1S2, and S2S1. In conclusion, determination of cardiac time intervals is feasible and reproducible by using an electrical stethoscope in nonhuman primates. Heart rate is a major determinant of QS2, S1S2, and S2S1 but not QS1; regression equations for reference values for cardiac time intervals in bonnet macaques are provided. PMID:21439218

  17. Macaque accessory optic system: I. Definition of the medial terminal nucleus

    International Nuclear Information System (INIS)

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

    1990-01-01

    The organization of the accessory optic system (AOS) has been studied in the macaque monkey following intravitreal injections of tritiated amino acids in one eye. Retinal projections to the dorsal (DTN) and the lateral (LTN) terminal nuclei are identical to those previously described in other primate species. We observed an additional group of retinorecipient cells of the AOS, located between the cerebral peduncle and the substantia nigra, which we define as the interstitial nucleus of the superior fasiculus, medial fibers. In this report, we focus our attention on the medial terminal nucleus (MTN). Although a ventral division of this nucleus (MTNv) was not observed in the macaque, the retina projects to a group of cells in the midbrain reticular formation (MRF), which we argue to be homologous to the dorsal division of the MTN (MTNd). To provide evidence in support of this homology, the retinal projection to the MTNv and MTNd was also examined in 21 additional species from 11 orders of mammals including carnivores, marsupials, lagomorphs, rodents, bats, insectivores, tree shrews, hyraxes, pholidotes, edentates, and five additional species of primates. Whereas the retina projects to both ventral and dorsal divisions in all species studied, in haplorhine primates only the projection to the MTNd is conserved. The relative topological position of the MTNd in the MRF, dorsomedial to the substantia nigra and ventrolateral to the red nucleus, remains constant throughout the mammals. The trajectory of fiber paths innervating the MTNd is also similar in all species. In addition, the MTNd has comparable afferent and efferent connections with retina, pretectum, and vestibular nuclei in all species thus far studied. These results support the unequivocal conclusion that the MTNd is an unvarying feature of the mammalian AOS

  18. Effect of feature-selective attention on neuronal responses in macaque area MT

    Science.gov (United States)

    Chen, X.; Hoffmann, K.-P.; Albright, T. D.

    2012-01-01

    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). PMID:22170961

  19. 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.

  20. Model-observer similarity, error modeling and social learning in rhesus macaques.

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    Elisabetta Monfardini

    Full Text Available 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.

  1. Development of sexual behavior in free-ranging female Japanese macaques.

    Science.gov (United States)

    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. © 2014 Wiley Periodicals, Inc.

  2. Does the Structure of Female Rhesus Macaque Coo Calls Reflect Relatedness and/or Familiarity?

    Directory of Open Access Journals (Sweden)

    Dana Pfefferle

    Full Text Available In social animals, kin relations strongly shape the social structure of a group. In female-bonded species, maternal relatedness is likely to be mediated via familiarity, but evidence is accumulating that non-human primates are able to recognize kin that they are not familiar with and adjust their behavior accordingly. In playback experiments, female rhesus macaques showed increased interest in 'coo' calls produced by unfamiliar paternal half-sisters compared to 'coo' calls produced by unfamiliar unrelated females, suggesting that these calls should have some common structural characteristics that facilitate the discrimination of kin from non-kin. Here we analyzed 'coo' calls of 67 adult female rhesus macaques from four groups and seven matrilines living on the island of Cayo Santiago (Puerto Rico. We tested whether the call structure of closely maternal and/or paternal related females, as determined from extensive pedigree data, differed from the call structure of unrelated females, while controlling for familiarity (i.e., group-matrilineal membership and age difference of subjects. In contrast to our expectation, kinship did not predict similarities in 'coo' call structure, whereas 'coo' structure was more similar when produced by females of similar age as well as by females with higher familiarity, suggesting that experience is more decisive than genetic background. The high number of individuals in the analysis and the high accuracy of the assignment of calls to individuals render a lack of power as an unlikely explanation. Thus, based on the results of this study, kin recognition in rhesus monkeys does neither appear to be based on the assessment of self-similarity, nor on the comparison among related subjects (i.e., acoustic phenotype matching, but appears to be mediated by different or multiple cues. Furthermore, the results support the notion that frequent social interactions result in increasing acoustic similarity within largely innate

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-15

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

  4. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mark Asquith

    2012-06-01

    Full Text Available Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i innate immune cell frequencies; (ii expression of pattern recognition receptors (PRRs and innate signaling molecules; (iii cytokine responses of monocytes and dendritic cells (DC following stimulation with PRR agonists; and (iv plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC. Moreover, we found toll-like receptor (TLR agonists lipopolysaccharide (TLR4, fibroblast stimulating ligand-1 (TLR2/6, and ODN2006 (TLR7/9 induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM, were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.

  5. Whom to groom and for what? Patterns of grooming in female Barbary macaques (Macaca sylvanus).

    Science.gov (United States)

    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.

  6. Making nuclear 'normal'

    International Nuclear Information System (INIS)

    Haehlen, Peter; Elmiger, Bruno

    2000-01-01

    The mechanics of the Swiss NPPs' 'come and see' programme 1995-1999 were illustrated in our contributions to all PIME workshops since 1996. Now, after four annual 'waves', all the country has been covered by the NPPs' invitation to dialogue. This makes PIME 2000 the right time to shed some light on one particular objective of this initiative: making nuclear 'normal'. The principal aim of the 'come and see' programme, namely to give the Swiss NPPs 'a voice of their own' by the end of the nuclear moratorium 1990-2000, has clearly been attained and was commented on during earlier PIMEs. It is, however, equally important that Swiss nuclear energy not only made progress in terms of public 'presence', but also in terms of being perceived as a normal part of industry, as a normal branch of the economy. The message that Swiss nuclear energy is nothing but a normal business involving normal people, was stressed by several components of the multi-prong campaign: - The speakers in the TV ads were real - 'normal' - visitors' guides and not actors; - The testimonials in the print ads were all real NPP visitors - 'normal' people - and not models; - The mailings inviting a very large number of associations to 'come and see' activated a typical channel of 'normal' Swiss social life; - Spending money on ads (a new activity for Swiss NPPs) appears to have resulted in being perceived by the media as a normal branch of the economy. Today we feel that the 'normality' message has well been received by the media. In the controversy dealing with antinuclear arguments brought forward by environmental organisations journalists nowadays as a rule give nuclear energy a voice - a normal right to be heard. As in a 'normal' controversy, the media again actively ask themselves questions about specific antinuclear claims, much more than before 1990 when the moratorium started. The result is that in many cases such arguments are discarded by journalists, because they are, e.g., found to be

  7. The in vitro protection of human decay accelerating factor and hDAF/heme oxygenase-1 transgenes in porcine aortic endothelial cells against sera of Formosan macaques.

    Science.gov (United States)

    Tu, C-F; Tai, H-C; Wu, C-P; Ho, L-L; Lin, Y-J; Hwang, C-S; Yang, T-S; Lee, J-M; Tseng, Y-L; Huang, C-C; Weng, C-N; Lee, P-H

    2010-01-01

    To mitigate hyperacute rejection, pigs have been generated with alpha-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC), an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15% MS reduced survived to 40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However, comparing with 10% MS and HS in pAEC of nontransgenic pigs, the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

    Science.gov (United States)

    Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

    2015-09-01

    Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion

  9. Anti emetic effect of 5HT3 receptor antagonists in macaques exposed to a neutron-gamma radiation; Effet antiemetique d`antiserotoninergiques de type 3 chez le macaque soumis a une irradiation neutron-gamma

    Energy Technology Data Exchange (ETDEWEB)

    Agay, D.; Martin, C.; Martin, S.; Roman, V.; Fatome, M.

    1994-12-31

    Ondansetron and granisetron were tested as antiemetics in cynomolgus macaques weighing 4 kg and submitted to a neutron-gamma irradiation with a high neutronic component. Compounds were delivered by oral way, each administration dose being 4 mg of ondansetron or 1 mg of granisetron. The effect was complete when were delivered before and after the irradiation. It was incomplete when there was a single administration be fore or after the exposure. No adverse side-effects were noted. (author). 4 refs.

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

    Directory of Open Access Journals (Sweden)

    Viraj Kulkarni

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

  11. Gene therapy strategy to reduced bone marrow aplasia: evaluation in cynomolgus macaque exposed to a gamma total body irradiation

    International Nuclear Information System (INIS)

    Becard, N.

    2003-01-01

    The aim of this work was to assess whether direct intra-marrow injection of an adeno-viral vector expressing human IL-1α gene stimulates hematopoiesis in healthy non-irradiated and gamma irradiated cynomolgus macaques. In the first hand, we have evaluated the feasibility of this gene therapy strategy in two healthy non-irradiated macaques. In this work, we have observed an increase of neutrophil, monocyte and platelets in the two animals treated with the therapeutic construct. This effect was associated with no abnormal clinical side effect. On the other hand, we have evaluated this strategy in non-human primate exposed to a sublethal gamma irradiation. Two of three animals treated by the therapeutic construct reduced significantly the neutropenia, thrombocytopenia and anemia radio-induced. In conclusion, this gene therapy strategy gave a similar clinical benefit comparatively to systemic administration of huIL-1α but without severe side effect. (author) [fr

  12. [Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer].

    Science.gov (United States)

    Qin, Zu-Xing; Huang, Gao-Bo; Luo, Jun; Ning, Shu-Fang; Lu, Sheng-Sheng; Lu, Ke-Huan

    2012-03-01

    Long-tailed macaque-pig interspecies somatic cell nuclear transfer (iSCNT) is beneficial to yield embryonic stem cells from iSCNT embryos with similar genetic background as human, which can be used as materials for medical and basic research. The primary objective of this study was to investigate the effects of concentrations and treatment duration of two histone deacetylase inhibitors-Trichostatin A (TSA) and Valproic acid (VPA) and two different embryo culture media (PZM-3 and HECM-10) on the in vitro development of iSCNT embryos. The results suggested that when PZM-3 was used as the embryo culture medium, the blastocyst rate of 10 nmol/L TSA treatment for 48 h was significantly higher than the control group (22.78% vs 9.86%, PTSA treatment could enhance the in vitro developmental potential of long-tailed macaque-pig iSCNT embryos.

  13. Computed tomography or necropsy diagnosis of multiple bullae and the treatment of pneumothorax in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Kim, Jong-Min; Han, Sungyoung; Shin, Jun-Seop; Min, Byoung-Hoon; Jeong, Won Young; Lee, Ga Eul; Kim, Min Sun; Kim, Ju Eun; Chung, Hyunwoo; Park, Chung-Gyu

    2017-10-01

    Pulmonary bullae and pneumothorax have various etiologies in veterinary medicine. We diagnosed multiple pulmonary bullae combined with or without pneumothorax by computed tomography (CT) or necropsy in seven rhesus macaques (Macaca mulatta) imported from China. Two of seven rhesus macaques accompanied by pneumothorax were cured by fixation of ruptured lung through left or right 3rd intercostal thoracotomy. Pneumonyssus simicola, one of the etiologies of pulmonary bullae, was not detected from tracheobronchiolar lavage. To the best of our knowledge, this is the first case report on the CT-aided diagnosis of pulmonary bullae and the successful treatment of combined pneumothorax by thoracotomy in non-human primates (NHPs). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Normal Pressure Hydrocephalus

    Science.gov (United States)

    ... improves the chance of a good recovery. Without treatment, symptoms may worsen and cause death. What research is being done? The NINDS conducts and supports research on neurological disorders, including normal pressure hydrocephalus. Research on disorders such ...

  15. Normality in Analytical Psychology

    Science.gov (United States)

    Myers, Steve

    2013-01-01

    Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity. PMID:25379262

  16. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  17. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  18. Normal growth and development

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002456.htm Normal growth and development To use the sharing features on this page, please enable JavaScript. A child's growth and development can be divided into four periods: ...

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

    Science.gov (United States)

    Vinson, Amanda; Prongay, Kamm; Ferguson, Betsy

    2013-01-01

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

  20. Metabolic changes in the visual cortex of binocular blindness macaque monkeys: a proton magnetic resonance spectroscopy study.

    Directory of Open Access Journals (Sweden)

    Lingjie Wu

    Full Text Available PURPOSE: To evaluate proton magnetic resonance spectroscopy ((1H-MRS in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys. MATERIALS AND METHODS: Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B to obtain binocular blindness. Two healthy macaque monkeys served as a control group (group A. After sixteen months post-procedure, (1H-MRS was performed in the visual cortex of all monkeys. We compared the peak areas of NAA, Cr, Cho, Glx and Ins and the ratios of NAA/Cr, Cho/Cr, Glx/Cr and Ins/Cr of each monkey in group B with group A. RESULTS: The peak area of NAA and the NAA/Cr ratio in the visual cortex of monkey 4 in group B were found to be dramatically decreased, the peak area of NAA slightly decreased and the NAA/Cr ratio clearly decreased in visual cortex of monkey 3 in group B than those in group A. The peak area of Ins and the Ins/Cr ratio in the visual cortex of monkey 4 in group B slightly increased. The peak area of Cho and the Cho/Cr ratio in the visual cortex of all monkeys in group B dramatically increased compared with group A. The peak area of Glx in the visual cortex of all monkeys in group B slightly increased compared with group A. CONCLUSIONS: (1H-MRS could detect biochemical and metabolic changes in the visual cortex and therefore this technique can be used to provide valuable information for investigating the mechanisms of cross-modal plasticity of binocular blindness in a macaque monkey model.

  1. Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Meropi Aravantinou

    2017-12-01

    Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

  2. Anti emetic effect of 5HT3 receptor antagonists in macaques exposed to a neutron-gamma radiation

    International Nuclear Information System (INIS)

    Agay, D.; Martin, C.; Martin, S.; Roman, V.; Fatome, M.

    1994-01-01

    Ondansetron and granisetron were tested as antiemetics in cynomolgus macaques weighing 4 kg and submitted to a neutron-gamma irradiation with a high neutronic component. Compounds were delivered by oral way, each administration dose being 4 mg of ondansetron or 1 mg of granisetron. The effect was complete when were delivered before and after the irradiation. It was incomplete when there was a single administration be fore or after the exposure. No adverse side-effects were noted. (author)

  3. Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

    Science.gov (United States)

    Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

    2017-11-13

    Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

  4. The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

    Science.gov (United States)

    Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

    2018-01-01

    Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average