A Method for Evaluating Tuning Functions of Single Neurons based on Mutual Information Maximization

NASA Astrophysics Data System (ADS)

Brostek, Lukas; Eggert, Thomas; Ono, Seiji; Mustari, Michael J.; Büttner, Ulrich; Glasauer, Stefan

2011-03-01

We introduce a novel approach for evaluation of neuronal tuning functions, which can be expressed by the conditional probability of observing a spike given any combination of independent variables. This probability can be estimated out of experimentally available data. By maximizing the mutual information between the probability distribution of the spike occurrence and that of the variables, the dependence of the spike on the input variables is maximized as well. We used this method to analyze the dependence of neuronal activity in cortical area MSTd on signals related to movement of the eye and retinal image movement.

Muscarinic acetylcholine receptors are expressed by most parvalbumin-immunoreactive neurons in area MT of the macaque.

PubMed

Disney, Anita A; Alasady, Hussein A; Reynolds, John H

2014-05-01

In the mammalian neocortex, cells that express parvalbumin (PV neurons) comprise a dominant class of inhibitory neuron that substantially overlaps with the fast/narrow-spiking physiological phenotype. Attention has pronounced effects on narrow-spiking neurons in the extrastriate cortex of macaques, and more consistently so than on their broad-spiking neighbors. Cortical neuromodulation by acetylcholine (ACh) is a candidate mechanism for aspects of attention and in the primary visual cortex (V1) of the macaque, receptors for ACh (AChRs) are strongly expressed by inhibitory neurons. In particular, most PV neurons in macaque V1 express m1 muscarinic AChRs and exogenously applied ACh can cause the release of γ-aminobutyric acid. In contrast, few PV neurons in rat V1 express m1 AChRs. While this could be a species difference, it has also been argued that macaque V1 is anatomically unique when compared with other cortical areas in macaques. The aim of this study was to better understand the extent to which V1 offers a suitable model circuit for cholinergic anatomy in the macaque occipital lobe, and to explore cholinergic modulation as a biological basis for the changes in circuit behavior seen with attention. We compared expression of m1 AChRs by PV neurons between area V1 and the middle temporal visual area (MT) in macaque monkeys using dual-immunofluorescence confocal microscopy. We find that, as in V1, most PV neurons in MT express m1 AChRs but, unlike in V1, it appears that so do most excitatory neurons. This provides support for V1 as a model of cholinergic modulation of inhibition in macaque visual cortex, but not of cholinergic modulation of visual cortical circuits in general. We also propose that ACh acting via m1 AChRs is a candidate underlying mechanism for the strong effects of attention on narrow-spiking neurons observed in behaving animals.

Alpha-beta and gamma rhythms subserve feedback and feedforward influences among human visual cortical areas

PubMed Central

Michalareas, Georgios; Vezoli, Julien; van Pelt, Stan; Schoffelen, Jan-Mathijs; Kennedy, Henry; Fries, Pascal

2016-01-01

Primate visual cortex is hierarchically organized. Bottom-up and top-down influences are exerted through distinct frequency channels, as was recently revealed in macaques by correlating inter-areal influences with laminar anatomical projection patterns. Because this anatomical data cannot be obtained in human subjects, we selected seven homologous macaque and human visual areas, and correlated the macaque laminar projection patterns to human inter-areal directed influences as measured with magnetoencephalography. We show that influences along feedforward projections predominate in the gamma band, whereas influences along feedback projections predominate in the alpha-beta band. Rhythmic inter-areal influences constrain a functional hierarchy of the seven homologous human visual areas that is in close agreement with the respective macaque anatomical hierarchy. Rhythmic influences allow an extension of the hierarchy to 26 human visual areas including uniquely human brain areas. Hierarchical levels of ventral and dorsal stream visual areas are differentially affected by inter-areal influences in the alpha-beta band. PMID:26777277

Mapping visual cortex in monkeys and humans using surface-based atlases

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Lewis, J. W.; Drury, H. A.; Hadjikhani, N.; Tootell, R. B.; Bakircioglu, M.; Miller, M. I.

2001-01-01

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

Functional evolution of new and expanded attention networks in humans

PubMed Central

Patel, Gaurav H.; Yang, Danica; Jamerson, Emery C.; Snyder, Lawrence H.; Corbetta, Maurizio; Ferrera, Vincent P.

2015-01-01

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks. PMID:26170314

Functional evolution of new and expanded attention networks in humans.

PubMed

Patel, Gaurav H; Yang, Danica; Jamerson, Emery C; Snyder, Lawrence H; Corbetta, Maurizio; Ferrera, Vincent P

2015-07-28

Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.

Muscarinic acetylcholine receptors are expressed by most parvalbumin-immunoreactive neurons in area MT of the macaque

PubMed Central

Disney, Anita A; Alasady, Hussein A; Reynolds, John H

2014-01-01

Background In the mammalian neocortex, cells that express parvalbumin (PV neurons) comprise a dominant class of inhibitory neuron that substantially overlaps with the fast/narrow-spiking physiological phenotype. Attention has pronounced effects on narrow-spiking neurons in the extrastriate cortex of macaques, and more consistently so than on their broad-spiking neighbors. Cortical neuromodulation by acetylcholine (ACh) is a candidate mechanism for aspects of attention and in the primary visual cortex (V1) of the macaque, receptors for ACh (AChRs) are strongly expressed by inhibitory neurons. In particular, most PV neurons in macaque V1 express m1 muscarinic AChRs and exogenously applied ACh can cause the release of γ-aminobutyric acid. In contrast, few PV neurons in rat V1 express m1 AChRs. While this could be a species difference, it has also been argued that macaque V1 is anatomically unique when compared with other cortical areas in macaques. Aims The aim of this study was to better understand the extent to which V1 offers a suitable model circuit for cholinergic anatomy in the macaque occipital lobe, and to explore cholinergic modulation as a biological basis for the changes in circuit behavior seen with attention. Materials and methods We compared expression of m1 AChRs by PV neurons between area V1 and the middle temporal visual area (MT) in macaque monkeys using dual-immunofluorescence confocal microscopy. Results and conclusion We find that, as in V1, most PV neurons in MT express m1 AChRs but, unlike in V1, it appears that so do most excitatory neurons. This provides support for V1 as a model of cholinergic modulation of inhibition in macaque visual cortex, but not of cholinergic modulation of visual cortical circuits in general. We also propose that ACh acting via m1 AChRs is a candidate underlying mechanism for the strong effects of attention on narrow-spiking neurons observed in behaving animals. PMID:24944872

Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex

PubMed Central

Mars, Rogier B.; Sallet, Jérôme; Neubert, Franz-Xaver; Rushworth, Matthew F. S.

2013-01-01

The human ability to infer the thoughts and beliefs of others, often referred to as “theory of mind,” as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor. PMID:23754406

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

PubMed

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

2012-09-01

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

The functional organization of the intraparietal sulcus in humans and monkeys

PubMed Central

Grefkes, Christian; Fink, Gereon R

2005-01-01

In macaque monkeys, the posterior parietal cortex (PPC) is concerned with the integration of multimodal information for constructing a spatial representation of the external world (in relation to the macaque's body or parts thereof), and planning and executing object-centred movements. The areas within the intraparietal sulcus (IPS), in particular, serve as interfaces between the perceptive and motor systems for controlling arm and eye movements in space. We review here the latest evidence for the existence of the IPS areas AIP (anterior intraparietal area), VIP (ventral intraparietal area), MIP (medial intraparietal area), LIP (lateral intraparietal area) and CIP (caudal intraparietal area) in macaques, and discuss putative human equivalents as assessed with functional magnetic resonance imaging. The data suggest that anterior parts of the IPS comprising areas AIP and VIP are relatively well preserved across species. By contrast, posterior areas such as area LIP and CIP have been found more medially in humans, possibly reflecting differences in the evolution of the dorsal visual stream and the inferior parietal lobule. Despite interspecies differences in the precise functional anatomy of the IPS areas, the functional relevance of this sulcus for visuomotor tasks comprising target selections for arm and eye movements, object manipulation and visuospatial attention is similar in humans and macaques, as is also suggested by studies of neurological deficits (apraxia, neglect, Bálint's syndrome) resulting from lesions to this region. PMID:16011542

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

PubMed

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

2009-05-01

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

Neural Representations of Faces and Body Parts in Macaque and Human Cortex: A Comparative fMRI Study

PubMed Central

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

2009-01-01

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part–selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part–selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas. PMID:19225169

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

PubMed

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

2015-02-01

Population densities of wildlife species tend to be correlated with resource productivity of habitats. However, wildlife density has been greatly modified by increasing human influences. For effective conservation, we must first identify the significant factors that affect wildlife density, and then determine the extent of the areas in which the factors should be managed. Here, we propose a protocol that accomplishes these two tasks. The main threats to wildlife are thought to be habitat alteration and hunting, with increases in alien carnivores being a concern that has arisen recently. Here, we examined the effect of these anthropogenic disturbances, as well as natural factors, on the local density of Yakushima macaques (Macaca fuscata yakui). We surveyed macaque densities at 30 sites across their habitat using data from 403 automatic cameras. We quantified the effect of natural vegetation (broad-leaved forest, mixed coniferous/broad-leaved forest, etc.), altered vegetation (forestry area and agricultural land), hunting pressure, and density of feral domestic dogs (Canis familiaris). The effect of each vegetation type was analyzed at numerous spatial scales (between 150 and 3,600-m radii from the camera locations) to determine the best scale for explaining macaque density (effective spatial scale). A model-selection procedure (generalized linear mixed model) was used to detect significant factors affecting macaque density. We detected that the most effective spatial scale was 400 m in radius, a scale that corresponded to group range size of the macaques. At this scale, the amount of broad-leaved forest was selected as a positive factor, whereas mixed forest and forestry area were selected as negative factors for macaque density. This study demonstrated the importance of the simultaneous evaluation of all possible factors of wildlife population density at the appropriate spatial scale. © 2014 Wiley Periodicals, Inc.

A preliminary study on activity budget, daily travel distance and feeding behaviour of long-tailed macaques and spectacled dusky leaf monkey in Bangi campus of Universiti Kebangsaan Malaysia, Selangor

NASA Astrophysics Data System (ADS)

Ruslin, Farhani; Yaakop, Salmah; Zain, Badrul Munir Md.

2014-09-01

The activity budget, ranging behaviour and feeding behaviour of a multimale-multifemale group of long-tailed macaques (Macaca fascicularis) and a multimale-multifemale group of spectacled dusky leaf monkey (Trachypithecus obscurus) were studied. A total of 145 hours and 143 hours have been spent to observe the group of long-tailed macaque and spectacled dusky leaf monkey that ranged the same habitat adjacent to the campus areas. The researchers examined the activity budgets, daily travel length and feeding activity of both species and distinguished how the sympatric species used the same forested habitat. Preliminary study found that the long-tailed macaques spent longer time feeding, moving than resting and other activities. On the other hand, the dusky leaf monkey spent much time in feeding and resting than moving. The differences of daily pattern between these two groups are significant. Macaques have higher daily mean of path length compared to the dusky leaf monkey and spent much time moving compare to the leaf monkey group. The spectacled dusky leaf monkey group also has fully utilized the forested areas where else the long-tailed macaques adopted foraging to the adjacent residential colleges.

Population dynamics of rhesus macaques and associated foamy virus in Bangladesh

PubMed Central

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

2013-01-01

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

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

PubMed

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

2015-01-01

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

Analysing Local Sparseness in the Macaque Brain Network

PubMed Central

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

2015-01-01

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

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

PubMed

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

2014-02-01

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

The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles.

PubMed

Gămănuţ, Răzvan; Kennedy, Henry; Toroczkai, Zoltán; Ercsey-Ravasz, Mária; Van Essen, David C; Knoblauch, Kenneth; Burkhalter, Andreas

2018-02-07

The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-07-01

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

Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques.

PubMed

Yamashita, Akiko; Fuchs, Eberhard; Taira, Masato; Yamamoto, Takamitsu; Hayashi, Motoharu

2012-06-01

Previously, we demonstrated decreased expression of somatostatin mRNA in aged macaque brain, particularly in the prefrontal cortex. To investigate whether or not this age-dependent decrease in mRNA is related to morphological changes, we analyzed somatostatin cells in the cerebra of aged Japanese macaques and compared them with those in rats and tree shrews, the latter of which are closely related to primates. Brains of aged macaques, tree shrews, and rats were investigated by immunohistochemistry with special emphasis on somatostatin. We observed degenerating somatostatin-immunoreactive cells in the cortices of aged macaques and tree shrews. Somatostatin-immunoreactive senile plaque-like structures were found in areas 6 and 8 and in the nucleus accumbens of macaques, as well as in the nucleus accumbens and the cortex of aged tree shrews, where amyloid accumulations were observed. Somatostatin degenerations may be related to amyloid accumulations and may play roles in impairments of cognitive functions during aging. © 2012 John Wiley & Sons A/S.

The Organization of Dorsal Frontal Cortex in Humans and Macaques

PubMed Central

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

2013-01-01

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

Auditory properties in the parabelt regions of the superior temporal gyrus in the awake macaque monkey: an initial survey.

PubMed

Kajikawa, Yoshinao; Frey, Stephen; Ross, Deborah; Falchier, Arnaud; Hackett, Troy A; Schroeder, Charles E

2015-03-11

The superior temporal gyrus (STG) is on the inferior-lateral brain surface near the external ear. In macaques, 2/3 of the STG is occupied by an auditory cortical region, the "parabelt," which is part of a network of inferior temporal areas subserving communication and social cognition as well as object recognition and other functions. However, due to its location beneath the squamous temporal bone and temporalis muscle, the STG, like other inferior temporal regions, has been a challenging target for physiological studies in awake-behaving macaques. We designed a new procedure for implanting recording chambers to provide direct access to the STG, allowing us to evaluate neuronal properties and their topography across the full extent of the STG in awake-behaving macaques. Initial surveys of the STG have yielded several new findings. Unexpectedly, STG sites in monkeys that were listening passively responded to tones with magnitudes comparable to those of responses to 1/3 octave band-pass noise. Mapping results showed longer response latencies in more rostral sites and possible tonotopic patterns parallel to core and belt areas, suggesting the reversal of gradients between caudal and rostral parabelt areas. These results will help further exploration of parabelt areas. Copyright © 2015 the authors 0270-6474/15/354140-11$15.00/0.

Three Divergent Subpopulations of the Malaria Parasite Plasmodium knowlesi

PubMed Central

Lin, Lee C.; Rovie-Ryan, Jeffrine J.; Kadir, Khamisah A.; Anderios, Fread; Hisam, Shamilah; Sharma, Reuben S.K.; Singh, Balbir; Conway, David J.

2017-01-01

Multilocus microsatellite genotyping of Plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of Borneo, each associated with a different macaque reservoir host species. Geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland Southeast Asia and Borneo. To resolve the overall population structure, multilocus microsatellite genotyping was conducted on a new sample of 182 P. knowlesi infections (obtained from 134 humans and 48 wild macaques) from diverse areas of Malaysia, first analyzed separately and then in combination with previous data. All analyses confirmed 2 divergent clusters of human cases in Malaysian Borneo, associated with long-tailed macaques and pig-tailed macaques, and a third cluster in humans and most macaques in peninsular Malaysia. High levels of pairwise divergence between each of these sympatric and allopatric subpopulations have implications for the epidemiology and control of this zoonotic species. PMID:28322705

Is Diet Flexibility an Adaptive Life Trait for Relictual and Peri-Urban Populations of the Endangered Primate Macaca sylvanus?

PubMed Central

Maibeche, Yasmina; Moali, Aissa; Yahi, Nassima; Menard, Nelly

2015-01-01

Habitat loss, fragmentation and urban expansion may drive some species to marginal habitats while others succeed in exploiting urban areas. Species that show dietary flexibility are more able to take advantage of human activities to supplement their diet with anthropogenically abundant and accessible resources. The Barbary macaque (Macaca sylvanus) is an endangered species due to the loss of its habitat, and human pressure. The population of Gouraya National Park (Algeria) lives in a relictual habitat that constitutes about 0.6% of the species range. In addition, this population is a unique case where urban expansion favours contact zones between Barbary macaque habitats and a big city (Bejaia). We quantified the dietary composition of Gouraya macaques over an annual cycle with the objective to understand how diet flexibility of this species may help it adapt to a relictual habitat or cope with urban expansion. We recorded the phenology of plant species every month. This study shows that Gouraya macaques, compared to those living in other forest types of the distribution area, are under lower seasonal constraints. They consume a greater amount of fruit and seeds that are available throughout much of the year, and a lesser amount of costly to find and extract subterranean foods. Therefore the Gouraya relictual habitat appears as a favourable environment compared to other major habitats of that species. This study also shows that colonizing peri-urban zones increases the availability and species richness of diet resources for Barbary macaques as they consume more human foods and exotic plants than in farther sites. Adult males eat more human foods than adult females and immatures do. The exploitation of high-energy anthropogenic food could favour macaque population growth and expansion towards the city center associated with human/macaque conflicts. We recommend applying management actions to restore macaques back to their natural habitat. PMID:25714476

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

PubMed

Enari, Hiroto; Sakamaki-Enari, Haruka

2013-07-01

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

Occurrence and distribution of Indian primates

USGS Publications Warehouse

Karanth, K.K.; Nichols, J.D.; Hines, J.E.

2010-01-01

Global and regional species conservation efforts are hindered by poor distribution data and range maps. Many Indian primates face extinction, but assessments of population status are hindered by lack of reliable distribution data. We estimated the current occurrence and distribution of 15 Indian primates by applying occupancy models to field data from a country-wide survey of local experts. We modeled species occurrence in relation to ecological and social covariates (protected areas, landscape characteristics, and human influences), which we believe are critical to determining species occurrence in India. We found evidence that protected areas positively influence occurrence of seven species and for some species are their only refuge. We found evergreen forests to be more critical for some primates along with temperate and deciduous forests. Elevation negatively influenced occurrence of three species. Lower human population density was positively associated with occurrence of five species, and higher cultural tolerance was positively associated with occurrence of three species. We find that 11 primates occupy less than 15% of the total land area of India. Vulnerable primates with restricted ranges are Golden langur, Arunachal macaque, Pig-tailed macaque, stump-tailed macaque, Phayre's leaf monkey, Nilgiri langur and Lion-tailed macaque. Only Hanuman langur and rhesus macaque are widely distributed. We find occupancy modeling to be useful in determining species ranges, and in agreement with current species ranking and IUCN status. In landscapes where monitoring efforts require optimizing cost, effort and time, we used ecological and social covariates to reliably estimate species occurrence and focus species conservation efforts. ?? Elsevier Ltd.

Genetic characteristics and antimicrobial resistance of Escherichia coli from Japanese macaques (Macaca fuscata) in rural Japan.

PubMed

Ogawa, Keiko; Yamaguchi, Keiji; Suzuki, Masatsugu; Tsubota, Toshio; Ohya, Kenji; Fukushi, Hideto

2011-04-01

Escherichia coli was isolated from wild and captive Japanese macaques (Macaca fuscata) to investigate the risk of zoonotic infections and the prevalence of antimicrobial-resistant Escherichia coli in the wild macaque population in Shimokita Peninsula, a rural area of Japan. We collected 265 fresh fecal samples from wild macaques and 20 samples from captive macaques in 2005 and 2006 for E. coli isolation. The predominant isolates were characterized by serotyping, virulence gene profiling, plasmid profiling, pulsed-field gel electrophoresis (PFGE), and microbial sensitivity tests. In total, 248 E. coli strains were isolated from 159 fecal samples from wild macaques, and 42 E. coli were isolated from 17 samples from captive macaques. None of the virulence genes eae, stx, elt, and est were detected in any of the isolates. The relatedness between wild- and captive-derived isolates was low by serotyping, PFGE, and plasmid profiling. Serotypes O8:H6, O8:H34, O8:H42, O8:HUT, O103:H27, O103:HNM, and OUT:H27 were found in wild macaque feces; serotypes O157:H42 and O119:H21 were recovered from captive macaques. O-and H-serotypes of the 26 isolates were not typed by commercial typing antisera and were named OUT and HUT, respectively. Twenty-eight isolates had no flagellar antigen, and their H-serotypes were named HNM. Similarity of PFGE patterns between wild-derived isolates and captive-derived isolates was <70%. No plasmid profile was shared between wild-derived and captive-derived isolates. The prevalence of antimicrobial-resistant E. coli was 6.5% (n=62) in wild macaques, and these isolates were resistant to cephalothin. We conclude that wild Japanese macaques in Shimokita Peninsula were unlikely to act as a reservoir of pathogenic E. coli for humans and that antimicrobial-resistant E. coli in wild macaques may be derived from humans.

Immunohistochemical characterization of slow and fast myosin heavy chain composition of muscle fibres in the styloglossus muscle of the human and macaque (Macaca rhesus).

PubMed

Sokoloff, Alan J; Yang, Betty; Li, Haiyan; Burkholder, Thomas J

2007-06-01

Muscle fibre contractile diversity is thought to be increased by the hybridization of multiple myosin heavy chain (MHC) isoforms in single muscle fibres. Reports of hybrid fibres composed of MHCI and MHCII isoforms in human, but not macaque, tongue muscles, suggest a human adaptation for increased tongue muscle contractile diversity. Here we test whether hybrid fibres composed of MHCI and MHCII are unique to human tongue muscles or are present as well in the macaque. MHC composition of the macaque and human styloglossus was characterized with antibodies that allowed identification of three muscle fibre phenotypes, a slow phenotype composed of MHCI, a fast phenotype composed of MHCII and a hybrid phenotype composed of MHCI and MHCII. The fast phenotype constitutes 68.5% of fibres in the macaque and 43.4% of fibres in the human (P<0.0001). The slow phenotype constitutes 20.2% of fibres in the macaque and 39.3% of fibres in the human (P<0.0001). The hybrid phenotype constitutes 11.2% of fibres in the macaque and 17.3% of fibres in the human (P=0.0002). Macaques and humans do not differ in fiber size (cross-sectional area, diameter). However, measures of fibre size differ by phenotype such that fast>hybrid>slow (P<0.05). These data demonstrate differences in the relative percent of muscle fibre phenotypes in the macaque and human styloglossus but also demonstrate that all three phenotypes are present in both species. These data suggest a similar range of mechanical properties in styloglossus muscle fibres of the macaque and human.

Processing of Egomotion-Consistent Optic Flow in the Rhesus Macaque Cortex

PubMed Central

Cottereau, Benoit R.; Smith, Andrew T.; Rima, Samy; Fize, Denis; Héjja-Brichard, Yseult; Renaud, Luc; Lejards, Camille; Vayssière, Nathalie; Trotter, Yves; Durand, Jean-Baptiste

2017-01-01

Abstract The cortical network that processes visual cues to self-motion was characterized with functional magnetic resonance imaging in 3 awake behaving macaques. The experimental protocol was similar to previous human studies in which the responses to a single large optic flow patch were contrasted with responses to an array of 9 similar flow patches. This distinguishes cortical regions where neurons respond to flow in their receptive fields regardless of surrounding motion from those that are sensitive to whether the overall image arises from self-motion. In all 3 animals, significant selectivity for egomotion-consistent flow was found in several areas previously associated with optic flow processing, and notably dorsal middle superior temporal area, ventral intra-parietal area, and VPS. It was also seen in areas 7a (Opt), STPm, FEFsem, FEFsac and in a region of the cingulate sulcus that may be homologous with human area CSv. Selectivity for egomotion-compatible flow was never total but was particularly strong in VPS and putative macaque CSv. Direct comparison of results with the equivalent human studies reveals several commonalities but also some differences. PMID:28108489

Contrasting Specializations for Facial Motion Within the Macaque Face-Processing System

PubMed Central

Fisher, Clark; Freiwald, Winrich A.

2014-01-01

SUMMARY Facial motion transmits rich and ethologically vital information [1, 2], but how the brain interprets this complex signal is poorly understood. Facial form is analyzed by anatomically distinct face patches in the macaque brain [3, 4], and facial motion activates these patches and surrounding areas [5, 6]. Yet it is not known whether facial motion is processed by its own distinct and specialized neural machinery, and if so, what that machinery’s organization might be. To address these questions, we used functional magnetic resonance imaging (fMRI) to monitor the brain activity of macaque monkeys while they viewed low- and high-level motion and form stimuli. We found that, beyond classical motion areas and the known face patch system, moving faces recruited a heretofore-unrecognized face patch. Although all face patches displayed distinctive selectivity for face motion over object motion, only two face patches preferred naturally moving faces, while three others preferred randomized, rapidly varying sequences of facial form. This functional divide was anatomically specific, segregating dorsal from ventral face patches, thereby revealing a new organizational principle of the macaque face-processing system. PMID:25578903

Organizing Principles of Human Cortical Development--Thickness and Area from 4 to 30 Years: Insights from Comparative Primate Neuroanatomy.

PubMed

Amlien, Inge K; Fjell, Anders M; Tamnes, Christian K; Grydeland, Håkon; Krogsrud, Stine K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2016-01-01

The human cerebral cortex undergoes a protracted, regionally heterogeneous development well into young adulthood. Cortical areas that expand the most during human development correspond to those that differ most markedly when the brains of macaque monkeys and humans are compared. However, it remains unclear to what extent this relationship derives from allometric scaling laws that apply to primate brains in general, or represents unique evolutionary adaptations. Furthermore, it is unknown whether the relationship only applies to surface area (SA), or also holds for cortical thickness (CT). In 331 participants aged 4 to 30, we calculated age functions of SA and CT, and examined the correspondence of human cortical development with macaque to human expansion, and with expansion across nonhuman primates. CT followed a linear negative age function from 4 to 30 years, while SA showed positive age functions until 12 years with little further development. Differential cortical expansion across primates was related to regional maturation of SA and CT, with age trajectories differing between high- and low-expanding cortical regions. This relationship adhered to allometric scaling laws rather than representing uniquely macaque-human differences: regional correspondence with human development was as large for expansion across nonhuman primates as between humans and macaque. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Contribution of correlated noise and selective decoding to choice probability measurements in extrastriate visual cortex.

PubMed

Gu, Yong; Angelaki, Dora E; DeAngelis, Gregory C

2014-07-01

Trial by trial covariations between neural activity and perceptual decisions (quantified by choice Probability, CP) have been used to probe the contribution of sensory neurons to perceptual decisions. CPs are thought to be determined by both selective decoding of neural activity and by the structure of correlated noise among neurons, but the respective roles of these factors in creating CPs have been controversial. We used biologically-constrained simulations to explore this issue, taking advantage of a peculiar pattern of CPs exhibited by multisensory neurons in area MSTd that represent self-motion. Although models that relied on correlated noise or selective decoding could both account for the peculiar pattern of CPs, predictions of the selective decoding model were substantially more consistent with various features of the neural and behavioral data. While correlated noise is essential to observe CPs, our findings suggest that selective decoding of neuronal signals also plays important roles.

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

PubMed Central

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

2015-01-01

While studies of rhesus macaques (Macaca mulatta) in the eastern (e.g., China) and western (e.g., India) parts of their geographic range have revealed major genetic differences that warrant the recognition of two different subspecies, little is known about genetic characteristics of rhesus macaques in the transitional zone extending from eastern India and Bangladesh through the northern part of Indo-China, the probable original homeland of the species. We analyzed genetic variation of 762 base pairs of mitochondrial DNA from 86 fecal swab samples and 19 blood samples from 25 local populations of rhesus macaque in Bangladesh collected from January 2010 to August 2012. These sequences were compared with those of rhesus macaques from India, China, and Myanmar. Forty-six haplotypes defined by 200 (26%) polymorphic nucleotide sites were detected. Estimates of gene diversity, expected heterozygosity, and nucleotide diversity for the total population were 0.9599 ± 0.0097, 0.0193 ± 0.0582, and 0.0196 ± 0.0098, respectively. A mismatch distribution of paired nucleotide differences yielded a statistically significantly negative value of Tajima's D, reflecting a population that rapidly expanded after the terminal Pleistocene. Most haplotypes throughout regions of Bangladesh, including an isolated region in the southwestern area (Sundarbans), clustered with haplotypes assigned to the minor haplogroup Ind-2 from India reflecting an east to west dispersal of rhesus macaques to India. Haplotypes from the southeast region of Bangladesh formed a cluster with those from Myanmar, and represent the oldest rhesus macaque haplotypes of Bangladesh. These results are consistent with the hypothesis that rhesus macaques first entered Bangladesh from the southeast, probably from Indo-China, then dispersed westward throughout eastern and central India. PMID:24810278

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

PubMed

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

2014-11-01

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

Visual Field Map Clusters in Macaque Extrastriate Visual Cortex

PubMed Central

Kolster, Hauke; Mandeville, Joseph B.; Arsenault, John T.; Ekstrom, Leeland B.; Wald, Lawrence L.; Vanduffel, Wim

2009-01-01

The macaque visual cortex contains more than 30 different functional visual areas, yet surprisingly little is known about the underlying organizational principles that structure its components into a complete ‘visual’ unit. A recent model of visual cortical organization in humans suggests that visual field maps are organized as clusters. Clusters minimize axonal connections between individual field maps that represent common visual percepts, with different clusters thought to carry out different functions. Experimental support for this hypothesis, however, is lacking in macaques, leaving open the question of whether it is unique to humans or a more general model for primate vision. Here we show, using high-resolution BOLD fMRI data in the awake monkey at 7 Tesla, that area MT/V5 and its neighbors are organized as a cluster with a common foveal representation and a circular eccentricity map. This novel view on the functional topography of area MT/V5 and satellites indicates that field map clusters are evolutionarily preserved and may be a fundamental organizational principle of the old world primate visual cortex. PMID:19474330

A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex

PubMed Central

Markov, N. T.; Ercsey-Ravasz, M. M.; Ribeiro Gomes, A. R.; Lamy, C.; Magrou, L.; Vezoli, J.; Misery, P.; Falchier, A.; Quilodran, R.; Gariel, M. A.; Sallet, J.; Gamanut, R.; Huissoud, C.; Clavagnier, S.; Giroud, P.; Sappey-Marinier, D.; Barone, P.; Dehay, C.; Toroczkai, Z.; Knoblauch, K.; Van Essen, D. C.; Kennedy, H.

2014-01-01

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks. PMID:23010748

A conserved pattern of differential expansion of cortical areas in simian primates.

PubMed

Chaplin, Tristan A; Yu, Hsin-Hao; Soares, Juliana G M; Gattass, Ricardo; Rosa, Marcello G P

2013-09-18

The layout of areas in the cerebral cortex of different primates is quite similar, despite significant variations in brain size. However, it is clear that larger brains are not simply scaled up versions of smaller brains: some regions of the cortex are disproportionately large in larger species. It is currently debated whether these expanded areas arise through natural selection pressures for increased cognitive capacity or as a result of the application of a common developmental sequence on different scales. Here, we used computational methods to map and quantify the expansion of the cortex in simian primates of different sizes to investigate whether there is any common pattern of cortical expansion. Surface models of the marmoset, capuchin, and macaque monkey cortex were registered using the software package CARET and the spherical landmark vector difference algorithm. The registration was constrained by the location of identified homologous cortical areas. When comparing marmosets with both capuchins and macaques, we found a high degree of expansion in the temporal parietal junction, the ventrolateral prefrontal cortex, and the dorsal anterior cingulate cortex, all of which are high-level association areas typically involved in complex cognitive and behavioral functions. These expanded maps correlated well with previously published macaque to human registrations, suggesting that there is a general pattern of primate cortical scaling.

Identification of Entamoeba polecki with Unique 18S rRNA Gene Sequences from Celebes Crested Macaques and Pigs in Tangkoko Nature Reserve, North Sulawesi, Indonesia.

PubMed

Tuda, Josef; Feng, Meng; Imada, Mihoko; Kobayashi, Seiki; Cheng, Xunjia; Tachibana, Hiroshi

2016-09-01

Unique species of macaques are distributed across Sulawesi Island, Indonesia, and the details of Entamoeba infections in these macaques are unknown. A total of 77 stool samples from Celebes crested macaques (Macaca nigra) and 14 stool samples from pigs were collected in Tangkoko Nature Reserve, North Sulawesi, and the prevalence of Entamoeba infection was examined by PCR. Entamoeba polecki was detected in 97% of the macaques and all of the pigs, but no other Entamoeba species were found. The nucleotide sequence of the 18S rRNA gene in E. polecki from M. nigra was unique and showed highest similarity with E. polecki subtype (ST) 4. This is the first case of identification of E. polecki ST4 from wild nonhuman primates. The sequence of the 18S rRNA gene in E. polecki from pigs was also unique and showed highest similarity with E. polecki ST1. These results suggest that the diversity of the 18S rRNA gene in E. polecki is associated with differences in host species and geographic localization, and that there has been no transmission of E. polecki between macaques and pigs in the study area. © 2016 The Author(s) Journal of Eukaryotic Microbiology © 2016 International Society of Protistologists.

A Putative Multiple-Demand System in the Macaque Brain.

PubMed

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

2016-08-17

In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex. Copyright © 2016 Mitchell et al.

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

PubMed

Van Essen, David C

2002-12-01

This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

Pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (Macaca fascicularis).

PubMed

Kuiken, Thijs; Buijs, Pascal; van Run, Peter; van Amerongen, Geert; Koopmans, Marion; van den Hoogen, Bernadette

2017-11-21

Although avian paramyxovirus type 1 is known to cause mild transient conjunctivitis in human beings, there are two recent reports of fatal respiratory disease in immunocompromised human patients infected with the pigeon lineage of the virus (PPMV-1). In order to evaluate the potential of PPMV-1 to cause respiratory tract disease, we inoculated a PPMV-1 isolate (hPPMV-1/Netherlands/579/2003) from an immunocompromised human patient into three healthy cynomolgus macaques (Macaca fascicularis) and examined them by clinical, virological, and pathological assays. In all three macaques, PPMV-1 replication was restricted to the respiratory tract and caused pulmonary consolidation affecting up to 30% of the lung surface. Both alveolar and bronchiolar epithelial cells expressed viral antigen, which co-localized with areas of diffuse alveolar damage. The results of this study demonstrate that PPMV-1 is a primary respiratory pathogen in cynomolgus macaques, and support the conclusion that PPMV-1 may cause fatal respiratory disease in immunocompromised human patients.

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

NASA Technical Reports Server (NTRS)

Van Essen, David C.

2002-01-01

This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

Performing monkeys of Bangladesh: characterizing their source and genetic variation.

PubMed

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

2016-04-01

The acquisition and training of monkeys to perform is a centuries-old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations, and may escape from their owners or may be released into other populations. In order to determine whether this tradition involving the acquisition and movement of animals has influenced the population structure of free-ranging rhesus macaques in Bangladesh, we first characterized the source of these monkeys. Biological samples from 65 performing macaques collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16 %) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89 %) were transitions, and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise differences for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. The collection of performing monkeys from India was also evident.

Performing monkeys of Bangladesh: characterizing their source and genetic variation

PubMed Central

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

2016-01-01

The acquisition and training of monkeys to perform is a century's old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations and may escape from their owners or be released into other populations. In order to determine whether this tradition, that involves the acquisition and movement of animals, has influenced the population structure of free-ranging rhesus macaques in Bangladesh we first characterized the source of these monkeys. Biological samples from 65 performing macaques, collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16%) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89%) were transitions and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise difference for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. Collection of performing monkeys from India was also evident. PMID:26758818

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

PubMed Central

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

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

PubMed Central

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

Understanding Human-Animal Relations in the Context of Primate Conservation: A Multispecies Ethnographic Approach in North Morocco.

PubMed

Waters, Siân; Bell, Sandra; Setchell, Joanna M

2018-01-01

Strategies for conserving species threatened with extinction are often driven by ecological data. However, in anthropogenic landscapes, understanding and incorporating local people's perceptions may enhance species conservation. We examine the relationships shepherds, living on the periphery of the mixed oak forest of Bouhachem in northern Morocco, have with animals in the context of a conservation project for Barbary macaques (Macaca sylvanus). We analyse ethnographic data to provide insights into shepherds' conceptions of Barbary macaques and the species which bring the shepherds into the forest - goats (Capra hircus), domestic dogs (Canis lupus familiaris), and the African wolf (Canis lupus lupaster). We interpret these data within the framework of boundary theory. Our multispecies ethnographic approach illuminates the different and, in the case of the domestic dog and the Barbary macaque, complex ways shepherds perceive each species. Some shepherds show intrinsic interest in the macaques, revealing potential recruits to conservation activities. As with any ethnographic study, our interpretations of human-animal relations in Bouhachem may not extrapolate to other areas of the Barbary macaque's distribution because of the unique nature of both people and the place. We recommend that conservationists examine complex place-based relations between humans and animals to improve wildlife conservation efforts. © 2018 S. Karger AG, Basel.

Quantitative Simulations of MST Visual Receptive Field Properties Using a Template Model of Heading Estimation

NASA Technical Reports Server (NTRS)

Stone, Leland S.; Perrone, J. A.

1997-01-01

We previously developed a template model of primate visual self-motion processing that proposes a specific set of projections from MT-like local motion sensors onto output units to estimate heading and relative depth from optic flow. At the time, we showed that that the model output units have emergent properties similar to those of MSTd neurons, although there was little physiological evidence to test the model more directly. We have now systematically examined the properties of the model using stimulus paradigms used by others in recent single-unit studies of MST: 1) 2-D bell-shaped heading tuning. Most MSTd neurons and model output units show bell-shaped heading tuning. Furthermore, we found that most model output units and the finely-sampled example neuron in the Duffy-Wurtz study are well fit by a 2D gaussian (sigma approx. 35deg, r approx. 0.9). The bandwidth of model and real units can explain why Lappe et al. found apparent sigmoidal tuning using a restricted range of stimuli (+/-40deg). 2) Spiral Tuning and Invariance. Graziano et al. found that many MST neurons appear tuned to a specific combination of rotation and expansion (spiral flow) and that this tuning changes little for approx. 10deg shifts in stimulus placement. Simulations of model output units under the same conditions quantitatively replicate this result. We conclude that a template architecture may underlie MT inputs to MST.

Contribution of correlated noise and selective decoding to choice probability measurements in extrastriate visual cortex

PubMed Central

Gu, Yong; Angelaki, Dora E; DeAngelis, Gregory C

2014-01-01

Trial by trial covariations between neural activity and perceptual decisions (quantified by choice Probability, CP) have been used to probe the contribution of sensory neurons to perceptual decisions. CPs are thought to be determined by both selective decoding of neural activity and by the structure of correlated noise among neurons, but the respective roles of these factors in creating CPs have been controversial. We used biologically-constrained simulations to explore this issue, taking advantage of a peculiar pattern of CPs exhibited by multisensory neurons in area MSTd that represent self-motion. Although models that relied on correlated noise or selective decoding could both account for the peculiar pattern of CPs, predictions of the selective decoding model were substantially more consistent with various features of the neural and behavioral data. While correlated noise is essential to observe CPs, our findings suggest that selective decoding of neuronal signals also plays important roles. DOI: http://dx.doi.org/10.7554/eLife.02670.001 PMID:24986734

Oblique effect in visual area 2 of macaque monkeys

PubMed Central

Shen, Guofu; Tao, Xiaofeng; Zhang, Bin; Smith, Earl L.; Chino, Yuzo M.

2014-01-01

The neural basis of an oblique effect, a reduced visual sensitivity for obliquely oriented stimuli, has been a matter of considerable debate. We have analyzed the orientation tuning of a relatively large number of neurons in the primary visual cortex (V1) and visual area 2 (V2) of anesthetized and paralyzed macaque monkeys. Neurons in V2 but not V1 of macaque monkeys showed clear oblique effects. This orientation anisotropy in V2 was more robust for those neurons that preferred higher spatial frequencies. We also determined whether V1 and V2 neurons exhibit a similar orientation anisotropy soon after birth. The oblique effect was absent in V1 of 4- and 8-week-old infant monkeys, but their V2 neurons showed a significant oblique effect. This orientation anisotropy in infant V2 was milder than that in adults. The results suggest that the oblique effect emerges in V2 based on the pattern of the connections that are established before birth and enhanced by the prolonged experience-dependent modifications of the neural circuitry in V2. PMID:24511142

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

PubMed

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

2014-11-01

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

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

PubMed Central

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

2014-01-01

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

An electrocorticographic electrode array for simultaneous recording from medial, lateral, and intrasulcal surface of the cortex in macaque monkeys.

PubMed

Fukushima, Makoto; Saunders, Richard C; Mullarkey, Matthew; Doyle, Alexandra M; Mishkin, Mortimer; Fujii, Naotaka

2014-08-15

Electrocorticography (ECoG) permits recording electrical field potentials with high spatiotemporal resolution over a large part of the cerebral cortex. Application of chronically implanted ECoG arrays in animal models provides an opportunity to investigate global spatiotemporal neural patterns and functional connectivity systematically under various experimental conditions. Although ECoG is conventionally used to cover the gyral cortical surface, recent studies have shown the feasibility of intrasulcal ECoG recordings in macaque monkeys. Here we developed a new ECoG array to record neural activity simultaneously from much of the medial and lateral cortical surface of a single hemisphere, together with the supratemporal plane (STP) of the lateral sulcus in macaque monkeys. The ECoG array consisted of 256 electrodes for bipolar recording at 128 sites. We successfully implanted the ECoG array in the left hemisphere of three rhesus monkeys. The electrodes in the auditory and visual cortex detected robust event related potentials to auditory and visual stimuli, respectively. Bipolar recording from adjacent electrode pairs effectively eliminated chewing artifacts evident in monopolar recording, demonstrating the advantage of using the ECoG array under conditions that generate significant movement artifacts. Compared with bipolar ECoG arrays previously developed for macaque monkeys, this array significantly expands the number of cortical target areas in gyral and intralsulcal cortex. This new ECoG array provides an opportunity to investigate global network interactions among gyral and intrasulcal cortical areas. Published by Elsevier B.V.

High-Level Prediction Signals in a Low-Level Area of the Macaque Face-Processing Hierarchy.

PubMed

Schwiedrzik, Caspar M; Freiwald, Winrich A

2017-09-27

Theories like predictive coding propose that lower-order brain areas compare their inputs to predictions derived from higher-order representations and signal their deviation as a prediction error. Here, we investigate whether the macaque face-processing system, a three-level hierarchy in the ventral stream, employs such a coding strategy. We show that after statistical learning of specific face sequences, the lower-level face area ML computes the deviation of actual from predicted stimuli. But these signals do not reflect the tuning characteristic of ML. Rather, they exhibit identity specificity and view invariance, the tuning properties of higher-level face areas AL and AM. Thus, learning appears to endow lower-level areas with the capability to test predictions at a higher level of abstraction than what is afforded by the feedforward sweep. These results provide evidence for computational architectures like predictive coding and suggest a new quality of functional organization of information-processing hierarchies beyond pure feedforward schemes. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of anthropic, ecological, and social factors in sleeping site choice by long-tailed macaques (Macaca fascicularis).

PubMed

Brotcorne, Fany; Maslarov, Cindy; Wandia, I Nengah; Fuentes, Agustin; Beudels-Jamar, Roseline C; Huynen, Marie-Claude

2014-12-01

When choosing their sleeping sites, primates make adaptive trade-offs between various biotic and abiotic constraints. In human-modified environments, anthropic factors may play a role. We assessed the influence of ecological (predation), social (intergroup competition), and anthropic (proximity to human settlements) factors in sleeping site choice by long-tailed macaques (Macaca fascicularis) occupying a habitat at the interface of natural forests and human-modified zones in Bali Barat National Park, Indonesia. Over the course of 56 nights, we collected data relating to physical features of sleeping trees, patterns of the use of sleeping sites within the home range, pre-sleep behavior, diurnal ranging patterns and availability of natural and human food. Overall, the macaques used 17 sleeping sites with 37 sleeping trees. When the monkeys slept in forest zones, they selected sleeping trees that had larger trunks but were not significantly taller than surrounding trees. Though the macaques rarely re-used sleeping sites on consecutive nights, they frequently re-used four sites over the study period. The group favored sleeping within the core area of its home range, despite the occurrence of frequent agonistic intergroup encounters there. Macaques preferentially selected sleeping trees located within or near human-modified zones, especially when human food was abundant and natural food was scarce. These results partially support the hypothesis that long-tailed macaques choose their sleeping sites to avoid predation; proximity to human settlements appears to be the primary factor influencing sleeping site choice in this primate species. Our results reflect the strong influence that anthropic factors have on primates, which subsist in increasingly human-dominated landscapes. © 2014 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

Elton, Sarah; O'Regan, Hannah J.

2014-07-01

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

Retinohypothalamic connections in the rhesus monkey

NASA Astrophysics Data System (ADS)

Chijuka, John C.

Previous studies of retinohypothalamic projections in macaques were performed with anterograde degeneration or autoradiographic techniques that were not sufficiently sensitive to fully define these projections. Results of studies in non-primates using sensitive tracers have revealed more extensive retinohypothalamic projection than previously seen. We hypothesize that there are more extensive retinohypothalamic projections in the higher primate, macaque monkey. Thus, the primary goal of this investigation was to characterize the retinohypothalamic projections in the macaque monkey using the more sensitive tract tracer, cholera toxin subunit B (CTB) unilaterally injected intravitreally. Secondary goals were to determine: (1) whether there is a retinal projection to the sleep-related ventrolateral preoptic area of the hypothalamus; (2) whether there are direct retinal projections to gonadotropin-releasing hormone neurons in the hypothalamus; and (3) whether any retinally-projecting hypothalamic neurons can be retrogradely labeled by intravitreal CTB injections. Our results confirmed our hypothesis that there are more extensive projections to the central targets. We found that, in addition to the well-described retinal projection to the suprachiasmatic nucleus, a number of other hypothalamic areas were labeled. We observed projections to the medial and lateral preoptic areas, including the sleep-related ventrolateral preoptic area. A number of retinal fibers terminated immediately dorsal to the supraoptic nucleus (SO), with a few fibers penetrating and terminating within the nucleus. A few fibers continued laterally beyond the SO into the substantia innominata immediately ventral to the nucleus basalis of Meynert. In addition, a dense plexus of CTB-labeled, retinal fibers were present in the subventricular nucleus and adjacent subventricular area. Some of these fibers coursed dorsally from this region to penetrate the ependyma lining the third ventricle and apparently contacted the cerebrospinal fluid (CSF). We also observed projections to the anterior hypothalamic area throughout its rostrocaudal extent and to the posterior region of the lateral preoptic area immediately dorsal to the supraoptic nucleus. More posteriorly, fibers projected to the arcuate/infundibular region, and a few fibers could be seen to course towards the paraventricular, parvicellular region and posterior hypothalamic region close to the third ventricle. Finally, some retrogradely-labeled neurons were present in most injected cases. Overall, these results show that retinohypothalamic projections in the macaque are more extensive than once thought, and presumably play more roles than solely entraining the suprachiasmatic nucleus, the central circadian controller. (Abstract shortened by UMI.)

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

PubMed

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

2017-01-01

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

An electrocorticographic electrode array for simultaneous recording from medial, lateral, and intrasulcal surface of the cortex in macaque monkeys

PubMed Central

Fukushima, Makoto; Saunders, Richard C.; Mullarkey, Matthew; Doyle, Alexandra M.; Mishkin, Mortimer; Fujii, Naotaka

2014-01-01

Background Electrocorticography (ECoG) permits recording electrical field potentials with high spatiotemporal resolution over a large part of the cerebral cortex. Application of chronically implanted ECoG arrays in animal models provides an opportunity to investigate global spatiotemporal neural patterns and functional connectivity systematically under various experimental conditions. Although ECoG is conventionally used to cover the gyral cortical surface, recent studies have shown the feasibility of intrasulcal ECoG recordings in macaque monkeys. New Method Here we developed a new ECoG array to record neural activity simultaneously from much of the medial and lateral cortical surface of a single hemisphere, together with the supratemporal plane (STP) of the lateral sulcus in macaque monkeys. The ECoG array consisted of 256 electrodes for bipolar recording at 128 sites. Results We successfully implanted the ECoG array in the left hemisphere of three rhesus monkeys. The electrodes in the auditory and visual cortex detected robust event related potentials to auditory and visual stimuli, respectively. Bipolar recording from adjacent electrode pairs effectively eliminated chewing artifacts evident in monopolar recording, demonstrating the advantage of using the ECoG array under conditions that generate significant movement artifacts. Comparison with Existing Methods Compared with bipolar ECoG arrays previously developed for macaque monkeys, this array significantly expands the number of cortical target areas in gyral and intralsulcal cortex. Conclusions This new ECoG array provides an opportunity to investigate global network interactions among gyral and intrasulcal cortical areas. PMID:24972186

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

PubMed Central

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

2015-01-01

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 3.2 mg/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. PMID:26191654

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

PubMed

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.

From the mouths of monkeys: Detection of Mycobacterium tuberculosis complex DNA from buccal swabs of synanthropic macaques

PubMed Central

Wilbur, AK; Engel, G; Rompis, A; Putra, IGA A; Lee, BP Y-H; Aggimarangsee, N; Chalise, M; Shaw, E; Oh, G; Schillaci, MA; Jones-Engel, L

2012-01-01

Although the Mycobacterium tuberculosis complex (MTBC) infects a third of all humans, little is known regarding the prevalence of mycobacterial infection in nonhuman primates (NHP). For more than a century, tuberculosis has been regarded as a serious infectious threat to NHP species. Advances in the detection of MTBC open new possibilities for investigating the effects of this poorly understood pathogen in diverse populations of NHP. Here we report results of a cross-sectional study using well-described molecular methods to detect a nucleic acid sequence (IS6110) unique to the MTBC. Sample collection was focused on the oral cavity, the presumed route of transmission of MTBC. Buccal swabs were collected from 263 macaques representing 11 species in four Asian countries and Gibraltar. Contexts of contact with humans included free ranging, pets, performing monkeys, zoos, and monkey temples. Following DNA isolation from buccal swabs, the PCR amplified IS6110 from 84 (31.9%) of the macaques. In general, prevalence of MTBC DNA was higher among NHP in countries where the World Health Organization reports higher prevalence of humans infected with MTBC. This is the first demonstration of MTBC DNA in the mouths of macaques. Further research is needed to establish the significance of this finding at both the individual and population levels. PCR of buccal samples holds promise as a method to elucidate the mycobacterial landscape among NHP, particularly macaques that thrive in areas of high human MTBC prevalence. PMID:22644580

Multidetector computed tomographic morphology of ovaries in cynomolgus macaques (Macaca fascicularis).

PubMed

Jones, Jeryl C; Appt, Susan E; Bourland, J Daniel; Hoyer, Patricia B; Clarkson, Thomas B; Kaplan, Jay R

2007-09-01

Macaques are important models for menopause and associated diseases in women. A sensitive, noninvasive technique for quantifying changes in ovarian morphology would facilitate longitudinal studies focused on the health-related sequelae of naturally occurring or experimentally induced alterations in ovarian structure and function. Multidetector computed tomography (MDCT) is a fast, non-invasive imaging technique that uses X-rays, multiple rows of detectors, and computers to generate detailed slice images of structures. The purpose of this study was to describe the utility of MDCT for reliably characterizing ovarian morphology in macaques. Five macaques were scanned using contrast-enhanced MDCT. The following characteristics were described: 1) appearance of ovaries and adjacent landmarks, 2) effects of varying technical protocols on ovarian image quality, 3) radiation doses delivered to the pelvic region during scanning, and 4) MDCT estimates of ovarian volume and antral follicle counts versus those measured directly in ovarian tissue. Ovaries were distinguishable in all MDCT scans and exhibited heterogeneous contrast enhancement. Antral follicles appeared as focal areas of nonenhancement. Ovarian image quality with 5 pediatric scanning protocols was sufficient for discriminating ovarian margins. Pelvic region radiation doses ranged from 0.5 to 0.7 rad. Antral follicles counted using MDCT ranged from 3 to 5 compared with 3 to 4 counted using histology. Ovarian volumes measured using MDCT ranged from 0.41 to 0.67 ml compared with 0.40 to 0.65 ml by water displacement. MDCT is a promising technique for measuring longitudinal changes in macaque ovarian morphology reliably and noninvasively.

Representation of continuous hand and arm movements in macaque areas M1, F5, and AIP: a comparative decoding study

NASA Astrophysics Data System (ADS)

Menz, Veera Katharina; Schaffelhofer, Stefan; Scherberger, Hansjörg

2015-10-01

Objective. In the last decade, multiple brain areas have been investigated with respect to their decoding capability of continuous arm or hand movements. So far, these studies have mainly focused on motor or premotor areas like M1 and F5. However, there is accumulating evidence that anterior intraparietal area (AIP) in the parietal cortex also contains information about continuous movement. Approach. In this study, we decoded 27 degrees of freedom representing complete hand and arm kinematics during a delayed grasping task from simultaneously recorded activity in areas M1, F5, and AIP of two macaque monkeys (Macaca mulatta). Main results. We found that all three areas provided decoding performances that lay significantly above chance. In particular, M1 yielded highest decoding accuracy followed by F5 and AIP. Furthermore, we provide support for the notion that AIP does not only code categorical visual features of objects to be grasped, but also contains a substantial amount of temporal kinematic information. Significance. This fact could be utilized in future developments of neural interfaces restoring hand and arm movements.

Resolving the organization of the third tier visual cortex in primates: a hypothesis-based approach.

PubMed

Angelucci, Alessandra; Rosa, Marcello G P

2015-01-01

As highlighted by several contributions to this special issue, there is still ongoing debate about the number, exact location, and boundaries of the visual areas located in cortex immediately rostral to the second visual area (V2), i.e., the "third tier" visual cortex, in primates. In this review, we provide a historical overview of the main ideas that have led to four models of third tier cortex organization, which are at the center of today's debate. We formulate specific predictions of these models, and compare these predictions with experimental evidence obtained primarily in New World primates. From this analysis, we conclude that only one of these models (the "multiple-areas" model) can accommodate the breadth of available experimental evidence. According to this model, most of the third tier cortex in New World primates is occupied by two distinct areas, both representing the full contralateral visual quadrant: the dorsomedial area (DM), restricted to the dorsal half of the third visual complex, and the ventrolateral posterior area (VLP), occupying its ventral half and a substantial fraction of its dorsal half. DM belongs to the dorsal stream of visual processing, and overlaps with macaque parietooccipital (PO) area (or V6), whereas VLP belongs to the ventral stream and overlaps considerably with area V3 proposed by others. In contrast, there is substantial evidence that is inconsistent with the concept of a single elongated area V3 lining much of V2. We also review the experimental evidence from macaque monkey and humans, and propose that, once the data are interpreted within an evolutionary-developmental context, these species share a homologous (but not necessarily identical) organization of the third tier cortex as that observed in New World monkeys. Finally, we identify outstanding issues, and propose experiments to resolve them, highlighting in particular the need for more extensive, hypothesis-driven investigations in macaque and humans.

B-virus from pet macaque monkeys: an emerging threat in the United States?

PubMed Central

Ostrowski, S. R.; Leslie, M. J.; Parrott, T.; Abelt, S.; Piercy, P. E.

1998-01-01

Of primary concern when evaluating macaque bites are bacterial and B-virus infections. B-virus infection is highly prevalent (80% to 90%) in adult macaques and may cause a potentially fatal meningoencephalitis in humans. We examined seven nonoccupational exposure incidents involving 24 persons and eight macaques. Six macaques were tested for herpes B; four (67%) were seropositive. A common observation was that children were more than three times as likely to be bitten than adults. The virus must be assumed to be a potential health hazard in macaque bite wounds; this risk makes macaques unsuitable as pets. PMID:9452406

Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis)

PubMed Central

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

2017-01-01

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

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

PubMed Central

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

2015-01-01

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

The organization of orientation selectivity throughout macaque visual cortex.

PubMed

Vanduffel, Wim; Tootell, Roger B H; Schoups, Aniek A; Orban, Guy A

2002-06-01

A double-label deoxyglucose technique was used to study orientation columns throughout visual cortex in awake behaving macaques. Four macaques were trained to fixate while contrastreversing, stationary gratings or one-dimensional noise of a single orientation or an orthogonal orientation were presented, during uptake of [14C]deoxyglucose ([14C]DG) or [3H]DG, respectively. The two orthogonal stimulus orientations produced DG-labeled columns that were maximally separated in the two isotope maps (inter-digitated) in four areas: V1, V2, V3 and VP. The topographic change from interdigitated to overlapping columns occurred abruptly rather than gradually, at corresponding cortical area borders (e.g. VP and V4v, respectively). In addition, the data suggest that orientation column topography systematically changes with retinotopic eccentricity. In V1, the orientation columns systematically avoided the cytochrome oxidase blobs in the parafoveal representation, but converged closer to the blobs in the foveal representation. A control experiment indicated that this was unlikely to reflect eccentricity-dependent differences in cortical spatial frequency sensitivity. A similar eccentricity-dependent change in the topography of orientation columns occurred in V2. In parafoveal but not foveal visual field representations of V2, the orientation columns were centered on the thick cytochrome oxidase stripes, extended into the adjacent interstripe region, but were virtually absent in the thin stripes.

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

PubMed

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

2015-02-01

Macaques live in close contact with humans across South and Southeast Asia, and direct interaction is frequent. Aggressive contact is a concern in many locations, particularly among populations of rhesus and longtail macaques that co-inhabit urbanized cities and towns with humans. We investigated the proximate factors influencing the occurrence of macaque aggression toward humans as well as human aggression toward macaques to determine the extent to which human behavior elicits macaque aggression and vice versa. We conducted a 3-month study of four free-ranging populations of rhesus macaques in Dehradun, India from October-December 2012, using event sampling to record all instances of human-macaque interaction (N = 3120). Our results show that while human aggression was predicted by the potential for economic losses or damage, macaque aggression was influenced by aggressive or intimidating behavior by humans as well as recent rates of conspecific aggression. Further, adult female macaques participated in aggression more frequently than expected, whereas adult and subadult males participated as frequently as expected. Our analyses demonstrate that neither human nor macaque aggression is unprovoked. Rather, both humans and macaques are responding to one another's behavior. Mitigation of human-primate conflict, and indeed other types of human-wildlife conflict in such coupled systems, will require a holistic investigation of the ways in which each participant is responding to, and consequently altering, the behavior of the other. © 2015 Wiley Periodicals, Inc.

The protective effect of dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion.

PubMed

Etensel, Barlas; Ozkisacik, Sezen; Ozkara, Esra; Serbest, Yeşim Aksu; Oztan, Onur; Yazici, Mesut; Gürsoy, Harun

2007-03-01

Despite the prompt diagnosis and treatment of testicular torsion (TT), there are problems with fertility and atrophy after testicular salvage. Dexpanthenol (Dxp) is the biologically active alcohol of pantothenic acid (PA). Dxp is converted to PA in tissues. PA increases the content of reduced glutathione (GSH), Coenzyme A and ATP synthesis in cells. GSH and glutathione-dependent peroxidases (GPX) are the major defense systems against oxidative stress. GPX-4 is the major antioxidant in testicular tissue. However, the activity of GPX-4 appeared and increased only after puberty. We investigated the effect of Dxp on testicular atrophy after TT at the 60th day. Rats were separated randomly into four groups. Group C: control group, group Td: torsion + detorsion, group Sal: torsion + saline + detorsion, group Dxp: torsion + Dxp + detorsion. The left testis was rotated 720 degrees for 2 h. In group Sal, normal saline and in group Dxp, Dexpanthenol were injected intraperitonally, 30 min before detorsion. After 60 days, the testicular weights and volumes were measured. Histopathology of the left testis was evaluated with mean seminiferous tubular diameter (MSTD) and mean testicular biopsy score (MTBS). The left (torsed) testicular weight and volume of groups Td and Sal were significantly lower compared to group Dxp. The MSTD and MTBS of group Td and Sal were significantly lower than group Dxp. Contralateral testicular weight and volume of groups Td, Sal and Dxp had no significant difference compared to the control group. Dxp significantly prevented testicular atrophy after 60 days of TT. Dxp has FDA approval, is safe, cost effective and readily available. Its relevance for clinical trials may especially be for the problem of testicular atrophy catastrophe, seen very frequently following testicular salvage.

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats.

PubMed

Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-Er; Wang, Zhen; Song, Wen-Gang

2017-06-27

To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells.

Hydrogen-rich saline attenuates spinal cord hemisection-induced testicular injury in rats

PubMed Central

Ge, Li; Wei, Li-Hua; Du, Chang-Qing; Song, Guo-Hua; Xue, Ya-Zhuo; Shi, Hao-Shen; Yang, Ming; Yin, Xin-Xin; Li, Run-Ting; Wang, Xue-er; Wang, Zhen; Song, Wen-Gang

2017-01-01

To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11–T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied. The results indicated that hSCI significantly decreased the hind limb neurological function, testis index, MSTD, and MSET, and induced severe testicular morphological injury. The MFN-2 level was decreased, and HO-1 and HMGB-1 were overexpressed in testicular tissues. In addition, hSCI accelerated the apoptosis of spermatogenic cells and the ultrastructural damage of cells in the hypophysis and testis. After HS administration, all these parameters were considerably improved, and the characteristics of hSCI testes were similar to those of normal control testes. Taken together, HS administration can promote the recovery of testicular biological function by anti-oxidative, anti-inflammatory, and anti-apoptotic action. More importantly, HS can inhibit the hSCI-induced ultrastructural changes in gonadotrophs, ameliorate the abnormal regulation of the hypothalamic-pituitary-testis axis, and thereby promote the recovery of testicular injury. HS administration also inhibited the hSCI-induced ultrastructural changes in testicular spermatogenic cells, Sertoli cells and interstitial cells. PMID:28404953

Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing

NASA Technical Reports Server (NTRS)

Astafiev, Serguei V.; Shulman, Gordon L.; Stanley, Christine M.; Snyder, Abraham Z.; Van Essen, David C.; Corbetta, Maurizio

2003-01-01

We studied the functional organization of human posterior parietal and frontal cortex using functional magnetic resonance imaging (fMRI) to map preparatory signals for attending, looking, and pointing to a peripheral visual location. The human frontal eye field and two separate regions in the intraparietal sulcus were similarly recruited in all conditions, suggesting an attentional role that generalizes across response effectors. However, the preparation of a pointing movement selectively activated a different group of regions, suggesting a stronger role in motor planning. These regions were lateralized to the left hemisphere, activated by preparation of movements of either hand, and included the inferior and superior parietal lobule, precuneus, and posterior superior temporal sulcus, plus the dorsal premotor and anterior cingulate cortex anteriorly. Surface-based registration of macaque cortical areas onto the map of fMRI responses suggests a relatively good spatial correspondence between human and macaque parietal areas. In contrast, large interspecies differences were noted in the topography of frontal areas.

Face Patch Resting State Networks Link Face Processing to Social Cognition

PubMed Central

Schwiedrzik, Caspar M.; Zarco, Wilbert; Everling, Stefan; Freiwald, Winrich A.

2015-01-01

Faces transmit a wealth of social information. How this information is exchanged between face-processing centers and brain areas supporting social cognition remains largely unclear. Here we identify these routes using resting state functional magnetic resonance imaging in macaque monkeys. We find that face areas functionally connect to specific regions within frontal, temporal, and parietal cortices, as well as subcortical structures supporting emotive, mnemonic, and cognitive functions. This establishes the existence of an extended face-recognition system in the macaque. Furthermore, the face patch resting state networks and the default mode network in monkeys show a pattern of overlap akin to that between the social brain and the default mode network in humans: this overlap specifically includes the posterior superior temporal sulcus, medial parietal, and dorsomedial prefrontal cortex, areas supporting high-level social cognition in humans. Together, these results reveal the embedding of face areas into larger brain networks and suggest that the resting state networks of the face patch system offer a new, easily accessible venue into the functional organization of the social brain and into the evolution of possibly uniquely human social skills. PMID:26348613

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

PubMed

Riley, Erin P; Wade, Tiffany W

2016-04-01

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

Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques.

PubMed

Wicker, Evan; Turchi, Janita; Malkova, Ludise; Forcelli, Patrick Alexander

2018-05-31

Reward contingencies are dynamic: outcomes that were valued at one point may subsequently lose value. Action selection in the face of dynamic reward associations requires several cognitive processes: registering a change in value of the primary reinforcer, adjusting the value of secondary reinforcers to reflect the new value of the primary reinforcer, and guiding action selection to optimal choices. Flexible responding has been evaluated extensively using reinforcer devaluation tasks. Performance on this task relies upon amygdala, Areas 11 and 13 of orbitofrontal cortex (OFC), and mediodorsal thalamus (MD). Differential contributions of amygdala and Areas 11 and 13 of OFC to specific sub-processes have been established, but the role of MD in these sub-processes is unknown. Pharmacological inactivation of the macaque MD during specific phases of this task revealed that MD is required for reward valuation and action selection. This profile is unique, differing from both amygdala and subregions of the OFC.

Distinct neuronal interactions in anterior inferotemporal areas of macaque monkeys during retrieval of object association memory.

PubMed

Hirabayashi, Toshiyuki; Tamura, Keita; Takeuchi, Daigo; Takeda, Masaki; Koyano, Kenji W; Miyashita, Yasushi

2014-07-09

In macaque monkeys, the anterior inferotemporal cortex, a region crucial for object memory processing, is composed of two adjacent, hierarchically distinct areas, TE and 36, for which different functional roles and neuronal responses in object memory tasks have been characterized. However, it remains unknown how the neuronal interactions differ between these areas during memory retrieval. Here, we conducted simultaneous recordings from multiple single-units in each of these areas while monkeys performed an object association memory task and examined the inter-area differences in neuronal interactions during the delay period. Although memory neurons showing sustained activity for the presented cue stimulus, cue-holding (CH) neurons, interacted with each other in both areas, only those neurons in area 36 interacted with another type of memory neurons coding for the to-be-recalled paired associate (pair-recall neurons) during memory retrieval. Furthermore, pairs of CH neurons in area TE showed functional coupling in response to each individual object during memory retention, whereas the same class of neuron pairs in area 36 exhibited a comparable strength of coupling in response to both associated objects. These results suggest predominant neuronal interactions in area 36 during the mnemonic processing, which may underlie the pivotal role of this brain area in both storage and retrieval of object association memory. Copyright © 2014 the authors 0270-6474/14/349377-12$15.00/0.

Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques

PubMed Central

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

Multiple pathways carry signals from short-wavelength-sensitive ('blue') cones to the middle temporal area of the macaque.

PubMed

Jayakumar, Jaikishan; Roy, Sujata; Dreher, Bogdan; Martin, Paul R; Vidyasagar, Trichur R

2013-01-01

We recorded spike activity of single neurones in the middle temporal visual cortical area (MT or V5) of anaesthetised macaque monkeys. We used flashing, stationary spatially circumscribed, cone-isolating and luminance-modulated stimuli of uniform fields to assess the effects of signals originating from the long-, medium- or short- (S) wavelength-sensitive cone classes. Nearly half (41/86) of the tested MT neurones responded reliably to S-cone-isolating stimuli. Response amplitude in the majority of the neurones tested further (19/28) was significantly reduced, though not always completely abolished, during reversible inactivation of visuotopically corresponding regions of the ipsilateral primary visual cortex (striate cortex, area V1). Thus, the present data indicate that signals originating in S-cones reach area MT, either via V1 or via a pathway that does not go through area V1. We did not find a significant difference between the mean latencies of spike responses of MT neurones to signals that bypass V1 and those that do not; the considerable overlap we observed precludes the use of spike-response latency as a criterion to define the routes through which the signals reach MT.

Serotype-dependent transduction efficiencies of recombinant adeno-associated viral vectors in monkey neocortex

PubMed Central

Gerits, Annelies; Vancraeyenest, Pascaline; Vreysen, Samme; Laramée, Marie-Eve; Michiels, Annelies; Gijsbers, Rik; Van den Haute, Chris; Moons, Lieve; Debyser, Zeger; Baekelandt, Veerle; Arckens, Lutgarde; Vanduffel, Wim

2015-01-01

Abstract. Viral vector-mediated expression of genes (e.g., coding for opsins and designer receptors) has grown increasingly popular. Cell-type specific expression is achieved by altering viral vector tropism through crosspackaging or by cell-specific promoters driving gene expression. Detailed information about transduction properties of most recombinant adeno-associated viral vector (rAAV) serotypes in macaque cortex is gradually becoming available. Here, we compare transduction efficiencies and expression patterns of reporter genes in two macaque neocortical areas employing different rAAV serotypes and promoters. A short version of the calmodulin-kinase-II (CaMKIIα0.4) promoter resulted in reporter gene expression in cortical neurons for all tested rAAVs, albeit with different efficiencies for spread: rAAV2/5>>rAAV2/7>rAAV2/8>rAAV2/9>>rAAV2/1 and proportion of transduced cells: rAAV2/1>rAAV2/5>rAAV2/7=rAAV2/9>rAAV2/8. In contrast to rodent studies, the cytomegalovirus (CMV) promoter appeared least efficient in macaque cortex. The human synapsin-1 promoter preceded by the CMV enhancer (enhSyn1) produced homogeneous reporter gene expression across all layers, while two variants of the CaMKIIα promoter resulted in different laminar transduction patterns and cell specificities. Finally, differences in expression patterns were observed when the same viral vector was injected in two neocortical areas. Our results corroborate previous findings that reporter-gene expression patterns and efficiency of rAAV transduction depend on serotype, promoter, cortical layer, and area. PMID:26839901

Decision-Related Activity in Macaque V2 for Fine Disparity Discrimination Is Not Compatible with Optimal Linear Readout

PubMed Central

Clery, Stephane; Cumming, Bruce G.

2017-01-01

Fine judgments of stereoscopic depth rely mainly on relative judgments of depth (relative binocular disparity) between objects, rather than judgments of the distance to where the eyes are fixating (absolute disparity). In macaques, visual area V2 is the earliest site in the visual processing hierarchy for which neurons selective for relative disparity have been observed (Thomas et al., 2002). Here, we found that, in macaques trained to perform a fine disparity discrimination task, disparity-selective neurons in V2 were highly selective for the task, and their activity correlated with the animals' perceptual decisions (unexplained by the stimulus). This may partially explain similar correlations reported in downstream areas. Although compatible with a perceptual role of these neurons for the task, the interpretation of such decision-related activity is complicated by the effects of interneuronal “noise” correlations between sensory neurons. Recent work has developed simple predictions to differentiate decoding schemes (Pitkow et al., 2015) without needing measures of noise correlations, and found that data from early sensory areas were compatible with optimal linear readout of populations with information-limiting correlations. In contrast, our data here deviated significantly from these predictions. We additionally tested this prediction for previously reported results of decision-related activity in V2 for a related task, coarse disparity discrimination (Nienborg and Cumming, 2006), thought to rely on absolute disparity. Although these data followed the predicted pattern, they violated the prediction quantitatively. This suggests that optimal linear decoding of sensory signals is not generally a good predictor of behavior in simple perceptual tasks. SIGNIFICANCE STATEMENT Activity in sensory neurons that correlates with an animal's decision is widely believed to provide insights into how the brain uses information from sensory neurons. Recent theoretical work developed simple predictions to differentiate decoding schemes, and found support for optimal linear readout of early sensory populations with information-limiting correlations. Here, we observed decision-related activity for neurons in visual area V2 of macaques performing fine disparity discrimination, as yet the earliest site for this task. These findings, and previously reported results from V2 in a different task, deviated from the predictions for optimal linear readout of a population with information-limiting correlations. Our results suggest that optimal linear decoding of early sensory information is not a general decoding strategy used by the brain. PMID:28100751

Reduced TCOF1 mRNA level in a rhesus macaque with Treacher Collins-like syndrome: further evidence for haploinsufficiency of treacle as the cause of disease.

PubMed

Shows, Kathryn H; Ward, Christy; Summers, Laura; Li, Lin; Ziegler, Gregory R; Hendrickx, Andrew G; Shiang, Rita

2006-02-01

Mutations in the human gene TCOF1 cause a mandibulofacial dysostosis known as Treacher Collins syndrome (TCS). An infant rhesus macaque (Macaca mulatta) that displayed the TCS phenotype was identified at the California National Primate Research Center. The TCOF1 coding region was cloned from a normal rhesus macaque and sequenced. The rhesus macaque homolog of TCOF1 is 91.6% identical in cDNA sequence and 93.8% identical in translated protein sequence compared to human TCOF1. Sequencing of TCOF1 in the TCS-affected rhesus macaque showed no mutations within the coding region or splice sites; however, real-time quantitative PCR showed an 87% reduction of spleen TCOF1 mRNA level in the TCS affected macaque when compared with normal macaque spleen.

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

PubMed

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.

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

PubMed Central

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

2002-01-01

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

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

PubMed

Koda, Hiroki

2012-09-01

Heterospecific communication signals sometimes convey relevant information for animal survival. For example, animals use or eavesdrop on heterospecific alarm calls concerning common predators. Indeed, most observations have been reported regarding anti-predator strategies. Use of heterospecific signals has rarely been observed as part of a foraging strategy. Here, I report empirical evidence, collected using playback experiments, showing that Japanese sika deer, Cevus nippon, use heterospecific food calls of Japanese macaques, Macaca fuscata yakui, for foraging efficiency. The deer and macaques both inhabit the wild forest of Yakushima Island with high population densities and share many food items. Anecdotal observations suggest that deer often wait to browse fruit falls under the tree where a macaque group is foraging. Furthermore, macaques frequently produce food calls during their foraging. If deer effectively obtain fruit from the leftovers of macaques, browsing fruit fall would provide a potential benefit to the deer, and, further, deer are likely to associate macaque food calls with feeding activity. The results showed that playback of macaque food calls under trees gathered significantly more deer than silence control periods. These results suggest that deer can associate macaque food calls with foraging activities and use heterospecific calls for foraging efficiency. Copyright © 2012 Elsevier B.V. All rights reserved.

Simian immunodeficiency virus SIVmac239 infection and simian human immunodeficiency virus SHIV89.6P infection result in progression to AIDS in cynomolgus macaques of Asian origin.

PubMed

Okamura, Tomotaka; Tsujimura, Yusuke; Soma, Shogo; Takahashi, Ichiro; Matsuo, Kazuhiro; Yasutomi, Yasuhiro

2016-12-01

Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian countries. In the present study, we analysed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated into cynomolgus macaques in Indonesian, Malaysian or Philippine origin. The plasma viral loads in macaques infected with either SIVmac239 or SHIV89.6P were maintained at high levels. CD4+ T cell levels in macaques infected with SIVmac239 gradually decreased. All of the macaques infected with SHIV89.6P showed greatly reduced CD4+ T-cell numbers within 6 weeks of infection. Eight of the 11 macaques infected with SIVmac239 were killed due to AIDS symptoms after 2-4.5 years, while four of the five macaques infected with SHIV89.6P were killed due to AIDS symptoms after 1-3.5 years. We also analysed cynomolgus macaques infected intrarectally with repeated low, medium or high doses of SIVmac239, SIVmac251 or SHIV89.6P. Infection was confirmed by quantitative RT-PCR at more than 5000, 300 and 500 TCID50 for SIVmac239, SIVmac251 and SHIV89.6P, respectively. The present study indicates that cynomolgus macaques of Asian origin are highly susceptible to SIVmac and SHIV infection by both intravenous and mucosal routes. These models will be useful for studies on virus pathogenesis, vaccination and therapeutics against human immunodeficiency virus/AIDS.

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

PubMed

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

2010-02-01

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

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

PubMed

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 (P<0.05, t-test). We also found a greater number of homozygous STRs than heterozygous STRs (P<0.05, t-test), with the Emei and Jianyang Tibetan macaques showing more heterozygous loci than Huangshan Tibetan macaques. The proportion of insertions and mean variation of alleles in the Emei and Jianyang individuals were slightly higher than those in the Huangshan individuals, thus revealing differences in STR allele size between the two populations. The polymorphic STR loci identified based on the reference genome 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.

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

PubMed

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.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

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

PubMed Central

Solomon, Christopher; Southwood, Scott; Hoof, Ilka; Rudersdorf, Richard; Peters, Bjoern; Sidney, John; Pinilla, Clemencia; Marcondes, Maria Cecilia Garibaldi; Ling, Binhua; Marx, Preston; Sette, Alessandro

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 macaque potentially being a more relevant model for AIDS outcomes than the Indian rhesus macaque, the Chinese-origin rhesus macaques have not been well-characterized for their major histocompatibility complex (MHC) composition and function, reducing their greater utilization. In this study, we characterized a total of 50 unique Chinese rhesus macaques from several varying origins for their entire MHC class I allele composition and identified a total of 58 unique complete MHC class I sequences. Only nine of the sequences had been associated with Indian rhesus macaques, and 28/58 (48.3%) 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 binding characteristics with the HLA-B7 supertype, the most frequent supertype in human populations. These studies provide the first functional characterization of an MHC class I molecule in the context of Chinese rhesus macaques and the first instance of HLA-B7 analogy for rhesus macaques. Electronic supplementary material The online version of this article (doi:10.1007/s00251-010-0450-3) contains supplementary material, which is available to authorized users. PMID:20480161

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

PubMed Central

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

2014-01-01

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

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

PubMed

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.

SIV Infection Impairs the Central Nervous System in Chinese Rhesus Macaques.

PubMed

Liu, Hang; Xiao, Qian-Hao; Liu, Jin-Biao; Li, Jie-Liang; Zhou, Li; Xian, Qiao-Yang; Wang, Yong; Zhang, Jing; Wang, Xu; Ho, Wen-Zhe; Zhuang, Ke

2016-09-01

The central nervous system (CNS) impairment is a consequence seen in SIV infection of rhesus macaques of Indian-origin, which is more common in infected macaques with rapid disease progression than in those with conventional disease progression. Here, we investigated the CNS damages in SIVmac239-infected Chinese rhesus macaques. We demonstrated that SIV infection of Chinese macaques could cause neuropathological impairments, which was evidenced by appearance of SIV-RNA positive cells, the infiltration of activated macrophages and abundant multinucleated giant cells (MNGCs) in the different regions of the brains. The animals with high viremia and short survival time (average of 16 weeks, rapid progression, RP) had severer neuropathological changes than those with conventional progression (CP). As compared with the RP animals, CP macaques had lower viremia and much longer survival time (average of 154 weeks). These findings indicate that SIVmac239 infection of Chinese rhesus macaque can be used as a suitable animal model and alternative resource for nueroAIDS research.

Age-Associated Pathology in Rhesus Macaques (Macaca mulatta)

PubMed Central

Simmons, H. A.

2018-01-01

The rhesus macaque (Macaca mulatta) is one of the most extensively used nonhuman primate models for human diseases. This article presents a literature review focusing on major organ systems and age-associated conditions in humans and primates, combined with information from the Wisconsin National Primate Research Center Electronic Health Record database to highlight and contrast age-associated lesions in geriatric rhesus macaques with younger cohorts. Rhesus macaques are excellent models for age-associated conditions, including diabetes, osteoarthritis, endometriosis, visual accommodation, hypertension, osteoporosis, and amyloidosis. Adenocarcinoma of the large intestine (ileocecocolic junction, cecum, and colon) is the most common spontaneous neoplasm in the rhesus macaque. A combination of cross-sectional and longitudinal studies is required to truly define mechanisms of maturation, aging, and the pathology of age-associated conditions in macaques and thus humans. The rhesus macaque is and will continue to be an appropriate and valuable model for investigation of the mechanisms and treatment of age-associated diseases. PMID:26864889

Effect of feature-selective attention on neuronal responses in macaque area MT

PubMed Central

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

Effect of feature-selective attention on neuronal responses in macaque area MT.

PubMed

Chen, X; Hoffmann, K-P; Albright, T D; Thiele, A

2012-03-01

Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color).

Experimental SSM-CVB3 infection in macaques.

PubMed

Han, Tiesuo; He, Wenqi; Song, Deguang; Zhao, Kui; Wu, Chenchen; Gao, Feng; Lu, Huijun; Gai, Xianying; Wang, Xinrui; Li, Fei; Ji, Cuicui; Lin, Xijuan

2012-02-01

To evaluate the pathogenicity of SSM-CVB3 in a macaque model. The clinical symptoms of macaques were recorded; hematological, biochemical and histopathological evaluations were completed; viral titers and neutralization titers (NT-titers) in sera were tested; and the mRNA levels of SSM-CVB3, coxsackievirus and adenovirus receptor (CAR) and decay accelerating factor (DAF) were determined. After SSM-CVB3 infection, the macaques showed a lack of activity, a poor appetite, a higher body temperature, and severe diarrhea. The macaques also developed hematuria and albuminuria at 4 to 10 days post-inoculation. Virus titers (5.1-6.5 LogTCID(50)/mL) were higher at 6 to 10 days post-inoculation, and NT-titers (6.5-7.3 Log2) reached plateaus at 8 to 14 days post-inoculation. The infected macaques developed serious anemia with decreased RBC and WBC, but the percentages of LYM were increased. The levels of CK, CK-MB, AST and ALT in the sera were 84-169 U/L, 87.6-271.1 U/L, 43-87 U/L and 43-82 U/L, respectively, and all of those were higher than normal. Histological analysis showed obvious cardiac, hepatic and renal damages in the infected macaques and the mRNA contents of SSM-CVB3, CAR and DAF in the heart, liver and kidneys of infected macaques were higher (P<0.05). This was the first report on experimental SSM-CVB3 infections in macaques with serious hepatic and renal damage, except for myocarditis. The information obtained from this study suggests that the SSM-CVB3 strain and this macaque model could be used for studying CVB3-induced cardiac, hepatic or renal diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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.

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences

PubMed Central

Xue, Cheng; Raveendran, Muthuswamy; Harris, R. Alan; Fawcett, Gloria L.; Liu, Xiaoming; White, Simon; Dahdouli, Mahmoud; Rio Deiros, David; Below, Jennifer E.; Salerno, William; Cox, Laura; Fan, Guoping; Ferguson, Betsy; Horvath, Julie; Johnson, Zach; Kanthaswamy, Sree; Kubisch, H. Michael; Liu, Dahai; Platt, Michael; Smith, David G.; Sun, Binghua; Vallender, Eric J.; Wang, Feng; Wiseman, Roger W.; Chen, Rui; Muzny, Donna M.; Gibbs, Richard A.; Yu, Fuli; Rogers, Jeffrey

2016-01-01

Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease. PMID:27934697

Cortico-Cortical, Cortico-Striatal, and Cortico-Thalamic White Matter Fiber Tracts Generated in the Macaque Brain via Dynamic Programming

PubMed Central

Lal, Rakesh M.; An, Michael; Poynton, Clare B.; Li, Muwei; Jiang, Hangyi; Oishi, Kenichi; Selemon, Lynn D.; Mori, Susumu; Miller, Michael I.

2013-01-01

Abstract Probabilistic methods have the potential to generate multiple and complex white matter fiber tracts in diffusion tensor imaging (DTI). Here, a method based on dynamic programming (DP) is introduced to reconstruct fibers pathways whose complex anatomical structures cannot be resolved beyond the resolution of standard DTI data. DP is based on optimizing a sequentially additive cost function derived from a Gaussian diffusion model whose covariance is defined by the diffusion tensor. DP is used to determine the optimal path between initial and terminal nodes by efficiently searching over all paths, connecting the nodes, and choosing the path in which the total probability is maximized. An ex vivo high-resolution scan of a macaque hemi-brain is used to demonstrate the advantages and limitations of DP. DP can generate fiber bundles between distant cortical areas (superior longitudinal fasciculi, arcuate fasciculus, uncinate fasciculus, and fronto-occipital fasciculus), neighboring cortical areas (dorsal and ventral banks of the principal sulcus), as well as cortical projections to the hippocampal formation (cingulum bundle), neostriatum (motor cortical projections to the putamen), thalamus (subcortical bundle), and hippocampal formation projections to the mammillary bodies via the fornix. Validation is established either by comparison with in vivo intracellular transport of horseradish peroxidase in another macaque monkey or by comparison with atlases. DP is able to generate known pathways, including crossing and kissing tracts. Thus, DP has the potential to enhance neuroimaging studies of cortical connectivity. PMID:23879573

Chronic alcohol consumption results in higher simian immunodeficiency virus replication in mucosally inoculated rhesus macaques.

PubMed

Poonia, Bhawna; Nelson, Steve; Bagby, Greg J; Zhang, Ping; Quniton, Lee; Veazey, Ronald S

2005-10-01

The influence of alcohol consumption on HIV pathogenesis is not well understood. In this study we used the simian immunodeficiency virus (SIV)/macaque model of HIV infection to study the influence of chronic binge alcohol consumption on SIV infection. Rhesus macaques were fed alcohol or isocaloric amounts of sucrose via indwelling intragastric catheters and then inoculated with SIVmac251 by the rectal route. Real-time RT-PCR for SIV gag mRNA showed significantly higher plasma viral copies in alcohol-consuming macaques at 4 and 6 weeks pi, compared with sucrose controls. The viral copies were 1 to 2 logs higher in these animals. The percentage of CD8+ lymphocytes in the duodenum of alcohol-consuming macaques was significantly lower than in sucrose-consuming macaques both before infection as well as at different time points postinfection. Also, the percentage of CD4(+)CD3+ lymphocytes in the intestines was significantly higher in alcohol-consuming macaques before infection. These findings suggest that a higher percentage of SIV target cells (CD4) in the gut coupled with lower percentages of CD8 cells, which could be important in controlling virus replication, may be responsible for the higher SIV loads observed in alcohol-consuming macaques.

Chronic alcohol consumption results in higher simian immunodeficiency virus replication in mucosally inoculated rhesus macaques.

PubMed

Poonia, Bhawna; Nelson, Steve; Bagby, Greg J; Zhang, Ping; Quniton, Lee; Veazey, Ronald S

2006-06-01

The influence of alcohol consumption on HIV pathogenesis is not well understood. In this study we used the SIV/macaque model of HIV infection to study the influence of chronic binge alcohol consumption on simian immunodeficiency virus (SIV) infection. Rhesus macaques were fed alcohol or isocaloric amounts of sucrose via indwelling intragastric catheters and then inoculated with SIVmac251 by the rectal route. Real-time RTPCR for SIV gag mRNA showed significantly higher plasma viral copies in alcohol-consuming macaques at 4 and 6 weeks pi, compared with sucrose controls. The viral copies were 1 to 2 logs higher in these animals. The percentage of CD8+ lymphocytes in the duodenum of alcohol-consuming macaques was significantly lower than in sucrose-consuming macaques both before infection as well as at different time points postinfection. Also, the percentage of CD4+CD3+ lymphocytes in the intestines was significantly higher in alcohol-consuming macaques before infection. These findings suggest that a higher percentage of SIV target cells (CD4) in the gut coupled with lower percentages of CD8 cells, which could be important in controlling virus replication, may be responsible for the higher SIV loads observed in alcohol-consuming macaques.

Preference for facial averageness: Evidence for a common mechanism in human and macaque infants

PubMed Central

Damon, Fabrice; Méary, David; Quinn, Paul C.; Lee, Kang; Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.; Pascalis, Olivier

2017-01-01

Human adults and infants show a preference for average faces, which could stem from a general processing mechanism and may be shared among primates. However, little is known about preference for facial averageness in monkeys. We used a comparative developmental approach and eye-tracking methodology to assess visual attention in human and macaque infants to faces naturally varying in their distance from a prototypical face. In Experiment 1, we examined the preference for faces relatively close to or far from the prototype in 12-month-old human infants with human adult female faces. Infants preferred faces closer to the average than faces farther from it. In Experiment 2, we measured the looking time of 3-month-old rhesus macaques (Macaca mulatta) viewing macaque faces varying in their distance from the prototype. Like human infants, macaque infants looked longer to faces closer to the average. In Experiments 3 and 4, both species were presented with unfamiliar categories of faces (i.e., macaque infants tested with adult macaque faces; human infants and adults tested with infant macaque faces) and showed no prototype preferences, suggesting that the prototypicality effect is experience-dependent. Overall, the findings suggest a common processing mechanism across species, leading to averageness preferences in primates. PMID:28406237

Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression?

PubMed

Kraskov, Alexander; Dancause, Numa; Quallo, Marsha M; Shepherd, Samantha; Lemon, Roger N

2009-12-24

The discovery of "mirror neurons" in area F5 of the ventral premotor cortex has prompted many theories as to their possible function. However, the identity of mirror neurons remains unknown. Here, we investigated whether identified pyramidal tract neurons (PTNs) in area F5 of two adult macaques exhibited "mirror-like" activity. About half of the 64 PTNs tested showed significant modulation of their activity while monkeys observed precision grip of an object carried out by an experimenter, with somewhat fewer showing modulation during precision grip without an object or grasping concealed from the monkey. Therefore, mirror-like activity can be transmitted directly to the spinal cord via PTNs. A novel finding is that many PTNs (17/64) showed complete suppression of discharge during action observation, while firing actively when the monkey grasped food rewards. We speculate that this suppression of PTN discharge might be involved in the inhibition of self-movement during action observation. 2009 Elsevier Inc. All rights reserved.

Behavioral and anatomical consequences of early versus late symbol training in macaques.

PubMed

Srihasam, Krishna; Mandeville, Joseph B; Morocz, Istvan A; Sullivan, Kevin J; Livingstone, Margaret S

2012-02-09

Distinct brain regions, reproducible from one person to the next, are specialized for processing different kinds of human expertise, such as face recognition and reading. Here, we explore the relationship between age of learning, learning ability, and specialized brain structures. Specifically, we ask whether the existence of reproducible cortical domains necessarily means that certain abilities are innate, or innately easily learned, or whether reproducible domains can be formed, or refined, by interactions between genetic programs and common early experience. Functional MRI showed that intensive early, but not late, experience caused the formation of category-selective regions in macaque temporal lobe for stimuli never naturally encountered by monkeys. And behaviorally, early training produced more fluent processing of these stimuli than the same training in adults. One explanation for these results is that in higher cortical areas, as in early sensory areas, experience drives functional clustering and functional clustering determines how that information is processed. Copyright © 2012 Elsevier Inc. All rights reserved.

Transcriptional architecture of the primate neocortex.

PubMed

Bernard, Amy; Lubbers, Laura S; Tanis, Keith Q; Luo, Rui; Podtelezhnikov, Alexei A; Finney, Eva M; McWhorter, Mollie M E; Serikawa, Kyle; Lemon, Tracy; Morgan, Rebecca; Copeland, Catherine; Smith, Kimberly; Cullen, Vivian; Davis-Turak, Jeremy; Lee, Chang-Kyu; Sunkin, Susan M; Loboda, Andrey P; Levine, David M; Stone, David J; Hawrylycz, Michael J; Roberts, Christopher J; Jones, Allan R; Geschwind, Daniel H; Lein, Ed S

2012-03-22

Genome-wide transcriptional profiling was used to characterize the molecular underpinnings of neocortical organization in rhesus macaque, including cortical areal specialization and laminar cell-type diversity. Microarray analysis of individual cortical layers across sensorimotor and association cortices identified robust and specific molecular signatures for individual cortical layers and areas, prominently involving genes associated with specialized neuronal function. Overall, transcriptome-based relationships were related to spatial proximity, being strongest between neighboring cortical areas and between proximal layers. Primary visual cortex (V1) displayed the most distinctive gene expression compared to other cortical regions in rhesus and human, both in the specialized layer 4 as well as other layers. Laminar patterns were more similar between macaque and human compared to mouse, as was the unique V1 profile that was not observed in mouse. These data provide a unique resource detailing neocortical transcription patterns in a nonhuman primate with great similarity in gene expression to human. Copyright © 2012 Elsevier Inc. All rights reserved.

Sexual partner preference in female Japanese macaques.

PubMed

Vasey, Paul L

2002-02-01

Whether animals ever exhibit a preference for same-sex sexual partners is a subject of debate. Japanese macaques represent excellent models for examining issues related to sexual preference in animals because females, in certain populations, routinely engage in both heterosexual and homosexual behavior over the course of their life spans. Multiple lines of evidence indicate that female homosexual behavior in Japanese macaques is a sexual behavior, not a sociosexual one. Additional evidence indicates that female Japanese macaques do not engage in homosexual behavior simply because acceptable male mates are unavailable or unmotivated to copulate. Patterns of sexual partner choice by female Japanese macaques that are the focus of intersexual competition indicate that females of this species choose same-sex sexual partners even when they are simultaneously presented with a motivated, opposite-sex alternative. Thus, in some populations of Japanese macaques, females prefer certain same-sex sexual partners relative to certain male mates, and vice versa. Taken together, this evidence suggests that female Japanese macaques are best characterized as bisexual in orientation, not preferentially homosexual or preferentially heterosexual.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Youjun; Graduate School, Chinese Academy of Sciences, Beijing; Qi, Jianxun

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 diffractsmore » 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.« less

Ipsilateral corticotectal projections from the primary, premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study

PubMed Central

Fregosi, Michela; Rouiller, Eric M.

2018-01-01

The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non-human primates, previous studies reported that cortical projections to the superior colliculus originated from the premotor cortex and the primary motor cortex, whereas no projection originated from the supplementary motor area. The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n=9). The anterograde tracer BDA was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral superior colliculus. The data confirmed the presence of strong corticotectal projections from the premotor cortex. A new observation was that strong corticotectal projections were also found to originate from the supplementary motor area (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or supplementary motor areas. The corticotectal projection from each motor area was directed mainly to the deep layer of the superior colliculus, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non-primary motor areas are in position to influence the preparation and planning of voluntary movements. PMID:28921678

Human Presence Increases Parasitic Load in Endangered Lion-Tailed Macaques (Macaca silenus) in Its Fragmented Rainforest Habitats in Southern India

PubMed Central

Hussain, Shaik; Ram, Muthuvarmadam Subramanian; Kumar, Ajith; Shivaji, Sisinthy; Umapathy, Govindhaswamy

2013-01-01

Background Understanding changes in the host-parasite relationship due to habitat fragmentation is necessary for better management and conservation of endangered species in fragmented landscapes. Pathogens and parasites can pose severe threat to species in restricted environments such as forest fragments where there is increased contact of wildlife with human and livestock populations. Environmental stress and reduced nutritional level in forest fragments can influence parasite infection and intensity on the native species. In this study, we examine the impact of habitat fragmentation on the prevalence of gastrointestinal parasites in lion-tailed macaques in a fragmented rainforest in Western Ghats. Methods The prevalence of different gastrointestinal parasites was estimated from 91 fecal samples collected from 9 lion-tailed macaque groups in nine forest fragments. The parasites were identified up to genus level on the basis of the morphology and coloration of the egg, larva and cyst. The covariates included forest fragment area, group size and the presence/absence of human settlements and livestock in proximity. We used a linear regression model to identify the covariates that significantly influenced the prevalence of different parasite taxa. Results Nine gastrointestinal parasite taxa were detected in lion-tailed macaque groups. The groups near human settlements had greater prevalence and number of taxa, and these variables also had significant positive correlations with group size. We found that these parameters were also greater in groups near human settlements after controlling for group size. Livestock were present in all five fragments that had human settlements in proximity. Conclusion The present study suggests that high prevalence and species richness of gastrointestinal parasites in lion-tailed macaque groups are directly related to habitat fragmentation, high anthropogenic activities and high host density. The parasite load partially explains the reason for the decline in immature survival and birth rate in small and isolated rainforest fragments in Anamalai Hills. PMID:23717465

Specific pathogen-free status alters immunophenotype in rhesus macaques: implications for the study of simian immunodeficiency virus.

PubMed

Santos, Rosemary V; Lin, Kuei-Chin; Mansfield, Keith; Wachtman, Lynn M

2011-10-01

The repertoire of viruses to which research primates are exposed, even in the absence of clinical disease, may contribute to experimental confounding. In this study we examined whether standard specific pathogen-free (SPF) rhesus macaques exposed to a wider spectrum of enzootic viruses and expanded SPF macaques derived to exclude a greater number of viral agents would display alterations in immune activation or immune cell populations. Given the impact of immunophenotype on human immunodeficiency virus (HIV) progression and the importance of the simian immunodeficiency virus (SIV) model for the study of HIV pathogenesis, we elected to additionally examine the impact of SPF status on the capacity of peripheral blood mononuclear cells (PBMCs) to support SIV replication. The expanded SPF group displayed significant immune alterations including increased serum interleukin (IL)-15 and a greater in vitro elaboration of GM-CSF, IL1ra, VEGF, IL-10, IL12/23, and MIP-1b. Consistent with reduced viral antigenic exposure in expanded SPF macaques, decreased CD4(+) and CD8(+) transitional and effector memory (T(EM)) cell populations were observed. Expanded SPF PBMC cultures also demonstrated an increased peak (192.61 ng/ml p27) and area under the curve in in vitro SIV production (1968.64 ng/ml p27) when compared to standard SPF macaques (99.32 ng/ml p27; p=0.03 and 915.17 ng/ml p27; p=0.03, respectively). In vitro SIV replication did not correlate with CD4(+) T(EM) cell counts but was highly correlated with serum IL-15 in the subset of animals examined. Findings suggest that an altered immunophenotype associated with the maintenance of primates under differing levels of bioexclusion has the potential to impact the outcome of SIV studies and models for which the measurement of immunologic endpoints is critical.

Human presence increases parasitic load in endangered lion-tailed macaques (Macaca silenus) in its fragmented rainforest habitats in Southern India.

PubMed

Hussain, Shaik; Ram, Muthuvarmadam Subramanian; Kumar, Ajith; Shivaji, Sisinthy; Umapathy, Govindhaswamy

2013-01-01

Understanding changes in the host-parasite relationship due to habitat fragmentation is necessary for better management and conservation of endangered species in fragmented landscapes. Pathogens and parasites can pose severe threat to species in restricted environments such as forest fragments where there is increased contact of wildlife with human and livestock populations. Environmental stress and reduced nutritional level in forest fragments can influence parasite infection and intensity on the native species. In this study, we examine the impact of habitat fragmentation on the prevalence of gastrointestinal parasites in lion-tailed macaques in a fragmented rainforest in Western Ghats. The prevalence of different gastrointestinal parasites was estimated from 91 fecal samples collected from 9 lion-tailed macaque groups in nine forest fragments. The parasites were identified up to genus level on the basis of the morphology and coloration of the egg, larva and cyst. The covariates included forest fragment area, group size and the presence/absence of human settlements and livestock in proximity. We used a linear regression model to identify the covariates that significantly influenced the prevalence of different parasite taxa. Nine gastrointestinal parasite taxa were detected in lion-tailed macaque groups. The groups near human settlements had greater prevalence and number of taxa, and these variables also had significant positive correlations with group size. We found that these parameters were also greater in groups near human settlements after controlling for group size. Livestock were present in all five fragments that had human settlements in proximity. The present study suggests that high prevalence and species richness of gastrointestinal parasites in lion-tailed macaque groups are directly related to habitat fragmentation, high anthropogenic activities and high host density. The parasite load partially explains the reason for the decline in immature survival and birth rate in small and isolated rainforest fragments in Anamalai Hills.

Transmission of Ebola virus from pigs to non-human primates.

PubMed

Weingartl, Hana M; Embury-Hyatt, Carissa; Nfon, Charles; Leung, Anders; Smith, Greg; Kobinger, Gary

2012-01-01

Ebola viruses (EBOV) cause often fatal hemorrhagic fever in several species of simian primates including human. While fruit bats are considered natural reservoir, involvement of other species in EBOV transmission is unclear. In 2009, Reston-EBOV was the first EBOV detected in swine with indicated transmission to humans. In-contact transmission of Zaire-EBOV (ZEBOV) between pigs was demonstrated experimentally. Here we show ZEBOV transmission from pigs to cynomolgus macaques without direct contact. Interestingly, transmission between macaques in similar housing conditions was never observed. Piglets inoculated oro-nasally with ZEBOV were transferred to the room housing macaques in an open inaccessible cage system. All macaques became infected. Infectious virus was detected in oro-nasal swabs of piglets, and in blood, swabs, and tissues of macaques. This is the first report of experimental interspecies virus transmission, with the macaques also used as a human surrogate. Our finding may influence prevention and control measures during EBOV outbreaks.

Isolation and Characterization of a Neuropathogenic Simian Immunodeficiency Virus Derived from a Sooty Mangabey

PubMed Central

Novembre, Francis J.; De Rosayro, Juliette; O’Neil, Shawn P.; Anderson, Daniel C.; Klumpp, Sherry A.; McClure, Harold M.

1998-01-01

Transfusion of blood from a simian immunodeficiency virus (SIV)- and simian T-cell lymphotropic virus-infected sooty mangabey (designated FGb) to rhesus and pig-tailed macaques resulted in the development of neurologic disease in addition to AIDS. To investigate the role of SIV in neurologic disease, virus was isolated from a lymph node of a pig-tailed macaque (designated PGm) and the cerebrospinal fluid of a rhesus macaque (designated ROn2) and passaged to additional macaques. SIV-related neuropathogenic effects were observed in 100% of the pig-tailed macaques inoculated with either virus. Lesions in these animals included extensive formation of SIV RNA-positive giant cells in the brain parenchyma and meninges. Based upon morphology, the majority of infected cells in both lymphoid and brain tissue appeared to be of macrophage lineage. The virus isolates replicated very well in pig-tailed and rhesus macaque peripheral blood mononuclear cells (PBMC) with rapid kinetics. Differential replicative abilities were observed in both PBMC and macrophage populations, with viruses growing to higher titers in pig-tailed macaque cells than in rhesus macaque cells. An infectious molecular clone of virus derived from the isolate from macaque PGm (PGm5.3) was generated and was shown to have in vitro replication characteristics similar to those of the uncloned virus stock. While molecular analyses of this virus revealed its similarity to SIV isolates from sooty mangabeys, significant amino acid differences in Env and Nef were observed. This virus should provide an excellent system for investigating the mechanism of lentivirus-induced neurologic disease. PMID:9765429

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

PubMed

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.

Activity of wild Japanese macaques in Yakushima revealed by camera trapping: Patterns with respect to season, daily period and rainfall

PubMed Central

Otani, Yosuke; Hongo, Shun; Honda, Takeaki; Okamura, Hiroki; Higo, Yuma

2018-01-01

Animals are subject to various scales of temporal environmental fluctuations, among which daily and seasonal variations are two of the most widespread and significant ones. Many biotic and abiotic factors change temporally, and climatic factors are particularly important because they directly affect the cost of thermoregulation. The purpose of the present study was to determine the activity patterns of wild Japanese macaques (Macaca fuscata) with a special emphasis on the effect of thermal conditions. We set 30 camera traps in the coniferous forest of Yakushima and monitored them for a total of 8658 camera-days between July 2014 and July 2015. Over the one-year period, temperature had a positive effect, and rainfall had a negative effect on the activity of macaques during the day. Capture rate was significantly higher during the time period of one hour after sunrise and during midday. During winter days, macaques concentrated their activity around noon, and activity shifted from the morning toward the afternoon. This could be interpreted as macaques shifting their activity to warmer time periods within a single day. Japanese macaques decreased their activity during the time before sunrise in seasons with lower temperatures. It was beneficial for macaques to be less active during cooler time periods in a cold season. Even small amounts of rainfall negatively affected the activity of Japanese macaques, with capture rates decreasing significantly even when rainfall was only 0.5–1 mm/min. In conclusion, thermal conditions significantly affected the activity of wild Japanese macaques at various time scales. PMID:29293657

Action observation circuits in the macaque monkey cortex.

PubMed

Nelissen, Koen; Borra, Elena; Gerbella, Marzio; Rozzi, Stefano; Luppino, Giuseppe; Vanduffel, Wim; Rizzolatti, Giacomo; Orban, Guy A

2011-03-09

In both monkeys and humans, the observation of actions performed by others activates cortical motor areas. An unresolved question concerns the pathways through which motor areas receive visual information describing motor acts. Using functional magnetic resonance imaging (fMRI), we mapped the macaque brain regions activated during the observation of grasping actions, focusing on the superior temporal sulcus region (STS) and the posterior parietal lobe. Monkeys viewed either videos with only the grasping hand visible or videos with the whole actor visible. Observation of both types of grasping videos activated elongated regions in the depths of both lower and upper banks of STS, as well as parietal areas PFG and anterior intraparietal (AIP). The correlation of fMRI data with connectional data showed that visual action information, encoded in the STS, is forwarded to ventral premotor cortex (F5) along two distinct functional routes. One route connects the upper bank of the STS with area PFG, which projects, in turn, to the premotor area F5c. The other connects the anterior part of the lower bank of the STS with premotor areas F5a/p via AIP. Whereas the first functional route emphasizes the agent and may relay visual information to the parieto-frontal mirror circuit involved in understanding the agent's intentions, the second route emphasizes the object of the action and may aid in understanding motor acts with respect to their immediate goal.

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.

PubMed

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

2016-10-28

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

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.

USGS Publications Warehouse

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 vCJD-infected human and macaque blood.

Refinement of the use of food and fluid control as motivational tools for macaques used in behavioural neuroscience research: report of a Working Group of the NC3Rs.

PubMed

Prescott, Mark J; Brown, Verity J; Flecknell, Paul A; Gaffan, David; Garrod, Kate; Lemon, Roger N; Parker, Andrew J; Ryder, Kathy; Schultz, Wolfram; Scott, Leah; Watson, Jayne; Whitfield, Lucy

2010-11-30

This report provides practical guidance on refinement of the use of food and fluid control as motivational tools for macaques used in behavioural neuroscience research. The guidance is based on consideration of the scientific literature and, where data are lacking, expert opinion and professional experience, including that of the members of a Working Group convened by the United Kingdom National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). The report should be useful to researchers, veterinarians and animal care staff responsible for the welfare of macaques used in food and fluid control protocols, as well as those involved with designing, performing and analysing studies that use these protocols. It should also assist regulatory authorities and members of local ethical review processes or institutional animal care and use committees concerned with evaluating such protocols. The report provides a framework for refinement that can be tailored to meet local requirements. It also identifies data gaps and areas for future research and sets out the Working Group's recommendations on contemporary best practice. Copyright © 2010 Elsevier B.V. All rights reserved.

Decision-Related Activity in Macaque V2 for Fine Disparity Discrimination Is Not Compatible with Optimal Linear Readout.

PubMed

Clery, Stephane; Cumming, Bruce G; Nienborg, Hendrikje

2017-01-18

Fine judgments of stereoscopic depth rely mainly on relative judgments of depth (relative binocular disparity) between objects, rather than judgments of the distance to where the eyes are fixating (absolute disparity). In macaques, visual area V2 is the earliest site in the visual processing hierarchy for which neurons selective for relative disparity have been observed (Thomas et al., 2002). Here, we found that, in macaques trained to perform a fine disparity discrimination task, disparity-selective neurons in V2 were highly selective for the task, and their activity correlated with the animals' perceptual decisions (unexplained by the stimulus). This may partially explain similar correlations reported in downstream areas. Although compatible with a perceptual role of these neurons for the task, the interpretation of such decision-related activity is complicated by the effects of interneuronal "noise" correlations between sensory neurons. Recent work has developed simple predictions to differentiate decoding schemes (Pitkow et al., 2015) without needing measures of noise correlations, and found that data from early sensory areas were compatible with optimal linear readout of populations with information-limiting correlations. In contrast, our data here deviated significantly from these predictions. We additionally tested this prediction for previously reported results of decision-related activity in V2 for a related task, coarse disparity discrimination (Nienborg and Cumming, 2006), thought to rely on absolute disparity. Although these data followed the predicted pattern, they violated the prediction quantitatively. This suggests that optimal linear decoding of sensory signals is not generally a good predictor of behavior in simple perceptual tasks. Activity in sensory neurons that correlates with an animal's decision is widely believed to provide insights into how the brain uses information from sensory neurons. Recent theoretical work developed simple predictions to differentiate decoding schemes, and found support for optimal linear readout of early sensory populations with information-limiting correlations. Here, we observed decision-related activity for neurons in visual area V2 of macaques performing fine disparity discrimination, as yet the earliest site for this task. These findings, and previously reported results from V2 in a different task, deviated from the predictions for optimal linear readout of a population with information-limiting correlations. Our results suggest that optimal linear decoding of early sensory information is not a general decoding strategy used by the brain. Copyright © 2017 the authors 0270-6474/17/370715-11$15.00/0.

Identification of MHC class I sequences in Chinese-origin rhesus macaques

PubMed Central

Karl, Julie A.; Wiseman, Roger W.; Campbell, Kevin J.; Blasky, Alex J.; Hughes, Austin L.; Ferguson, Betsy; Read, Daniel S.

2010-01-01

The rhesus macaque (Macaca mulatta) is an excellent model for human disease and vaccine research. Two populations exhibiting distinctive morphological and physiological characteristics, Indian- and Chinese-origin rhesus macaques, are commonly used in research. Genetic analysis has focused on the Indian macaque population, but the accessibility of these animals for research is limited. Due to their greater availability, Chinese rhesus macaques are now being used more frequently, particularly in vaccine and biodefense studies, although relatively little is known about their immunogenetics. In this study, we discovered major histocompatibility complex (MHC) class I cDNAs in 12 Chinese rhesus macaques and detected 41 distinct Mamu-A and Mamu-B sequences. Twenty-seven of these class I cDNAs were novel, while six and eight of these sequences were previously reported in Chinese and Indian rhesus macaques, respectively. We then performed microsatellite analysis on DNA from these 12 animals, as well as an additional 18 animals, and developed sequence specific primer PCR (PCR-SSP) assays for eight cDNAs found in multiple animals. We also examined our cohort for potential admixture of Chinese and Indian origin animals using a recently developed panel of single nucleotide polymorphisms (SNPs). The discovery of 27 novel MHC class I sequences in this analysis underscores the genetic diversity of Chinese rhesus macaques and contributes reagents that will be valuable for studying cellular immunology in this population. PMID:18097659

Estimation of Shear Wave Speed in the Rhesus Macaques Uterine Cervix

PubMed Central

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 microstructure in both humans and macaques. PMID:26886979

DIFFUSION-WEIGHTED IMAGING TRACTOGRAPHY-BASED PARCELLATION OF THE HUMAN PARIETAL CORTEX AND COMPARISON WITH HUMAN AND MACAQUE RESTING STATE FUNCTIONAL CONNECTIVITY

PubMed Central

Mars, Rogier B.; Jbabdi, Saad; Sallet, Jérôme; O’Reilly, Jill X.; Croxson, Paula L.; Olivier, Etienne; Noonan, MaryAnn P.; Bergmann, Caroline; Mitchell, Anna S.; Baxter, Mark G.; Behrens, Timothy E.J.; Johansen-Berg, Heidi; Tomassini, Valentina; Miller, Karla L.; Rushworth, Matthew F.S.

2011-01-01

Despite the prominence of parietal activity in human neuromaging investigations of sensorimotor and cognitive processes there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI) based tractography and functional interactions were assessed by correlations in activity measured with functional MRI (fMRI) at rest. Resting state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into ten component clusters. The resting state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex. PMID:21411650

Retrospective Analysis of the Incidence of Retained Placenta in 3 Large Colonies of NHP

PubMed Central

Bauer, Cassondra; Harrison, Tara

2016-01-01

During 1999 through 2014, retained placenta was the most common cause of clinical admission for reproductive complications in breeding colonies of baboons (approximate colony size, 2000 animals), cynomolgus macaques (approximately 1000), and rhesus macaques (approximately 500) at the Southwest National Primate Research Center. Retained placentas occurred in 2.7% of baboons, 3.3% of cynomolgus macaques, and 1.0% of rhesus macaques. Apparent risk factors for retained placenta included stillbirth or abortion and at least one prior cesarean section. There was a significant association between stillbirth and retained placenta in all species. Cesarean sections were performed routinely for baboons to meet research objectives but occurred only as needed for cynomolgus and rhesus macaques. Having had at least one prior cesarean section was an incidence factor for retained placenta in 37.0% of baboons and 4.7% of cynomolgus macaques; none of the rhesus macaques with retained placentas had undergone cesarean section previously. More than 90% of dams with retained placenta returned to a successful reproductive life or assignment to a nonbreeding research protocol. Advances in reproductive management will benefit from prospective studies that capture additional data from all members of a breeding group prior to reproductive complications. PMID:27053569

Retrospective Analysis of the Incidence of Retained Placenta in 3 Large Colonies of NHP.

PubMed

Bauer, Cassondra; Harrison, Tara

2016-04-01

During 1999 through 2014, retained placenta was the most common cause of clinical admission for reproductive complications in breeding colonies of baboons (approximate colony size, 2000 animals), cynomolgus macaques (approximately 1000), and rhesus macaques (approximately 500) at the Southwest National Primate Research Center. Retained placentas occurred in 2.7% of baboons, 3.3% of cynomolgus macaques, and 1.0% of rhesus macaques. Apparent risk factors for retained placenta included stillbirth or abortion and at least one prior cesarean section. There was a significant association between stillbirth and retained placenta in all species. Cesarean sections were performed routinely for baboons to meet research objectives but occurred only as needed for cynomolgus and rhesus macaques. Having had at least one prior cesarean section was an incidence factor for retained placenta in 37.0% of baboons and 4.7% of cynomolgus macaques; none of the rhesus macaques with retained placentas had undergone cesarean section previously. More than 90% of dams with retained placenta returned to a successful reproductive life or assignment to a nonbreeding research protocol. Advances in reproductive management will benefit from prospective studies that capture additional data from all members of a breeding group prior to reproductive complications.

Annual variations in sexual hormones and births' frequency in female stump-tailed macaques (Macaca arctoides).

PubMed

Mondragón-Ceballos, R; García-Granados, M D; Matamoros-Trejo, G; Hernández-López, L E

2018-03-01

Although the breeding seasonality in Macaca arctoides have been studied over a long period of time, it is still controversial whether reproduction in this primate tend to increase during certain months of the year as it happens in most of the macaque species. Many authors have classified Macaca arctoides as not being seasonal species. Nonetheless, there were no reports, about seasonal variations of female sexual hormones to demonstrate that asseveration. Therefore, in the present study we collect 1611 fecal samples from June 2009 to November 2010 from 10 female stump-tailed macaques to measure 17β-estradiol and progesterone concentrations. Also, we included the birth frequency per year, in order to identify if sexual hormones peaked at a certain period of the year, thus, births would be occurring six months later according to the gestation length of stump-tailed macaques. Our results indicate two mating seasons per year in stump-tailed macaques: one in July-August and a second one in November. The distribution of the birth frequency, throughout the year support these results. We conclude that stump-tail macaques have a discrete seasonality no different than most of macaques' species. Copyright © 2017 Elsevier Inc. All rights reserved.

A Microneedle Patch for Measles and Rubella Vaccination Is Immunogenic and Protective in Infant Rhesus Macaques.

PubMed

Joyce, Jessica C; Carroll, Timothy D; Collins, Marcus L; Chen, Min-Hsin; Fritts, Linda; Dutra, Joseph C; Rourke, Tracy L; Goodson, James L; McChesney, Michael B; Prausnitz, Mark R; Rota, Paul A

2018-04-26

New methods to increase measles and rubella (MR) vaccination coverage are needed to achieve global and regional MR elimination goals. Here, we developed microneedle (MN) patches designed to administer MR vaccine by minimally trained personnel, leave no biohazardous sharps waste, remove the need for vaccine reconstitution, and provide thermostability outside the cold chain. This study evaluated the immunogenicity of MN patches delivering MR vaccine to infant rhesus macaques. Protective titers of measles neutralizing antibodies (>120 mIU/mL) were detected in 100% of macaques in the MN group and 75% of macaques in the subcutaneous (SC) injection group. Rubella neutralizing antibody titers were >10 IU/mL for all groups. All macaques in the MN group were protected from challenge with wild-type measles virus, whereas 75% were protected in the SC group. However, vaccination by the MN or SC route was unable to generate protective immune responses to measles in infant macaques pretreated with measles immunoglobulin to simulate maternal antibody. These results show, for the first time, that MR vaccine delivered by MN patch generated protective titers of neutralizing antibodies to both measles and rubella in infant rhesus macaques and afforded complete protection from measles virus challenge.

Evidence of Placentophagia and Mother-Infant Cannibalism in Free-Ranging Macaca mulatta tcheliensis in Mount Taihangshan, Jiyuan, China.

PubMed

Tian, Jundong; Zhang, Shiqiang; Guo, Yongman; Garber, Paul A; Guo, Weijie; Kuang, San''ao; Lu, Jiqi

2016-01-01

Placentophagia or the consumption of the afterbirth is reported in many primate species, whereas cannibalism is a relatively rare event. Based on our field observations over the course of 3 years, we present evidence of placentophagia and mother-infant cannibalism in a free-ranging population of the Taihangshan macaque, Macaca mulatta tcheliensis, in the Mt. Taihangshan area, Jiyuan, Henan, China. We documented 1 case in which a mother consumed the afterbirth of her infant. In a second instance, we observed a fresh placenta discarded on the ground by an unknown individual. We also present a description of the first documented instance of mother-infant cannibalism in the same group of free-ranging rhesus macaques. © 2017 S. Karger AG, Basel.

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

PubMed Central

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

2014-01-01

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

Disseminated Hemangiosarcoma in a Juvenile Rhesus Macaque (Macaca mulatta)

PubMed Central

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

2016-01-01

Hemangiosarcoma is a malignant tumor of vascular endothelial origin that is sporadically reported in rhesus macaques. This report describes the clinicopathologic features of a 1-y-old rhesus macaque with spontaneous disseminated hemangiosarcoma that originally presented as a focal cutaneous mass. Histopathologic examination of multiple tumor foci revealed regions in which the neoplastic cells formed diffuse sheets, as well as the well-defined vascular channels typically associated with hemangiosarcoma. Multiple endothelial cell immunomarkers were used to confirm the diagnosis in this rhesus macaque. The tumor exhibited staining properties consistent with those seen in domestic animals and humans. In addition, to our knowledge, this animal represents the youngest case of any form of spontaneous hemangiosarcoma reported in the rhesus macaque to date. PMID:27298251

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

PubMed

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

2016-01-01

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

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

PubMed

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.

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

PubMed Central

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

Establishment of an immortal cynomolgus macaque fibroblast cell line for propagation of cynomolgus macaque cytomegalovirus (CyCMV).

PubMed

Ambagala, Aruna P; Marsh, Angie K; Chan, Jacqueline K; Mason, Rosemarie; Pilon, Richard; Fournier, Jocelyn; Sandstrom, Paul; Willer, David O; MacDonald, Kelly S

2013-05-01

Cynomolgus macaques are widely used as an animal model in biomedical research. We have established an immortalized cynomolgus macaque fibroblast cell line (MSF-T) by transducing primary dermal fibroblasts isolated from a 13-year-old male cynomolgus macaque with a retrovirus vector expressing human telomerase reverse transcriptase (hTERT). The MSF-T cells showed increased telomerase enzyme activity and reached over 200 in vitro passages compared to the non-transduced dermal fibroblasts, which reached senescence after 43 passages. The MSF-T cell line is free of mycoplasma contamination and is permissive to the newly identified cynomolgus macaque cytomegalovirus (CyCMV). CyCMV productively infects MSF-T cells and induces down-regulation of MHC class I expression. The MSF-T cell line will be extremely useful for the propagation of CyCMV and other cynomolgus herspesviruses in host-derived fibroblast cells, allowing for the retention of host-specific viral genes. Moreover, this cell line will be beneficial for many in vitro experiments related to this animal model.

Differential cross-reactivity of monoclonal antibody OPD4 (anti-CD45RO) in macaques.

PubMed

Wang, Xiaolei; Pahar, Bapi; Rasmussen, Terri; Alvarez, Xavier; Dufour, Jason; Rasmussen, Kelsi; Lackner, Andrew A; Veazey, Ronald S

2008-01-01

Immunologic research in nonhuman primates is occasionally limited by the availability of reagents that cross-react in nonhuman primates. One major limitation has been the lack of a monoclonal antibody to CD45RO. Although the monoclonal antibody UCHL-1 is used to detect CD45RO isoforms in humans, it does not react with nonhuman primates, mandating the use of alternative strategies to define "memory" T cell responses in nonhuman primates. The current study examined the reactivity and specificity of another antibody against CD45RO, clone OPD4, in macaques. Here we demonstrate that OPD4 specifically labels memory CD4+ T cells in approximately 44% of rhesus macaques (Macaca mulatta) of Indian but not Chinese origin. In contrast, tissues from pigtail macaques (Macaca nemestrina) react with this clone, indicating that OPD4 may be useful for examining memory CD4+ T cells in certain macaques, but its utility may be limited in other species or even among individual macaques.

Differential cross-reactivity of monoclonal antibody OPD4 (anti-CD45RO) in macaques

PubMed Central

Wang, Xiaolei; Pahar, Bapi; Rasmussen, Terri; Alvarez, Xavier; Dufour, Jason; Rasmussen, Kelsi; Lackner, Andrew A.; Veazey, Ronald S.

2008-01-01

Immunologic research in nonhuman primates is occasionally limited by the availability of reagents that cross react in nonhuman primates. One major limitation has been the lack of a monoclonal antibody to CD45RO. Although the monoclonal antibody UCHL-1 is used to detect CD45RO isoforms in humans, it does not react with nonhuman primates, mandating the use of alternative strategies to define “memory” T cell responses in nonhuman primates. The current study examined the reactivity and specificity of another antibody against CD45RO, clone OPD4, in macaques. Here we demonstrate that OPD4 specifically labels memory CD4+ T cells in ~44% of rhesus macaques (Macaca mulatta) of Indian, but not Chinese origin. In contrast, tissues from pigtail macaques (Macaca nemestrina) react with this clone, indicating that OPD4 may be useful for examining memory CD4+ T cells in certain macaques, but its utility may be limited in other species or even among individual macaques. PMID:18304631

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

PubMed

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.

Gastrointestinal Disease in Simian Immunodeficiency Virus-Infected Rhesus Macaques Is Characterized by Proinflammatory Dysregulation of the Interleukin-6-Janus Kinase/Signal Transducer and Activator of Transcription3 Pathway

PubMed Central

Mohan, Mahesh; Aye, Pyone P.; Borda, Juan T.; Alvarez, Xavier; Lackner, Andrew A.

2007-01-01

Gastrointestinal disease and inflammation are common sequelae of human and simian immunodeficiency virus (SIV) infection. Nevertheless, the molecular mechanisms that lead to gastrointestinal dysfunction remain unclear. We investigated regulation of the interleukin (IL)-6-JAK-STAT3 pathway in jejunum and colon, collected at necropsy, from 10 SIV-infected macaques with diarrhea (group 1), 10 non-SIV-infected macaques with diarrhea (group 2), and 7 control uninfected macaques (group 3). All group 1 and 2 macaques had chronic diarrhea, wasting, and colitis, but group 1 animals had more frequent and severe lesions in the jejunum. A significant increase in IL-6 and SOCS-3 gene expression along with constitutive STAT3 activation was observed in the colon of all group 1 and 2 macaques and in the jejunum of only group 1 macaques compared to controls. Further, in colon, histopathology severity scores correlated significantly with IL-6 (groups 1 and 2) and SOCS-3 (group 2) gene expression. In jejunum, a similar correlation was observed only in group 1 animals. Phosphorylated STAT3 (p-STAT3) was localized to lymphocytes (CD3+) and macrophages (CD68+), with fewer CD3+ lymphocytes expressing p-STAT3 in group 1 macaques. Despite high SOCS-3 expression, STAT3 remained constitutively active, providing a possible explanation for persistent intestinal inflammation and immune activation that may favor viral replication and disease progression. PMID:18055558

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

PubMed

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.

Modulation of the Intracortical LFP during Action Execution and Observation

PubMed Central

Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N.; Kraskov, Alexander

2015-01-01

The activity of mirror neurons in macaque ventral premotor cortex (PMv) and primary motor cortex (M1) is modulated by the observation of another's movements. This modulation could underpin well documented changes in EEG/MEG activity indicating the existence of a mirror neuron system in humans. Because the local field potential (LFP) represents an important link between macaque single neuron and human noninvasive studies, we focused on mirror properties of intracortical LFPs recorded in the PMv and M1 hand regions in two macaques while they reached, grasped and held different objects, or observed the same actions performed by an experimenter. Upper limb EMGs were recorded to control for covert muscle activity during observation. The movement-related potential (MRP), investigated as intracortical low-frequency LFP activity (<9 Hz), was modulated in both M1 and PMv, not only during action execution but also during action observation. Moreover, the temporal LFP modulations during execution and observation were highly correlated in both cortical areas. Beta power in both PMv and M1 was clearly modulated in both conditions. Although the MRP was detected only during dynamic periods of the task (reach/grasp/release), beta decreased during dynamic and increased during static periods (hold). Comparison of LFPs for different grasps provided evidence for partially nonoverlapping networks being active during execution and observation, which might be related to different inputs to motor areas during these conditions. We found substantial information about grasp in the MRP corroborating its suitability for brain–machine interfaces, although information about grasp was generally low during action observation. PMID:26041914

The Retinotopic Organization of Macaque Occipitotemporal Cortex Anterior to V4 and Caudoventral to the Middle Temporal (MT) Cluster

PubMed Central

Janssens, Thomas; Orban, Guy A.

2014-01-01

The retinotopic organization of macaque occipitotemporal cortex rostral to area V4 and caudorostral to the recently described middle temporal (MT) cluster of the monkey (Kolster et al., 2009) is not well established. The proposed number of areas within this region varies from one to four, underscoring the ambiguity concerning the functional organization in this region of extrastriate cortex. We used phase-encoded retinotopic functional MRI mapping methods to reveal the functional topography of this cortical domain. Polar-angle maps showed one complete hemifield representation bordering area V4 anteriorly, split into dorsal and ventral counterparts corresponding to the lower and upper visual field quadrants, respectively. The location of this hemifield representation corresponds to area V4A. More rostroventrally, we identified three other complete hemifield representations. Two of these correspond to the dorsal and the ventral posterior inferotemporal areas (PITd and PITv, respectively) as identified in the Felleman and Van Essen (1991) scheme. The third representation has been tentatively named dorsal occipitotemporal area (OTd). Areas V4A, PITd, PITv, and OTd share a central visual field representation, similar to the areas constituting the MT cluster. Furthermore, they vary widely in size and represent the complete contralateral visual field. Functionally, these four areas show little motion sensitivity, unlike those of the MT cluster, and two of them, OTd and PITd, displayed pronounced two-dimensional shape sensitivity. In general, these results suggest that retinotopically organized tissue extends farther into rostral occipitotemporal cortex of the monkey than generally assumed. PMID:25080580

Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

PubMed

Chaplin, Tristan A; Allitt, Benjamin J; Hagan, Maureen A; Price, Nicholas S C; Rajan, Ramesh; Rosa, Marcello G P; Lui, Leo L

2017-09-01

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural basis of motion perception in the marmoset, a small primate species that is becoming increasingly popular as an experimental model. Copyright © 2017 the American Physiological Society.

Characterization of full-length MHC class II sequences in Indonesian and Vietnamese cynomolgus macaques.

PubMed

Creager, Hannah M; Becker, Ericka A; Sandman, Kelly K; Karl, Julie A; Lank, Simon M; Bimber, Benjamin N; Wiseman, Roger W; Hughes, Austin L; O'Connor, Shelby L; O'Connor, David H

2011-09-01

In recent years, the use of cynomolgus macaques in biomedical research has increased greatly. However, with the exception of the Mauritian population, knowledge of the MHC class II genetics of the species remains limited. Here, using cDNA cloning and Sanger sequencing, we identified 127 full-length MHC class II alleles in a group of 12 Indonesian and 12 Vietnamese cynomolgus macaques. Forty two of these were completely novel to cynomolgus macaques while 61 extended the sequence of previously identified alleles from partial to full length. This more than doubles the number of full-length cynomolgus macaque MHC class II alleles available in GenBank, significantly expanding the allele library for the species and laying the groundwork for future evolutionary and functional studies.

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

PubMed

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.

Allogeneic lymphocytes persist and traffic in feral MHC-matched mauritian cynomolgus macaques.

PubMed

Greene, Justin M; Burwitz, Benjamin J; Blasky, Alex J; Mattila, Teresa L; Hong, Jung Joo; Rakasz, Eva G; Wiseman, Roger W; Hasenkrug, Kim J; Skinner, Pamela J; O'Connor, Shelby L; O'Connor, David H

2008-06-11

Thus far, live attenuated SIV has been the most successful method for vaccinating macaques against pathogenic SIV challenge; however, it is not clear what mechanisms are responsible for this protection. Adoptive transfer studies in mice have been integral to understanding live attenuated vaccine protection in models like Friend virus. Previous adoptive transfers in primates have failed as transferred cells are typically cleared within hours after transfer. Here we describe adoptive transfer studies in Mauritian origin cynomolgus macaques (MCM), a non-human primate model with limited MHC diversity. Cells transferred between unrelated MHC-matched macaques persist for at least fourteen days but are rejected within 36 hours in MHC-mismatched macaques. Cells trafficked from the blood to peripheral lymphoid tissues within 12 hours of transfer. MHC-matched MCM provide the first viable primate model for adoptive transfer studies. Because macaques infected with SIV are the best model for HIV/AIDS pathogenesis, we can now directly study the correlates of protective immune responses to AIDS viruses. For example, plasma viral loads following pathogenic SIV challenge are reduced by several orders of magnitude in macaques previously immunized with attenuated SIV. Adoptive transfer of lymphocyte subpopulations from vaccinated donors into SIV-naïve animals may define the immune mechanisms responsible for protection and guide future vaccine development.

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

PubMed

Regaiolli, Barbara; Spiezio, Caterina; Vallortigara, Giorgio

2016-01-01

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

Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir

PubMed Central

García-Lerma, J. Gerardo; Otten, Ron A; Qari, Shoukat H; Jackson, Eddie; Cong, Mian-er; Masciotra, Silvina; Luo, Wei; Kim, Caryn; Adams, Debra R; Monsour, Michael; Lipscomb, Jonathan; Johnson, Jeffrey A; Delinsky, David; Schinazi, Raymond F; Janssen, Robert; Folks, Thomas M; Heneine, Walid

2008-01-01

Background In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. Methods and Findings We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. Conclusions This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities. PMID:18254653

Development of Broadly Neutralizing Antibodies and Their Mapping by Monomeric gp120 in Human Immunodeficiency Virus Type 1-Infected Humans and Simian-Human Immunodeficiency Virus SHIVSF162P3N-Infected Macaques.

PubMed

Jia, Manxue; Lu, Hong; Markowitz, Martin; Cheng-Mayer, Cecilia; Wu, Xueling

2016-04-01

To improve our understanding of the similarities and differences between neutralizing antibodies elicited by simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and human immunodeficiency virus type 1 (HIV-1)-infected humans, we examined the plasma of 13 viremic macaques infected with SHIVSF162P3Nand 85 HIV-1-infected humans with known times of infection. We identified 5 macaques (38%) from 1 to 2 years postinfection (p.i.) with broadly neutralizing antibodies (bnAbs) against tier 2 HIV-1. In comparison, only 2 out of 42 (5%) human plasma samples collected in a similar time frame of 1 to 3 years p.i. exhibited comparable neutralizing breadths and potencies, with the number increasing to 7 out of 21 (30%) after 3 years p.i. Plasma mapping with monomeric gp120 identified only 2 out of 9 humans and 2 out of 4 macaques that contained gp120-reactive neutralizing antibodies, indicating distinct specificities in these plasma samples, with most of them recognizing the envelope trimer (including gp41) rather than the gp120 monomer. Indeed, a total of 20 gp120-directed monoclonal antibodies (MAbs) isolated from a human subject (AD358) and a Chinese rhesus macaque (GB40) displayed no or limited neutralizing activity against tier 2 strains. These isolated MAbs, mapped to the CD4-binding site, the V3 loop, the inner domain, and the C5 region of gp120, revealed genetic similarity between the human and macaque immunoglobulin genes used to encode some V3-directed MAbs. These results also support the use of envelope trimer probes for efficient isolation of HIV-1 bnAbs. HIV-1 vaccine research can benefit from understanding the development of broadly neutralizing antibodies (bnAbs) in rhesus macaques, commonly used to assess vaccine immunogenicity and efficacy. Here, we examined 85 HIV-1-infected humans and 13 SHIVSF162P3N-infected macaques for bnAbs and found that, similar to HIV-1-infected humans, bnAbs in SHIV-infected macaques are also rare, but their development might have been faster in some of the studied macaques. Plasma mapping with monomeric gp120 indicated that most bnAbs bind to the envelope trimer rather than the gp120 monomer. In support of this, none of the isolated gp120-reactive monoclonal antibodies (MAbs) displayed the neutralization breadth observed in the corresponding plasma. However, the MAb sequences revealed similarity between human and macaque genes used to encode some V3-directed MAbs. Our study sheds light on the timing and development of bnAbs in SHIV-infected macaques in comparison to HIV-1-infected humans and highlights the use of envelope trimer probes for efficient recovery of bnAbs. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

USGS Publications Warehouse

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

2014-01-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre

2007-01-20

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

Intrasulcal Electrocorticography in Macaque Monkeys with Minimally Invasive Neurosurgical Protocols

PubMed Central

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

2011-01-01

Electrocorticography (ECoG), multichannel brain-surface recording and stimulation with probe electrode arrays, has become a potent methodology not only for clinical neurosurgery but also for basic neuroscience using animal models. The highly evolved primate's brain has deep cerebral sulci, and both gyral and intrasulcal cortical regions have been implicated in important functional processes. However, direct experimental access is typically limited to gyral regions, since placing probes into sulci is difficult without damaging the surrounding tissues. Here we describe a novel methodology for intrasulcal ECoG in macaque monkeys. We designed and fabricated ultra-thin flexible probes for macaques with micro-electro-mechanical systems technology. We developed minimally invasive operative protocols to implant the probes by introducing cutting-edge devices for human neurosurgery. To evaluate the feasibility of intrasulcal ECoG, we conducted electrophysiological recording and stimulation experiments. First, we inserted parts of the Parylene-C-based probe into the superior temporal sulcus to compare visually evoked ECoG responses from the ventral bank of the sulcus with those from the surface of the inferior temporal cortex. Analyses of power spectral density and signal-to-noise ratio revealed that the quality of the ECoG signal was comparable inside and outside of the sulcus. Histological examination revealed no obvious physical damage in the implanted areas. Second, we placed a modified silicone ECoG probe into the central sulcus and also on the surface of the precentral gyrus for stimulation. Thresholds for muscle twitching were significantly lower during intrasulcal stimulation compared to gyral stimulation. These results demonstrate the feasibility of intrasulcal ECoG in macaques. The novel methodology proposed here opens up a new frontier in neuroscience research, enabling the direct measurement and manipulation of electrical activity in the whole brain. PMID:21647392

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

PubMed Central

Ferrero, Enza; Orciani, Monia; Vacca, Paola; Ortolan, Erika; Crovella, Sergio; Titti, Fausto; Saccucci, Franca; Malavasi, Fabio

2004-01-01

Background The CD38 transmembrane glycoprotein is an ADP-ribosyl cyclase that moonlights as a receptor in cells of the immune system. Both functions are independently implicated in numerous areas related to human health. This study originated from an inherent interest in studying CD38 in the cynomolgus monkey (Macaca fascicularis), a species closely related to humans that also represents a cogent animal model for the biomedical analysis of CD38. Results A cDNA was isolated from cynomolgus macaque peripheral blood leukocytes and is predicted to encode a type II membrane protein of 301 amino acids with 92% identity to human CD38. Both RT-PCR-mediated cDNA cloning and genomic DNA PCR surveying were possible with heterologous human CD38 primers, demonstrating the striking conservation of CD38 in these primates. Transfection of the cDNA coincided with: (i) surface expression of cynomolgus macaque CD38 by immunofluorescence; (ii) detection of ~42 and 84 kDa proteins by Western blot and (iii) the appearance of ecto-enzymatic activity. Monoclonal antibodies were raised against the cynomolgus CD38 ectodomain and were either species-specific or cross-reactive with human CD38, in which case they were directed against a common disulfide-requiring conformational epitope that was mapped to the C-terminal disulfide loop. Conclusion This multi-faceted characterization of CD38 from cynomolgus macaque demonstrates its high genetic and biochemical similarities with human CD38 while the immunological comparison adds new insights into the dominant epitopes of the primate CD38 ectodomain. These results open new prospects for the biomedical and pharmacological investigations of this receptor-enzyme. PMID:15383153

Social Tolerance in Wild Female Crested Macaques (Macaca nigra) in Tangkoko-Batuangus Nature Reserve, Sulawesi, Indonesia

PubMed Central

Duboscq, Julie; Micheletta, Jérôme; Agil, Muhammad; Hodges, Keith; Thierry, Bernard; Engelhardt, Antje

2013-01-01

In primates, females typically drive the evolution of the social system and present a wide diversity of social structures. To understand this diversity, it is necessary to document the consistency and/or flexibility of female social structures across and within species, contexts, and environments. Macaques (Macaca sp.) are an ideal taxon for such comparative study, showing both consistency and variation in their social relations. Their social styles, constituting robust sets of social traits, can be classified in four grades, from despotic to tolerant. However, tolerant species are still understudied, especially in the wild. To foster our understanding of tolerant societies and to assess the validity of the concept of social style, we studied female crested macaques, Macaca nigra, under entirely natural conditions. We assessed their degree of social tolerance by analyzing the frequency, intensity, and distribution of agonistic and affiliative behaviors, their dominance gradient, their bared-teeth display, and their level of conciliatory tendency. We also analyzed previously undocumented behavioral patterns in grade 4 macaques: reaction upon approach and distribution of affiliative behavior across partners. We compared the observed patterns to data from other populations of grade 4 macaques and from species of other grades. Overall, female crested macaques expressed a tolerant social style, with low intensity, frequently bidirectional, and reconciled conflicts. Dominance asymmetry was moderate, associated with an affiliative bared-teeth display. Females greatly tolerated one another in close proximity. The observed patterns matched the profile of other tolerant macaques and were outside the range of patterns of more despotic species. This study is the first comprehensive analysis of females’ social behavior in a tolerant macaque species under natural conditions and as such, contributes to a better understanding of macaque societies. It also highlights the relevance of the social style concept in the assessment of the degree of tolerance/despotism in social systems. Am. J. Primatol. 75:361-375, 2013. © 2013 Wiley Periodicals, Inc. PMID:23307343

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

PubMed

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 power structure. We discuss how these three major pathways leading to greater understanding and predictability of deleterious aggression in macaque social groups. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

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 < 0.001), and there were no significant differences between the two datasets (t test, p = 0.13 and 0.41; n = 42 and 17 for %RTL and Cb*, respectively). The reproducibilities of the %RTL and Cb* measurements (calculated in the photogrammetric case by taking photographs of the same macaques in two different environments) were significantly correlated between the datasets (r = 0.983 and 0.914, p < 0.001 and 0.005), and there were no significant differences between the datasets (t test, p = 0.539 and 0.344; n = 30 each for %RTL and Cb*, respectively). The %RTL and Cb* data were combined with data on the crown and cheek hair patterns and sex skin reddening of the macaques, and this combined data set was then analyzed by multiple correspondence analysis and agglomerative hierarchical cluster analysis, leading to the categorization of the rhesus macaques, long-tailed macaques, and hybrids at KKZ into five groups. Thus, photogrammetry can be utilized to identify macaque species or hybrids when species identification relies mainly on tail length and pelage color.

Feedforward and recurrent processing in scene segmentation: electroencephalography and functional magnetic resonance imaging.

PubMed

Scholte, H Steven; Jolij, Jacob; Fahrenfort, Johannes J; Lamme, Victor A F

2008-11-01

In texture segregation, an example of scene segmentation, we can discern two different processes: texture boundary detection and subsequent surface segregation [Lamme, V. A. F., Rodriguez-Rodriguez, V., & Spekreijse, H. Separate processing dynamics for texture elements, boundaries and surfaces in primary visual cortex of the macaque monkey. Cerebral Cortex, 9, 406-413, 1999]. Neural correlates of texture boundary detection have been found in monkey V1 [Sillito, A. M., Grieve, K. L., Jones, H. E., Cudeiro, J., & Davis, J. Visual cortical mechanisms detecting focal orientation discontinuities. Nature, 378, 492-496, 1995; Grosof, D. H., Shapley, R. M., & Hawken, M. J. Macaque-V1 neurons can signal illusory contours. Nature, 365, 550-552, 1993], but whether surface segregation occurs in monkey V1 [Rossi, A. F., Desimone, R., & Ungerleider, L. G. Contextual modulation in primary visual cortex of macaques. Journal of Neuroscience, 21, 1698-1709, 2001; Lamme, V. A. F. The neurophysiology of figure ground segregation in primary visual-cortex. Journal of Neuroscience, 15, 1605-1615, 1995], and whether boundary detection or surface segregation signals can also be measured in human V1, is more controversial [Kastner, S., De Weerd, P., & Ungerleider, L. G. Texture segregation in the human visual cortex: A functional MRI study. Journal of Neurophysiology, 83, 2453-2457, 2000]. Here we present electroencephalography (EEG) and functional magnetic resonance imaging data that have been recorded with a paradigm that makes it possible to differentiate between boundary detection and scene segmentation in humans. In this way, we were able to show with EEG that neural correlates of texture boundary detection are first present in the early visual cortex around 92 msec and then spread toward the parietal and temporal lobes. Correlates of surface segregation first appear in temporal areas (around 112 msec) and from there appear to spread to parietal, and back to occipital areas. After 208 msec, correlates of surface segregation and boundary detection also appear in more frontal areas. Blood oxygenation level-dependent magnetic resonance imaging results show correlates of boundary detection and surface segregation in all early visual areas including V1. We conclude that texture boundaries are detected in a feedforward fashion and are represented at increasing latencies in higher visual areas. Surface segregation, on the other hand, is represented in "reverse hierarchical" fashion and seems to arise from feedback signals toward early visual areas such as V1.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

Rhesus Macaques Infected with Macrophage-Tropic Simian Immunodeficiency Virus (SIVmacR71/17E) Exhibit Extensive Focal Segmental and Global Glomerulosclerosis

PubMed Central

Stephens, Edward B.; Tian, Chunqiao; Li, Zhuang; Narayan, Opendra; Gattone, Vincent H.

1998-01-01

We previously showed that inoculation of rhesus macaques with molecularly cloned lymphocytetropic simian immunodeficiency virus (SIVmac239) results in SIV-associated nephropathy (SIVAN) and that the glomerulosclerotic lesions were associated with the selection of macrophagetropic (M-tropic) variants (V. H. Gattone et al., AIDS Res. Hum. Retroviruses 14:1163–1180, 1998). In the present study, seven rhesus macaques were inoculated with M-tropic SIVmacR71/17E, and the renal pathology was examined at necropsy. All SIVmacR71/17E-infected macaques developed AIDS, and most developed other systemic complications, including SIV-induced encephalitis and lentivirus interstitial pneumonia. There was no correlation between the length of infection (42 to 97 days), circulating CD4+ T-cell counts, and renal disease. Of the seven macaques inoculated with SIVmacR71/17E, five developed significant mesangial hyperplasia and expansion of matrix and four were clearly azotemic (serum urea nitrogen concentration of 40 to 112 mg/dl). These same five macaques developed focal segmental to global glomerulosclerotic lesions. Increased numbers of glomerular CD68+ cells (monocytes/macrophages) were found in glomeruli but not the tubulointerstitium of the macaques inoculated with SIVmacR71/17E. All macaques had glomerular deposits of immunoglobulin G (IgG), IgM, and tubuloreticular inclusions, and six of seven had IgA deposition. However, there was no correlation between the presence of circulating anti-SIVmac antibodies, immunoglobulin deposition, and glomerular disease. Tubulointerstitial infiltrates were mild, with little or no correlation to azotemia, while microcystic tubules were evident in those with glomerulosclerosis or azotemia. The four most severely affected macaques were positive for diffuse glomerular immunostaining for viral core p27 antigen, and there was intense staining in the glomeruli of the two macaques with the most severe glomerulosclerosis. Viral sequences were isolated from glomerular and tubulointerstitial fractions from macaques with severe glomerulosclerosis but only from the tubulointerstitial compartment of those that did not develop glomerulosclerosis. Interviral recombinant viruses generated with env sequences isolated from glomeruli confirmed the M-tropic nature of the virus found in the glomeruli. The correlation between the increased number of CD68+ cells (monocytes/macrophages) in the glomeruli, the localization of p27 antigen in the glomeruli, and the glomerular pathology confirms and extends our previous observations of an association between glomerular infection and infiltration by M-tropic virus and SIVAN. PMID:9765427

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

PubMed Central

Myers, Amy J.; Jarvela, Jessica; Flynn, JoAnne; Rutledge, Tara; Bonfield, Tracey

2016-01-01

Immune cells of the distal airways serve as “first responders” of host immunity to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (LTBI) to active tuberculosis of various degrees of severity. To further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and cynomolgus macaques before and after Mtb infection. A simple gating strategy effectively defined BAL T-cell and phagocyte populations in both species. BAL from Mtb-naive humans and macaques showed similar differential cell counts. BAL T cells of macaques were composed of fewer CD4+cells but more CD8+ and CD4+CD8+ double-positive cells than were BAL T cells of humans. The most common mononuclear phagocyte population in BAL of both species displayed coexpression of HLA-DR, CD206, CD11b, and CD11c; however, multiple phagocyte subsets displaying only some of these markers were observed as well. Macaques with LTBI displayed a marked BAL lymphocytosis that was not observed in humans with LTBI. In macaques, the prevalence of specific mononuclear phagocyte subsets in baseline BAL correlated with ultimate outcomes of Mtb infection (i.e., LTBI versus active disease). Overall, these findings demonstrate the comparability of studies of pulmonary immunity to Mtb in humans and macaques. They also indicate a previously undescribed complexity of airway mononuclear phagocyte populations that suggests further lines of investigation relevant to understanding the mechanisms of both protection from and susceptibility to the development of active tuberculosis within the lung. PMID:27509488

Whole Mitochondrial Genomic and Y-Chromosomal Phylogenies of Burmese Long-Tailed Macaque (Macaca fascicularis aurea) Suggest Ancient Hybridization between fascicularis and sinica Species Groups.

PubMed

Matsudaira, Kazunari; Hamada, Yuzuru; Bunlungsup, Srichan; Ishida, Takafumi; San, Aye Mi; Malaivijitnond, Suchinda

2018-05-11

Macaca fascicularis aurea (Burmese long-tailed macaque) is 1 of the 10 subspecies of Macaca fascicularis. Despite having few morphological differences from other subspecies, a recent phylogeographic study showed that M. f. aurea is clearly distinct genetically from Macaca fascicularis fascicularis (common long-tailed macaque) and suggests that M. f. aurea experienced a disparate evolutionary pathway versus other subspecies. To construct a detailed evolutionary history of M. f. aurea and its relationships with other macaque species, we performed phylogenetic analyses and divergence time estimation of whole mitochondrial genomes (2 M. f. aurea, 8 M. f. fascicularis, and 16 animals of 12 macaque species) and 2871 bp of the Y chromosome (1 M. f. aurea, 2 M. f. fascicularis, and 5 animals of 5 macaque species) and haplotype network analysis of 758 bp of the Y chromosome (1 M. f. aurea, 2 M. f. fascicularis, and 21 animals of 19 macaque species). Whereas the Y chromosome of M. f. aurea clustered with those of the fascicularis species group in the phylogenetic and haplotype network analyses, its mtDNA clustered within the clade of the sinica species group. Based on this phylogenetic incongruence and the estimated divergence times, we propose that proto-M. f. aurea underwent hybridization with a population of the sinica species group between 2.5 and 0.95 MYA after divergence from the common ancestor of M. fascicularis. Hybridization and introgression might have been central in the evolution of M. f. aurea, similar to what occurred in the evolution of other macaque species and subspecies.

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

PubMed

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 < 0.001). Efficacy was reduced to 60% when TFV gel was applied 3 days before SHIV challenge (P = 0.07). Plasma TFV and TFV diphosphate concentrations in tissues and 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.

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

PubMed

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

2016-10-01

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

Multiple parietal-frontal pathways mediate grasping in macaque monkeys

PubMed Central

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

2011-01-01

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

A multi-standard approach for GIAO (13)C NMR calculations.

PubMed

Sarotti, Ariel M; Pellegrinet, Silvina C

2009-10-02

The influence of the reference standard employed in the calculation of (13)C NMR chemical shifts was investigated over a large variety of known organic compounds, using different quantum chemistry methods and basis sets. After detailed analysis of the collected data, we found that methanol and benzene are excellent reference standards for computing NMR shifts of sp(3)- and sp-sp(2)-hybridized carbon atoms, respectively. This multi-standard approach (MSTD) performs better than TMS in terms of accuracy and precision and also displays much lower dependence on the level of theory employed. The use of mPW1PW91/6-31G(d)//mPW1PW91/6-31G(d) level is recommended for accurate (13)C NMR chemical shift prediction at low computational cost.

Temporally evolving gain mechanisms of attention in macaque area V4.

PubMed

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 American Physiological Society.

Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey

PubMed Central

Scott, Brian H.; Leccese, Paul A.; Saleem, Kadharbatcha S.; Kikuchi, Yukiko; Mullarkey, Matthew P.; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C.

2017-01-01

Abstract In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex. PMID:26620266

Synanthropic Primates in Asia: Potential Sentinels for Environmental Toxins

PubMed Central

Engel, Gregory; O’Hara, Todd M.; Cardona-Marek, Tamara; Heidrich, John; Chalise, Mukesh K.; Kyes, Randall; Jones-Engel, Lisa

2010-01-01

Macaques are similar to humans both physiologically and behaviorally. In South and Southeast Asia they are also synanthropic, ecologically associated with humans. Synanthropy with humans raises the possibility that macaques come into contact with anthropogenic toxicants, such as lead and mercury, and might be appropriate sentinels for human exposures to certain toxic materials. We measured lead (Pb) and mercury (Hg) levels and characterized the stable isotopic compositions of δ15N and δ13C in hair from three groups of free-ranging macaques at the Swoyambhu temple in Kathmandhu, Nepal, an urban population that has abundant contact with humans. Hair lead levels were significantly higher among young macaques and differed among the three groups of macaques that were sampled. Hair Hg levels were low. No statistical association was found between stable isotopic compositions (δ15N and δ13C) and Pb and Hg levels. Our data did not find evidence that lead levels were associated with diet. We conclude that, in this population of macaques, behavioral and/or physiologic factors may play a significant role in determining exposure to lead. Chemical analysis of hair is a promising, noninvasive technique for determining exposure to toxic elements in free-ranging nonhuman primates. PMID:20033917

The high-affinity receptor for IgG, FcγRI, of humans and non-human primates.

PubMed

Chenoweth, Alicia M; Trist, Halina M; Tan, Peck-Szee; Wines, Bruce D; Hogarth, P Mark

2015-11-01

Non-human primate (NHP) models, especially involving macaques, are considered important models of human immunity and have been essential in preclinical testing for vaccines and therapeutics. Despite this, much less characterization of macaque Fc receptors has occurred compared to humans or mice. Much of the characterization of macaque Fc receptors so far has focused on the low-affinity Fc receptors, particularly FcγRIIIa. From these studies, it is clear that there are distinct differences between the human and macaque low-affinity receptors and their interaction with human IgG. Relatively little work has been performed on the high-affinity IgG receptor, FcγRI, especially in NHPs. This review will focus on what is currently known of how FcγRI interacts with IgG, from mutation studies and recent crystallographic studies of human FcγRI, and how amino acid sequence differences in the macaque FcγRI may affect this interaction. Additionally, this review will look at the functional consequences of differences in the amino acid sequences between humans and macaques. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

Gibson, Luke

2011-07-01

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

Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm viruslike particles.

PubMed Central

Bradley, D W; Krawczynski, K; Cook, E H; McCaustland, K A; Humphrey, C D; Spelbring, J E; Myint, H; Maynard, J E

1987-01-01

An experimental model of enterically transmitted non-A, non-B hepatitis (ET-NANBH) was established in tamarins (Saguinus mystax mystax) and cynomolgus macaques (Macaca fascicularis). First-passage animals were inoculated with two different stool suspensions obtained from human patients with well-defined ET-NANBH that originated from Burma and Pakistan, where epidemics of ET-NANBH occur. Both inocula contained 27- ato 34-nm-diameter viruslike particles (VLPs) that were specifically aggregated by acute-phase ET-NANBH sera. ET-NANBH was subpassaged in both tamarins and cynomolgus macaques by using pools of stool suspensions from first-passage animals. One additional passage of disease in cynomolgus macaques resulted in a significantly shortened incubation period and increased severity of disease. VLPs similar to those found in the human inocula were observed in stool specimens of first-, second-, and third-passage cynomolgus macaques and in first- and second-passage tamarins. Our findings indicate that cynomolgus macaques are particularly suitable experimental models for studies of human ET-NANBH. The 27- to 34-nm VLPs found in infected human and primate stools appear to be etiologically linked to disease. Images PMID:3114746

Mirror Neurons in Humans: Consisting or Confounding Evidence?

ERIC Educational Resources Information Center

Turella, Luca; Pierno, Andrea C.; Tubaldi, Federico; Castiello, Umberto

2009-01-01

The widely known discovery of mirror neurons in macaques shows that premotor and parietal cortical areas are not only involved in executing one's own movement, but are also active when observing the action of others. The goal of this essay is to critically evaluate the substance of functional magnetic resonance imaging (fMRI) and positron emission…

Cervical carotid and circle of willis arterial anatomy of macaque monkeys: a comparative anatomy study.

PubMed

Kumar, Nishant; Lee, John J; Perlmutter, Joel S; Derdeyn, Colin P

2009-07-01

Macaque monkeys are used in many research applications, including cerebrovascular investigations. However, detailed catalogs of the relevant vascular anatomy are scarce. We present our experience with macaque vessel patterns as determined by digital subtraction angiography of 34 different monkeys. We retrospectively analyzed digital subtraction angiograms obtained during experimental internal carotid artery (ICA) catheterization and subsequent injection of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine. Results were catalogued according to vascular distribution and variants observed. Macaque monkeys have a bovine aortic arch. The carotid vessels generally bifurcate, but are occasionally observed to divide into three vessels. The external carotid gives rise primarily to two trunks: an occipital branch and a common vessel that subsequently gives off the lingual, facial, and superior thyroid arteries. The internal maxillary artery may be present as a terminal branch of the external carotid or as a branch of the occipital artery. The ICA is similar in course to that of the human. The anterior circle of Willis was intact in all monkeys in our study. Its primary difference from that of the human is the union of the bilateral anterior cerebral arteries as a single (azygous) median vessel. Macaque cervical carotid and circle of Willis arterial anatomy differs from humans in a couple of specific patterns. Knowledge of these differences and similarities between human and macaque anatomy is important in developing endovascular macaque models of human diseases, such as ischemic stroke.

Sustained release of the CCR5 inhibitors CMPD167 and maraviroc from vaginal rings in rhesus macaques.

PubMed

Malcolm, R Karl; Veazey, Ronald S; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M; Murphy, Diarmaid J; Boyd, Peter; Major, Ian; Shattock, Robin J; Klasse, Per Johan; Doyle, Lara A; Rasmussen, Kelsi K; Goldman, Laurie; Ketas, Thomas J; Moore, John P

2012-05-01

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ~10(6)-fold greater than the 50% inhibitory concentrations (IC(50)s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.

Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

PubMed Central

Veazey, Ronald S.; Geer, Leslie; Lowry, Deborah; Fetherston, Susan M.; Murphy, Diarmaid J.; Boyd, Peter; Major, Ian; Shattock, Robin J.; Klasse, Per Johan; Doyle, Lara A.; Rasmussen, Kelsi K.; Goldman, Laurie; Ketas, Thomas J.; Moore, John P.

2012-01-01

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 μg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ∼106-fold greater than the 50% inhibitory concentrations (IC50s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle. PMID:22330914

Niche partitioning between sympatric rhesus macaques and Yunnan snub-nosed monkeys at Baimaxueshan Nature Reserve, China.

PubMed

Grueter, Cyril C; Li, Da-Yong; Feng, Shun-Kai; Ren, Bao-Ping

2010-10-01

Here we provide a preliminary assessment of dietary and habitat requirements of two sympatric primate taxa, a "simple-stomached" and "complex-stomached" species (Rhinopithecus bieti Colobinae vs. Macaca mulatta Cercopithecinae), as a basis for illuminating how the two coexist. Of ca. 22 plant food species consumed by the macaques, at least 16 were also eaten by the snub-nosed monkeys. Both species showed a preference for fruits. While the snub-nosed monkeys did not utilize any resources associated with human communities, rhesus macaques did occasionally raid agricultural crops. The mean elevation of the snub-nosed monkey group was 3,218 m, while the mean elevation of the macaque group was 2,995 m. Macaques were also spotted on meadows whereas snub-nosed monkeys evidently avoided these. For both species, mixed deciduous broadleaf/conifer forest was the most frequently used ecotype, but whereas evergreen broadleaf forest (Cyclobalanopsis community) accounted for only 3% of the location records of the snub-nosed monkeys, it accounted for 36% of the location records of the macaques. Groups of the two species usually kept a considerable spatial distance from one another (mean 2.4 km). One close encounter and confrontation between groups of the two species resulted in the macaque group moving away. Our findings suggest that the coexistence of the two taxa is facilitated via differential macrohabitat use and spatial avoidance. Although divergent habitat-use strategies may reflect interspecific competition, they may also merely reflect different physiological or ecological requirements.

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

PubMed

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

2015-02-01

Limestone hills are an unusual habitat for primates, prompting them to evolve specific behavioral adaptations to the component karst habitat. From September 2012 to August 2013, we collected data on the diet of one group of Assamese macaques living in limestone forests at Nonggang National Nature Reserve, Guangxi Province, China, using instantaneous scan sampling. Assamese macaques were primarily folivorous, young leaves accounting for 75.5% and mature leaves an additional 1.8% of their diet. In contrast, fruit accounted for only 20.1%. The young leaves of Bonia saxatilis, a shrubby, karst-endemic bamboo that is superabundant in limestone hills, comprised the bulk of the average monthly diet. Moreover, macaques consumed significantly more bamboo leaves during the season when the availability of fruit declined, suggesting that bamboo leaves are an important fallback food for Assamese macaques in limestone forests. In addition, diet composition varied seasonally. The monkeys consumed significantly more fruit and fewer young leaves in the fruit-rich season than in the fruit-lean season. Fruit consumption was positively correlated with fruit availability, indicating that fruit is a preferred food for Assamese macaques. Of seventy-eight food species, only nine contributed >0.5% of the annual diet, and together these nine foods accounted for 90.7% of the annual diet. Our results suggest that bamboo consumption represents a key factor in the Assamese macaque's dietary adaptation to limestone habitat. © 2014 Wiley Periodicals, Inc.

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

PubMed Central

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

2012-01-01

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

Different macaque models of cognitive aging exhibit task-dependent behavioral disparities.

PubMed

Comrie, Alison E; Gray, Daniel T; Smith, Anne C; Barnes, Carol A

2018-05-15

Deficits in cognitive functions that rely on the integrity of the frontal and temporal lobes are characteristic of normative human aging. Due to similar aging phenotypes and homologous cortical organization between nonhuman primates and humans, several species of macaque monkeys are used as models to explore brain senescence. These macaque species are typically regarded as equivalent models of cognitive aging, yet no direct comparisons have been made to support this assumption. Here we used adult and aged rhesus and bonnet macaques (Macaca mulatta and Macaca radiata) to characterize the effect of age on acquisition and retention of information across delays in a battery of behavioral tasks that rely on prefrontal cortex and medial temporal lobe networks. The cognitive functions that were tested include visuospatial short-term memory, object recognition memory, and object-reward association memory. In general, bonnet macaques at all ages outperformed rhesus macaques on tasks thought to rely primarily on the prefrontal cortex, and were more resilient to age-related deficits in these behaviors. On the other hand, both species were comparably impaired by age on tasks thought to preferentially engage the medial temporal lobe. Together, these results suggest that rhesus and bonnet macaques are not equivalent models of cognitive aging and highlight the value of cross-species comparisons. These observations should enable improved design and interpretation of future experiments aimed at understanding changes in cognition across the lifespan. Copyright © 2018 Elsevier B.V. All rights reserved.

Cervical Carotid and Circle of Willis Arterial Anatomy of Macaque Monkeys: A Comparative Anatomy Study

PubMed Central

Kumar, Nishant; Lee, John J.; Perlmutter, Joel S.; Derdeyn, Colin P.

2009-01-01

Macaque monkeys are used in many research applications, including cerebrovascular investigations. However, detailed catalogs of the relevant vascular anatomy are scarce. We present our experience with macaque vessel patterns as determined by digital subtraction angiography of 34 different monkeys. METHODS AND MATERIALS: We retrospectively analyzed digital subtraction angiograms obtained during experimental internal carotid artery catheterization and subsequent injection of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP). Results were catalogued according to vascular distribution and variants observed. RESULTS: Macaque monkeys have a bovine aortic arch. The carotid vessels generally bifurcate, but are occasionally observed to divide into three vessels. The external carotid gives rise primarily to two trunks: an occipital branch and a common vessel that subsequently gives off the lingual, facial, and superior thyroid arteries. The internal maxillary artery may be present as a terminal branch of the external carotid or as a branch of the occipital artery. The internal carotid artery is similar in course to that of the human. The anterior circle of Willis was intact in all monkeys in our study. Its primary difference from that of the human is the union of the bilateral anterior cerebral arteries as a single (azygous) median vessel. CONCLUSIONS: Macaque cervical carotid and circle of Willis arterial anatomy differs from humans in a couple of specific patterns. Knowledge of these differences and similarities between human and macaque anatomy is important in developing endovascular macaque models of human diseases, such as ischemic stroke. PMID:19434671

Color vision test for dichromatic and trichromatic macaque monkeys.

PubMed

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

2013-11-01

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

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

PubMed Central

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

2015-01-01

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

Attentional modulation of cell-class specific gamma-band synchronization in awake monkey area V4

PubMed Central

Vinck, Martin; Womelsdorf, Thilo; Buffalo, Elizabeth A.; Desimone, Robert; Fries, Pascal

2013-01-01

Summary Selective visual attention is subserved by selective neuronal synchronization, entailing precise orchestration among excitatory and inhibitory cells. We tentatively identified these as broad (BS) and narrow spiking (NS) cells and analyzed their synchronization to the local field potential in two macaque monkeys performing a selective visual attention task. Across cells, gamma phases scattered widely but were unaffected by stimulation or attention. During stimulation, NS cells lagged BS cells on average by ~60° and gamma synchronized twice as strongly. Attention enhanced and reduced the gamma locking of strongly and weakly activated cells, respectively. During a pre-stimulus attentional cue period, BS cells showed weak gamma synchronization, while NS cells gamma synchronized as strongly as with visual stimulation. These analyses reveal the cell-type specific dynamics of the gamma cycle in macaque visual cortex and suggest that attention affects neurons differentially depending on cell type and activation level. PMID:24267656

Figure-Ground Organization in Visual Cortex for Natural Scenes

PubMed Central

2016-01-01

Abstract Figure-ground organization and border-ownership assignment are essential for understanding natural scenes. It has been shown that many neurons in the macaque visual cortex signal border-ownership in displays of simple geometric shapes such as squares, but how well these neurons resolve border-ownership in natural scenes is not known. We studied area V2 neurons in behaving macaques with static images of complex natural scenes. We found that about half of the neurons were border-ownership selective for contours in natural scenes, and this selectivity originated from the image context. The border-ownership signals emerged within 70 ms after stimulus onset, only ∼30 ms after response onset. A substantial fraction of neurons were highly consistent across scenes. Thus, the cortical mechanisms of figure-ground organization are fast and efficient even in images of complex natural scenes. Understanding how the brain performs this task so fast remains a challenge. PMID:28058269

Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats.

PubMed

Ghasemnejad-Berenji, Morteza; Ghazi-Khansari, Mahmoud; Pashapour, Sarvin; Jafari, Abbas; Yazdani, Iraj; Ghasemnejad-Berenji, Hojjat; Saeedi Saravi, Seyed Soheil; Sadeghpour, Sonia; Nobakht, Maliheh; Abdollahi, Alireza; Mohajer Ansari, Javad; Dehpour, Ahmad Reza

2018-06-11

The aim of this study was to investigate the effects of rapamycin (rapa) and metformin (met), combined administration on testicular torsion-detorsion (T/D) injury. A total of 108 male rats were divided randomly into six groups (n = 18), control, sham-operated, T/D, T/D + met (100 mg/kg), T/D + rapa (0.25 mg/kg) and T/D + met (100 mg/kg)+rapa (0.25 mg/kg). Except for the control and sham groups, torsion was created by rotating the right testis 720° in a clockwise direction for 1 h. Treatment groups received drug intraperitoneally, 30 min before detorsion. The right testis of 6 animals from each group was excised 4 h after detorsion for the measurement of lipid peroxidation, caspase-3, and antioxidant enzyme activities. Histopathological changes and germ cell apoptosis were determined by measuring mean of seminiferous tubules diameters (MSTD) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) test in rest of animals, 24 h after detorsion. In T/D group tissue malondialdehyde (MDA) level and caspase-3 activity increased and the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased in comparison with the control group after detorsion. Met and rapa separately pre-treatment reduced MDA and caspase-3 levels, normalized antioxidant enzyme activities, reduced germ cell apoptosis and improved the MSTD in comparison with T/D group. However combined administration of met and rapa indicated a significant augmented effect as compared to the individual drug interventions on the reversal of T/D induced oxidative stress, apoptosis, and histologic changes, suggesting a synergistic response. Thus, this study shows that rapa and met combination have significant synergistic effects against oxidative stress and apoptosis and opens up further possibilities for the design of new combinatorial therapies to prevent tissue damage after ischemia-reperfusion (I/R). Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Comparison of rectal and infrared thermometry for obtaining body temperature in cynomolgus macaques (Macaca fascicularis).

PubMed

Sikoski, P; Banks, M L; Gould, R; Young, R W; Wallace, J M; Nader, M A

2007-12-01

It would be clinically advantageous to develop a method of body temperature evaluation in cynomolgus macaques (Macaca fascicularis) that did not require sedation, restraint, surgical manipulation, or expensive equipment. Body temperatures of 51 cynomolgus macaques were taken with rectal thermometry and non-contact infrared thermometry (NIFT) on the shoulder, face, abdomen, and axillary region. Body temperature measurements from NIFT were statistically different (P < 0.0001) from rectal thermometry. In addition, there was greater between- and within-subject variability in values using NIFT. There was no correlation between any sites of the NIFT and rectal thermometry. It was concluded that NIFT was not a valid alternative to rectal thermometry in cynomolgus macaques.

Occipital White Matter Tracts in Human and Macaque

PubMed Central

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

2017-01-01

Abstract 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. PMID:28369290

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

PubMed

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

2015-01-01

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

Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

PubMed Central

Whitehouse, Chris A.; Chase, Kitty; Embers, Monica E.; Kulesh, David A.; Ladner, Jason T.; Palacios, Gustavo F.; Minogue, Timothy D.

2016-01-01

Background Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. Methods We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. Results All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. Conclusions We developed several accurate, sensitive, and species-specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID:26365904

Specific Pathogen Free Macaque Colonies: A Review of Principles and Recent Advances for Viral Testing and Colony Management

PubMed Central

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

2016-01-01

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

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

PubMed

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

2013-02-19

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

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

PubMed Central

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

2013-01-01

The strict tropism of many pathogens for man hampers the development of animal models that recapitulate important microbe–host interactions. We developed a rhesus macaque model for studying Neisseria–host interactions using Neisseria species indigenous to the animal. We report that Neisseria are common inhabitants of the rhesus macaque. Neisseria isolated from the rhesus macaque recolonize animals after laboratory passage, persist in the animals for at least 72 d, and are transmitted between animals. Neisseria are naturally competent and acquire genetic markers from each other in vivo, in the absence of selection, within 44 d after colonization. Neisseria macacae encodes orthologs of known or presumed virulence factors of human-adapted Neisseria, as well as current or candidate vaccine antigens. We conclude that the rhesus macaque model will allow studies of the molecular mechanisms of Neisseria colonization, transmission, persistence, and horizontal gene transfer. The model can potentially be developed further for preclinical testing of vaccine candidates. PMID:23382234

Heterospecific SNP diversity in humans and rhesus macaque (Macaca mulatta)

PubMed Central

Ng, Jillian; Trask, Jessica Satkoski; Smith, David Glenn; Kanthaswamy, Sree

2018-01-01

Background Conservation of single nucleotide polymorphisms (SNPs) between human and other primates (i.e., heterospecific SNPs) in candidate genes can be used to assess the utility of those organisms as models for human biomedical research. Methods 59,691 heterospecific SNPs in 22 rhesus macaques and 20 humans were analyzed for human trait associations and 4,207 heterospecific SNPs biallelic in both taxa were compared for genetic variation. Results Variation comparisons at the 4,207 SNPs showed that humans were more genetically diverse than rhesus macaques with observed and expected heterozygosities of 0.337 and 0.323 versus 0.119 and 0.102, and minor allele frequencies of 0.239 and 0.063, respectively. 431 of the 59,691 heterospecific SNPs are reportedly associated with human-specific traits. Conclusion While comparisons between human and rhesus macaque genomes are plausible, functional studies of heterospecific SNPs are necessary to determine whether rhesus macaque alleles are associated with the same phenotypes as their corresponding human alleles. PMID:25963897

Hematologic abnormalities associated with Simian Immunodeficieny Virus (SIV) Infection mimic those in HIV infection

PubMed Central

Gill, Amy F.; Ahsan, Muhammad H.; Lackner, Andrew A.; Veazey, Ronald S.

2012-01-01

Studies of hematologic abnormalities in HIV infected patients are confounded by a multitude of factors. A retrospective data analysis of SIV infected Rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. Hematologic data from rhesus macaques inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared to non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggest that, like in HIV infection, hematologic abnormalities are major complications of SIV infection. PMID:22620272

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-05-01

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

Rotational displacement skills in rhesus macaques (Macaca mulatta).

PubMed

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.

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

PubMed

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

2014-05-01

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

Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

PubMed

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.

Brief communication: Hip joint mobility in free-ranging rhesus macaques

PubMed Central

Hammond, Ashley S.; Johnson, Victoria P.; Higham, James P.

2016-01-01

Objectives We aimed to test for differences in hip joint range of motion (ROM) between captive and free-ranging rhesus macaques (Macaca mulatta), particularly for hip joint abduction, which previous studies of captive macaques have found to be lower than predicted. Materials and Methods Hip ROM was assessed following standard joint measurement methodology in anesthetized adult free-ranging rhesus macaques (n=39) from Cayo Santiago, and compared to published ROM data from captive rhesus macaques (n=16) (Hammond 2014a, American Journal of Physical Anthropology). Significant differences between populations were detected using one-way analysis of variance (p<0.05). Results In a sample of pooled sexes and ages, free-ranging macaques are capable of increased hip abduction, flexion, and internal rotation compared to captive individuals. These differences in joint excursion resulted in free-ranging individuals having significantly increased ROM for hip adduction-abduction, rotation, flexion-extension, and the distance spanned by the knee during hip abduction. When looking at data for a smaller sample of age-matched males, fewer ROM differences are significant, but free-ranging males have significantly increased hip abduction, internal rotation, range of flexion-extension, and distance spanned by the knee during hip abduction compared to captive males of similar age. Discussion Our results suggest that a spatially restrictive environment results in decreased hip mobility in cage-confined animals and ultimately limits the potential limb postures in captive macaques. These results have implications for selection of animal samples in model validation studies, as well as laboratory animal husbandry practices. PMID:27731892

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

PubMed

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

2016-04-01

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

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

PubMed

Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

2016-03-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

Spatial Embedding and Wiring Cost Constrain the Functional Layout of the Cortical Network of Rodents and Primates

PubMed Central

Magrou, Loïc; Gămănuț, Bianca; Van Essen, David C.; Burkhalter, Andreas; Knoblauch, Kenneth; Toroczkai, Zoltán; Kennedy, Henry

2016-01-01

Mammals show a wide range of brain sizes, reflecting adaptation to diverse habitats. Comparing interareal cortical networks across brains of different sizes and mammalian orders provides robust information on evolutionarily preserved features and species-specific processing modalities. However, these networks are spatially embedded, directed, and weighted, making comparisons challenging. Using tract tracing data from macaque and mouse, we show the existence of a general organizational principle based on an exponential distance rule (EDR) and cortical geometry, enabling network comparisons within the same model framework. These comparisons reveal the existence of network invariants between mouse and macaque, exemplified in graph motif profiles and connection similarity indices, but also significant differences, such as fractionally smaller and much weaker long-distance connections in the macaque than in mouse. The latter lends credence to the prediction that long-distance cortico-cortical connections could be very weak in the much-expanded human cortex, implying an increased susceptibility to disconnection syndromes such as Alzheimer disease and schizophrenia. Finally, our data from tracer experiments involving only gray matter connections in the primary visual areas of both species show that an EDR holds at local scales as well (within 1.5 mm), supporting the hypothesis that it is a universally valid property across all scales and, possibly, across the mammalian class. PMID:27441598

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

PubMed Central

Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

2016-01-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

I scan, therefore I decline: The time course of difficulty monitoring in humans (homo sapiens) and macaques (macaca mulatta).

PubMed

Smith, J David; Boomer, Joseph; Church, Barbara A; Zakrzewski, Alexandria C; Beran, Michael J; Baum, Michael L

2018-05-01

The study of nonhumans' metacognitive judgments about trial difficulty has grown into an important comparative literature. However, the potential for associative-learning confounds in this area has left room for behaviorist interpretations that are strongly asserted and hotly debated. This article considers how researchers may be able to observe animals' strategic cognitive processes more clearly by creating temporally extended problems within which associative cues are not always immediately available. We asked humans and rhesus macaques to commit to completing spatially extended mazes or to decline completing them through a trial-decline response. The mazes could sometimes be completed successfully, but other times had a constriction that blocked completion. A deliberate, systematic scanning process could preevaluate a maze and determine the appropriate response. Latency analyses charted the time course of the evaluative process. Both humans and macaques appeared, from the pattern of their latencies, to scan the mazes through before committing to completing them. Thus monkeys, too, can base trial-decline responses on temporally extended evaluation processes, confirming that those responses have strategic cognitive-processing bases in addition to behavioral-reactive bases. The results also show the value of temporally and spatially extended problems to let researchers study the trajectory of animals' online cognitive processes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Park Rangers’ Behaviors and Their Effects on Tourists and Tibetan Macaques (Macaca thibetana) at Mt. Huangshan, China

PubMed Central

Usui, Rie; Sheeran, Lori K.; Li, Jin-hua; Sun, Lixing; Wang, Xi; Pritchard, Alexander J.; DuVall-Lash, Alexander S.; Wagner, R. Steve

2014-01-01

Simple Summary Conflict between macaques and humans is a commonly reported problem in Asian tourism. However, without understanding how macaques are managed, the establishment of an effective management design is impracticable. This study explored how monkeys were managed and tourists were regulated at the Valley of the Wild Monkeys in Mt. Huangshan, Anhui Province, China, through a field observation. Two teams of park rangers alternated monthly and managed a group of macaques. The results suggested that undesired tourists’ interactions with monkeys were not regularly intervened by park rangers, and park rangers established dominance over the monkeys by using physical threats to manage them. Abstract Previous studies have reported the negative impacts of tourism on nonhuman primates (NHPs) and tourists and advocated the improvement of tourism management, yet what constitutes good quality management remains unclear. We explored whether rates of macaque aggression and self-directed behaviors (SDBs) differed under the supervision of two park ranger teams at the Valley of the Wild Monkeys (VWM) in Mt. Huangshan, Anhui Province, China. The two ranger teams provisioned and managed a group of macaques on an alternating monthly basis. Monkey, tourist and ranger behaviors were collected from August 16–September 30, 2012. Macaque aggression and SDB rates did not differ significantly under the management of the two teams. Overall, there was little intervention in tourist-macaque interactions by park rangers, and even when rangers discouraged tourists’ undesirable behaviors, tourist interactions with monkeys persisted. Furthermore, only one or sometimes two park rangers managed monkeys and tourists, and rangers established dominance over the monkeys to control them. In order to effectively manage tourists and monkeys by a single park ranger, we recommend that rangers: (1) prohibit tourists from feeding; (2) move around the viewing platform more frequently; and (3) limit the number of tourists each visiting session. PMID:26480324

Spontaneous Urinary Bladder Leiomyoma in a Rhesus Macaque (Macaca mulatta).

PubMed

Scott, Kathleen E; Frydman, Galit; Fox, James G; Bakthavatchalu, Vasudevan

2018-06-01

Here we report the case of a urinary bladder leiomyoma in a rhesus macaque. The animal was clinically normal and had a lipoma localized to the stifle. Endovesicular leiomyomas are the most common form of urinary bladder leiomyoma in humans. In contrast, this macaque's tumor exhibited extravesicular localization in the bladder. Urinary bladder leiomyomas account for less than 0.5% of all bladder tumors in humans, with only 250 cases reported in total.

Smallpox DNA Vaccine Protects Nonhuman Primates Against Lethal Monkeypox

DTIC Science & Technology

2004-05-01

skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four...administered to the skin, the vaccine itself can pose a serious health risk. Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting...vaccine to protect rhesus macaques from severe monkeypox. MATERIALS AND METHODS Viruses and cells. The VACV Connaught vaccine strain (derived from the New

Isolation and sequence analysis of a novel rhesus macaque foamy virus isolate with a serotype-1-like env.

PubMed

Ensser, Armin; Großkopf, Anna K; Mätz-Rensing, Kerstin; Roos, Christian; Hahn, Alexander S

2018-06-02

SFVmmu-DPZ9524 represents the third completely sequenced rhesus macaque simian foamy virus (SFV) isolate, alongside SFVmmu_K3T with a similar SFV-1-type env, and R289HybAGM with a SFV-2-like env. Sequence analysis demonstrates that, in gag and pol, SFVmmu-DPZ9524 is more closely related to R289HybAGM than to SFVmmu_K3T, which, outside of env, is more similar to a Japanese macaque isolate than to the other two rhesus macaque isolates SFVmmu-DPZ9524 and R289HybAGM. Further, we identify bel as another recombinant locus in R289HybAGM, confirming that recombination contributes to sequence diversity in SFV.

Neuropeptide Y-immunoreactive neurons in the cerebral cortex of humans and other haplorrhine primates

PubMed Central

Raghanti, Mary Ann; Conley, Tiffini; Sudduth, Jessica; Erwin, Joseph M.; Stimpson, Cheryl D.; Hof, Patrick R.; Sherwood, Chet C.

2012-01-01

We examined the distribution of neurons immunoreactive for neuropeptide Y (NPY) in the posterior part of the superior temporal cortex (Brodmann's area 22 or area Tpt) of humans and nonhuman haplorrhine primates. NPY has been implicated in learning and memory and the density of NPY-expressing cortical neurons and axons is reduced in depression, bipolar disorder, schizophrenia, and Alzheimer's disease. Due to the role that NPY plays in both cognition and neurodegenerative diseases, we tested the hypothesis that the density of cortical and interstitial neurons expressing NPY was increased in humans relative to other primate species. The study sample included great apes (chimpanzee and gorilla), Old World monkeys (pigtailed macaque, moor macaque, and baboon) and New World monkeys (squirrel monkey and capuchin). Stereologic methods were used to estimate the density of NPY-immunoreactive (-ir) neurons in layers I-VI of area Tpt and the subjacent white matter. Adjacent Nissl-stained sections were used to calculate local densities of all neurons. The ratio of NPY-ir neurons to total neurons within area Tpt and the total density of NPY-ir neurons within the white matter were compared among species. Overall, NPY-ir neurons represented only an average of 0.006% of the total neuron population. While there were significant differences among species, phylogenetic trends in NPY-ir neuron distributions were not observed and humans did not differ from other primates. However, variation among species warrants further investigation into the distribution of this neuromodulator system. PMID:23042407

Gestures, vocalizations, and memory in language origins.

PubMed

Aboitiz, Francisco

2012-01-01

THIS ARTICLE DISCUSSES THE POSSIBLE HOMOLOGIES BETWEEN THE HUMAN LANGUAGE NETWORKS AND COMPARABLE AUDITORY PROJECTION SYSTEMS IN THE MACAQUE BRAIN, IN AN ATTEMPT TO RECONCILE TWO EXISTING VIEWS ON LANGUAGE EVOLUTION: one that emphasizes hand control and gestures, and the other that emphasizes auditory-vocal mechanisms. The capacity for language is based on relatively well defined neural substrates whose rudiments have been traced in the non-human primate brain. At its core, this circuit constitutes an auditory-vocal sensorimotor circuit with two main components, a "ventral pathway" connecting anterior auditory regions with anterior ventrolateral prefrontal areas, and a "dorsal pathway" connecting auditory areas with parietal areas and with posterior ventrolateral prefrontal areas via the arcuate fasciculus and the superior longitudinal fasciculus. In humans, the dorsal circuit is especially important for phonological processing and phonological working memory, capacities that are critical for language acquisition and for complex syntax processing. In the macaque, the homolog of the dorsal circuit overlaps with an inferior parietal-premotor network for hand and gesture selection that is under voluntary control, while vocalizations are largely fixed and involuntary. The recruitment of the dorsal component for vocalization behavior in the human lineage, together with a direct cortical control of the subcortical vocalizing system, are proposed to represent a fundamental innovation in human evolution, generating an inflection point that permitted the explosion of vocal language and human communication. In this context, vocal communication and gesturing have a common history in primate communication.

Temporal Plasticity Involved in Recovery from Manual Dexterity Deficit after Motor Cortex Lesion in Macaque Monkeys

PubMed Central

Higo, Noriyuki; Hayashi, Takuya; Nishimura, Yukio; Sugiyama, Yoko; Oishi, Takao; Tsukada, Hideo; Isa, Tadashi; Onoe, Hirotaka

2015-01-01

The question of how intensive motor training restores motor function after brain damage or stroke remains unresolved. Here we show that the ipsilesional ventral premotor cortex (PMv) and perilesional primary motor cortex (M1) of rhesus macaque monkeys are involved in the recovery of manual dexterity after a lesion of M1. A focal lesion of the hand digit area in M1 was made by means of ibotenic acid injection. This lesion initially caused flaccid paralysis in the contralateral hand but was followed by functional recovery of hand movements, including precision grip, during the course of daily postlesion motor training. Brain imaging of regional cerebral blood flow by means of H215O-positron emission tomography revealed enhanced activity of the PMv during the early postrecovery period and increased functional connectivity within M1 during the late postrecovery period. The causal role of these areas in motor recovery was confirmed by means of pharmacological inactivation by muscimol during the different recovery periods. These findings indicate that, in both the remaining primary motor and premotor cortical areas, time-dependent plastic changes in neural activity and connectivity are involved in functional recovery from the motor deficit caused by the M1 lesion. Therefore, it is likely that the PMv, an area distant from the core of the lesion, plays an important role during the early postrecovery period, whereas the perilesional M1 contributes to functional recovery especially during the late postrecovery period. PMID:25568105

Organization of the Macaque Extrastriate Visual Cortex Re-Examined Using the Principle of Spatial Continuity of Function

PubMed Central

Aflalo, T. N.

2011-01-01

How is the macaque monkey extrastriate cortex organized? Is vision divisible into separate tasks, such as object recognition and spatial processing, each emphasized in a different anatomical stream? If so, how many streams exist? What are the hierarchical relationships among areas? The present study approached the organization of the extrastriate cortex in a novel manner. A principled relationship exists between cortical function and cortical topography. Similar functions tend to be located near each other, within the constraints of mapping a highly dimensional space of functions onto the two-dimensional space of the cortex. We used this principle to re-examine the functional organization of the extrastriate cortex given current knowledge about its topographic organization. The goal of the study was to obtain a model of the functional relationships among the visual areas, including the number of functional streams into which they are grouped, the pattern of informational overlap among the streams, and the hierarchical relationships among areas. To test each functional description, we mapped it to a model cortex according to the principle of optimal continuity and assessed whether it accurately reconstructed a version of the extrastriate topography. Of the models tested, the one that best reconstructed the topography included four functional streams rather than two, six levels of hierarchy per stream, and a specific pattern of informational overlap among streams and areas. A specific mixture of functions was predicted for each visual area. This description matched findings in the physiological literature, and provided predictions of functional relationships that have yet to be tested physiologically. PMID:21068269

An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques.

PubMed

Derby, Nina; Aravantinou, Meropi; Kenney, Jessica; Ugaonkar, Shweta R; Wesenberg, Asa; Wilk, Jolanta; Kizima, Larisa; Rodriguez, Aixa; Zhang, Shimin; Mizenina, Olga; Levendosky, Keith; Cooney, Michael L; Seidor, Samantha; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José; Zydowsky, Thomas M; Robbiani, Melissa

2017-12-01

Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG). Previously, we showed that an MZC gel has potent activity against immunodeficiency viruses, HSV-2, and HPV and that the MZCL (MZC with LNG) IVR releases all four components in macaques in vivo at levels associated with efficacy. Vaginal fluid from treated macaques has in vitro activity against HIV, HSV-2, and HPV. Herein, we assessed the ability of the MZCL IVR to protect macaques against repeated co-challenge with HSV-2 and SHIV-RT (simian immunodeficiency virus [SIV] containing the reverse transcriptase gene from HIV) and prevent hormonal cycling. We evaluated in vivo drug release in co-challenged macaques by measuring drug levels in blood and vaginal fluid and residual drug levels in used IVRs. The MZCL IVR significantly prevented SHIV-RT infection, reduced HSV-2 vaginal shedding, and prevented cycling. No non-nucleoside HIV reverse transcriptase inhibitor (NNRTI)-resistant SHIV was detected in macaques that became infected after continuous exposure to MZC from the IVR. Macaques wearing the MZCL IVR also had carrageenan levels in vaginal fluid expected to protect from HPV (extrapolated from mice) and LNG levels in blood associated with contraceptive efficacy. The MZCL IVR is a promising MPT candidate that warrants further development.

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

PubMed Central

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

2017-01-01

Abstract 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. PMID:28213922

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

PubMed

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

2016-01-01

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

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

PubMed

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.

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

PubMed Central

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.

2017-01-01

ABSTRACT 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. PMID:28811349

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

PubMed

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

2015-03-01

Artificial grammars (AG) can be used to generate rule-based sequences of stimuli. Some of these can be used to investigate sequence-processing computations in non-human animals that might be related to, but not unique to, human language. Previous AG learning studies in non-human animals have used different AGs to separately test for specific sequence-processing abilities. However, given that natural language and certain animal communication systems (in particular, song) have multiple levels of complexity, mixed-complexity AGs are needed to simultaneously evaluate sensitivity to the different features of the AG. Here, we tested humans and Rhesus macaques using a mixed-complexity auditory AG, containing both adjacent (local) and non-adjacent (longer-distance) relationships. Following exposure to exemplary sequences generated by the AG, humans and macaques were individually tested with sequences that were either consistent with the AG or violated specific adjacent or non-adjacent relationships. We observed a considerable level of cross-species correspondence in the sensitivity of both humans and macaques to the adjacent AG relationships and to the statistical properties of the sequences. We found no significant sensitivity to the non-adjacent AG relationships in the macaques. A subset of humans was sensitive to this non-adjacent relationship, revealing interesting between- and within-species differences in AG learning strategies. The results suggest that humans and macaques are largely comparably sensitive to the adjacent AG relationships and their statistical properties. However, in the presence of multiple cues to grammaticality, the non-adjacent relationships are less salient to the macaques and many of the humans. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days.

PubMed

Nuttall, Jeremy P; Thake, Daryl C; Lewis, Mark G; Ferkany, John W; Romano, Joseph W; Mitchnick, Mark A

2008-03-01

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine ( approximately 0.1 mg/ml [15 microCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of microg/g of tissue) and remained detectable at 24 h (mean, >or=2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application.

Laboratory Rhesus Macaque Social Housing and Social Changes: Implications for Research

PubMed Central

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. PMID:26848542

Distribution of Vesicular Glutamate Transporter 2 (VGluT2) in the Primary Visual Cortex of the Macaque and Human

PubMed Central

Garcia-Marin, Virginia; Ahmed, Tunazzina H.; Afzal, Yasmeen C.; Hawken, Michael J.

2014-01-01

The majority of thalamic terminals in V1 arise from lateral geniculate nucleus (LGN) afferents. Thalamic afferent terminals are preferentially labeled by an isoform of the vesicular glutamate transporter, VGluT2. The goal of our study was to determine the distribution of VGluT2-ir puncta in macaque and human visual cortex. First, we investigated the distribution of VGluT2-ir puncta in all layers of macaque monkey primary visual cortex (V1), and found a very close correspondence between the known distribution of LGN afferents from previous studies and the distribution of VGluT2-immunoreactive (-ir) puncta. There was also a close correspondence between cytochrome oxidase density and VGluT2-ir puncta distribution. After validating the correspondence in macaque, we made a comparative study in human V1. In many aspects, the distribution of VGluT2-ir puncta in human was qualitatively similar to that of the macaque: high densities in layer 4C, patches of VGluT2-ir puncta in the supragranular layer (2/3), lower but clear distribution in layers 1 and 6, and very few puncta in layers 5 and 4B. However, there were also important differences between macaques and humans. In layer 4A of human, there was a sparse distribution of VGluT2-ir puncta, whereas in macaque, there was a dense distribution with the characteristic honeycomb organization. The results suggest important changes in the pattern of cortical VGluT2 immunostaining that may be related to evolutionary differences in the cortical organization of LGN afferents between Old World monkeys and humans. PMID:22684983

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

PubMed

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.

Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey.

PubMed

Scott, Brian H; Leccese, Paul A; Saleem, Kadharbatcha S; Kikuchi, Yukiko; Mullarkey, Matthew P; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C

2017-01-01

In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Multimodal analysis of cortical chemoarchitecture and macroscale fMRI resting‐state functional connectivity

PubMed Central

Scholtens, Lianne H.; Turk, Elise; Mantini, Dante; Vanduffel, Wim; Feldman Barrett, Lisa

2016-01-01

Abstract The cerebral cortex is well known to display a large variation in excitatory and inhibitory chemoarchitecture, but the effect of this variation on global scale functional neural communication and synchronization patterns remains less well understood. Here, we provide evidence of the chemoarchitecture of cortical regions to be associated with large‐scale region‐to‐region resting‐state functional connectivity. We assessed the excitatory versus inhibitory chemoarchitecture of cortical areas as an ExIn ratio between receptor density mappings of excitatory (AMPA, M1) and inhibitory (GABAA, M2) receptors, computed on the basis of data collated from pioneering studies of autoradiography mappings as present in literature of the human (2 datasets) and macaque (1 dataset) cortex. Cortical variation in ExIn ratio significantly correlated with total level of functional connectivity as derived from resting‐state functional connectivity recordings of cortical areas across all three datasets (human I: P = 0.0004; human II: P = 0.0008; macaque: P = 0.0007), suggesting cortical areas with an overall more excitatory character to show higher levels of intrinsic functional connectivity during resting‐state. Our findings are indicative of the microscale chemoarchitecture of cortical regions to be related to resting‐state fMRI connectivity patterns at the global system's level of connectome organization. Hum Brain Mapp 37:3103–3113, 2016. © 2016 Wiley Periodicals, Inc. PMID:27207489

Individual Differences in the Alignment of Structural and Functional Markers of the V5/MT Complex in Primates

PubMed Central

Large, I.; Bridge, H.; Ahmed, B.; Clare, S.; Kolasinski, J.; Lam, W. W.; Miller, K. L.; Dyrby, T. B.; Parker, A. J.; Smith, J. E. T.; Daubney, G.; Sallet, J.; Bell, A. H.; Krug, K.

2016-01-01

Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (sMRI). First, we compared the identification of V5/MT using both sMRI and histology in Rhesus macaques. A section-by-section comparison of histological slices with in vivo and postmortem sMRI for the same block of cortical tissue showed precise correspondence in localizing heavy myelination for V5/MT and neighboring MST. Thus, sMRI in macaques accurately locates histologically defined myelin within areas known to be motion selective. Second, we investigated the functionally homologous human motion complex (hMT+) using high-resolution in vivo imaging. Humans showed considerable intersubject variability in hMT+ location, when defined with myelin-weighted sMRI signals to reveal structure. When comparing sMRI markers to functional MRI in response to moving stimuli, a region of high myelin signal was generally located within the hMT+ complex. However, there were considerable differences in the alignment of structural and functional markers between individuals. Our results suggest that variation in area identification for hMT+ based on structural and functional markers reflects individual differences in human regional brain architecture. PMID:27371764

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

PubMed Central

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

2015-01-01

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

Using Hematology Data from Malaria Vaccine Research Trials in Humans and Rhesus Macaques (Macaca mulatta) To Guide Volume Limits for Blood Withdrawal.

PubMed

Hegge, Sara R; Hickey, Bradley W; Mcgrath, Shannon M; Stewart, V Ann

2016-12-01

Guidelines on safe volume limits for blood collection from research participants in both humans and laboratory animals vary widely between institutions. The main adverse event that may be encountered in large blood volume withdrawal is iron-deficiency anemia. Monitoring various parameters in a standard blood panel may help to prevent this outcome. To this end, we analyzed the Hgb and MCV values from 43 humans and 46 macaques in malaria vaccine research trials. Although the percentage of blood volume removed was greater for macaques than humans, macaques demonstrated an overall increase of MCV over time, indicating the ability to respond appropriately to frequent volume withdrawals. In contrast, humans showed a consistent declining trend in MCV. These declines in human MCV and Hgb were significant from the beginning to end of the study despite withdrawals that were smaller than recommended volume limits. Limiting the volume withdrawn to no more than 12.5% seemed to be sufficient for macaques, and at 14% or more individual animals tended to fail to respond appropriately to large-volume blood loss, as demonstrated by a decrease in MCV. The overall positive erythropoietic response seen in macaques was likely due to the controlled, iron-fortified diet they received. The lack of erythropoietic response in the human subjects may warrant iron supplementation or reconsideration of current blood volume withdrawal guidelines.

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

PubMed

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

2014-12-01

Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-ε, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-ε in tissues remain uncertain. In addition, the expression of IFN-ε in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-ε expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the detection of IFN-ε expression in situ in the lung, foreskin, vaginal, cervical, and small and large intestinal mucosae of rhesus macaques. We found that the expression of IFN-ε was exclusive to the epithelial cells in all of the aforementioned mucosal tissues. Furthermore, the macaque IFN-ε sequence in this study revealed that macaque IFN-ε is highly conserved among human and other nonhuman primates. Lastly, SIV rectal infection did not significantly alter the expression of IFN-ε in rectal mucosae. Together, these findings indicate that IFN-ε may function as the first line of defense against the invasion of mucosal pathogens. Further studies should be conducted to examine IFN-ε protection against gastrointestinal as well as respiratory infections. © 2014 Society for Leukocyte Biology.

The mucosal expression pattern of interferon-ε in rhesus macaques

PubMed Central

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

2014-01-01

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

Rotational Displacement Skills in Rhesus Macaques (Macaca mulatta)

PubMed Central

Hughes, Kelly D.; Santos, Laurie R.

2016-01-01

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

Short Communication: Lack of Immune Response in Rapid Progressor Morphine-Dependent and SIV/SHIV-Infected Rhesus Macaques Is Correlated with Downregulation of TH1 Cytokines

PubMed Central

Kumar, Rakesh; Noel, Richard J.; Garcia, Yashira; Rodriguez, Idia V.; Martinez, Melween; Sariol, Carlos A.; Kraiselburd, Edmundo; Iszard, Marcus; Mukherji, Mridul; Kumar, Santosh; Giavedoni, Luis D.; Kumar, Anil

2010-01-01

Abstract Our previous studies have shown two distinct disease patterns (rapid and normal onset of clinical symptoms) in morphine-dependent SHIV/SIV-inoculated rhesus macaques. We have also shown that control as well as 50% of morphine-dependent macaques (normal progressor) developed humoral and cellular immune responses whereas the other half of the morphine-dependent macaques (rapid progressor) did not develop antiviral immune responses after infection with SIV/SHIV. In the present study, we analyzed the association between cytokine production, immune response, and disease progression. To study the immunological effects of morphine at cytokine levels in the context of a lentiviral infection, we inoculated rhesus macaques with a mixture of SHIVKU−18, SHIV89.6P, and SIV/17E-Fr. These animals were followed for a period of 56 weeks for cytokine level production in plasma. Drug-dependent rapid disease progressors exhibited an increase in IL-18 and IL-1Ra and a decrease in IL-12 levels in the plasma. Morphine-dependent normal progressors and control macaques exhibited an increase in both IL-18 and IL-12, whereas IL-Ra levels remained constant throughout the observation period. These results suggest that rapid disease progression in relation to morphine dependency may be the result of an altered cytokine profile. PMID:20672973

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

PubMed

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 identifies a simple computational function of serotonin for state-dependent sensory processing, depending on the animal's affective or motivational state. Copyright © 2017 Seillier, Lorenz et al.

Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1

PubMed Central

Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Pourriahi, Paria

2017-01-01

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 identifies a simple computational function of serotonin for state-dependent sensory processing, depending on the animal's affective or motivational state. PMID:29042433

Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques

PubMed Central

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

2015-01-01

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

Infection of Mice, Ferrets, and Rhesus Macaques with a Clinical Mumps Virus Isolate

PubMed Central

Xu, Pei; Huang, Zhixiang; Gao, Xiudan; Michel, Frank J.; Hirsch, Gwen; Hogan, Robert J.; Sakamoto, Kaori; Ho, Wenzhe; Wu, Jianguo

2013-01-01

In recent years, many mumps outbreaks have occurred in vaccinated populations worldwide. The reasons for these outbreaks are not clear. Animal models are needed to investigate the causes of outbreaks and to understand the pathogenesis of mumps virus (MuV). In this study, we have examined the infection of three animal models with an isolate of mumps virus from a recent outbreak (MuV-IA). We have found that while both ferrets and mice generated humoral and cellular immune responses to MuV-IA infection, no obvious signs of illness were observed in these animals; rhesus macaques were the most susceptible to MuV-IA infection. Infection of rhesus macaques via both intranasal and intratracheal routes with MuV-IA led to the typical clinical signs of mumps 2 weeks to 4 weeks postinfection. However, none of the infected macaques showed any fever or neurologic signs during the experimental period. Mumps viral antigen was detected in parotid glands by immunohistochemistry (IHC). Rhesus macaques represent the best animal model for the study of mumps virus pathogenesis. PMID:23678169

Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections

PubMed Central

Asmal, Mohammed; Lane, Sophie; Tian, Meijuan; Nickle, Gabrielle; Venner, Colin; Dirk, Brennan; Dikeakos, Jimmy; Luedemann, Corinne; Mach, Linh; Balachandran, Harikrishnan; Buzby, Adam; Rao, Srinivas; Letvin, Norman; Gao, Yong; Arts, Eric J.

2016-01-01

For studies on vaccines and therapies for HIV disease, SIV-HIV chimeric viruses harboring the HIV-1 env gene (SHIVenv) remain the best virus in non-human primate models. However, there are still very few SHIVenv viruses that can cause AIDS in non-CD8-depleted animals. In the present study, a recently created CCR5-using SHIVenv_B3 virus with env gene derived from acute/early HIV-1 infections (AHI) successfully established pathogenic infection in macaques. Through a series of investigations on the evolution, mutational profile, and phenotype of the virus and the resultant humoral immune response in infected rhesus macaques, we found that the E32K mutation in the Env C1 domain was associated with macaque pathogenesis, and that the electrostatic interactions in Env may favor E32K at the gp120 N terminus and “lock” the binding to heptad repeat 1 of gp41 in the trimer and produce a SHIVenv with increased fitness and pathogenesis during macaque infections. PMID:27723488

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

PubMed

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

2015-08-01

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

Resource depletion through primate stone technology

PubMed Central

Tan, Amanda; Haslam, Michael; Kulik, Lars; Proffitt, Tomos; Malaivijitnond, Suchinda; Gumert, Michael

2017-01-01

Tool use has allowed humans to become one of the most successful species. However, tool-assisted foraging has also pushed many of our prey species to extinction or endangerment, a technology-driven process thought to be uniquely human. Here, we demonstrate that tool-assisted foraging on shellfish by long-tailed macaques (Macaca fascicularis) in Khao Sam Roi Yot National Park, Thailand, reduces prey size and prey abundance, with more pronounced effects where the macaque population size is larger. We compared availability, sizes and maturation stages of shellfish between two adjacent islands inhabited by different-sized macaque populations and demonstrate potential effects on the prey reproductive biology. We provide evidence that once technological macaques reach a large enough group size, they enter a feedback loop – driving shellfish prey size down with attendant changes in the tool sizes used by the monkeys. If this pattern continues, prey populations could be reduced to a point where tool-assisted foraging is no longer beneficial to the macaques, which in return may lessen or extinguish the remarkable foraging technology employed by these primates. PMID:28884681

Smooth-pursuit eye-movement deficits with chemical lesions in macaque nucleus reticularis tegmenti pontis.

PubMed

Suzuki, D A; Yamada, T; Hoedema, R; Yee, R D

1999-09-01

Anatomic and neuronal recordings suggest that the nucleus reticularis tegmenti pontis (NRTP) of macaques may be a major pontine component of a cortico-ponto-cerebellar pathway that subserves the control of smooth-pursuit eye movements. The existence of such a pathway was implicated by the lack of permanent pursuit impairment after bilateral lesions in the dorsolateral pontine nucleus. To provide more direct evidence that NRTP is involved with regulating smooth-pursuit eye movements, chemical lesions were made in macaque NRTP by injecting either lidocaine or ibotenic acid. Injection sites first were identified by the recording of smooth-pursuit-related modulations in neuronal activity. The resulting lesions caused significant deficits in both the maintenance and the initiation of smooth-pursuit eye movements. After lesion formation, the gain of constant-velocity, maintained smooth-pursuit eye movements decreased, on the average, by 44%. Recovery of the ability to maintain smooth-pursuit eye movements occurred over approximately 3 days when maintained pursuit gains attained normal values. The step-ramp, "Rashbass" task was used to investigate the effects of the lesions on the initiation of smooth-pursuit eye movements. Eye accelerations averaged over the initial 80 ms of pursuit initiation were determined and found to be decremented, on the average, by 48% after the administration of ibotenic acid. Impairments in the initiation and maintenance of smooth-pursuit eye movements were directional in nature. Upward pursuit seemed to be the most vulnerable and was impaired in all cases independent of lesioning agent and type of pursuit investigated. Downward smooth pursuit seemed more resistant to the effects of chemical lesions in NRTP. Impairments in horizontal tracking were observed with examples of deficits in ipsilaterally and contralaterally directed pursuit. The results provide behavioral support for the physiologically and anatomic-based conclusion that NRTP is a component of a cortico-ponto-cerebellar circuit that presumably involves the pursuit area of the frontal eye field (FEF) and projects to ocular motor-related areas of the cerebellum. This FEF-NRTP-cerebellum path would parallel a middle and medial superior temporal cerebral cortical area-dorsolateral pontine nucleus-cerebellum pathway also known to be involved with regulating smooth-pursuit eye movements.

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

PubMed

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 Elsevier Ltd.. All rights reserved.

Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand.

PubMed

Nakgoi, Khajornpong; Nitatpattana, Narong; Wajjwalku, Worawidh; Pongsopawijit, Pornsawan; Kaewchot, Supakarn; Yoksan, Sutee; Siripolwat, Voravit; Souris, Marc; Gonzalez, Jean-Paul

2014-01-01

The potential of macaque Macaca nemestrina leonina in Thailand to be infected by endemic arboviruses was assessed. The prevalence of antibodies of three arboviruses actively circulating in Thailand was determined by Plaque Reduction Neutralization assay procedures using samples from captive colonies in Northern Thailand. Out of 38 macaques, 9 (24%) presented reacting antibodies against dengue virus, 5 (13%) against Japanese encephalitis virus, and 4 (10%) against Chikungunya virus. Our results indicate that the northern pig-tailed macaque in Thailand can be infected by these arboviruses, inferring therefore that their virus specific vectors have bitten them. Given that, northern pig-tailed macaque represents an abundant population, living in close range to human or in peridomestic setting, they could play a role as potential reservoir host for arboviruses circulating in Thailand. © 2013 Wiley Periodicals, Inc.

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

PubMed

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

2010-07-01

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

Sequencing the transcriptome of milk production: milk trumps mammary tissue.

PubMed

Lemay, Danielle G; Hovey, Russell C; Hartono, Stella R; Hinde, Katie; Smilowitz, Jennifer T; Ventimiglia, Frank; Schmidt, Kimberli A; Lee, Joyce W S; Islas-Trejo, Alma; Silva, Pedro Ivo; Korf, Ian; Medrano, Juan F; Barry, Peter A; German, J Bruce

2013-12-12

Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation.

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

PubMed

Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

2016-03-01

Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott

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.more » 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.« less

Binding of Complement Factor H (FH) Decreases Protective Anti-FH Binding Protein Antibody Responses of Infant Rhesus Macaques Immunized With a Meningococcal Serogroup B Vaccine

PubMed Central

Granoff, Dan M.; Costa, Isabella; Konar, Monica; Giuntini, Serena; Van Rompay, Koen K. A.; Beernink, Peter T.

2015-01-01

Background. The meningococcal vaccine antigen, factor H (FH)–binding protein (FHbp), binds human complement FH. In human FH transgenic mice, binding decreased protective antibody responses. Methods. To investigate the effect of primate FH binding, we immunized rhesus macaques with a 4-component serogroup B vaccine (4CMenB). Serum FH in 6 animals bound strongly to FHbp (FHbp-FHhigh) and, in 6 animals, bound weakly to FHbp (FHbp-FHlow). Results. There were no significant differences between the respective serum bactericidal responses of the 2 groups against meningococcal strains susceptible to antibody to the NadA or PorA vaccine antigens. In contrast, anti-FHbp bactericidal titers were 2-fold lower in FHbp-FHhigh macaques against a strain with an exact FHbp match to the vaccine (P = .08) and were ≥4-fold lower against 4 mutants with other FHbp sequence variants (P ≤ .005, compared with FHbp-FHlow macaques). Unexpectedly, postimmunization sera from all 12 macaques enhanced FH binding to meningococci. In contrast, serum anti-FHbp antibodies elicited by 4CMenB in mice whose mouse FH did not bind to the vaccine antigen inhibited FH binding. Conclusions. Binding of FH to FHbp decreases protective anti-FHbp antibody responses of macaques to 4CMenB. Even low levels of FH binding skew the antibody repertoire to FHbp epitopes outside of the FH-binding site, which enhance FH binding. PMID:25676468

Organization and evolution of parieto-frontal processing streams in macaque monkeys and humans.

PubMed

Caminiti, Roberto; Innocenti, Giorgio M; Battaglia-Mayer, Alexandra

2015-09-01

The functional organization of the parieto-frontal system is crucial for understanding cognitive-motor behavior and provides the basis for interpreting the consequences of parietal lesions in humans from a neurobiological perspective. The parieto-frontal connectivity defines some main information streams that, rather than being devoted to restricted functions, underlie a rich behavioral repertoire. Surprisingly, from macaque to humans, evolution has added only a few, new functional streams, increasing however their complexity and encoding power. In fact, the characterization of the conduction times of parietal and frontal areas to different target structures has recently opened a new window on cortical dynamics, suggesting that evolution has amplified the probability of dynamic interactions between the nodes of the network, thanks to communication patterns based on temporally-dispersed conduction delays. This might allow the representation of sensory-motor signals within multiple neural assemblies and reference frames, as to optimize sensory-motor remapping within an action space characterized by different and more complex demands across evolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of breeding populations of rhesus macaques (Macaca mulatta) that are specific pathogen-free for rhesus cytomegalovirus.

PubMed

Barry, Peter A; Strelow, Lisa

2008-02-01

Development of breeding colonies of rhesus macaques (Macaca mulatta) that are specific pathogen-free (SPF) for rhesus cytomegalovirus (RhCMV) is relatively straightforward and requires few modifications from current SPF programs. Infants separated from the dam at or within a few days of birth and cohoused with similarly treated animals remain RhCMV seronegative indefinitely, provided they are never directly or indirectly exposed to a RhCMV-infected monkey. By systematically cohousing seronegative animals into larger social cohorts, breeding populations of animals SPF for RhCMV can be established. The additional costs involved in expanding the current definition of SPF status to include RhCMV are incremental compared with the money already being spent on existing SPF efforts. Moreover, the large increase in research opportunities available for RhCMV-free animals arguably would far exceed the development costs. Potential new areas of research and further expansion of existing research efforts involving these newly defined SPF animals would have direct implications for improvements in human health.

Functional MRI of the vocalization-processing network in the macaque brain

PubMed Central

Ortiz-Rios, Michael; Kuśmierek, Paweł; DeWitt, Iain; Archakov, Denis; Azevedo, Frederico A. C.; Sams, Mikko; Jääskeläinen, Iiro P.; Keliris, Georgios A.; Rauschecker, Josef P.

2015-01-01

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. PMID:25883546

Integration of faces and vocalizations in ventral prefrontal cortex: Implications for the evolution of audiovisual speech

PubMed Central

Romanski, Lizabeth M.

2012-01-01

The integration of facial gestures and vocal signals is an essential process in human communication and relies on an interconnected circuit of brain regions, including language regions in the inferior frontal gyrus (IFG). Studies have determined that ventral prefrontal cortical regions in macaques [e.g., the ventrolateral prefrontal cortex (VLPFC)] share similar cytoarchitectonic features as cortical areas in the human IFG, suggesting structural homology. Anterograde and retrograde tracing studies show that macaque VLPFC receives afferents from the superior and inferior temporal gyrus, which provide complex auditory and visual information, respectively. Moreover, physiological studies have shown that single neurons in VLPFC integrate species-specific face and vocal stimuli. Although bimodal responses may be found across a wide region of prefrontal cortex, vocalization responsive cells, which also respond to faces, are mainly found in anterior VLPFC. This suggests that VLPFC may be specialized to process and integrate social communication information, just as the IFG is specialized to process and integrate speech and gestures in the human brain. PMID:22723356

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

PubMed

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

2017-01-01

Facial expressions convey key cues of human emotions, and may also be important for interspecies interactions. The universality hypothesis suggests that six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) should be expressed by similar facial expressions in close phylogenetic species such as humans and nonhuman primates. However, some facial expressions have been shown to differ in meaning between humans and nonhuman primates like macaques. This ambiguity in signalling emotion can lead to an increased risk of aggression and injuries for both humans and animals. This raises serious concerns for activities such as wildlife tourism where humans closely interact with wild animals. Understanding what factors (i.e., experience and type of emotion) affect ability to recognise emotional state of nonhuman primates, based on their facial expressions, can enable us to test the validity of the universality hypothesis, as well as reduce the risk of aggression and potential injuries in wildlife tourism. The present study investigated whether different levels of experience of Barbary macaques, Macaca sylvanus , affect the ability to correctly assess different facial expressions related to aggressive, distressed, friendly or neutral states, using an online questionnaire. Participants' level of experience was defined as either: (1) naïve: never worked with nonhuman primates and never or rarely encountered live Barbary macaques; (2) exposed: shown pictures of the different Barbary macaques' facial expressions along with the description and the corresponding emotion prior to undertaking the questionnaire; (3) expert: worked with Barbary macaques for at least two months. Experience with Barbary macaques was associated with better performance in judging their emotional state. Simple exposure to pictures of macaques' facial expressions improved the ability of inexperienced participants to better discriminate neutral and distressed faces, and a trend was found for aggressive faces. However, these participants, even when previously exposed to pictures, had difficulties in recognising aggressive, distressed and friendly faces above chance level. These results do not support the universality hypothesis as exposed and naïve participants had difficulties in correctly identifying aggressive, distressed and friendly faces. Exposure to facial expressions improved their correct recognition. In addition, the findings suggest that providing simple exposure to 2D pictures (for example, information signs explaining animals' facial signalling in zoos or animal parks) is not a sufficient educational tool to reduce tourists' misinterpretations of macaque emotion. Additional measures, such as keeping a safe distance between tourists and wild animals, as well as reinforcing learning via videos or supervised visits led by expert guides, could reduce such issues and improve both animal welfare and tourist experience.

Aerosol exposure to Zaire ebolavirus in three nonhuman primate species: differences in disease course and clinical pathology.

PubMed

Reed, Douglas S; Lackemeyer, Matthew G; Garza, Nicole L; Sullivan, Lawrence J; Nichols, Donald K

2011-10-01

There is little known concerning the disease caused by Zaire ebolavirus (ZEBOV) when inhaled, the likely route of exposure in a biological attack. Cynomolgus macaques, rhesus macaques, and African green monkeys were exposed to aerosolized ZEBOV to determine which species might be the most relevant model of the human disease. A petechial rash was noted on cynomolgus and rhesus macaques after fever onset but not on African green monkeys. Fever duration was shortest in rhesus macaques (62.7 ± 16.3 h) and longest in cynomolgus macaques (82.7 ± 22.3h) and African green monkeys (88.4 ± 16.7h). Virus was first detectable in the blood 3 days after challenge; the level of viremia was comparable among all three species. Hematological changes were noted in all three species, including decreases in lymphocyte and platelet counts. Increased blood coagulation times were most pronounced in African green monkeys. Clinical signs and time to death in all three species were comparable to what has been reported previously for each species after parenteral inoculation with ZEBOV. These data will be useful in selection of an animal model for efficacy studies. Published by Elsevier Masson SAS.

Methemoglobin and sulfhemoglobin formation due to benzocaine and lidocaine in macaques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, D.G.; Woodard, C.L.; Gold, M.B.

1993-05-13

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

Indoleamine 2,3-dioxygenase is differentially expressed by different white blood cell populations of rhesus macaques (Macaca mulatta).

PubMed

Lei, N; Wang, Y; Zhang, W-J; Duan, J-Z; Yang, G-B

2013-08-01

Indoleamine 2,3-dioxygenase (IDO) is involved in immune processes such as transplant and fetal rejection, autoimmunity, cancer, and infection; however, its expression in rhesus macaques has not been fully addressed. Indoleamine 2,3-dioxygenase mRNA and protein in the white blood cells (WBCs) of Chinese rhesus macaques were examined by RT-PCR, western blotting, real-time RT-PCR, and flow cytometry. Both IDO protein and mRNA could be readily detected in WBCs or peripheral blood mononuclear cells (PBMCs) of normal rhesus macaques. IDO+ cell frequency was the highest among CD14(+) mononuclear cells, followed by CD56(+) cells and DCs. No difference in the frequency of IDO+ cells between CD4(+) and CD8(+) T cells; however, Th17 cells have higher frequency of IDO+ cells than Th1 cells, with Th2 cells the lowest. Toll-like receptor (TLR) stimulation significantly increased IDO protein level in CD14(+) , CD56(+) , CD1c(+) , CD11c(+) , and CD123(+) myeloid cells. Rhesus macaques express IDO differentially in their leukocyte subsets and are suitable for IDO-related pathophysiological studies. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2017-01-30

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

Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease.

PubMed

Perry, Donna L; Huzella, Louis M; Bernbaum, John G; Holbrook, Michael R; Jahrling, Peter B; Hagen, Katie R; Schnell, Matthias J; Johnson, Reed F

2018-03-01

Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy. In four female and eight male macaques that succumbed to EVD between 6 and 9 days after EBOV challenge, we demonstrate widespread EBOV infection of the interstitial tissues and endothelium in the ovary, uterus, testis, seminal vesicle, epididymis, and prostate gland, with minimal associated tissue immune response or organ pathology. Given the widespread involvement of EBOV in the reproductive tracts of both male and female macaques, it is reasonable to surmise that our understanding of the mechanisms underlying sexual transmission of EVD and persistence of EBOV in immune-privileged sites would be facilitated by the development of a nonhuman primate model in which the macaques survived past the acute stage into convalescence. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Personality of Wild Male Crested Macaques (Macaca nigra)

PubMed Central

Neumann, Christof; Agil, Muhammad; Widdig, Anja; Engelhardt, Antje

2013-01-01

Animal personalities, i.e. consistent differences in behavior across time and/or context, have received increased attention of behavioral biologists over the last years. Recent research shows that personalities represent traits on which natural and sexual selection work and which can have substantial fitness consequences. The aim of this study is to establish the personality structure of crested macaque (Macaca nigra) males as foundation for future studies on its adaptive value. We collected behavioral data through focal animal sampling and additionally conducted two sets of playback experiments. Results of a factor analysis on the behavioral data revealed a four factor structure with components we labeled Anxiety, Sociability, Connectedness and Aggressiveness. Results from the experiments revealed an additional and independent Boldness factor but the absence of Neophilia. Overall, this structure resembles other macaque and animal species with the exception of Connectedness, which might be a consequence of the species' tolerant social style. Our results thus not only form the basis for future studies on the adaptive value of personality in crested macaques but also contribute an important data point for investigating the evolution of personality structure from a comparative perspective by refining, for example, which personality factors characterized the last common ancestor of hominids and macaques. PMID:23940517

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

PubMed Central

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. 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 x 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 higher in HSR than SS animals (p<0.04). There was no change in either group after 5 days of moderate stress. The ratio of serotonin/TH correlates with ovarian estrogen production with a sensitivity x stress interaction. Therefore, it appears that the serotonin system determines stress sensitivity and the NE system responds to stress. We hypothesize that elevated NE with low serotonin functionality ultimately leads to stress-induced infertililty. In contrast, high serotonin functionality maintains ovulation in the presence of stress even with elevated NE. PMID:23069677

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

PubMed

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 higher in HSR than SS animals (p<0.04). There was no change in either group after 5 days of moderate stress. The ratio of serotonin/TH correlates with ovarian estrogen production with a sensitivity×stress interaction. Therefore, it appears that the serotonin system determines stress sensitivity and the NE system responds to stress. We hypothesize that elevated NE with low serotonin functionality ultimately leads to stress-induced infertility. In contrast, high serotonin functionality maintains ovulation in the presence of stress even with elevated NE. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2005-12-01

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

The Role of Binocular Disparity in Stereoscopic Images of Objects in the Macaque Anterior Intraparietal Area

PubMed Central

Romero, Maria C.; Van Dromme, Ilse C. L.; Janssen, Peter

2013-01-01

Neurons in the macaque Anterior Intraparietal area (AIP) encode depth structure in random-dot stimuli defined by gradients of binocular disparity, but the importance of binocular disparity in real-world objects for AIP neurons is unknown. We investigated the effect of binocular disparity on the responses of AIP neurons to images of real-world objects during passive fixation. We presented stereoscopic images of natural and man-made objects in which the disparity information was congruent or incongruent with disparity gradients present in the real-world objects, and images of the same objects where such gradients were absent. Although more than half of the AIP neurons were significantly affected by binocular disparity, the great majority of AIP neurons remained image selective even in the absence of binocular disparity. AIP neurons tended to prefer stimuli in which the depth information derived from binocular disparity was congruent with the depth information signaled by monocular depth cues, indicating that these monocular depth cues have an influence upon AIP neurons. Finally, in contrast to neurons in the inferior temporal cortex, AIP neurons do not represent images of objects in terms of categories such as animate-inanimate, but utilize representations based upon simple shape features including aspect ratio. PMID:23408970

The Representation of Orientation in Macaque V2: Four Stripes Not Three

PubMed Central

Felleman, Daniel J.; Lim, Heejin; Xiao, Youping; Wang, Yi; Eriksson, Anastasia; Parajuli, Arun

2015-01-01

Area V2 of macaque monkeys is traditionally thought to consist of 3 distinct functional compartments with characteristic cortical connections and functional properties. Orientation selectivity is one property that has frequently been used to distinguish V2 stripes, however, this receptive field property has been found in a high percentage of neurons across V2 compartments. Using quantitative intrinsic cortical imaging, we derived maps of preferred orientation, orientation selectivity, and orientation gradient in thin stripes, thick stripes, and interstripes in area V2. Orientation-selective responses were found in each V2 stripe, but the magnitude and organization of orientation selectivity differed significantly from stripe to stripe. Remarkably, the 2 pale stripes flanking each cytochrome oxidase dense stripe differed significantly in their representation of orientation resulting in their distinction as type-I and type-II interstripes. V2 orientation maps are characterized by clockwise and anticlockwise “orientation pinwheels”, but unlike V1, they are not homogeneously distributed across V2. Furthermore, V2 stripes contain large-scale sequences of preferred orientation. These analyses demonstrate that V2 consists of 4 distinct functional compartments; thick stripes and type-II interstripes, which are strongly orientation selective and thin stripes and type-I interstripes, which are significantly less selective for orientation and exhibit larger orientation gradient magnitudes. PMID:24614951

Complete Genome Sequence of Pig-Tailed Macaque Rhadinovirus 2 and Its Evolutionary Relationship with Rhesus Macaque Rhadinovirus and Human Herpesvirus 8/Kaposi's Sarcoma-Associated Herpesvirus

PubMed Central

Bruce, A. Gregory; Thouless, Margaret E.; Haines, Anthony S.; Pallen, Mark J.; Grundhoff, Adam

2015-01-01

ABSTRACT Two rhadinovirus lineages have been identified in Old World primates. The rhadinovirus 1 (RV1) lineage consists of human herpesvirus 8, Kaposi's sarcoma-associated herpesvirus (KSHV), and closely related rhadinoviruses of chimpanzees, gorillas, macaques and other Old World primates. The RV2 rhadinovirus lineage is distinct and consists of closely related viruses from the same Old World primate species. Rhesus macaque rhadinovirus (RRV) is the RV2 prototype, and two RRV isolates, 26-95 and 17577, were sequenced. We determined that the pig-tailed macaque RV2 rhadinovirus, MneRV2, is highly associated with lymphomas in macaques with simian AIDS. To further study the role of rhadinoviruses in the development of lymphoma, we sequenced the complete genome of MneRV2 and identified 87 protein coding genes and 17 candidate microRNAs (miRNAs). A strong genome colinearity and sequence homology were observed between MneRV2 and RRV26-95, although the open reading frame (ORF) encoding the KSHV ORFK15 homolog was disrupted in RRV26-95. Comparison with MneRV2 revealed several genomic anomalies in RRV17577 that were not present in other rhadinovirus genomes, including an N-terminal duplication in ORF4 and a recombinative exchange of more distantly related homologs of the ORF22/ORF47 interacting glycoprotein genes. The comparison with MneRV2 has revealed novel genes and important conservation of protein coding domains and transcription initiation, termination, and splicing signals, which have added to our knowledge of RV2 rhadinovirus genetics. Further comparisons with KSHV and other RV1 rhadinoviruses will provide important avenues for dissecting the biology, evolution, and pathology of these closely related tumor-inducing viruses in humans and other Old World primates. IMPORTANCE This work provides the sequence characterization of MneRV2, the pig-tailed macaque homolog of rhesus rhadinovirus (RRV). MneRV2 and RRV belong to the rhadinovirus 2 (RV2) rhadinovirus lineage of Old World primates and are distinct but related to Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma. Pig-tailed macaques provide important models of human disease, and our previous studies have indicated that MneRV2 plays a causal role in AIDS-related lymphomas in macaques. Delineation of the MneRV2 sequence has allowed a detailed characterization of the genome structure, and evolutionary comparisons with RRV and KSHV have identified conserved promoters, splice junctions, and novel genes. This comparison provides insight into RV2 rhadinovirus biology and sets the groundwork for more intensive next-generation (Next-Gen) transcript and genetic analysis of this class of tumor-inducing herpesvirus. This study supports the use of MneRV2 in pig-tailed macaques as an important model for studying rhadinovirus biology, transmission and pathology. PMID:25609822

Visual motion integration by neurons in the middle temporal area of a New World monkey, the marmoset

PubMed Central

Solomon, Selina S; Tailby, Chris; Gharaei, Saba; Camp, Aaron J; Bourne, James A; Solomon, Samuel G

2011-01-01

Abstract The middle temporal area (MT/V5) is an anatomically distinct region of primate visual cortex that is specialized for the processing of image motion. It is generally thought that some neurons in area MT are capable of signalling the motion of complex patterns, but this has only been established in the macaque monkey. We made extracellular recordings from single units in area MT of anaesthetized marmosets, a New World monkey. We show through quantitative analyses that some neurons (35 of 185; 19%) are capable of signalling pattern motion (‘pattern cells’). Across several dimensions, the visual response of pattern cells in marmosets is indistinguishable from that of pattern cells in macaques. Other neurons respond to the motion of oriented contours in a pattern (‘component cells’) or show intermediate properties. In addition, we encountered a subset of neurons (22 of 185; 12%) insensitive to sinusoidal gratings but very responsive to plaids and other two-dimensional patterns and otherwise indistinguishable from pattern cells. We compared the response of each cell class to drifting gratings and dot fields. In pattern cells, directional selectivity was similar for gratings and dot fields; in component cells, directional selectivity was weaker for dot fields than gratings. Pattern cells were more likely to have stronger suppressive surrounds, prefer lower spatial frequencies and prefer higher speeds than component cells. We conclude that pattern motion sensitivity is a feature of some neurons in area MT of both New and Old World monkeys, suggesting that this functional property is an important stage in motion analysis and is likely to be conserved in humans. PMID:21946851

Corticobulbar projections from distinct motor cortical areas to the reticular formation in macaque monkeys.

PubMed

Fregosi, Michela; Contestabile, Alessandro; Hamadjida, Adjia; Rouiller, Eric M

2017-06-01

Corticospinal and corticobulbar descending pathways act in parallel with brainstem systems, such as the reticulospinal tract, to ensure the control of voluntary movements via direct or indirect influences onto spinal motoneurons. The aim of this study was to investigate the corticobulbar projections from distinct motor cortical areas onto different nuclei of the reticular formation. Seven adult macaque monkeys were analysed for the location of corticobulbar axonal boutons, and one monkey for reticulospinal neurons' location. The anterograde tracer BDA was injected in the premotor cortex (PM), in the primary motor cortex (M1) or in the supplementary motor area (SMA), in 3, 3 and 1 monkeys respectively. BDA anterograde labelling of corticobulbar axons were analysed on brainstem histological sections and overlapped with adjacent Nissl-stained sections for cytoarchitecture. One adult monkey was analysed for retrograde CB tracer injected in C5-C8 hemispinal cord to visualise reticulospinal neurons. The corticobulbar axons formed bilateral terminal fields with boutons terminaux and en passant, which were quantified in various nuclei belonging to the Ponto-Medullary Reticular Formation (PMRF). The corticobulbar projections from both PM and SMA tended to end mainly ipsilaterally in PMRF, but contralaterally when originating from M1. Furthermore, the corticobulbar projection was less dense when originating from M1 than from non-primary motor areas (PM, SMA). The main nuclei of bouton terminals corresponded to the regions where reticulospinal neurons were located with CB retrograde tracing. In conclusion, the corticobulbar projection differs according to the motor cortical area of origin in density and laterality. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

PubMed

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.

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine.

PubMed

Giuntini, Serena; Beernink, Peter T; Granoff, Dan M

2015-12-16

FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FH(high)), and six with FH(low) baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FH(low) baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FH(high) phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (p<0.02). In macaques with the FH(high) baseline phenotype, the respective anti-FHbp C4b deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FH(low) baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FH(high), the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH. Copyright © 2015 Elsevier Ltd. All rights reserved.

Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

PubMed Central

Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

2008-01-01

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine (∼0.1 mg/ml [15 μCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of μg/g of tissue) and remained detectable at 24 h (mean, ≥2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application. PMID:18086845

Real-time monitoring of cardiovascular function in rhesus macaques infected with Zaire ebolavirus.

PubMed

Kortepeter, Mark G; Lawler, James V; Honko, Anna; Bray, Mike; Johnson, Joshua C; Purcell, Bret K; Olinger, Gene G; Rivard, Robert; Hepburn, Matthew J; Hensley, Lisa E

2011-11-01

Nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with Zaire ebolavirus. All animals developed viremia, fever, a hemorrhagic rash, and typical changes of Ebola hemorrhagic fever in clinical laboratory tests. Three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. After the onset of fever, lethal illness was characterized by a decline in mean arterial blood pressure, an increase in pulse and respiratory rate, lactic acidosis, and renal failure. Survivors showed less pronounced change in these parameters. Four macaques were randomized to receive supplemental volumes of intravenous normal saline when they became hypotensive. Although those animals had less severe renal compromise, no apparent survival benefit was observed. This is the first report of continuous physiologic monitoring in filovirus-infected nonhuman primates and the first to attempt cardiovascular support with intravenous fluids.

Exceptional Evolutionary Divergence of Human Muscle and Brain Metabolomes Parallels Human Cognitive and Physical Uniqueness

PubMed Central

Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Pieszek, Raik; Sherwood, Chet C.; Hof, Patrick R.; Ely, John J.; Steinhauser, Dirk; Willmitzer, Lothar; Bangsbo, Jens; Hansson, Ola; Call, Josep; Giavalisco, Patrick; Khaitovich, Philipp

2014-01-01

Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys. PMID:24866127

Allometry and Interspecific Differences in the Facial Cranium of Two Closely Related Macaque Species

PubMed Central

Ito, Tsuyoshi; Nishimura, Takeshi; Takai, Masanaru

2011-01-01

Interpreting evolutionary history of macaque monkeys from fossil evidence is difficult, because their evolutionary fluctuations in body size might have removed or formed important morphological features differently in each lineage. We employed geometric morphometrics to explore allometric trajectories of craniofacial shape in two closely related species, Macaca fascicularis and M. fuscata. These two species exhibit a single shared allometric trajectory in superoinferior deflection of the anterior face, indicating that the differences in this feature can be explained by size variation. In contrast, two parallel trajectories are demonstrated in craniofacial protrusion, indicating that even if they are comparable in size, M. fuscata has a higher and shorter face than M. fascicularis. The degree of facial protrusion is most likely a critical feature for phyletic evaluation in the fascicularis group. Such analyses in various macaques would help to resolve controversies regarding phyletic interpretations of fossil macaques. PMID:22567301

Virus-specific T cell responses in macaques acutely infected with SHIV(sf162p3).

PubMed

Pahar, Bapi; Wang, Xiaolei; Dufour, Jason; Lackner, Andrew A; Veazey, Ronald S

2007-06-20

CD4(+) T helper and CD8(+) cytotoxic T lymphocyte responses are believed to play an important role in the control of primary HIV and SIV infection. However, the role of these cells in macaques acutely infected with SHIV(sf162p3) has not been well characterized. In this study, ten adult rhesus macaques were intravaginally infected with SHIV(sf162p3), and antigen-specific cytokine responses to SHIV-Tat, Nef, Gag and Env peptide pools were examined through 70 days post inoculation (p.i.) using ELISPOT and/or cytokine flow cytometry (CFC). Peak plasma viral replication occurred between 14 and 21 days p.i. followed by low to undetectable plasma viremia by 70 days of infection in most macaques. Although some animals had strong virus-specific cellular immune responses, many had weak or minimal responses that did not correlate with the post peak decline in plasma viremia.

Virus-specific T cell responses in macaques acutely infected with SHIVsf162p3

PubMed Central

Pahar, Bapi; Wang, Xiaolei; Dufour, Jason; Lackner, Andrew A.; Veazey, Ronald S.

2007-01-01

CD4+ T helper and CD8+ cytotoxic T lymphocyte responses are believed to play an important role in the control of primary HIV and SIV infection. However, the role of these cells in macaques acutely infected with SHIVsf162p3 has not been well characterized. In this study, ten adult rhesus macaques were intravaginally infected with SHIVsf162p3, and antigen specific cytokine responses to SHIV-Tat, Nef, Gag and Env peptide pools were examined through 70 days post inoculation (p.i.) using ELISPOT and/or cytokine flow cytometry (CFC). Peak plasma viral replication occurred between 14 and 21 days p.i., followed by low to undetectable plasma viremia by 70 days of infection in most macaques. Although some animals had strong virus-specific cellular immune responses, many had weak or minimal responses that did not correlate with the post peak decline in plasma viremia. PMID:17307212

Chronic Administration of Δ9-Tetrahydrocannabinol Induces Intestinal Anti-Inflammatory MicroRNA Expression during Acute Simian Immunodeficiency Virus Infection of Rhesus Macaques

PubMed Central

Chandra, Lawrance C.; Kumar, Vinay; Torben, Workineh; Stouwe, Curtis Vande; Winsauer, Peter; Amedee, Angela; Molina, Patricia E.

2014-01-01

ABSTRACT Recreational and medical use of cannabis among human immunodeficiency virus (HIV)-infected individuals has increased in recent years. In simian immunodeficiency virus (SIV)-infected macaques, chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC) inhibited viral replication and intestinal inflammation and slowed disease progression. Persistent gastrointestinal disease/inflammation has been proposed to facilitate microbial translocation and systemic immune activation and promote disease progression. Cannabinoids including Δ9-THC attenuated intestinal inflammation in mouse colitis models and SIV-infected rhesus macaques. To determine if the anti-inflammatory effects of Δ9-THC involved differential microRNA (miRNA) modulation, we profiled miRNA expression at 14, 30, and 60 days postinfection (days p.i.) in the intestine of uninfected macaques receiving Δ9-THC (n = 3) and SIV-infected macaques administered either vehicle (VEH/SIV; n = 4) or THC (THC/SIV; n = 4). Chronic Δ9-THC administration to uninfected macaques significantly and positively modulated intestinal miRNA expression by increasing the total number of differentially expressed miRNAs from 14 to 60 days p.i. At 60 days p.i., ∼28% of miRNAs showed decreased expression in the VEH/SIV group compared to none showing decrease in the THC/SIV group. Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149, and miR-187, previously been shown to target proinflammatory molecules. NOX4, a potent reactive oxygen species generator, was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV macaques compared to the THC/SIV group. We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage. These results support a role for differential miRNA induction in THC-mediated suppression of intestinal inflammation. Whether similar miRNA modulation occurs in other tissues requires further investigation. IMPORTANCE Gastrointestinal (GI) tract disease/inflammation is a hallmark of HIV/SIV infection. Previously, we showed that chronic treatment of SIV-infected macaques with Δ9-tetrahydrocannabinol (Δ9-THC) increased survival and decreased viral replication and infection-induced gastrointestinal inflammation. Here, we show that chronic THC administration to SIV-infected macaques induced an anti-inflammatory microRNA expression profile in the intestine at 60 days p.i. These included several miRNAs bioinformatically predicted to directly target CXCL12, a chemokine known to regulate lymphocyte and macrophage trafficking into the intestine. Specifically, miR-99b was significantly upregulated in THC-treated SIV-infected macaques and confirmed to directly target NADPH oxidase 4 (NOX4), a reactive oxygen species generator known to damage intestinal epithelial cells. Elevated miR-99b expression was associated with a significantly decreased number of NOX4+ epithelial cells in the intestines of THC-treated SIV-infected macaques. Overall, our results show that selective upregulation of anti-inflammatory miRNA expression contributes to THC-mediated suppression of gastrointestinal inflammation and maintenance of intestinal homeostasis. PMID:25378491

Sequencing the transcriptome of milk production: milk trumps mammary tissue

PubMed Central

2013-01-01

Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

Quantitative and qualitative iNKT repertoire associations with disease susceptibility and outcome in macaque tuberculosis infection.

PubMed

Chancellor, Andrew; White, Andrew; Tocheva, Anna S; Fenn, Joe R; Dennis, Mike; Tezera, Liku; Singhania, Akul; Elliott, Tim; Tebruegge, Marc; Elkington, Paul; Gadola, Stephan; Sharpe, Sally; Mansour, Salah

2017-07-01

Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies. Animals studied included four genetically distinct groups of macaques within cynomolgus and rhesus species that differ in their susceptibility to Mtb infection. We demonstrate significant differences in ex vivo iNKT frequency between groups, which trends towards an association with susceptibility to Mtb, but no significant difference in overall iNKT proliferative responses. Susceptible animals exhibited a skewed CD4 + /CD8 + iNKT subset ratio in comparison to more Mtb-resistant groups. Correlation of iNKT subsets post BCG vaccination with clinical disease manifestations following Mtb challenge in the Chinese cynomolgus and Indian rhesus macaques identified a consistent trend linking increased CD8 + iNKTs with favourable disease outcome. Finally, a similar iNKT profile was conferred by BCG vaccination in rhesus macaques. Our study provides the first detailed characterisation of iNKT cells in macaque tuberculosis infection, suggesting that iNKT repertoire differences may impact on disease outcome, which warrants further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-01-01

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

Does the Macaque Monkey Provide a Good Model for Studying Human Executive Control? A Comparative Behavioral Study of Task Switching

PubMed Central

Caselli, Luana; Chelazzi, Leonardo

2011-01-01

The ability to swiftly and smoothly switch from one task set to another is central to intelligent behavior, because it allows an organism to flexibly adapt to ever changing environmental conditions and internal needs. For this reason, researchers interested in executive control processes have often relied on task-switching paradigms as powerful tools to uncover the underlying cognitive and brain architecture. In order to gather fundamental information at the single-cell level, it would be greatly helpful to demonstrate that non-human primates, especially the macaque monkey, share with us similar behavioral manifestations of task-switching and therefore, in all likelihood, similar underlying brain mechanisms. Unfortunately, prior attempts have provided negative results (e.g., Stoet & Snyder, 2003b), in that it was reported that macaques do not show the typical signature of task-switching operations at the behavioral level, represented by switch costs. If confirmed, this would indicate that the macaque cannot be used as a model approach to explore human executive control mechanisms by means of task-switching paradigms. We have therefore decided to re-explore this issue, by conducting a comparative experiment on a group of human participants and two macaque monkeys, whereby we measured and compared performance costs linked to task switching and resistance to interference across the two species. Contrary to what previously reported, we found that both species display robust task switching costs, thus supporting the claim that macaque monkeys provide an exquisitely suitable model to study the brain mechanisms responsible for maintaining and switching task sets. PMID:21720549

Characterization of a Moraxella species that causes epistaxis in macaques

PubMed Central

Embers, Monica E.; Doyle, Lara A.; Whitehouse, Chris A.; Selby, Edward B.; Chappell, Mark; Philipp, Mario T.

2014-01-01

Bacteria of the genus Moraxella have been isolated from a variety of mammalian hosts. In a prior survey of bacteria that colonize the rhesus macaque nasopharynx, performed at the Tulane National Primate Research Center, organisms of the Moraxella genus were isolated from animals with epistaxis, or “bloody nose syndrome.” They were biochemically identified as Moraxella catarrhalis, and cryopreserved. Another isolate was obtained from an epistatic cynomolgus macaque at the U.S. Army Medical Research Institute of Infectious Diseases. Based on differences in colony and cell morphologies between rhesus and human M. catarrhalis isolates, we hypothesized that the nonhuman primate Moraxella might instead be a different species. Despite morphological differences, the rhesus isolates, by several biochemical tests, were indistinguishable from M. catarrhalis. Analysis of the cynomolgus isolate by Vitek 2 Compact indicated that it belonged to a Moraxella group, but could not differentiate among species. However, sequencing of the 16S ribosomal RNA gene from four representative rhesus isolates and the cynomolgus isolate showed closest homology to Moraxella lincolnii, a human respiratory tract inhabitant, with 90.16% identity. To examine rhesus macaques as potential hosts for M. catarrhalis, eight animals were inoculated with human M. catarrhalis isolates. Only one of the animals was colonized and showed disease, whereas four of four macaques became epistatic after inoculation with the rhesus Moraxella isolate. The nasopharyngeal isolates in this study appear uniquely adapted to a macaque host and, though they share many of the phenotypic characteristics of M. catarrhalis, appear to form a genotypically distinct species. PMID:20667430

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

PubMed

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.

Non-invasive surveillance for Plasmodium in reservoir macaque species.

PubMed

Siregar, Josephine E; Faust, Christina L; Murdiyarso, Lydia S; Rosmanah, Lis; Saepuloh, Uus; Dobson, Andrew P; Iskandriati, Diah

2015-10-12

Primates are important reservoirs for human diseases, but their infection status and disease dynamics are difficult to track in the wild. Within the last decade, a macaque malaria, Plasmodium knowlesi, has caused disease in hundreds of humans in Southeast Asia. In order to track cases and understand zoonotic risk, it is imperative to be able to quantify infection status in reservoir macaque species. In this study, protocols for the collection of non-invasive samples and isolation of malaria parasites from naturally infected macaques are optimized. Paired faecal and blood samples from 60 Macaca fascicularis and four Macaca nemestrina were collected. All animals came from Sumatra or Java and were housed in semi-captive breeding colonies around West Java. DNA was extracted from samples using a modified protocol. Nested polymerase chain reactions (PCR) were run to detect Plasmodium using primers targeting mitochondrial DNA. Sensitivity of screening faecal samples for Plasmodium was compared to other studies using Kruskal Wallis tests and logistic regression models. The best primer set was 96.7 % (95 % confidence intervals (CI): 83.3-99.4 %) sensitive for detecting Plasmodium in faecal samples of naturally infected macaques (n = 30). This is the first study to produce definitive estimates of Plasmodium sensitivity and specificity in faecal samples from naturally infected hosts. The sensitivity was significantly higher than some other studies involving wild primates. Faecal samples can be used for detection of malaria infection in field surveys of macaques, even when there are no parasites visible in thin blood smears. Repeating samples from individuals will improve inferences of the epidemiology of malaria in wild primates.

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta).

PubMed

Freeman, Sara M; Inoue, Kiyoshi; Smith, Aaron L; Goodman, Mark M; Young, Larry J

2014-07-01

The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foley, Brian T; Korber, Bette T

2008-01-01

Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicatemore » 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.« less

The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

PubMed Central

Freeman, Sara M.; Inoue, Kiyoshi; Smith, Aaron L.; Goodman, Mark M.; Young, Larry J.

2014-01-01

The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication. PMID:24845184

Diagnosis of Amyloidosis and Differentiation from Chronic, Idiopathic Enterocolitis in Rhesus (Macaca mulatta) and Pig-Tailed (M. nemestrina) Macaques

PubMed Central

Rice, Kelly A; Chen, Edward S; Pate, Kelly A Metcalf; Hutchinson, Eric K; Adams, Robert J

2013-01-01

Amyloidosis is a progressive and ultimately fatal disease in which amyloid, an insoluble fibrillar protein, is deposited inappropriately in multiple organs, eventually leading to organ dysfunction. Although this condition commonly affects macaques, there is currently no reliable method of early diagnosis. Changes in clinical pathology parameters have been associated with amyloidosis but occur in late stages of disease, are nonspecific, and resemble those seen in chronic, idiopathic enterocolitis. A review of animal records revealed that amyloidosis was almost always diagnosed postmortem, with prevalences of 15% and 25% in our rhesus and pig-tailed macaque colonies, respectively. As a noninvasive, high-throughput diagnostic approach to improve antemortem diagnosis of amyloidosis in macaques, we evaluated serum amyloid A (SAA), an acute-phase protein and the precursor to amyloid. Using necropsy records and ELISA analysis of banked serum, we found that SAA is significantly elevated in both rhesus and pig-tailed macaques with amyloid compared with those with chronic enterocolitis and healthy controls. At necropsy, 92% of rhesus and 83% of pig-tailed had amyloid deposition in either the intestines or liver. Minimally invasive biopsy techniques including endoscopy of the small intestine, mucosal biopsy of the colon, and ultrasound-guided trucut biopsy of the liver were used to differentiate macaques in our colonies with similar clinical presentations as either having amyloidosis or chronic, idiopathic enterocolitis. Our data suggest that SAA can serve as an effective noninvasive screening tool for amyloidosis and that minimally invasive biopsies can be used to confirm this diagnosis. PMID:23759529

Playing it cool: Characterizing social play, bout termination, and candidate play signals of juvenile and infant Tibetan macaques (Macaca thibetana).

PubMed

Wright, Kaitlin R; Mayhew, Jessica A; Sheeran, Lori K; Funkhouser, Jake A; Wagner, Ronald S; Sun, Li-Xing; Li, Jin-Hua

2018-07-18

Play behaviors and signals during playful interactions with juvenile conspecifics are important for both the social and cognitive development of young animals. The social organization of a species can also influence juvenile social play. We examined the relationships among play behaviors, candidate play signals, and play bout termination in Tibetan macaques (Macaca thibetana) during juvenile and infant social play to characterize the species play style. As Tibetan macaques are despotic and live in groups with strict linear dominance hierarchies and infrequent reconciliation, we predicted that play would be at risk of misinterpretation by both the individuals engaged in the play bout and by those watching, possibly leading to injury of the players. Animals living in such societies might need to frequently and clearly signal playful intent to play partners and other group members to avoid aggressive outcomes. We gathered video data on 21 individually-identified juvenile and infant macaques (one month to five years of age) from the Valley of the Wild Monkeys, Mt. Huangshan, China. We used all-occurrence sampling to record play behaviors and candidate play signals based on an ethogram. We predicted that play groups would use multiple candidate play signals in a variety of contexts and in association with the number of audience members in proximity to the players and play bout length. In the 283 playful interactions we scored, juvenile and infant macaques used multiple body and facial candidate play signals. Our data showed that juvenile and infant Tibetan macaques use a versatile repertoire of play behaviors and signals to sustain play.

Lentiviral Infection of Rhesus Macaques Causes Long-Term Injury to Cortical and Hippocampal Projections of Prostaglandin-Expressing Cholinergic Basal Forebrain Neurons

PubMed Central

Depboylu, Candan; Weihe, Eberhard; Eiden, Lee E.

2011-01-01

The simian immunodeficiency virus (SIV) macaque model resembles human HIV-AIDS and associated brain dysfunction. Altered expression of synaptic markers and transmitters in neuro-AIDS has been reported, but limited data exist for the cholinergic system and lipid mediators such as prostaglandins. Here, we analyzed cholinergic basal forebrain neurons with their telencephalic projections and the rate-limiting enzymes for prostaglandin synthesis, cyclooxygenases 1 and 2 (COX1 and 2) in brains of SIV-infected macaques with and without encephalitis and antiretroviral therapy, and uninfected controls. COX1 but not COX2 was co-expressed with markers of cholinergic phenotype, i.e. choline acetyltransferase and vesicular acetylcholine transporter (VAChT), in basal forebrain neurons of monkey, as well as human samples. COX1 was decreased in basal forebrain neurons in macaques with AIDS vs. uninfected and asymptomatic SIV-infected macaques. VAChT-positive fiber density was reduced in frontal, parietal and hippocampal-entorhinal cortex. Although brain SIV burden and associated COX1- and COX2-positive mononuclear and endothelial inflammatory reactions were mostly reversed in AIDS-diseased macaques that received 6-chloro-2′,3′-dideoxyguanosine treatment, decreased VAChT-positive terminal density and reduced cholinergic COX1 expression were not. Thus, COX1 expression is a feature of primate cholinergic basal forebrain neurons; it may be functionally important and a critical biomarker of cholinergic dysregulation accompanying lentiviral encephalopathy. These results imply that insufficiently prompt initiation of antiretroviral therapy in lentiviral infection may lead to neurostructurally unremarkable but neurochemically prominent, irreversible brain damage. PMID:22157616

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

PubMed

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.

Enriched Expression of Serotonin 1B and 2A Receptor Genes in Macaque Visual Cortex and their Bidirectional Modulatory Effects on Neuronal Responses

PubMed Central

Watakabe, Akiya; Komatsu, Yusuke; Sadakane, Osamu; Shimegi, Satoshi; Takahata, Toru; Higo, Noriyuki; Tochitani, Shiro; Hashikawa, Tsutomu; Naito, Tomoyuki; Osaki, Hironobu; Sakamoto, Hiroshi; Okamoto, Masahiro; Ishikawa, Ayako; Hara, Shin-ichiro; Akasaki, Takafumi; Sato, Hiromichi

2009-01-01

To study the molecular mechanism how cortical areas are specialized in adult primates, we searched for area-specific genes in macaque monkeys and found striking enrichment of serotonin (5-hydroxytryptamine, 5-HT) 1B receptor mRNA, and to a lesser extent, of 5-HT2A receptor mRNA, in the primary visual area (V1). In situ hybridization analyses revealed that both mRNA species were highly concentrated in the geniculorecipient layers IVA and IVC, where they were coexpressed in the same neurons. Monocular inactivation by tetrodotoxin injection resulted in a strong and rapid (<3 h) downregulation of these mRNAs, suggesting the retinal activity dependency of their expression. Consistent with the high expression level in V1, clear modulatory effects of 5-HT1B and 5-HT2A receptor agonists on the responses of V1 neurons were observed in in vivo electrophysiological experiments. The modulatory effect of the 5-HT1B agonist was dependent on the firing rate of the recorded neurons: The effect tended to be facilitative for neurons with a high firing rate, and suppressive for those with a low firing rate. The 5-HT2A agonist showed opposite effects. These results suggest that this serotonergic system controls the visual response in V1 for optimization of information processing toward the incoming visual inputs. PMID:19056862

Topographically Organized Projection to Posterior Insular Cortex from the Posterior Portion of the Ventral Medial Nucleus (VMpo) in the Long-tailed Macaque Monkey

PubMed Central

Craig, A.D. (Bud)

2014-01-01

Prior anterograde tracing work identified somatotopically organized lamina I trigemino- and spino-thalamic terminations in a cytoarchitectonically distinct portion of posterolateral thalamus of the macaque monkey, named the posterior part of the ventral medial nucleus (VMpo; Craig, 2004b). Microelectrode recordings from clusters of selectively thermoreceptive or nociceptive neurons were used to guide precise micro-injections of various tracers in VMpo. A prior report (Craig and Zhang, 2006) described retrograde tracing results, which confirmed the selective lamina I input to VMpo and the antero-posterior (head to foot) topography. The present report describes the results of micro-injections of anterograde tracers placed at different levels in VMpo, based on the antero-posterior topographic organization of selectively nociceptive units and clusters over nearly the entire extent of VMpo. Each injection produced dense, patchy terminal labeling in a single coherent field within a distinct granular cortical area centered in the fundus of the superior limiting sulcus. The terminations were distributed with a consistent antero-posterior topography over the posterior half of the superior limiting sulcus. These observations demonstrate a specific VMpo projection area in dorsal posterior insular cortex that provides the basis for a somatotopic representation of selectively nociceptive lamina I spinothalamic activity. These results also identify the VMpo terminal area as the posterior half of interoceptive cortex; the anterior half receives input from the vagal-responsive and gustatory neurons in the basal part of the ventral medial nucleus (VMb). PMID:23853108

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

PubMed

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.

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

PubMed Central

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. PMID:28761385

Intelligent Information Loss: The Coding of Facial Identity, Head Pose, and Non-Face Information in the Macaque Face Patch System

PubMed Central

Borzello, Mia; Freiwald, Winrich A.; Tsao, Doris

2015-01-01

Faces are a behaviorally important class of visual stimuli for primates. Recent work in macaque monkeys has identified six discrete face areas where most neurons have higher firing rates to images of faces compared with other objects (Tsao et al., 2006). While neurons in these areas appear to have different tuning (Freiwald and Tsao, 2010; Issa and DiCarlo, 2012), exactly what types of information and, consequently, which visual behaviors neural populations within each face area can support, is unknown. Here we use population decoding to better characterize three of these face patches (ML/MF, AL, and AM). We show that neural activity in all patches contains information that discriminates between the broad categories of face and nonface objects, individual faces, and nonface stimuli. Information is present in both high and lower firing rate regimes. However, there were significant differences between the patches, with the most anterior patch showing relatively weaker representation of nonface stimuli. Additionally, we find that pose-invariant face identity information increases as one moves to more anterior patches, while information about the orientation of the head decreases. Finally, we show that all the information we can extract from the population is present in patterns of activity across neurons, and there is relatively little information in the total activity of the population. These findings give new insight into the representations constructed by the face patch system and how they are successively transformed. PMID:25948258

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

PubMed

Lerche, Nicholas W; Simmons, Joe H

2008-02-01

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

Beyond Specific Pathogen-Free: Biology and Effect of Common Viruses in Macaques

PubMed Central

Lerche, Nicholas W; Simmons, Joe H

2008-01-01

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

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

PubMed

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

2016-09-01

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

Reference Intervals for Preprandial and Postprandial Serum Bile Acid in Adult Rhesus Macaques (Macaca mulatta)

PubMed Central

Lemoy, Marie-Josee MF; Westworth, Diccon R; Ardeshir, Amir; Tarara, Ross P

2013-01-01

The purpose of this study was to determine the 12-h fasting preprandial and 2-h postprandial serum bile acid concentration (SBAC) reference intervals for healthy, adult rhesus macaques (Macaca mulatta). We hypothesized that the mean 2-h postprandial SBAC would be significantly higher than the mean preprandial SBAC. We included 40 (24 male, 16 female) macaques after confirming that their health records, physical examinations, CBC, serum chemistry panels, and urinalyses were all within normal limits. In addition, hepatitis A titers were determined, an ultrasound examination of the liver was performed, and two 16-gauge ultrasound guided percutaneous liver biopsies were collected and submitted for histopathology. Macaques were confirmed healthy according to hepatitis A screens and sonographic and histologic evaluation of hepatic tissue. Within 2 wk of the screening procedures, preprandial and postprandial SBACs were measured. Preprandial SBAC (mean ± 1 SD) was 11.1 ± 1.9 µmol/L and postprandial SBAC was 19.7 ± 8.0 µmol/L, which was significantly higher than the preprandial value. Sex and hepatitis titers did not significantly influence preprandial and postprandial SBAC. The current study indicates that the SBAC reference values for rhesus macaques are higher than those reported for humans and companion animals. PMID:23849441

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

PubMed

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).

Reference intervals for preprandial and postprandial serum bile acid in adult rhesus macaques (Macaca mulatta).

PubMed

Lemoy, Marie-Josee M F; Westworth, Diccon R; Ardeshir, Amir; Tarara, Ross P

2013-07-01

The purpose of this study was to determine the 12-h fasting preprandial and 2-h postprandial serum bile acid concentration (SBAC) reference intervals for healthy, adult rhesus macaques (Macaca mulatta). We hypothesized that the mean 2-h postprandial SBAC would be significantly higher than the mean preprandial SBAC. We included 40 (24 male, 16 female) macaques after confirming that their health records, physical examinations, CBC, serum chemistry panels, and urinalyses were all within normal limits. In addition, hepatitis A titers were determined, an ultrasound examination of the liver was performed, and two 16-gauge ultrasound guided percutaneous liver biopsies were collected and submitted for histopathology. Macaques were confirmed healthy according to hepatitis A screens and sonographic and histologic evaluation of hepatic tissue. Within 2 wk of the screening procedures, preprandial and postprandial SBACs were measured. Preprandial SBAC (mean ± 1 SD) was 11.1 ± 1.9 μmol/L and postprandial SBAC was 19.7 ± 8.0 μmol/L, which was significantly higher than the preprandial value. Sex and hepatitis titers did not significantly influence preprandial and postprandial SBAC. The current study indicates that the SBAC reference values for rhesus macaques are higher than those reported for humans and companion animals.

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

PubMed

Walter, Lutz; Petersen, Beatrix

2017-02-01

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

Complex assembly, crystallization and preliminary X-ray crystallographic studies of rhesus macaque MHC Mamu-A*01 complexed with an immunodominant SIV-Gag nonapeptide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu, Fuliang; Graduate School, Chinese Academy of Sciences, Beijing; Lou, Zhiyong

2005-06-01

Crystallization of the first rhesus macaque MHC class I complex. Simian immunodeficiency virus (SIV) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (HIV) infection in humans, especially in the cytotoxic T-lymphocyte (CTL) response. However, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class I (MHC I) presenting a specific peptide (the ligand for CTL) has not yet been elucidated. Here, using in vitro refolding, the preparation of the complex of the rhesus macaque MHC I allele (Mamu-A*01) with human β{sub 2}m and an immunodominant peptide,more » CTPYDINQM (Gag-CM9), derived from SIV Gag protein is reported. The complex (45 kDa) was crystallized; the crystal belongs to space group I422, with unit-cell parameters a = b = 183.8, c = 155.2 Å. The crystal contains two molecules in the asymmetric unit and diffracts X-rays to 2.8 Å resolution. The structure is being solved by molecular replacement and this is the first attempt to determined the crystal structure of a peptide–nonhuman primate MHC complex.« less

Comparison of Saliva Collection Methods for the Determination of Salivary Cortisol Levels in Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), and African Green Monkeys (Chlorocebus aethiops)

PubMed Central

Rapp-Santos, Kamala J; Altamura, Louis A; Norris, Sarah L; Lugo-Roman, Luis A; Rico, Pedro J; Hofer, Christian C

2017-01-01

The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis) and African green monkeys (Chlorocebus aethiops) at 2 collection time points. Serum and salivary cortisol levels were determined using a competitive quantitative ELISA. In addition, both saliva collection methods were evaluated for volume collected and ease of use. Compared with passive drool, the experimental collection device was more reliable in collecting sufficient volumes of saliva, and the resulting salivary cortisol values demonstrated stronger correlation with serum cortisol concentration in all species and collection days except cynomolgus macaques on day 1. This saliva collection device allows quick and reliable sample collection for the determination of salivary cortisol levels. In addition, the results might provide a useful tool for evaluating hypothalamic-pituitary-adrenal axis activity or the physiologic stress reaction in NHP as well as a biomarker of psychologic stress states in a variety of situations. PMID:28315649

Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

PubMed

Malkevitch, Nina V; Patterson, L Jean; Aldrich, M Kristine; Wu, Yichen; Venzon, David; Florese, Ruth H; Kalyanaraman, V S; Pal, Ranajit; Lee, Eun Mi; Zhao, Jun; Cristillo, Anthony; Robert-Guroff, Marjorie

2006-09-15

Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting <50 SIV RNA copies. Decreased viremia compared to naïve controls was observed in the other three. The SIV-infected unimmunized macaques modestly controlled viremia but exhibited CD4 counts < or =200, unlike the protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained <50 SIV RNA copies; SIV RNA emerged in 6. Re-appearance of CD8 cells and restoration of SIV-specific cellular immunity coincided with viremia suppression. Overall, cellular immunity induced by vaccination and/or low-level, inapparent viremia post-first SIV(mac251) challenge, was associated with durable protection against re-challenge.

Personality structure and social style in macaques.

PubMed

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

2015-08-01

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

Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques.

PubMed

Borges, Maria Beatriz; Marchevsky, Renato Sergio; Mendes, Ygara S; Mendes, Luiz Gustavo; Duarte, Ana Claudia; Cruz, Michael; de Filippis, Ana Maria Bispo; Vasconcelos, Pedro Fernando C; Freire, Marcos; Homma, Akira; Mossman, Sally; Lepine, Edith; Vanloubbeeck, Yannick; Lorin, Clarisse; Malice, Marie-Pierre; Caride, Elena; Warter, Lucile

2018-01-01

The macaque is widely accepted as a suitable model for preclinical characterization of dengue vaccine candidates. However, the only vaccine for which both preclinical and clinical efficacy results were reported so far showed efficacy levels that were substantially different between macaques and humans. We hypothesized that this model's predictive capacity may be improved using recent and minimally passaged dengue virus isolates, and by assessing vaccine efficacy by characterizing not only the post-dengue virus challenge viremia/RNAemia but also the associated-cytokine profile. Ten recent and minimally passaged Brazilian clinical isolates from the four dengue virus serotypes were tested for their infectivity in rhesus macaques. For the strains showing robust replication capacity, the associated-changes in soluble mediator levels, and the elicited dengue virus-neutralizing antibody responses, were also characterized. Three isolates from dengue virus serotypes 1, 2 and 4 induced viremia of high magnitude and longer duration relative to previously reported viremia kinetics in this model, and robust dengue virus-neutralizing antibody responses. Consistent with observations in humans, increased MCP-1, IFN-γ and VEGF-A levels, and transiently decreased IL-8 levels were detected after infection with the selected isolates. These results may contribute to establishing a dengue macaque model showing a higher predictability for vaccine efficacy in humans.

Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques

PubMed Central

Borges, Maria Beatriz; Marchevsky, Renato Sergio; Mendes, Ygara S.; Mendes, Luiz Gustavo; Duarte, Ana Claudia; Cruz, Michael; de Filippis, Ana Maria Bispo; Vasconcelos, Pedro Fernando C.; Freire, Marcos; Homma, Akira; Mossman, Sally; Lepine, Edith; Vanloubbeeck, Yannick; Lorin, Clarisse; Malice, Marie-Pierre; Caride, Elena

2018-01-01

The macaque is widely accepted as a suitable model for preclinical characterization of dengue vaccine candidates. However, the only vaccine for which both preclinical and clinical efficacy results were reported so far showed efficacy levels that were substantially different between macaques and humans. We hypothesized that this model’s predictive capacity may be improved using recent and minimally passaged dengue virus isolates, and by assessing vaccine efficacy by characterizing not only the post-dengue virus challenge viremia/RNAemia but also the associated-cytokine profile. Ten recent and minimally passaged Brazilian clinical isolates from the four dengue virus serotypes were tested for their infectivity in rhesus macaques. For the strains showing robust replication capacity, the associated-changes in soluble mediator levels, and the elicited dengue virus-neutralizing antibody responses, were also characterized. Three isolates from dengue virus serotypes 1, 2 and 4 induced viremia of high magnitude and longer duration relative to previously reported viremia kinetics in this model, and robust dengue virus-neutralizing antibody responses. Consistent with observations in humans, increased MCP-1, IFN-γ and VEGF-A levels, and transiently decreased IL-8 levels were detected after infection with the selected isolates. These results may contribute to establishing a dengue macaque model showing a higher predictability for vaccine efficacy in humans. PMID:29694440

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

PubMed

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/SIV-infected macrophages persist despite ART. Markers of macrophage activation and neuronal damage are observed in the CSF of HIV-infected individuals and of SIV-infected macaques on suppressive ART regimens, suggesting that the CNS has continued virus infection and latent infection. A controversy exists as to whether brain macrophages represent a latent source of replication-competent virus capable of reestablishing infection upon treatment interruption. In this study, we demonstrated the presence of the latent macrophage reservoir in brains of SIV-infected ART-treated macaques and analyzed the reservoir using our established outgrowth assay to quantitate macrophages harboring replication-competent SIV genomes. Our results support the idea of the existence of other latent reservoirs in addition to resting CD4 + T cells and underscore the importance of macrophages in developing strategies to eradicate HIV. Copyright © 2017 Avalos et al.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1983-02-01

The authors have used 2-deoxy-D-(/sup 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 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 themore » cortex, while the cytochrome label in these animals remained patchy. In macaque (Macaca nemestrina) monkeys, binocular stimulation with many orientations and spatial frequencies produced radial zones of high 2-DG uptake. 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.« less

Macaque Parieto-Insular Vestibular Cortex: Responses to self-motion and optic flow

PubMed Central

Chen, Aihua; DeAngelis, Gregory C.; Angelaki, Dora E.

2011-01-01

The parieto-insular vestibular cortex (PIVC) is thought to contain an important representation of vestibular information. Here we describe responses of macaque PIVC neurons to three-dimensional (3D) vestibular and optic flow stimulation. We found robust vestibular responses to both translational and rotational stimuli in the retroinsular (Ri) and adjacent secondary somatosensory (S2) cortices. PIVC neurons did not respond to optic flow stimulation, and vestibular responses were similar in darkness and during visual fixation. Cells in the upper bank and tip of the lateral sulcus (Ri and S2) responded to sinusoidal vestibular stimuli with modulation at the first harmonic frequency, and were directionally tuned. Cells in the lower bank of the lateral sulcus (mostly Ri) often modulated at the second harmonic frequency, and showed either bimodal spatial tuning or no tuning at all. All directions of 3D motion were represented in PIVC, with direction preferences distributed roughly uniformly for translation, but showing a preference for roll rotation. Spatio-temporal profiles of responses to translation revealed that half of PIVC cells followed the linear velocity profile of the stimulus, one-quarter carried signals related to linear acceleration (in the form of two peaks of direction selectivity separated in time), and a few neurons followed the derivative of linear acceleration (jerk). In contrast, mainly velocity-coding cells were found in response to rotation. Thus, PIVC comprises a large functional region in macaque areas Ri and S2, with robust responses to 3D rotation and translation, but is unlikely to play a significant role in visual/vestibular integration for self-motion perception. PMID:20181599

The Intracytoplasmic Domain of the Env Transmembrane Protein Is a Locus for Attenuation of Simian Immunodeficiency Virus SIVmac in Rhesus Macaques

PubMed Central

Shacklett, Barbara L.; Weber, Claudia Jo; Shaw, Karen E. S.; Keddie, Elise M.; Gardner, Murray B.; Sonigo, Pierre; Luciw, Paul A.

2000-01-01

The human and simian immunodeficiency virus (HIV-1 and SIVmac) transmembrane proteins contain unusually long intracytoplasmic domains (ICD-TM). These domains are suggested to play a role in envelope fusogenicity, interaction with the viral matrix protein during assembly, viral infectivity, binding of intracellular calmodulin, disruption of membranes, and induction of apoptosis. Here we describe a novel mutant virus, SIVmac-M4, containing multiple mutations in the coding region for the ICD-TM of pathogenic molecular clone SIVmac239. Parental SIVmac239-Nef+ produces high-level persistent viremia and simian AIDS in both juvenile and newborn rhesus macaques. The ICD-TM region of SIVmac-M4 contains three stop codons, a +1 frameshift, and mutation of three highly conserved, charged residues in the conserved C-terminal alpha-helix referred to as lentivirus lytic peptide 1 (LLP-1). Overlapping reading frames for tat, rev, and nef are not affected by these changes. In this study, four juvenile macaques received SIVmac-M4 by intravenous injection. Plasma viremia, as measured by branched-DNA (bDNA) assay, reached a peak at 2 weeks postinoculation but dropped to below detectable levels by 12 weeks. At over 1.5 years postinoculation, all four juvenile macaques remain healthy and asymptomatic. In a subsequent experiment, four neonatal rhesus macaques were given SIVmac-M4 intravenously. These animals exhibited high levels of viremia in the acute phase (2 weeks postinoculation) but are showing a relatively low viral load in the chronic phase of infection, with no clinical signs of disease for 1 year. These findings demonstrated that the intracytoplasmic domain of the transmembrane Env (Env-TM) is a locus for attenuation in rhesus macaques. PMID:10846063

Sagittal Plane Kinematics of the Jaw and Hyolingual Apparatus During Swallowing in Macaca mulatta

PubMed Central

Iriarte-Diaz, Jose; Arce-McShane, Fritzie; Orsbon, Courtney P.; Brown, Kevin A.; Eastment, McKenna; Avivi-Arber, Limor; Sessle, Barry J.; Inoue, Makoto; Hatsopoulos, Nicholas G.; Ross, Callum F.

2018-01-01

Studies of mechanisms of feeding behavior are important in a society where aging- and disease-related feeding disorders are increasingly prevalent. It is important to evaluate the clinical relevance of animal models of the disease and the control. Our present study quantifies macaque hyolingual and jaw kinematics around swallowing cycles to determine the extent to which macaque swallowing resembles that of humans. One female and one male adult Macaca mulatta were trained to feed in a primate chair. Videofluoroscopy was used to record kinematics in a sagittal view during natural feeding on solid food, and the kinematics of the hyoid bone, thyroid cartilage, mandibular jaw, and anterior-, middle-, and posterior-tongue. Jaw gape cycles were defined by consecutive maximum gapes, and the kinematics of the swallow cycles were compared with those of the two consecutive non-swallow cycles preceding and succeeding the swallow cycles. Although there are size differences between macaques and humans, and macaques have shorter durations of jaw gape cycles and hyoid and thyroid upward movements, there are several important similarities between our macaque data and human data reported in the literature: (1) The durations of jaw gape cycles during swallow cycles are longer than those of non-swallow cycles as a result of an increased duration of the jaw-opening phase; (2) Hyoid and thyroid upward movement is linked with a posterior tongue movement and is faster during swallow than non-swallow cycles; (3) Tongue elevation propagates from anterior to posterior during swallow and non-swallow cycles. These findings suggest that macaques can be a useful experimental model for human swallowing studies. PMID:28528492

Bridging the Gap between the Human and Macaque Connectome: A Quantitative Comparison of Global Interspecies Structure-Function Relationships and Network Topology

PubMed Central

Miranda-Dominguez, Oscar; Mills, Brian D.; Grayson, David; Woodall, Andrew; Grant, Kathleen A.; Kroenke, Christopher D.

2014-01-01

Resting state functional connectivity MRI (rs-fcMRI) may provide a powerful and noninvasive “bridge” for comparing brain function between patients and experimental animal models; however, the relationship between human and macaque rs-fcMRI remains poorly understood. Here, using a novel surface deformation process for species comparisons in the same anatomical space (Van Essen, 2004, 2005), we found high correspondence, but also unique hub topology, between human and macaque functional connectomes. The global functional connectivity match between species was moderate to strong (r = 0.41) and increased when considering the top 15% strongest connections (r = 0.54). Analysis of the match between functional connectivity and the underlying anatomical connectivity, derived from a previous retrograde tracer study done in macaques (Markov et al., 2012), showed impressive structure–function correspondence in both the macaque and human. When examining the strongest structural connections, we found a 70–80% match between structural and functional connectivity matrices in both species. Finally, we compare species on two widely used metrics for studying hub topology: degree and betweenness centrality. The data showed topological agreement across the species, with nodes of the posterior cingulate showing high degree and betweenness centrality. In contrast, nodes in medial frontal and parietal cortices were identified as having high degree and betweenness in the human as opposed to the macaque. Our results provide: (1) a thorough examination and validation for a surface-based interspecies deformation process, (2) a strong theoretical foundation for making interspecies comparisons of rs-fcMRI, and (3) a unique look at topological distinctions between the species. PMID:24741045

Early Whole Blood Transcriptional Signatures Are Associated with Severity of Lung Inflammation in Cynomolgus Macaques with Mycobacterium tuberculosis Infection.

PubMed

Gideon, Hannah P; Skinner, Jason A; Baldwin, Nicole; Flynn, JoAnne L; Lin, Philana Ling

2016-12-15

Whole blood transcriptional profiling offers great diagnostic and prognostic potential. Although studies identified signatures for pulmonary tuberculosis (TB) and transcripts that predict the risk for developing active TB in humans, the early transcriptional changes immediately following Mycobacterium tuberculosis infection have not been evaluated. We evaluated the gene expression changes in the cynomolgus macaque model of TB, which recapitulates all clinical aspects of human M. tuberculosis infection, using a human microarray and analytics platform. We performed genome-wide blood transcriptional analysis on 38 macaques at 11 postinfection time points during the first 6 mo of M. tuberculosis infection. Of 6371 differentially expressed transcripts between preinfection and postinfection, the greatest change in transcriptional activity occurred 20-56 d postinfection, during which fluctuation of innate and adaptive immune response-related transcripts was observed. Modest transcriptional differences between active TB and latent infection were observed over the time course with substantial overlap. The pattern of module activity previously published for human active TB was similar in macaques with active disease. Blood transcript activity was highly correlated with lung inflammation (lung [ 18 F]fluorodeoxyglucose [FDG] avidity) measured by positron emission tomography and computed tomography at early time points postinfection. The differential signatures between animals with high and low lung FDG were stronger than between clinical outcomes. Analysis of preinfection signatures of macaques revealed that IFN signatures could influence eventual clinical outcomes and lung FDG avidity, even before infection. Our data support that transcriptional changes in the macaque model are translatable to human M. tuberculosis infection and offer important insights into early events of M. tuberculosis infection. Copyright © 2016 by The American Association of Immunologists, Inc.

Partial protection against multiple RT-SHIV162P3 vaginal challenge of rhesus macaques by a silicone elastomer vaginal ring releasing the NNRTI MC1220

PubMed Central

Fetherston, Susan M.; Geer, Leslie; Veazey, Ronald S.; Goldman, Laurie; Murphy, Diarmaid J.; Ketas, Thomas J.; Klasse, Per Johan; Blois, Sylvain; La Colla, Paolo; Moore, John P.; Malcolm, R. Karl

2013-01-01

Objectives The non-nucleoside reverse transcriptase inhibitor MC1220 has potent in vitro activity against HIV type 1 (HIV-1). A liposome gel formulation of MC1220 has previously been reported to partially protect rhesus macaques against vaginal challenge with a simian HIV (SHIV). Here, we describe the pre-clinical development of an MC1220-releasing silicone elastomer vaginal ring (SEVR), including pharmacokinetic (PK) and efficacy studies in macaques. Methods In vitro release studies were conducted on SEVRs loaded with 400 mg of MC1220, using simulated vaginal fluid (SVF, n = 4) and 1 : 1 isopropanol/water (IPA/H2O, n = 4) as release media. For PK evaluation, SEVRs were inserted into adult female macaques (n = 6) for 30 days. Following a 1week washout period, fresh rings were placed in the same animals, which were then challenged vaginally with RT-SHIV162P3 once weekly for 4 weeks. Results SEVRs released 1.66 and 101 mg of MC1220 into SVF and IPA/H2O, respectively, over 30 days, the differential reflecting the low aqueous solubility of the drug. In macaque PK studies, MC1220 was consistently detected in vaginal fluid (peak 845 ng/mL) and plasma (peak 0.91 ng/mL). Kaplan–Meier analysis over 9weeks showed significantly lower infection rates for animals given MC1220-containing SEVRs than placebo rings (hazard ratio 0.20, P = 0.0037). Conclusions An MC1220-releasing SEVR partially protected macaques from vaginal challenge. Such ring devices are a practical method for providing sustained, coitally independent protection against vaginal exposure to HIV-1. PMID:23109186

Molecular Cytogenetic Analysis of One African and Five Asian Macaque Species Reveals Identical Karyotypes as in Mandrill.

PubMed

Sangpakdee, Wiwat; Tanomtong, Alongkoad; Chaveerach, Arunrat; Pinthong, Krit; Trifonov, Vladimir; Loth, Kristina; Hensel, Christiana; Liehr, Thomas; Weise, Anja; Fan, Xiaobo

2018-04-01

The question how evolution and speciation work is one of the major interests of biology. Especially, genetic including karyotypic evolution within primates is of special interest due to the close phylogenetic position of Macaca and Homo sapiens and the role as in vivo models in medical research, neuroscience, behavior, pharmacology, reproduction and Acquired Immune Deficiency Syndrome (AIDS). Karyotypes of five macaque species from South East Asia and of one macaque species as well as mandrill from Africa were analyzed by high resolution molecular cytogenetics to obtain new insights into karyotypic evolution of old world monkeys. Molecular cytogenetics applying human probes and probe sets was applied in chromosomes of Macaca arctoides, M. fascicularis, M. nemestrina, M. assamensis, M. sylvanus, M. mulatta and Mandrillus sphinx. Established two- to multicolor-fluorescence in situ hybridization (FISH) approaches were applied. Locus-specific probes, whole and partial chromosome paint probes were hybridized. Especially the FISH-banding approach multicolor-banding (MCB) as well as probes oriented towards heterochromatin turned out to be highly efficient for interspecies comparison. Karyotypes of all seven studied species could be characterized in detail. Surprisingly, no evolutionary conserved differences were found among macaques, including mandrill. Between the seven here studied and phenotypically so different species we expected several via FISH detectable karyoypic and submicroscopic changes and were surprised to find none of them on a molecular cytogenetic level. Spatial separation, may explain the speciation and different evolution for some of them, like African M. sylvanus, Mandrillus sphinx and the South Asian macaques. However, for the partially or completely overlapping habitats of the five studied South Asian macaques the species separation process can also not be deduced to karyotypic separation.

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

PubMed Central

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

Pharmacokinetic profile of raltegravir, elvitegravir and dolutegravir in plasma and mucosal secretions in rhesus macaques.

PubMed

Massud, Ivana; Martin, Amy; Dinh, Chuong; Mitchell, James; Jenkins, Leecresia; Heneine, Walid; Pau, Chou-Pong; García-Lerma, J Gerardo

2015-05-01

Pharmacokinetic studies in animal models are important for assessing the prophylactic potential of antiretroviral drugs for HIV prevention. This study sought to identify clinically relevant doses of the marketed integrase inhibitors raltegravir, elvitegravir and dolutegravir in macaques and investigate drug penetration and antiviral activity in mucosal secretions. Macaques received one oral dose of raltegravir, elvitegravir or dolutegravir alone or in combination with emtricitabine and tenofovir disoproxil fumarate followed by drug level measurements in blood and rectal and vaginal secretions. Antiviral activity was investigated in TZM-bl cells exposed to SHIV162p3 in the presence of rectal secretions collected from treated animals. Plasma drug concentrations with 50 mg/kg raltegravir or elvitegravir were within the range seen in humans receiving 400-800 mg of raltegravir or 800 mg of unboosted elvitegravir but lower than with 150 mg of elvitegravir boosted with cobicistat. AUC0-24 values for dolutegravir increased proportionally with the dose, with a calculated human-equivalent dose of 20 mg/kg. Elvitegravir showed the highest penetration in rectal and vaginal fluids despite the absence of pharmacological boosting, followed by raltegravir and dolutegravir. Rectal secretions collected at 24 h from treated macaques blocked infection of TZM-bl cells by 50% at dilutions of 1/1000 (raltegravir), 1/800 (dolutegravir) and >1/30 000 (elvitegravir). We defined macaque doses of HIV integrase inhibitors that recapitulate human clinical doses, which will facilitate efficacy and dose escalation studies in macaques. High and sustained drug concentrations and activity in mucosal secretions suggest that integrase inhibitors are promising candidates for HIV prevention. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Partial protection against multiple RT-SHIV162P3 vaginal challenge of rhesus macaques by a silicone elastomer vaginal ring releasing the NNRTI MC1220.

PubMed

Fetherston, Susan M; Geer, Leslie; Veazey, Ronald S; Goldman, Laurie; Murphy, Diarmaid J; Ketas, Thomas J; Klasse, Per Johan; Blois, Sylvain; La Colla, Paolo; Moore, John P; Malcolm, R Karl

2013-02-01

The non-nucleoside reverse transcriptase inhibitor MC1220 has potent in vitro activity against HIV type 1 (HIV-1). A liposome gel formulation of MC1220 has previously been reported to partially protect rhesus macaques against vaginal challenge with a simian HIV (SHIV). Here, we describe the pre-clinical development of an MC1220-releasing silicone elastomer vaginal ring (SEVR), including pharmacokinetic (PK) and efficacy studies in macaques. In vitro release studies were conducted on SEVRs loaded with 400 mg of MC1220, using simulated vaginal fluid (SVF, n = 4) and 1 : 1 isopropanol/water (IPA/H(2)O, n = 4) as release media. For PK evaluation, SEVRs were inserted into adult female macaques (n = 6) for 30 days. Following a 1 week washout period, fresh rings were placed in the same animals, which were then challenged vaginally with RT-SHIV162P3 once weekly for 4 weeks. SEVRs released 1.66 and 101 mg of MC1220 into SVF and IPA/H(2)O, respectively, over 30 days, the differential reflecting the low aqueous solubility of the drug. In macaque PK studies, MC1220 was consistently detected in vaginal fluid (peak 845 ng/mL) and plasma (peak 0.91 ng/mL). Kaplan-Meier analysis over 9 weeks showed significantly lower infection rates for animals given MC1220-containing SEVRs than placebo rings (hazard ratio 0.20, P = 0.0037). An MC1220-releasing SEVR partially protected macaques from vaginal challenge. Such ring devices are a practical method for providing sustained, coitally independent protection against vaginal exposure to HIV-1.

Sequence variation in the env gene of simian immunodeficiency virus recovered from immunized macaques is predominantly in the V1 region.

PubMed

Almond, N; Jenkins, A; Heath, A B; Kitchin, P

1993-05-01

Three cynomolgus macaques were immunized with recombinant envelope protein preparations derived from simian immunodeficiency virus (SIV). Although humoral and cellular responses were elicited by the immunization regime, all macaques became infected upon challenge with 10 MID50 of the 11/88 virus challenge stock of SIVmac251-32H. The polymerase chain reaction was used to amplify proviral SIV gp120 sequences present in the blood of both immunized and control macaques at 2 months post-infection. A comparison of the predominant sequences found in the region from V2 to V5 of gp120 failed to differentiate provirus recovered from either immunized or control animals. A detailed investigation of sequences obtained from the hypervariable V1 region identified a mixture of sequences in both immunized and control macaques. Some sequences were identical to those previously detected in the virus challenge stock, whereas others had not been detected previously. Phenogram analysis of the new V1 sequences found in immunized animals revealed that they were quite distinct from those from the virus challenge stock and that they included alterations to potential N-linked glycosylation sites. In contrast, new sequence variants recovered from the control animals were closely related to sequences from the virus challenge stock. The difference in diversity of new V1 sequences recovered from immunized and control macaques was highly significant (P < 0.001). Thus, the presence of pre-existing immune responses to SIV envelope protein is associated with greater genetic change in the V1 region of gp120. These data are discussed in relation to the epitopes of SIV gp120 that may confer protection from in vivo challenge.

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

PubMed

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.

Lentiviral infection of rhesus macaques causes long-term injury to cortical and hippocampal projections of prostaglandin-expressing cholinergic basal forebrain neurons.

PubMed

Depboylu, Candan; Weihe, Eberhard; Eiden, Lee E

2012-01-01

The simian immunodeficiency virus (SIV) macaque model resembles human immunodeficiency virus-acquired immunodeficiency syndrome (AIDS) and associated brain dysfunction. Altered expression of synaptic markers and transmitters in neuro-AIDS has been reported, but limited data exist for the cholinergic system and lipid mediators such as prostaglandins. Here, we analyzed cholinergic basal forebrain neurons with their telencephalic projections and the rate-limiting enzymes for prostaglandin synthesis, cyclooxygenase isotypes 1 and 2 (COX1 and COX2) in the brains of SIV-infected macaques with or without encephalitis and antiretroviral therapy and uninfected controls.Cyclooxygenase isotype 1, but not COX2, was coexpressed with markers of cholinergic phenotype, that is, choline acetyltransferase and vesicular acetylcholine transporter (VAChT), in basal forebrain neurons of monkey, as well as human, brain. Cyclooxygenase isotype 1 was decreased in basal forebrain neurons in macaques with AIDS versus uninfected and asymptomatic SIV-infected macaques. The VAChT-positive fiber density was reduced in frontal, parietal, and hippocampal-entorhinal cortex. Although brain SIV burden and associated COX1- and COX2-positive mononuclear and endothelial inflammatory reactions were mostly reversed in AIDS-diseased macaques that received 6-chloro-2',3'-dideoxyguanosine treatment, decreased VAChT-positive terminal density and reduced cholinergic COX1 expression were not. Thus, COX1 expression is a feature of primate cholinergic basal forebrain neurons; it may be functionally important and a critical biomarker of cholinergic dysregulation accompanying lentiviral encephalopathy. These results further imply that insufficiently prompt initiation of antiretroviral therapy in lentiviral infection may lead to neurostructurally unremarkable but neurochemically prominent irreversible brain damage.

Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

PubMed

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

2015-01-01

Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice.

Analysis of a library of macaque nuclear mitochondrial sequences confirms macaque origin of divergent sequences from old oral polio vaccine samples.

PubMed

Vartanian, Jean-Pierre; Wain-Hobson, Simon

2002-05-28

Nuclear mtDNA sequences (numts) are a widespread family of paralogs evolving as pseudogenes in chromosomal DNA [Zhang, D. E. & Hewitt, G. M. (1996) TREE 11, 247-251 and Bensasson, D., Zhang, D., Hartl, D. L. & Hewitt, G. M. (2001) TREE 16, 314-321]. When trying to identify the species origin of an unknown DNA sample by way of an mtDNA locus, PCR may amplify both mtDNA and numts. Indeed, occasionally numts dominate confounding attempts at species identification [Bensasson, D., Zhang, D. X. & Hewitt, G. M. (2000) Mol. Biol. Evol. 17, 406-415; Wallace, D. C., et al. (1997) Proc. Natl. Acad. Sci. USA 94, 14900-14905]. Rhesus and cynomolgus macaque mtDNA haplotypes were identified in a study of oral polio vaccine samples dating from the late 1950s [Blancou, P., et al. (2001) Nature (London) 410, 1045-1046]. They were accompanied by a number of putative numts. To confirm that these putative numts were of macaque origin, a library of numts corresponding to a small segment of 12S rDNA locus has been made by using DNA from a Chinese rhesus macaque. A broad distribution was found with up to 30% sequence variation. Phylogenetic analysis showed that the evolutionary trajectories of numts and bona fide mtDNA haplotypes do not overlap with the signal exception of the host species; mtDNA fragments are continually crossing over into the germ line. In the case of divergent mtDNA sequences from old oral polio vaccine samples [Blancou, P., et al. (2001) Nature (London) 410, 1045-1046], all were closely related to numts in the Chinese macaque library.

Sex and rank affect how infant rhesus macaques look at faces

PubMed Central

Paukner, Annika; Slonecker, Emily M.; Murphy, Ashley M.; Wooddell, Lauren J.; Dettmer, Amanda M.

2017-01-01

We investigated how differences in infant sex and mothers’ dominance status affect infant rhesus macaques’ (Macaca mulatta) interest in visually exploring emotional facial expressions. Thirty-eight infants were presented with animated avatars of macaque facial expressions during the first month of life. Sons of high-ranking mothers looked more at faces, especially the eye region, than sons of low-ranking mothers, but no difference in looking duration was found for daughters. Males looked significantly more at eyes than females, but this effect was reversed in infants who were reared without mothers in a primate nursery facility. In addition, in mother-infant interactions, mothers of sons were more likely to gaze at their infant’s face compared to mothers of daughters. Combined with previous research indicating that rhesus macaque mothers interact differently with infants based on their own rank and infant’s sex, these results support the view that social experiences shape early face preferences in rhesus macaques. PMID:29165801

Artifact correction in diffusion MRI of non-human primate brains on a clinical 3T scanner.

PubMed

Zhang, Xiaodong; Kirsch, John E; Zhong, Xiaodong

2016-02-01

Smearing artifacts were observed and investigated in diffusion tensor imaging (DTI) studies of macaque monkeys on a clinical whole-body 3T scanner. Four adult macaques were utilized to evaluate DTI artifacts. DTI images were acquired with a single-shot echo-planar imaging (EPI) sequence using a parallel imaging technique. The smearing artifacts observed on the diffusion-weighted images and fractional anisotropy maps were caused by the incomplete fat suppression due to the irregular macaque frontal skull geometry and anatomy. The artifact can be reduced substantially using a novel three-dimensional (3D) shimming procedure. The smearing artifacts observed on diffusion weighted images and fractional anisotropy (FA) maps of macaque brains can be reduced substantially using a robust 3D shimming approach. The DTI protocol combined with the shimming procedure could be a robust approach to examine brain connectivity and white matter integrity of non-human primates using a conventional clinical setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A structural comparison of female-male and female-female mounting in Japanese macaques (Macaca fuscata).

PubMed

Ottenheimer Carrier, Lydia; Leca, Jean-Baptiste; Pellis, Sergio; Vasey, Paul L

2015-10-01

In certain populations, female Japanese macaques (Macaca fuscata) mount both males and females. Vasey (2007) proposed that female-female sexual mounting in Japanese macaques may be a neutral evolutionary by-product of a purported adaptation, namely, female-male mounting. In this study, we aim to further examine the proposed link between female-male and female-female mounting in Japanese macaques by comparing the structural characteristics that define both forms of mounting. We do so using Eshkol-Wachman Movement Notation (EWMN), a globographic reference system that can be used to describe the position of body segments. No significant differences were observed in the female mounters' positioning of eight different body segments (i.e., lower torso, mid-torso, upper torso, upper arm, lower arm, upper leg, lower leg, and foot) during female-male and female-female mounting. This finding lends support to the conclusion that female-female and female-male mounting are structurally, and thus, evolutionarily, related. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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.

The Roles of Dopamine D2 Receptor in the Social Hierarchy of Rodents and Primates.

PubMed

Yamaguchi, Yoshie; Lee, Young-A; Kato, Akemi; Jas, Emanuel; Goto, Yukiori

2017-02-24

Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals.

The Roles of Dopamine D2 Receptor in the Social Hierarchy of Rodents and Primates

PubMed Central

Yamaguchi, Yoshie; Lee, Young-A.; Kato, Akemi; Jas, Emanuel; Goto, Yukiori

2017-01-01

Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals. PMID:28233850

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

PubMed

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.

Process Versus Product in Social Learning: Comparative Diffusion Tensor Imaging of Neural Systems for Action Execution–Observation Matching in Macaques, Chimpanzees, and Humans

PubMed Central

Hecht, Erin E.; Gutman, David A.; Preuss, Todd M.; Sanchez, Mar M.; Parr, Lisa A.; Rilling, James K.

2013-01-01

Social learning varies among primate species. Macaques only copy the product of observed actions, or emulate, while humans and chimpanzees also copy the process, or imitate. In humans, imitation is linked to the mirror system. Here we compare mirror system connectivity across these species using diffusion tensor imaging. In macaques and chimpanzees, the preponderance of this circuitry consists of frontal–temporal connections via the extreme/external capsules. In contrast, humans have more substantial temporal–parietal and frontal–parietal connections via the middle/inferior longitudinal fasciculi and the third branch of the superior longitudinal fasciculus. In chimpanzees and humans, but not in macaques, this circuitry includes connections with inferior temporal cortex. In humans alone, connections with superior parietal cortex were also detected. We suggest a model linking species differences in mirror system connectivity and responsivity with species differences in behavior, including adaptations for imitation and social learning of tool use. PMID:22539611

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

PubMed Central

Hessell, Ann J.; Jaworski, J. Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F.; Hammond, Katherine B.; Cheever, Tracy A.; Barnette, Philip T.; Legasse, Alfred W.; Planer, Shannon; Stanton, Jeffrey J.; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S.; Axthelm, Michael K.; Lewis, Anne; Hirsch, Vanessa M.; Graham, Barney S.; Mascola, John R.; Sacha, Jonah B.; Haigwood, Nancy L.

2016-01-01

Prevention of mother to child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested anti-HIV-1 human neutralizing monoclonal antibodies (NmAb) as post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with SHIVSF162P3. On days 1, 4, 7, and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h following administration. Replicating virus was found in multiple tissues by day 1 in animals without treatment. All NmAb-treated macaques were free of virus in blood and tissues at 6 months post-exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged following CD8+ T cell depletion. These results suggest early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs. PMID:26998834

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

PubMed Central

Vatter, Heather A.; Donaldson, Eric F.; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F.; Lewis, Anne D.; Colgin, Lois M.A.; Axthelm, Michael K.; Pecotte, Jerilyn K.; Baric, Ralph S.; Wong, Scott W.; Brinton, Margo A.

2014-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. PMID:25463617

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques.

PubMed

Vatter, Heather A; Donaldson, Eric F; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F; Lewis, Anne D; Colgin, Lois M A; Axthelm, Michael K; Pecotte, Jerilyn K; Baric, Ralph S; Wong, Scott W; Brinton, Margo A

2015-01-01

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100-1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. Copyright © 2014 Elsevier Inc. All rights reserved.

Hematologic abnormalities associated with simian immunodeficieny virus (SIV) infection mimic those in HIV infection.

PubMed

Gill, Amy F; Ahsan, Muhammad H; Lackner, Andrew A; Veazey, Ronald S

2012-06-01

Studies of hematologic abnormalities in HIV-infected patients are confounded by a multitude of factors. A retrospective data analysis of simian immunodeficieny virus (SIV)-infected rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. Hematologic data from RM inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared with non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggests that, like in HIV infection, hematologic abnormalities are major complications of SIV infection. © 2012 John Wiley & Sons A/S.

Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.

PubMed

Del Prete, Gregory Q; Ailers, Braiden; Moldt, Brian; Keele, Brandon F; Estes, Jacob D; Rodriguez, Anthony; Sampias, Marissa; Oswald, Kelli; Fast, Randy; Trubey, Charles M; Chertova, Elena; Smedley, Jeremy; LaBranche, Celia C; Montefiori, David C; Burton, Dennis R; Shaw, George M; Markowitz, Marty; Piatak, Michael; KewalRamani, Vineet N; Bieniasz, Paul D; Lifson, Jeffrey D; Hatziioannou, Theodora

2014-09-10

Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

The temporal dynamics of heading perception in the presence of moving objects

PubMed Central

Fajen, Brett R.

2015-01-01

Many forms of locomotion rely on the ability to accurately perceive one's direction of locomotion (i.e., heading) based on optic flow. Although accurate in rigid environments, heading judgments may be biased when independently moving objects are present. The aim of this study was to systematically investigate the conditions in which moving objects influence heading perception, with a focus on the temporal dynamics and the mechanisms underlying this bias. Subjects viewed stimuli simulating linear self-motion in the presence of a moving object and judged their direction of heading. Experiments 1 and 2 revealed that heading perception is biased when the object crosses or almost crosses the observer's future path toward the end of the trial, but not when the object crosses earlier in the trial. Nonetheless, heading perception is not based entirely on the instantaneous optic flow toward the end of the trial. This was demonstrated in Experiment 3 by varying the portion of the earlier part of the trial leading up to the last frame that was presented to subjects. When the stimulus duration was long enough to include the part of the trial before the moving object crossed the observer's path, heading judgments were less biased. The findings suggest that heading perception is affected by the temporal evolution of optic flow. The time course of dorsal medial superior temporal area (MSTd) neuron responses may play a crucial role in perceiving heading in the presence of moving objects, a property not captured by many existing models. PMID:26510765

Pharmacokinetics of a Novel, Transdermal Fentanyl Solution in Rhesus Macaques (Macaca mulatta)

PubMed Central

Salyards, Gregory W; Lemoy, Marie-Josee; Knych, Heather K; Hill, Ashley E; Christe, Kari L

2017-01-01

Rhesus macaques (Macaca mulatta) are the most commonly used NHP biomedical model and experience both research and clinical procedures requiring analgesia. Opioids are a mainstay of analgesic therapy. A novel, transdermal fentanyl solution (TFS) has been developed as a long-acting, single-administration topical opioid and was reported to provide at least 4 d of effective plasma concentrations in beagles (Canis familiaris). To evaluate the pharmacokinetic profile of TFS in healthy adult rhesus macaques, we used a 2-period, 2-treatment crossover study of a single topical administration of 1.3 (25) and 2.6 mg/kg (50 μL/kg) TFS. TFS was applied to the clipped dorsal skin of adult rhesus macaques (n = 6; 3 male, 3 female) under ketamine sedation (10 mg/kg IM). We hypothesized that TFS in rhesus macaques would provide at least 4 d of effective plasma concentrations (assumed to be ≥ 0.2 ng/mL, based on human studies). Plasma fentanyl concentrations were determined by liquid chromatography–tandem mass spectrometry before drug administration and at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 240, 336, 408, and 504 h afterward. Noncompartmental pharmacokinetic analysis was performed. For each dose (1.3 and 2.6 mg/kg), respectively, the maximal plasma concentration was 1.95 ± 0.40 and 4.19 ± 0.69 ng/mL, occurring at 21.3 ± 4.1 and 30.7 ± 8.7 h; the AUC was 227.3 ± 31.7 and 447.0 ± 49.1 h/ng/mL, and the terminal elimination half-life was 93.7 ± 7.1 and 98.8 ± 5.4 h. No adverse effects were noted after drug administration at either dose. Macaques maintained plasma fentanyl concentrations of 0.2 ng/mL or greater for at least 7 d after 1.3 mg/kg and at least 10 d after 2.6 mg/kg topical administration of TFS. A single TFS dose may provide efficacious analgesia to rhesus macaques and reduce stress, discomfort, and risk to animals and personnel. PMID:28724494

Brain regions with mirror properties: a meta-analysis of 125 human fMRI studies.

PubMed

Molenberghs, Pascal; Cunnington, Ross; Mattingley, Jason B

2012-01-01

Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

A neural circuit covarying with social hierarchy in macaques.

PubMed

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.

A Neural Circuit Covarying with Social Hierarchy in Macaques

PubMed Central

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

Cortical and subcortical connections of V1 and V2 in early postnatal macaque monkeys.

PubMed

Baldwin, Mary K L; Kaskan, Peter M; Zhang, Bin; Chino, Yuzo M; Kaas, Jon H

2012-02-15

Connections of primary (V1) and secondary (V2) visual areas were revealed in macaque monkeys ranging in age from 2 to 16 weeks by injecting small amounts of cholera toxin subunit B (CTB). Cortex was flattened and cut parallel to the surface to reveal injection sites, patterns of labeled cells, and patterns of cytochrome oxidase (CO) staining. Projections from the lateral geniculate nucleus and pulvinar to V1 were present at 4 weeks of age, as were pulvinar projections to thin and thick CO stripes in V2. Injections into V1 in 4- and 8-week-old monkeys labeled neurons in V2, V3, middle temporal area (MT), and dorsolateral area (DL)/V4. Within V1 and V2, labeled neurons were densely distributed around the injection sites, but formed patches at distances away from injection sites. Injections into V2 labeled neurons in V1, V3, DL/V4, and MT of monkeys 2-, 4-, and 8-weeks of age. Injections in thin stripes of V2 preferentially labeled neurons in other V2 thin stripes and neurons in the CO blob regions of V1. A likely thick stripe injection in V2 at 4 weeks of age labeled neurons around blobs. Most labeled neurons in V1 were in superficial cortical layers after V2 injections, and in deep layers of other areas. Although these features of adult V1 and V2 connectivity were in place as early as 2 postnatal weeks, labeled cells in V1 and V2 became more restricted to preferred CO compartments after 2 weeks of age. Copyright © 2011 Wiley-Liss, Inc.

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways

NASA Technical Reports Server (NTRS)

Hof, P. R.; Ungerleider, L. G.; Webster, M. J.; Gattass, R.; Adams, M. M.; Sailstad, C. A.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1996-01-01

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons.

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

PubMed

Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

2017-09-01

Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4 + T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU + ] CD163 + ), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. Copyright © 2017 American Society for Microbiology.

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques

PubMed Central

Sugimoto, Chie; Merino, Kristen M.; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A.; Wakao, Hiroshi; Kim, Woong-Ki; Veazey, Ronald S.; Didier, Elizabeth S.

2017-01-01

ABSTRACT Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4+ T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU+] CD163+), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. PMID:28566378

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

PubMed

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.

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

PubMed

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.

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

PubMed Central

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; Le Grand, Roger; Fomsgaard, Anders

2013-01-01

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. PMID:26344115

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

PubMed

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

2016-01-01

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

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

PubMed

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

2013-01-01

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

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

PubMed Central

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

2013-01-01

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

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques.

PubMed

McConville, Christopher; Smith, James M; McCoy, Clare F; Srinivasan, Priya; Mitchell, James; Holder, Angela; Otten, Ron A; Butera, Salvatore; Doncel, Gustavo F; Friend, David R; Malcolm, R Karl

2015-02-01

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.

Complete Taiwanese Macaque (Macaca cyclopis) Mitochondrial Genome: Reference-Assisted de novo Assembly with Multiple k-mer Strategy.

PubMed

Huang, Yu-Feng; Midha, Mohit; Chen, Tzu-Han; Wang, Yu-Tai; Smith, David Glenn; Pei, Kurtis Jai-Chyi; Chiu, Kuo Ping

2015-01-01

The Taiwanese (Formosan) macaque (Macaca cyclopis) is the only nonhuman primate endemic to Taiwan. This primate species is valuable for evolutionary studies and as subjects in medical research. However, only partial fragments of the mitochondrial genome (mitogenome) of this primate species have been sequenced, not mentioning its nuclear genome. We employed next-generation sequencing to generate 2 x 90 bp paired-end reads, followed by reference-assisted de novo assembly with multiple k-mer strategy to characterize the M. cyclopis mitogenome. We compared the assembled mitogenome with that of other macaque species for phylogenetic analysis. Our results show that, the M. cyclopis mitogenome consists of 16,563 nucleotides encoding for 13 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Phylogenetic analysis indicates that M. cyclopis is most closely related to M. mulatta lasiota (Chinese rhesus macaque), supporting the notion of Asia-continental origin of M. cyclopis proposed in previous studies based on partial mitochondrial sequences. Our work presents a novel approach for assembling a mitogenome that utilizes the capabilities of de novo genome assembly with assistance of a reference genome. The availability of the complete Taiwanese macaque mitogenome will facilitate the study of primate evolution and the characterization of genetic variations for the potential usage of this species as a non-human primate model for medical research.

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

PubMed

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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 < 0.0002). 3D ultrasound also showed a homogeneous mass in the 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.

CD8+ lymphocytes are required to maintain virus suppression in SIV-infected macaques treated with short-term antiretroviral therapy

PubMed Central

Cartwright, Emily K.; Spicer, Lori; Smith, S. Abigail; Lee, David; Fast, Randy; Paganini, Sara; Lawson, Benton O.; Nega, Melon; Easley, Kirk; Schmitz, Joern E.; Bosinger, Steven E.; Paiardini, Mirko; Chahroudi, Ann; Vanderford, Thomas H.; Estes, Jacob D.; Lifson, Jeffrey D.; Derdeyn, Cynthia A.; Silvestri, Guido

2016-01-01

Infection with HIV persists despite suppressive antiretroviral therapy (ART) and treatment interruption results in rapid viral rebound. Antibody-mediated CD8+ lymphocyte depletion in simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs) shows these cells contribute to virus control in untreated animals. However, the contribution of CD8+ lymphocytes to maintaining virus suppression under ART remains unknown. We showed that in SIV-infected RMs treated with short-term ART (i.e., 8-32 weeks), depletion of CD8+ lymphocytes resulted in increased plasma viremia in all animals, and that repopulation of CD8+ T cells was associated with prompt reestablishment of virus control. Although the number of SIV-DNA-positive cells remained unchanged after CD8 depletion and reconstitution, the frequency of SIV-infected CD4+ T cells pre-depletion positively correlated with both peak and area-under-the-curve of viremia post-depletion. These results suggest a role for CD8+ T cells in controlling virus production during ART, thus providing rationale to explore immunotherapeutic approaches in ART-treated HIV-infected individuals. PMID:27653601

Untuned Suppression Makes a Major Contribution to the Enhancement of Orientation Selectivity in Macaque V1

PubMed Central

Ringach, Dario L.; Hawken, Michael J.; Shapley, Robert M.

2011-01-01

One of the functions of the cerebral cortex is to increase the selectivity for stimulus features. Finding more about the mechanisms of increased cortical selectivity is important for understanding how the cortex works. Up to now, studies in multiple cortical areas have reported that suppressive mechanisms are involved in feature selectivity. However, the magnitude of the contribution of suppression to tuning selectivity is not yet determined. We use orientation selectivity in macaque primary visual cortex, V1, as an archetypal example of cortical feature selectivity and develop a method to estimate the magnitude of the contribution of suppression to orientation selectivity. The results show that untuned suppression, one form of cortical suppression, decreases the orthogonal-to-preferred response ratio (O/P ratio) of V1 cells from an average of 0.38 to 0.26. Untuned suppression has an especially large effect on orientation selectivity for highly selective cells (O/P < 0.2). Therefore, untuned suppression is crucial for the generation of highly orientation-selective cells in V1 cortex. PMID:22049440

Sleeping of a Complex Brain Networks with Hierarchical Organization

NASA Astrophysics Data System (ADS)

Zhang, Ying-Yue; Yang, Qiu-Ying; Chen, Tian-Lun

2009-01-01

The dynamical behavior in the cortical brain network of macaque is studied by modeling each cortical area with a subnetwork of interacting excitable neurons. We characterize the system by studying how to perform the transition, which is now topology-dependent, from the active state to that with no activity. This could be a naive model for the wakening and sleeping of a brain-like system, i.e., a multi-component system with two different dynamical behavior.

Processing of Own Hand Visual Feedback during Object Grasping in Ventral Premotor Mirror Neurons.

PubMed

Maranesi, Monica; Livi, Alessandro; Bonini, Luca

2015-08-26

Mirror neurons (MNs) discharge during action execution as well as during observation of others' actions. Our own actions are those that we have the opportunity to observe more frequently, but no study thus far to our knowledge has addressed the issue of whether, and to what extent, MNs can code own hand visual feedback (HVF) during object grasping. Here, we show that MNs of the ventral premotor area F5 of macaque monkeys are particularly sensitive to HVF relative to non-MNs simultaneously recorded in the same penetrations. Importantly, the HVF effect is more evident on MN activity during hand-object interaction than during the hand-shaping phase. Furthermore, the increase of MN activity induced by HVF and others' actions observed from a subjective perspective were positively correlated. These findings indicate that at least part of ventral premotor MNs can process the visual information coming from own hand interacting with objects, likely playing a role in self-action monitoring. We show that mirror neurons (MNs) of area F5 of the macaque, in addition to encoding others' observed actions, are particularly sensitive, relative to simultaneously recorded non-MNs, to the sight of the monkey's own hand during object grasping, likely playing a role in self-action monitoring. Copyright © 2015 the authors 0270-6474/15/3511824-06$15.00/0.

Natural asynchronies in audiovisual communication signals regulate neuronal multisensory interactions in voice-sensitive cortex.

PubMed

Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K; Petkov, Christopher I

2015-01-06

When social animals communicate, the onset of informative content in one modality varies considerably relative to the other, such as when visual orofacial movements precede a vocalization. These naturally occurring asynchronies do not disrupt intelligibility or perceptual coherence. However, they occur on time scales where they likely affect integrative neuronal activity in ways that have remained unclear, especially for hierarchically downstream regions in which neurons exhibit temporally imprecise but highly selective responses to communication signals. To address this, we exploited naturally occurring face- and voice-onset asynchronies in primate vocalizations. Using these as stimuli we recorded cortical oscillations and neuronal spiking responses from functional MRI (fMRI)-localized voice-sensitive cortex in the anterior temporal lobe of macaques. We show that the onset of the visual face stimulus resets the phase of low-frequency oscillations, and that the face-voice asynchrony affects the prominence of two key types of neuronal multisensory responses: enhancement or suppression. Our findings show a three-way association between temporal delays in audiovisual communication signals, phase-resetting of ongoing oscillations, and the sign of multisensory responses. The results reveal how natural onset asynchronies in cross-sensory inputs regulate network oscillations and neuronal excitability in the voice-sensitive cortex of macaques, a suggested animal model for human voice areas. These findings also advance predictions on the impact of multisensory input on neuronal processes in face areas and other brain regions.

Areas V1 and V2 show microsaccade-related 3-4-Hz covariation in gamma power and frequency.

PubMed

Lowet, E; Roberts, M J; Bosman, C A; Fries, P; De Weerd, P

2016-05-01

Neuronal gamma-band synchronization (25-80 Hz) in visual cortex appears sustained and stable during prolonged visual stimulation when investigated with conventional averages across trials. However, recent studies in macaque visual cortex have used single-trial analyses to show that both power and frequency of gamma oscillations exhibit substantial moment-by-moment variation. This has raised the question of whether these apparently random variations might limit the functional role of gamma-band synchronization for neural processing. Here, we studied the moment-by-moment variation in gamma oscillation power and frequency, as well as inter-areal gamma synchronization, by simultaneously recording local field potentials in V1 and V2 of two macaque monkeys. We additionally analyzed electrocorticographic V1 data from a third monkey. Our analyses confirm that gamma-band synchronization is not stationary and sustained but undergoes moment-by-moment variations in power and frequency. However, those variations are neither random and nor a possible obstacle to neural communication. Instead, the gamma power and frequency variations are highly structured, shared between areas and shaped by a microsaccade-related 3-4-Hz theta rhythm. Our findings provide experimental support for the suggestion that cross-frequency coupling might structure and facilitate the information flow between brain regions. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Developmental and Cross-Situational Stability in Infant Pigtailed Macaque Temperament

ERIC Educational Resources Information Center

Sussman, Adrienne; Ha, James

2011-01-01

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

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

PubMed Central

Peters, Ryan M.; Staibano, Phillip

2015-01-01

The ability to resolve the orientation of edges is crucial to daily tactile and sensorimotor function, yet the means by which edge perception occurs is not well understood. Primate cortical area 3b neurons have diverse receptive field (RF) spatial structures that may participate in edge orientation perception. We evaluated five candidate RF models for macaque area 3b neurons, previously recorded while an oriented bar contacted the monkey's fingertip. We used a Bayesian classifier to assign each neuron a best-fit RF structure. We generated predictions for human performance by implementing an ideal observer that optimally decoded stimulus-evoked spike counts in the model neurons. The ideal observer predicted a saturating reduction in bar orientation discrimination threshold with increasing bar length. We tested 24 humans on an automated, precision-controlled bar orientation discrimination task and observed performance consistent with that predicted. We next queried the ideal observer to discover the RF structure and number of cortical neurons that best matched each participant's performance. Human perception was matched with a median of 24 model neurons firing throughout a 1-s period. The 10 lowest-performing participants were fit with RFs lacking inhibitory sidebands, whereas 12 of the 14 higher-performing participants were fit with RFs containing inhibitory sidebands. Participants whose discrimination improved as bar length increased to 10 mm were fit with longer RFs; those who performed well on the 2-mm bar, with narrower RFs. These results suggest plausible RF features and computational strategies underlying tactile spatial perception and may have implications for perceptual learning. PMID:26354318

Functional organization of area V2 in the alert macaque.

PubMed

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.

Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

PubMed Central

Romanski, L. M.; Tian, B.; Fritz, J.; Mishkin, M.; Goldman-Rakic, P. S.; Rauschecker, J. P.

2009-01-01

‘What’ and ‘where’ visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory–prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. PMID:10570492

Meningoencephalitis Due to Listeria monocytogenes in a Pregnant Rhesus Macaque (Macaca mulatta)

PubMed Central

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

2012-01-01

We here report a spontaneous case of meningoencephalitis due to Listeria monocytogenes in an adult primiparous rhesus macaque (Macaca mulatta) during an outbreak of listeriosis in an outdoor enclosure. Clinical signs included tremors, abnormal posture, and altered mental status. Hematology and analyses of cerebrospinal fluid were consistent with bacterial infection. Pure cultures of L. monocytogenes were recovered from the placenta–abortus, cerebrospinal fluid, and brain tissue. The macaque did not respond to treatment and was euthanized. Histopathologic examination of the brain revealed acute meningoencephalitis. This case represents an unusual clinical and pathologic presentation of listeriosis in a nonhuman primate in which the dam and fetus both were affected. PMID:23114049

Demonstration of vaginal colonization with GusA-expressing Lactobacillus jensenii following oral delivery in rhesus macaques

PubMed Central

Lagenaur, Laurel A; Lee, Peter P; Hamer, Dean H; Sanders-Beer, Brigitte E

2012-01-01

The vaginal microbiome, which harbors beneficial Lactobacillus strains, is believed to be a major host defense mechanism for preventing infections of the urogenital tract. It has been suggested that the gastrointestinal tract serves as a reservoir for lactobacilli that colonize the vagina. Using rhesus macaques, we examined whether oral delivery of human vaginal Lactobacillus jensenii-1153-1646, a GusA-producing strain, would result in colonization of the rectum and the vagina. Lactobacilli were identified from the vagina tracts of three macaques on the basis of β-glucuronidase enzyme production, 16S rRNA gene sequence and DNA homology using a repetitive sequence-based polymerase chain reaction. PMID:21907793

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

PubMed

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

2016-01-01

A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian-human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Long-term direct visualization of passively transferred fluorophore-conjugated antibodies.

PubMed

Schneider, Jeffrey R; Carias, Ann M; Bastian, Arangaserry R; Cianci, Gianguido C; Kiser, Patrick F; Veazey, Ronald S; Hope, Thomas J

2017-11-01

The use of therapeutic antibodies, delivered by intravenous (IV) instillation, is a rapidly expanding area of biomedical treatment for a variety of conditions. However, little is known about how the antibodies are anatomically distributed following infusion and the underlying mechanism mediating therapeutic antibody distribution to specific anatomical sites remains to be elucidated. Current efforts utilize low resolution and sensitivity methods such as ELISA and indirect labeling imaging techniques, which often leads to high background and difficulty in assessing biodistribution. Here, using the in vivo non-human primate model, we demonstrate that it is possible to utilize the fluorophores Cy5 and Cy3 directly conjugated to antibodies for direct visualization and quantification of passively transferred antibodies in plasma, tissue, and in mucosal secretions. Antibodies were formulated with 1-2 fluorophores per antibody to minimally influence antibody function. Fluorophore conjugated Gamunex-C (pooled human IgG) were tested for binding to protein A, via surface plasmon resonance, and showed similar levels of binding when compared to unlabeled Gamunex-C. In order to assess the effect fluorophore labeling has on turnover and localization, rhesus macaques were IV infused with either labeled or unlabeled Gamunex-C. Plasma, vaginal Weck-Cel fluid, cervicovaginal mucus, and vaginal/rectal tissue biopsies were collected up to 8weeks. Similar turnover and biodistribution was observed between labeled and unlabeled antibodies, showing that the labeling process did not have an obvious deleterious effect on localization or turnover. Cy5 and Cy3 labeled antibodies were readily detected in the same pattern regardless of fluorophore. Tissue distribution was measured in macaque vaginal and rectal biopsies. The labeled antibody in macaque biopsies was found to have similar biodistribution pattern to endogenous antibodies in macaque and human tissues. In the vaginal and rectal mucosa, endogenous and infused antibodies were found primarily within the lamina propria. In the mucosal squamous epithelium of the vaginal vault, significant antibody was also observed in a striated pattern in the superficial, nonviable, stratum corneum. Endogenous antibody distribution in both human and macaque squamous tissues exhibited a similar pattern as seen with the labeled and unlabeled antibodies. This proof-of-principle study reveals that the labeled antibody is stable and physiologically similar relative to endogenous antibody setting the stage for future work to better understand the mechanisms of how antibodies reach unique anatomical sites. Direct visualization of fluorophore-conjugated antibodies following passive infusion can be utilized to assess the kinetics of biodistribution of infused antibodies and may be a useful approach to monitor and predict efficacy of therapeutic antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

Neutralizing antibody fails to impact the course of Ebola virus infection in monkeys.

PubMed

Oswald, Wendelien B; Geisbert, Thomas W; Davis, Kelly J; Geisbert, Joan B; Sullivan, Nancy J; Jahrling, Peter B; Parren, Paul W H I; Burton, Dennis R

2007-01-01

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody.

Deer Mates: A Quantitative Study of Heterospecific Sexual Behaviors Performed by Japanese Macaques Toward Sika Deer.

PubMed

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

2018-05-01

This is the first quantitative study of heterospecific sexual behavior between a non-human primate and a non-primate species. We observed multiple occurrences of free-ranging adolescent female Japanese macaques (Macaca fuscata) performing mounts and sexual solicitations toward sika deer (Cervus nippon) at Minoo, central Japan. Our comparative description of monkey-deer versus monkey-monkey interactions supported the "heterospecific sexual behavior" hypothesis: the mounts and demonstrative solicitations performed by adolescent female Japanese macaques toward sika deer were sexual in nature. In line with our previous research on the development of homospecific sexual behavior in immature female Japanese macaques, this study will allow us to test other hypotheses in the future, such as the "practice for homospecific sex," the "safe sex," the "homospecific sex deprivation," the "developmental by-product," and the "cultural heterospecific sex" hypotheses. Further research will be necessary to ascertain whether this group-specific sexual behavior was a short-lived fad or an incipient cultural phenomenon and may also contribute to better understanding the proximate and ultimate causes of reproductive interference.

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

PubMed Central

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

2016-01-01

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

Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Protects Nonhuman Primates from Intramuscular and Aerosol Challenge with Ebolavirus

PubMed Central

Herbert, Andrew S.; Kuehne, Ana I.; Barth, James F.; Ortiz, Ramon A.; Nichols, Donald K.; Zak, Samantha E.; Stonier, Spencer W.; Muhammad, Majidat A.; Bakken, Russell R.; Prugar, Laura I.; Olinger, Gene G.; Groebner, Jennifer L.; Lee, John S.; Pratt, William D.; Custer, Max; Kamrud, Kurt I.; Smith, Jonathan F.; Hart, Mary Kate

2013-01-01

There are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. Previously, a replicon vaccine based on Venezuelan equine encephalitis virus (VEEV) demonstrated protective efficacy against Marburg virus in nonhuman primates. Here, we report the protective efficacy of Sudan virus (SUDV)- and Ebola virus (EBOV)-specific VEEV replicon particle (VRP) vaccines in nonhuman primates. VRP vaccines were developed to express the glycoprotein (GP) of either SUDV or EBOV. A single intramuscular vaccination of cynomolgus macaques with VRP expressing SUDV GP provided complete protection against intramuscular challenge with SUDV. Vaccination against SUDV and subsequent survival of SUDV challenge did not fully protect cynomolgus macaques against intramuscular EBOV back-challenge. However, a single simultaneous intramuscular vaccination with VRP expressing SUDV GP combined with VRP expressing EBOV GP did provide complete protection against intramuscular challenge with either SUDV or EBOV in cynomolgus macaques. Finally, intramuscular vaccination with VRP expressing SUDV GP completely protected cynomolgus macaques when challenged with aerosolized SUDV, although complete protection against aerosol challenge required two vaccinations with this vaccine. PMID:23408633

Venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus.

PubMed

Herbert, Andrew S; Kuehne, Ana I; Barth, James F; Ortiz, Ramon A; Nichols, Donald K; Zak, Samantha E; Stonier, Spencer W; Muhammad, Majidat A; Bakken, Russell R; Prugar, Laura I; Olinger, Gene G; Groebner, Jennifer L; Lee, John S; Pratt, William D; Custer, Max; Kamrud, Kurt I; Smith, Jonathan F; Hart, Mary Kate; Dye, John M

2013-05-01

There are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. Previously, a replicon vaccine based on Venezuelan equine encephalitis virus (VEEV) demonstrated protective efficacy against Marburg virus in nonhuman primates. Here, we report the protective efficacy of Sudan virus (SUDV)- and Ebola virus (EBOV)-specific VEEV replicon particle (VRP) vaccines in nonhuman primates. VRP vaccines were developed to express the glycoprotein (GP) of either SUDV or EBOV. A single intramuscular vaccination of cynomolgus macaques with VRP expressing SUDV GP provided complete protection against intramuscular challenge with SUDV. Vaccination against SUDV and subsequent survival of SUDV challenge did not fully protect cynomolgus macaques against intramuscular EBOV back-challenge. However, a single simultaneous intramuscular vaccination with VRP expressing SUDV GP combined with VRP expressing EBOV GP did provide complete protection against intramuscular challenge with either SUDV or EBOV in cynomolgus macaques. Finally, intramuscular vaccination with VRP expressing SUDV GP completely protected cynomolgus macaques when challenged with aerosolized SUDV, although complete protection against aerosol challenge required two vaccinations with this vaccine.

Anti-CeHV1 antibodies of two cynomolgus macaques cross-react with HSV2 but not HSV1 antigens in ELISA.

PubMed

Coutrot, Edwin; Blancher-Sardou, Marie; Blancher, Antoine

2008-02-01

The aim of the study was to compare the cross-reactivity of macaque anti-CeHV1 antibodies with type 1 and type 2 human herpes simplex viruses (HSV1 and HSV2). We studied the serum of 344 animals which had been tested either positive (n = 39) or negative (n = 305) for the presence of CeHV1 antibodies by expert laboratories. Macaque serums were studied by means of two ELISA: one based on HSV1 antigen-coated wells, the other on polystyrene beads coated with HSV1 and HSV2 antigens in approximately equal proportions. In the serum of two animals originating from Vietnam, we found anti-CeHV1 antibodies cross-reacting with HSV2 but not with HSV1 antigens. For the serum with the highest titer, inhibition by soluble antigens confirmed the high affinity of the antibodies for HSV2 antigens. Tests using HSV1 and HSV2 in a combined way are better suited to macaque screening than tests using only HSV1 antigens.

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

PubMed

Hessell, Ann J; Jaworski, J Pablo; Epson, Erin; Matsuda, Kenta; Pandey, Shilpi; Kahl, Christoph; Reed, Jason; Sutton, William F; Hammond, Katherine B; Cheever, Tracy A; Barnette, Philip T; Legasse, Alfred W; Planer, Shannon; Stanton, Jeffrey J; Pegu, Amarendra; Chen, Xuejun; Wang, Keyun; Siess, Don; Burke, David; Park, Byung S; Axthelm, Michael K; Lewis, Anne; Hirsch, Vanessa M; Graham, Barney S; Mascola, John R; Sacha, Jonah B; Haigwood, Nancy L

2016-04-01

Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8(+) T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.

Quantitative stability of hematopoietic stem and progenitor cell clonal output in rhesus macaques receiving transplants

PubMed Central

Koelle, Samson J.

2017-01-01

Autologous transplantation of hematopoietic stem and progenitor cells lentivirally labeled with unique oligonucleotide barcodes flanked by sequencing primer targets enables quantitative assessment of the self-renewal and differentiation patterns of these cells in a myeloablative rhesus macaque model. Compared with other approaches to clonal tracking, this approach is highly quantitative and reproducible. We documented stable multipotent long-term hematopoietic clonal output of monocytes, granulocytes, B cells, and T cells from a polyclonal pool of hematopoietic stem and progenitor cells in 4 macaques observed for up to 49 months posttransplantation. A broad range of clonal behaviors characterized by contribution level and biases toward certain cell types were extremely stable over time. Correlations between granulocyte and monocyte clonalities were greatest, followed by correlations between these cell types and B cells. We also detected quantitative expansion of T cell–biased clones consistent with an adaptive immune response. In contrast to recent data from a nonquantitative murine model, there was little evidence for clonal succession after initial hematopoietic reconstitution. These findings have important implications for human hematopoiesis, given the similarities between macaque and human physiologies. PMID:28087539

Thoracic Radiography as a Refinement Methodology for the Study of H1N1 Influenza in Cynomologus Macaques (Macaca fascicularis)

PubMed Central

Brining, Douglas L; Mattoon, John S; Kercher, Lisa; LaCasse, Rachael A; Safronetz, David; Feldmann, Heinz; Parnell, Michael J

2010-01-01

Recent advances in the technology associated with digital radiography have created new opportunities for biomedical research applications. Here we evaluated the use of thoracic radiography as a noninvasive refinement methodology for the cynomologus macaque (Macaca fascicularis) model of H1N1 infection. Thoracic radiographic evaluations of macaques infected with any of 3 strains of emerging H1N1 swine-associated influenza virus isolated during the recent pandemic were compared with those of macaques infected with the currently circulating Kawasaki strain of H1N1 influenza. Ventrodorsal, right, and left lateral thoracic radiographs were obtained at days 0, 1, 6, 8, 11, and 14 after infection. A board-certified veterinary radiologist who was blinded to the study design evaluated the images. Numeric scores of extent and severity of lung involvement assigned to each radiograph were compared and demonstrated a significant and substantial difference among groups. The radiographic evaluation allowed for noninvasive assessment of lung involvement, disease onset, progression, and resolution of radiographic changes associated with H1N1 influenza infection. PMID:21262125

Laser Capture Microdissection Assessment of Virus Compartmentalization in the Central Nervous Systems of Macaques Infected with Neurovirulent Simian Immunodeficiency Virus

PubMed Central

Matsuda, Kenta; Brown, Charles R.; Foley, Brian; Goeken, Robert; Whitted, Sonya; Dang, Que; Wu, Fan; Plishka, Ronald; Buckler-White, Alicia

2013-01-01

Nonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments. PMID:23720733

Differential expression of vesicular glutamate transporters 1 and 2 may identify distinct modes of glutamatergic transmission in the macaque visual system

PubMed Central

Balaram, Pooja; Hackett, Troy A.; Kaas, Jon H.

2013-01-01

Glutamate is the primary neurotransmitter utilized by the mammalian visual system for excitatory neurotransmission. The sequestration of glutamate into synaptic vesicles, and the subsequent transport of filled vesicles to the presynaptic terminal membrane, is regulated by a family of proteins known as vesicular glutamate transporters (VGLUTs). Two VGLUT proteins, VGLUT1 and VGLUT2, characterize distinct sets of glutamatergic projections between visual structures in rodents and prosimian primates, yet little is known about their distributions in the visual system of anthropoid primates. We have examined the mRNA and protein expression patterns of VGLUT1 and VGLUT2 in the visual system of macaque monkeys, an Old World anthropoid primate, in order to determine their relative distributions in the superior colliculus, lateral geniculate nucleus, pulvinar complex, V1 and V2. Distinct expression patterns for both VGLUT1 and VGLUT2 identified architectonic boundaries in all structures, as well as anatomical subdivisions of the superior colliculus, pulvinar complex, and V1. These results suggest that VGLUT1 and VGLUT2 clearly identify regions of glutamatergic input in visual structures, and may identify common architectonic features of visual areas and nuclei across the primate radiation. Additionally, we find that VGLUT1 and VGLUT2 characterize distinct subsets of glutamatergic projections in the macaque visual system; VGLUT2 predominates in driving or feedforward projections from lower order to higher order visual structures while VGLUT1 predominates in modulatory or feedback projections from higher order to lower order visual structures. The distribution of these two proteins suggests that VGLUT1 and VGLUT2 may identify class 1 and class 2 type glutamatergic projections within the primate visual system (Sherman and Guillery, 2006). PMID:23524295

Differential expression of vesicular glutamate transporters 1 and 2 may identify distinct modes of glutamatergic transmission in the macaque visual system.

PubMed

Balaram, Pooja; Hackett, Troy A; Kaas, Jon H

2013-05-01

Glutamate is the primary neurotransmitter utilized by the mammalian visual system for excitatory neurotransmission. The sequestration of glutamate into synaptic vesicles, and the subsequent transport of filled vesicles to the presynaptic terminal membrane, is regulated by a family of proteins known as vesicular glutamate transporters (VGLUTs). Two VGLUT proteins, VGLUT1 and VGLUT2, characterize distinct sets of glutamatergic projections between visual structures in rodents and prosimian primates, yet little is known about their distributions in the visual system of anthropoid primates. We have examined the mRNA and protein expression patterns of VGLUT1 and VGLUT2 in the visual system of macaque monkeys, an Old World anthropoid primate, in order to determine their relative distributions in the superior colliculus, lateral geniculate nucleus, pulvinar complex, V1 and V2. Distinct expression patterns for both VGLUT1 and VGLUT2 identified architectonic boundaries in all structures, as well as anatomical subdivisions of the superior colliculus, pulvinar complex, and V1. These results suggest that VGLUT1 and VGLUT2 clearly identify regions of glutamatergic input in visual structures, and may identify common architectonic features of visual areas and nuclei across the primate radiation. Additionally, we find that VGLUT1 and VGLUT2 characterize distinct subsets of glutamatergic projections in the macaque visual system; VGLUT2 predominates in driving or feedforward projections from lower order to higher order visual structures while VGLUT1 predominates in modulatory or feedback projections from higher order to lower order visual structures. The distribution of these two proteins suggests that VGLUT1 and VGLUT2 may identify class 1 and class 2 type glutamatergic projections within the primate visual system (Sherman and Guillery, 2006). Copyright © 2013 Elsevier B.V. All rights reserved.

Correlation of Acute Humoral Response with Brain Virus Burden and Survival Time in Pig-Tailed Macaques Infected with the Neurovirulent Simian Immunodeficiency Virus SIVsmmFGb

PubMed Central

O’Neil, Shawn P.; Suwyn, Carolyn; Anderson, Daniel C.; Niedziela, Genevieve; Bradley, Juliette; Novembre, Francis J.; Herndon, James G.; McClure, Harold M.

2004-01-01

Infection of pig-tailed macaques with the simian immunodeficiency virus (SIV) isolate SIVsmmFGb frequently results in SIV encephalitis (SIVE) in addition to immunodeficiency and acquired immune deficiency syndrome. We used in situ hybridization to quantitate the number of SIV-infected cells in brain parenchyma, choroid plexus, and meninges from 17 macaques that developed acquired immune deficiency syndrome after infection with SIVsmmFGb. SIV-infected cells and histopathological lesions of SIVE were identified in 15 of 17 animals (88.2%), including 12 of 12 rapid progressors (RP) and 3 of 5 slow progressors (SP). The parenchymal virus burden was much greater in RP macaques than in the three SP macaques with SIVE (median values of 24.3 versus 0.3 infected cells/mm2, respectively; P < 0.05). Viral load differences between RP and SP with SIVE were less marked in choroid plexus (29.6 versus 12.8 infected cells/mm2, respectively) and meninges (133.0 versus 34.2 infected cells/mm2, respectively). A significant negative correlation was observed between the magnitude of the anti-SIV antibody titer at 1 month after inoculation and brain virus burden at necropsy (r = −0.614; P < 0.01). The close association between immune response and SIVE in this model should prove useful for identifying correlates of immune protection against primate lentiviral encephalitis. PMID:15039205

A multivariate ecogeographic analysis of macaque craniodental variation.

PubMed

Grunstra, Nicole D S; Mitteroecker, Philipp; Foley, Robert A

2018-06-01

To infer the ecogeographic conditions that underlie the evolutionary diversification of macaques, we investigated the within- and between-species relationships of craniodental dimensions, geography, and environment in extant macaque species. We studied evolutionary processes by contrasting macroevolutionary patterns, phylogeny, and within-species associations. Sixty-three linear measurements of the permanent dentition and skull along with data about climate, ecology (environment), and spatial geography were collected for 711 specimens of 12 macaque species and analyzed by a multivariate approach. Phylogenetic two-block partial least squares was used to identify patterns of covariance between craniodental and environmental variation. Phylogenetic reduced rank regression was employed to analyze spatial clines in morphological variation. Between-species associations consisted of two distinct multivariate patterns. The first represents overall craniodental size and is negatively associated with temperature and habitat, but positively with latitude. The second pattern shows an antero-posterior tooth size contrast related to diet, rainfall, and habitat productivity. After controlling for phylogeny, however, the latter dimension was diminished. Within-species analyses neither revealed significant association between morphology, environment, and geography, nor evidence of isolation by distance. We found evidence for environmental adaptation in macaque body and craniodental size, primarily driven by selection for thermoregulation. This pattern cannot be explained by the within-species pattern, indicating an evolved genetic basis for the between-species relationship. The dietary signal in relative tooth size, by contrast, can largely be explained by phylogeny. This cautions against adaptive interpretations of phenotype-environment associations when phylogeny is not explicitly modelled. © 2018 Wiley Periodicals, Inc.

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

PubMed

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.

Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251

PubMed Central

Gay, Wilfried; Lauret, Evelyne; Boson, Bertrand; Larghero, Jérome; Matheux, Franck; Peyramaure, Sophie; Rousseau, Véronique; Dormont, Dominique; De Maeyer, Edward; Le Grand, Roger

2004-01-01

Background The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. Results Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 106 peripheral mononuclear cells. Conclusion Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4+ cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection. PMID:15447786

Local and Systemic Changes Associated with Long-term, Percutaneous, Static Implantation of Titanium Alloys in Rhesus Macaques (Macaca mulatta)

PubMed Central

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

2017-01-01

Metal alloys are frequently used as implant materials in veterinary medicine. Recent studies suggest that many alloys induce both local and systemic inflammatory responses. In this study, 37 rhesus macaques with long-term skull-anchored percutaneous titanium alloy implants (duration, 0 to 14 y) were evaluated for changes in their hematology, coagulation, and serum chemistry profiles. Negative controls (n = 28) did not have implants. Macaques with implants had higher plasma D-dimer and lower antithrombin III concentrations than nonimplanted animals. In addition, animals with implants had higher globulin and lower albumin and calcium concentrations compared with nonimplanted macaques. Many of these changes were positively correlated with duration of implantation and the number of implants. Chronic bacterial infection of the skin was present around many of the implant sites and within deeper tissues. Representative histopathology around the implant site of 2 macaques 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 2 animals revealed significantly higher levels of free metal ions in the tissue, including titanium and iron. The higher levels of free metal ions persisted in the tissues for as long as 6 mo after explantation. These results suggest that long-term skull-anchored percutaneous titanium alloy implants can be associated with localized inflammation, chronic infection, and leaching of metal ions into local tissues. PMID:28381317

Clinical and microbiological parameters of naturally occurring periodontitis in the non-human primate Macaca mulatta

PubMed Central

Colombo, A. P. V.; Paster, B. J.; Grimaldi, G.; Lourenço, T. G. B.; Teva, A.; Campos-Neto, A.; McCluskey, J.; Kleanthous, H.; Van Dyke, T. E.; Stashenko, P.

2017-01-01

ABSTRACT Background: Non-human primates appear to represent the most faithful model of human disease, but to date the oral microbiome in macaques has not been fully characterized using next-generation sequencing. Objective: In the present study, we characterized the clinical and microbiological features of naturally occurring periodontitis in non-human primates (Macaca mulatta). Design: Clinical parameters of periodontitis including probing pocket depth (PD) and bleeding on probing (BOP) were measured in 40 adult macaques (7–22 yrs), at six sites per tooth. Subgingival plaque was collected from diseased and healthy sites, and subjected to 16S rDNA sequencing and identification at the species or higher taxon level. Results: All macaques had mild periodontitis at minimum, with numerous sites of PD ≥ 4 mm and BOP. A subset (14/40) had moderate-severe disease, with >2 sites with PD ≥ 5mm, deeper mean PD, and more BOP. Animals with mild vs moderate-severe disease were identical in age, suggesting genetic heterogeneity. 16S rDNA sequencing revealed that all macaques had species that were identical to those in humans or closely related to human counterparts, including Porphyromonas gingivalis which was present in all animals. Diseased and healthy sites harboured distinct microbiomes; however there were no significant differences in the microbiomes in moderate-severe vs. mild periodontitis. Conclusions: Naturally occurring periodontitis in older macaques closely resembles human adult periodontitis, thus validating a useful model to evaluate novel anti-microbial therapies. PMID:29805776

Naive, captive long-tailed macaques (Macaca fascicularis fascicularis) fail to individually and socially learn pound-hammering, a tool-use behaviour

PubMed Central

Tennie, Claudio

2018-01-01

A subspecies of long-tailed macaques (Macaca fascicularis aurea; Mfa) has been reported to use stone tools and a specific technique to process nuts in Southeast Asia, a behaviour known as ‘pound-hammering’. The aim of this study was to examine the development of pound-hammering in long-tailed macaques: whether this behavioural form can be individually learnt or whether it has to rely on some forms of social learning. Given the absence of Mfa from captivity, long-tailed macaques of a highly related subspecies (Macaca fascicularis fascicularis; Mff) were experimentally tested by providing them with the ecological materials necessary to show pound-hammering. A baseline was first carried out to observe whether pound-hammering would emerge spontaneously without social information. As this was not the case, different degrees of social information, culminating in a full demonstration of the behaviour, were provided. None of the subjects (n = 31) showed pound-hammering in any of the individual or social learning conditions. Although these data do not support the hypothesis that individual learning underlies this behaviour, no evidence was found that (at least) Mff learn pound-hammering socially either. We propose that other—potentially interacting—factors may determine whether this behaviour emerges in the various subspecies of long-tailed macaques, and provide a novel methodology to test the role of social and individual learning in the development of animal tool-use. PMID:29892375

Is male rhesus macaque red color ornamentation attractive to females?

PubMed Central

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

2014-01-01

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

Focal damage to macaque photoreceptors produces persistent visual loss

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2012-01-01

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

Cartography and Connectomes Perspective article for Neuron 25th Anniversary Issue

PubMed Central

Van Essen, David C.

2013-01-01

The past 25 years have seen great progress in parcellating the cerebral cortex into a mosaic of many distinct areas in mice, monkeys, and humans. Quantitative studies of inter-areal connectivity have revealed unexpectedly many pathways and a wide range of connection strengths in mouse and macaque cortex. In humans, advances in analyzing ‘structural’ and ‘functional’ connectivity using powerful but indirect noninvasive neuroimaging methods are yielding intriguing insights about brain circuits, their variability across individuals, and their relationship to behavior. PMID:24183027

In vivo virulence of MHC-adapted AIDS virus serially-passaged through MHC-mismatched hosts

PubMed Central

Yamamoto, Hiroyuki; Ishii, Hiroshi; Matsuoka, Saori; Mizuta, Kazuta; Sakawaki, Hiromi; Miura, Tomoyuki; Naruse, Taeko K.; Kimura, Akinori

2017-01-01

CD8+ T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness. The first passage simian immunodeficiency virus (1pSIV) obtained 1 year after SIVmac239 infection in a macaque possessing a protective MHC-I haplotype 90-120-Ia was transmitted into 90-120-Ia- macaques, whose plasma 1 year post-infection was transmitted into other 90-120-Ia- macaques to obtain the third passage SIV (3pSIV). Most of the 90-120-Ia-associated mutations selected in 1pSIV did not revert even in 3pSIV. 3pSIV showed lower in vitro viral fitness but induced persistent viremia in 90-120-Ia- macaques. Remarkably, 3pSIV infection in 90-120-Ia+ macaques resulted in significantly higher viral loads and reduced survival compared to wild-type SIVmac239. These results indicate that MHC-I-adapted SIVs serially-transmitted through MHC-I-mismatched hosts can have higher virulence in MHC-I-matched hosts despite their lower in vitro viral fitness. This study suggests that multiply-passaged HIVs could result in loss of HIV-specific CD8+ T cell responses in human populations and the in vivo pathogenic potential of these escaped viruses may be enhanced. PMID:28931083

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

PubMed

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

2009-03-01

Ecotourism involving feeding wildlife has raised public attention and is a controversial issue, especially concerning nonhuman primates. Between July 2002 and April 2005, the behavior of monkeys and tourists was collected through scan samplings, focal samplings and behavior samplings at the Shou-Shan Nature Park located in Taiwan's second largest city--Kaohsiung. In addition, the number of tourists and monkeys was counted in different hours and places within the park. Four hundred visitors were interviewed using a questionnaire to gather data on sex, age, purpose and frequency of visit to the park. The number of tourists was significantly higher during weekends than in weekdays in all locations. Humans dominated in the initiation of interspecies interactions--the overall ratio of human-initiated and monkey-initiated interactions was 2.44:1. Human-monkey conflicts accounted for only 16.4% of the total interactions (n=2,166), and adult human males and adult male macaques participated in higher rates than other age/sex groups in these conflicts. Visitors showed more affiliative behavior (15.9%) than agonistic behavior (8%) toward the macaques. In response to visitors' threat or attack, the Formosan macaques mostly showed submissive behavior with bared teeth, squealed or ran away to avoid confrontation (69.1%)--only few responded with counteraggression (18.7%). This study for the first time provided evidence that food provisioning increased both the frequency and duration of aggression among Formosan macaques (P<0.001). During food provisioning, the average frequency and the duration of agonistic events of macaques were more than 4 times higher compared with those without food provisioning. The average frequency of food provision by tourists was 0.73 times/hr--more than twice the incident that monkeys grabbed the food from tourists (0.34 times/hr). If people refrain from feeding monkeys and destroying the city park's natural vegetation, monkeys can be used to educate public about nature conservation in an urban setting. (c) 2008 Wiley-Liss, Inc.

Asian Elephant (Elephas maximus), Pig-Tailed Macaque (Macaca nemestrina) and Tiger (Panthera tigris) Populations at Tourism Venues in Thailand and Aspects of Their Welfare

PubMed Central

Schmidt-Burbach, Jan; Ronfot, Delphine; Srisangiam, Rossukon

2015-01-01

This study focused on determining the size and welfare aspects of Asian elephant, pig-tailed macaque and tiger populations at facilities open to tourists in Thailand. Data were gathered from 118 venues through direct observations and interviews with staff. A score sheet-based welfare assessment was used to calculate scores between 1 and 10, indicating each venue’s welfare situation. Factors such as freedom of movement for the animals, access to veterinary care, environmental noise quality, hygiene standards and work intensity were included in the score sheet. 1688 elephants, 371 macaques and 621 tigers were found at the venues. 89 venues exclusively kept elephants, 9 designated ‘Monkey schools’ offered macaque shows, 4 venues kept primarily tigers, mostly for petting and photo opportunities, and the remaining venues kept a mix of these animals. A strong imbalance in female to male gender ratios was recorded with about 4:1 for adult elephants and 1:4 for adult macaques. Severely inadequate welfare conditions were common, with 75% of macaques and 99% of tigers being kept at venues with scores less than 5. 86% of elephants were kept in inadequate conditions at venues with scores between 3 and 5, but a significant number of venues with scores above 5 were found. 4.6% of elephants were provided commendable conditions, reaching assessment scores of 8 and above. 71% of venues did not offer any sort of education about animals to visitors. This study is the first to assess welfare aspects of captive wild animals at tourism venues across Thailand. It concludes that significant concerns exist about the welfare of wild animals in the tourism sector of Thailand. Urgent attention needs to be given to address these concerns and prevent further suffering. But also to ensure the demand for wild animals doesn’t have a negative impact on wild populations. PMID:26407173

[Analysis on content of serum monoamine neurotransmitters in macaques with anger-in-induced premenstrual syndrome and liver-qi depression syndrome].

PubMed

Wei, Sheng; Hou, Jin-Liang; Chao, Yu-Bin; Du, Xi-Yang; Zong, Shao-Bo

2012-08-01

To observe the changes in content of monoamine neurotransmitters in the serum of rhesus macaques, and explore the role of serum monoamine neurotransmitters in premenstrual syndrome (PMS) and liver-qi depression induced by anger-in emotion. Social level pressure was applied on 24 female macaques to induce the angry emotional reaction, and then nine of the low-status macaques with anger-in emotional reaction were screened out and were divided into anger-in emotion group, PMS and liver-qi depression group (model group) and Jingqianshu Granule group. Macaques in the last two groups were suffered extruding in a pack cage for inducing PMS liver-qi depression. After 5 d of extruding, experimental animals were evaluated according to the emotional evaluation scale, meanwhile, macaque serum of follicular phase and middle-late luteal phase was collected to analyze the content of serum norepinephrine, dopamine, and 5-hydroxytryptamine. Compared with the normal control group, the scores of depression of the model group and the anger-in emotion group evaluated with emotional evaluation scale were significantly increased (P<0.01, P<0.05); while the score of the model group was significantly higher than that of the anger-in emotion group (P<0.05), and it returned to normal after Jingqianshu Granule treatment. As compared to the normal control group, serum monoamine neurotransmitter levels of the model group and the anger-in emotion group were increased (P<0.05, P<0.01), and the serum monoamine neurotransmitter levels of the model group were significantly higher than those of the anger-in emotion group (P<0.05), while there was no significant difference when compared with the normal control group after the treatment. Anger-in emotion can induce liver-qi depression syndrome which is related to the changes in monoamine neurotransmitters.

Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant.

PubMed

Barnett, Susan W; Burke, Brian; Sun, Yide; Kan, Elaine; Legg, Harold; Lian, Ying; Bost, Kristen; Zhou, Fengmin; Goodsell, Amanda; Zur Megede, Jan; Polo, John; Donnelly, John; Ulmer, Jeffrey; Otten, Gillis R; Miller, Christopher J; Vajdy, Michael; Srivastava, Indresh K

2010-06-01

We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV(SF162P4) following sequential immunization with alphavirus replicon particles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1(SF162) gp140DeltaV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV(SF162P4) (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against HIV infection at a relevant mucosal portal of entry.

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

PubMed Central

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

2016-01-01

ABSTRACT Simian arteriviruses are a diverse clade of viruses infecting captive and wild nonhuman primates. We recently reported that Kibale red colobus virus 1 (KRCV-1) causes a mild and self-limiting disease in experimentally infected crab-eating macaques, while simian hemorrhagic fever virus (SHFV) causes lethal viral hemorrhagic fever. Here we characterize how these viruses evolved during replication in cell culture and in experimentally infected macaques. During passage in cell culture, 68 substitutions that were localized in open reading frames (ORFs) likely associated with host cell entry and exit became fixed in the KRCV-1 genome. However, we did not detect any strong signatures of selection during replication in macaques. We uncovered patterns of evolution that were distinct from those observed in surveys of wild red colobus monkeys, suggesting that these species may exert different adaptive challenges for KRCV-1. During SHFV infection, we detected signatures of selection on ORF 5a and on a small subset of sites in the genome. Overall, our data suggest that patterns of evolution differ markedly among simian arteriviruses and among host species. IMPORTANCE Certain RNA viruses can cross species barriers and cause disease in new hosts. Simian arteriviruses are a diverse group of related viruses that infect captive and wild nonhuman primates, with associated disease severity ranging from apparently asymptomatic infections to severe, viral hemorrhagic fevers. We infected nonhuman primate cell cultures and then crab-eating macaques with either simian hemorrhagic fever virus (SHFV) or Kibale red colobus virus 1 (KRCV-1) and assessed within-host viral evolution. We found that KRCV-1 quickly acquired a large number of substitutions in its genome during replication in cell culture but that evolution in macaques was limited. In contrast, we detected selection focused on SHFV ORFs 5a and 5, which encode putative membrane proteins. These patterns suggest that in addition to diverse pathogenic phenotypes, these viruses may also exhibit distinct patterns of within-host evolution both in vitro and in vivo. PMID:27974564

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

PubMed

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 habit of hot spring bathing by Japanese macaques illustrates how behavioural flexibility can help counter cold climate stress, with likely implications for reproduction and survival.

Distribution of simian immunodeficiency virus target cells in vaginal tissues of normal rhesus macaques: implications for virus transmission.

PubMed

Poonia, Bhawna; Wang, Xiaolei; Veazey, Ronald S

2006-12-01

Most new cases of HIV-1 infection occur as the result of vaginal transmission. Identifying the phenotype and distribution of potential viral target cells in the vagina is important for understanding events in viral transmission and for developing effective prevention strategies. For example, compounds that prevent CD4 or CCR5 binding have been demonstrated recently to prevent vaginal transmission in rhesus macaques, but the expression and distribution of CCR5 has not been examined in the macaque vagina. The objective of this study was to examine the distribution and phenotype of cells and molecules in the vagina of rhesus macaques that may be involved in HIV transmission, including CCR5, CD3, CD4, CD8, CD1a, CD28, CD95, CD123 and HLA-DR. Normal juvenile and adult female rhesus macaques were examined by multicolor immunohistochemistry and flow cytometry. Although both CD4 and CCR5 were observed in the lamina propria, essentially no CD4 or CCR5 expression was detected within the squamous or keratinized layers of the vaginal epithelium. CCR5 expression was higher in the vaginal lamina propria of mature macaques compared to 1-3-year-old juveniles. The vast majority of CD4(+)CCR5(+) lymphocytes in the vagina had a central memory (CD95(+)CD28(+)) phenotype. Numerous CCR5-expressing dendritic cells (CD123(+)) or macrophages (CD68(+)) were observed in the lamina propria, but no CCR5, CD4 or DC-SIGN expression was detectable in the epithelium. Thus, the multiple layers of squamous epithelium normally covering the vaginal mucosa may provide an effective barrier against vaginal HIV-1 transmission. Microbicides that block CD4 or CCR5 expression may act within the deeper layers of the vaginal epithelium rather than on the epithelial surface.

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

PubMed

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 antitetanus immunity to offspring.

Asian Elephant (Elephas maximus), Pig-Tailed Macaque (Macaca nemestrina) and Tiger (Panthera tigris) Populations at Tourism Venues in Thailand and Aspects of Their Welfare.

PubMed

Schmidt-Burbach, Jan; Ronfot, Delphine; Srisangiam, Rossukon

2015-01-01

This study focused on determining the size and welfare aspects of Asian elephant, pig-tailed macaque and tiger populations at facilities open to tourists in Thailand. Data were gathered from 118 venues through direct observations and interviews with staff. A score sheet-based welfare assessment was used to calculate scores between 1 and 10, indicating each venue's welfare situation. Factors such as freedom of movement for the animals, access to veterinary care, environmental noise quality, hygiene standards and work intensity were included in the score sheet. 1688 elephants, 371 macaques and 621 tigers were found at the venues. 89 venues exclusively kept elephants, 9 designated 'Monkey schools' offered macaque shows, 4 venues kept primarily tigers, mostly for petting and photo opportunities, and the remaining venues kept a mix of these animals. A strong imbalance in female to male gender ratios was recorded with about 4:1 for adult elephants and 1:4 for adult macaques. Severely inadequate welfare conditions were common, with 75% of macaques and 99% of tigers being kept at venues with scores less than 5. 86% of elephants were kept in inadequate conditions at venues with scores between 3 and 5, but a significant number of venues with scores above 5 were found. 4.6% of elephants were provided commendable conditions, reaching assessment scores of 8 and above. 71% of venues did not offer any sort of education about animals to visitors. This study is the first to assess welfare aspects of captive wild animals at tourism venues across Thailand. It concludes that significant concerns exist about the welfare of wild animals in the tourism sector of Thailand. Urgent attention needs to be given to address these concerns and prevent further suffering. But also to ensure the demand for wild animals doesn't have a negative impact on wild populations.

What Cortisol Can Tell us About the Costs of Sociality and Reproduction Among Free-Ranging Rhesus Macaque Females on Cayo Santiago

PubMed Central

Maestripieri, Dario; Georgiev, Alexander V.

2015-01-01

Research with the rhesus macaque population on Cayo Santiago can provide a unique perspective on the costs of sociality and reproduction in primates. Because the Cayo macaques live in unusually large groups and in a predator-free environment, in which their artificial food source lacks seasonal variation in abundance or quality, these monkeys constitute a semi-experimental study of the costs and benefits of group living. Here we review several long- and short-term studies that have focused on female life history and stress physiology. Long-term demographic data have shown that rhesus macaque females of middle- and low-ranking matrilines have lower adult survival probabilities than females of high-ranking matrilines. Costs of reproductive effort are also evident: adult females were more likely to die during the birth than during the mating season and they experienced higher cortisol levels when lactating. Lower-ranking females, in particular, experienced greater relative increase in cortisol production during lactation, in comparison to middle- and high-ranking females. Older high-ranking females had lower plasma cortisol levels than younger ones but cortisol levels were similarly high among young and old middle- and low-ranking females. Higher plasma cortisol levels and/or fecal glucocorticoid concentrations are associated with higher plasma concentrations of some proinflammatory cytokines. High cortisol, in turn, may be associated with chronic inflammation, and perhaps also with immunosuppression. In sum, the studies reviewed here provide multiple lines of evidence that sociality and reproductive effort impose measurable costs on female rhesus macaques. In line with socioecological theory, female dominance rank consistently emerges as an important modulator of variation in female life histories and physiology. The Cayo Santiago macaques are therefore a valuable model for elucidating the mechanisms by which within-group competition and reproduction impact health and survival in nonhuman primates and in humans. Am. J. Primatol. PMID:25643836

Infection of rhesus macaques with a pool of simian immunodeficiency virus with the envelope genes from acute HIV-1 infections.

PubMed

Krebs, Kendall C; Tian, Meijuan; Asmal, Mohammed; Ling, Binhua; Nelson, Kenneth; Henry, Kenneth; Gibson, Richard; Li, Yuejin; Han, Weining; Shattock, Robin J; Veazey, Ronald S; Letvin, Norman; Arts, Eric J; Gao, Yong

2016-11-25

New simian-human immunodeficiency chimeric viruses with an HIV-1 env (SHIVenv) are critical for studies on HIV pathogenesis, vaccine development, and microbicide testing. Macaques are typically exposed to single CCR5-using SHIVenv which in most instances does not reflect the conditions during acute/early HIV infection (AHI) in humans. Instead of individual and serial testing new SHIV constructs, a pool of SHIVenv_B derived from 16 acute HIV-1 infections were constructed using a novel yeast-based SHIV cloning approach and then used to infect macaques. Even though none of the 16 SHIVenvs contained the recently reported mutations in env genes that could significantly enhance their binding affinity to RhCD4, one SHIVenv (i.e. SHIVenv_B3-PRB926) established infection in macaques exposed to this pool. AHI SHIVenv_B viruses as well as their HIVenv_B counterparts were analyzed for viral protein content, function, and fitness to identify possible difference between SHIVenv_B3-PRB926 and the other 15 SHIVenvs in the pool. All of the constructs produced SHIV or HIV chimeric with wild type levels of capsid (p27 and p24) content, reverse transcriptase (RT) activity, and expressed envelope glycoproteins that could bind to cell receptors CD4/CCR5 and mediate virus entry. HIV-1env_B chimeric viruses were propagated in susceptible cell lines but the 16 SHIVenv_B variants showed only limited replication in macaque peripheral blood mononuclear cells (PBMCs) and 174×CEM.CCR5 cell line. AHI chimeric viruses including HIVenv_B3 showed only minor variations in cell entry efficiency and kinetics as well as replicative fitness in human PBMCs. Reduced number of N-link glycosylation sites and slightly greater CCR5 affinity/avidity was the only distinguishing feature of env_B3 versus other AHI env's in the pool, a feature also observed in the HIV establishing new infections in humans. Despite the inability to propagate in primary cells and cell lines, a pool of 16 SHIVenv viruses could establish infection but only one virus, SHIVenv_B3 was isolated in the macaque and then shown to repeatedly infected macaques. This SHIVenv_B3 virus did not show any distinct phenotypic property from the other 15 SHIVenv viruses but did have the fewest N-linked glycosylation sites.

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

PubMed

Wahl-Jensen, Victoria; Johnson, Joshua C; Lauck, Michael; Weinfurter, Jason T; Moncla, Louise H; Weiler, Andrea M; Charlier, Olivia; Rojas, Oscar; Byrum, Russell; Ragland, Dan R; Huzella, Louis; Zommer, Erika; Cohen, Melanie; Bernbaum, John G; Caì, Yíngyún; Sanford, Hannah B; Mazur, Steven; Johnson, Reed F; Qin, Jing; Palacios, Gustavo F; Bailey, Adam L; Jahrling, Peter B; Goldberg, Tony L; O'Connor, David H; Friedrich, Thomas C; Kuhn, Jens H

2016-02-23

Simian hemorrhagic fever (SHF) is a highly lethal disease in captive macaques. Three distinct arteriviruses are known etiological agents of past SHF epizootics, but only one, simian hemorrhagic fever virus (SHFV), has been isolated in cell culture. The natural reservoir(s) of the three viruses have yet to be identified, but African nonhuman primates are suspected. Eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy African cercopithecid monkeys. Here, we report the successful isolation in MARC-145 cell culture of one of these viruses, Kibale red colobus virus 1 (KRCV-1), from serum of a naturally infected red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles) sampled in Kibale National Park, Uganda. Intramuscular (i.m.) injection of KRCV-1 into four cynomolgus macaques (Macaca fascicularis) resulted in a self-limiting nonlethal disease characterized by depressive behavioral changes, disturbance in coagulation parameters, and liver enzyme elevations. In contrast, i.m. injection of SHFV resulted in typical lethal SHF characterized by mild fever, lethargy, lymphoid depletion, lymphoid and hepatocellular necrosis, low platelet counts, increased liver enzyme concentrations, coagulation abnormalities, and increasing viral loads. As hypothesized based on the genetic and presumed antigenic distance between KRCV-1 and SHFV, all four macaques that had survived KRCV-1 injection died of SHF after subsequent SHFV injection, indicating a lack of protective heterotypic immunity. Our data indicate that SHF is a disease of macaques that in all likelihood can be caused by a number of distinct simian arteriviruses, although with different severity depending on the specific arterivirus involved. Consequently, we recommend that current screening procedures for SHFV in primate-holding facilities be modified to detect all known simian arteriviruses. Outbreaks of simian hemorrhagic fever (SHF) have devastated captive Asian macaque colonies in the past. SHF is caused by at least three viruses of the family Arteriviridae: simian hemorrhagic fever virus (SHFV), simian hemorrhagic encephalitis virus (SHEV), and Pebjah virus (PBJV). Nine additional distant relatives of these three viruses were recently discovered in apparently healthy African nonhuman primates. We hypothesized that all simian arteriviruses are potential causes of SHF. To test this hypothesis, we inoculated cynomolgus macaques with a highly divergent simian arterivirus (Kibale red colobus virus 1 [KRCV-1]) from a wild Ugandan red colobus. Despite being only distantly related to red colobuses, all of the macaques developed disease. In contrast to SHFV-infected animals, KRCV-1-infected animals survived after a mild disease presentation. Our study advances the understanding of an important primate disease. Furthermore, our data indicate a need to include the full diversity of simian arteriviruses in nonhuman primate SHF screening assays. Copyright © 2016 Wahl-Jensen et al.

Influenza virus A/Anhui/1/2013 (H7N9) replicates efficiently in the upper and lower respiratory tracts of cynomolgus macaques.

PubMed

de Wit, Emmie; Rasmussen, Angela L; Feldmann, Friederike; Bushmaker, Trenton; Martellaro, Cynthia; Haddock, Elaine; Okumura, Atsushi; Proll, Sean C; Chang, Jean; Gardner, Don; Katze, Michael G; Munster, Vincent J; Feldmann, Heinz

2014-08-12

In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277-2285, 2013, doi:10.1056/NEJMoa1305584). Influenza A virus H7N9 emerged early in 2013, and human cases have continued to emerge since then. Although H7N9 virus-induced disease in humans is often very severe and even lethal, the majority of reported H7N9 cases occurred in older people and people with underlying medical conditions. To better understand the pathogenicity of this virus, healthy cynomolgus macaques were inoculated with influenza A virus H7N9. Cynomolgus macaques were used as a model because the receptor distribution for H7N9 virus in macaques was recently shown to be more similar to that in humans than that of other frequently used animal models. From comparison with previous studies, we conclude that the emerging H7N9 influenza virus was more pathogenic in cynomolgus macaques than seasonal influenza A viruses and most isolates of the pandemic H1N1 virus but less pathogenic than the 1918 Spanish influenza virus or highly pathogenic avian influenza (HPAI) H5N1 virus. Copyright © 2014 de Wit et al.

Repertoire comparison of the B-cell receptor encoding loci in humans and rhesus macaques by next generation sequencing

USDA-ARS?s Scientific Manuscript database

Rhesus macaques are a widely used model system for the study of vaccines, infectious diseases, and microbial pathogenesis. Their value as a model lies in their close evolutionary relationship to humans, which, in theory, allows them to serve as a close approximation of the human immune system. Howev...

Spatial Relational Memory in 9-Month-Old Macaque Monkeys

ERIC Educational Resources Information Center

Lavenex, Pierre; Lavenex, Pamela Banta

2006-01-01

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

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

ERIC Educational Resources Information Center

Hauser, Marc D.; Carey, Susan

2003-01-01

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

Monkey vocal tracts are speech-ready.

PubMed

Fitch, W Tecumseh; de Boer, Bart; Mathur, Neil; Ghazanfar, Asif A

2016-12-01

For four decades, the inability of nonhuman primates to produce human speech sounds has been claimed to stem from limitations in their vocal tract anatomy, a conclusion based on plaster casts made from the vocal tract of a monkey cadaver. We used x-ray videos to quantify vocal tract dynamics in living macaques during vocalization, facial displays, and feeding. We demonstrate that the macaque vocal tract could easily produce an adequate range of speech sounds to support spoken language, showing that previous techniques based on postmortem samples drastically underestimated primate vocal capabilities. Our findings imply that the evolution of human speech capabilities required neural changes rather than modifications of vocal anatomy. Macaques have a speech-ready vocal tract but lack a speech-ready brain to control it.

Short Communication: Comparative Susceptibility of Rhesus Macaques of Indian and Chinese Origin to Vaginal Simian-Human Immunodeficiency Virus Transmission as Models for HIV Prevention Research.

PubMed

Veazey, Ronald S; Ling, Binhua

2017-12-01

Historically, Indian rhesus macaques (iRMs) have been preferred for simian immunodeficiency virus (SIV)/HIV prevention, pathogenesis, and treatment studies, yet their supply is limited. Chinese rhesus macaques (cRMs) are currently more available, yet little is known regarding the relative susceptibility of this subspecies to vaginal transmission of SIV or simian-human immunodeficiency virus (SHIV). In this study, we compared the susceptibility of 40 cRMs and 21 iRMs with a single vaginal challenge with SHIVsf162P. Our results showed that cRMs have comparable primary SHIV infection as iRMs, underscoring their equal importance in studies of HIV transmission and prevention.

Molecular and functional aspects of menstruation in the macaque.

PubMed

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).

Otoacoustic Estimates of Cochlear Tuning: Testing Predictions in Macaque

NASA Astrophysics Data System (ADS)

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

2011-11-01

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

Neural noise and movement-related codes in the macaque supplementary motor area.

PubMed

Averbeck, Bruno B; Lee, Daeyeol

2003-08-20

We analyzed the variability of spike counts and the coding capacity of simultaneously recorded pairs of neurons in the macaque supplementary motor area (SMA). We analyzed the mean-variance functions for single neurons, as well as signal and noise correlations between pairs of neurons. All three statistics showed a strong dependence on the bin width chosen for analysis. Changes in the correlation structure of single neuron spike trains over different bin sizes affected the mean-variance function, and signal and noise correlations between pairs of neurons were much smaller at small bin widths, increasing monotonically with the width of the bin. Analyses in the frequency domain showed that the noise between pairs of neurons, on average, was most strongly correlated at low frequencies, which explained the increase in noise correlation with increasing bin width. The coding performance was analyzed to determine whether the temporal precision of spike arrival times and the interactions within and between neurons could improve the prediction of the upcoming movement. We found that in approximately 62% of neuron pairs, the arrival times of spikes at a resolution between 66 and 40 msec carried more information than spike counts in a 200 msec bin. In addition, in 19% of neuron pairs, inclusion of within (11%)- or between-neuron (8%) correlations in spike trains improved decoding accuracy. These results suggest that in some SMA neurons elements of the spatiotemporal pattern of activity may be relevant for neural coding.

Natural asynchronies in audiovisual communication signals regulate neuronal multisensory interactions in voice-sensitive cortex

PubMed Central

Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K.; Petkov, Christopher I.

2015-01-01

When social animals communicate, the onset of informative content in one modality varies considerably relative to the other, such as when visual orofacial movements precede a vocalization. These naturally occurring asynchronies do not disrupt intelligibility or perceptual coherence. However, they occur on time scales where they likely affect integrative neuronal activity in ways that have remained unclear, especially for hierarchically downstream regions in which neurons exhibit temporally imprecise but highly selective responses to communication signals. To address this, we exploited naturally occurring face- and voice-onset asynchronies in primate vocalizations. Using these as stimuli we recorded cortical oscillations and neuronal spiking responses from functional MRI (fMRI)-localized voice-sensitive cortex in the anterior temporal lobe of macaques. We show that the onset of the visual face stimulus resets the phase of low-frequency oscillations, and that the face–voice asynchrony affects the prominence of two key types of neuronal multisensory responses: enhancement or suppression. Our findings show a three-way association between temporal delays in audiovisual communication signals, phase-resetting of ongoing oscillations, and the sign of multisensory responses. The results reveal how natural onset asynchronies in cross-sensory inputs regulate network oscillations and neuronal excitability in the voice-sensitive cortex of macaques, a suggested animal model for human voice areas. These findings also advance predictions on the impact of multisensory input on neuronal processes in face areas and other brain regions. PMID:25535356

Local sensitivity to stimulus orientation and spatial frequency within the receptive fields of neurons in visual area 2 of macaque monkeys

PubMed Central

Tao, X.; Zhang, B.; Smith, E. L.; Nishimoto, S.; Ohzawa, I.

2012-01-01

We used dynamic dense noise stimuli and local spectral reverse correlation methods to reveal the local sensitivities of neurons in visual area 2 (V2) of macaque monkeys to orientation and spatial frequency within their receptive fields. This minimized the potentially confounding assumptions that are inherent in stimulus selections. The majority of neurons exhibited a relatively high degree of homogeneity for the preferred orientations and spatial frequencies in the spatial matrix of facilitatory subfields. However, about 20% of all neurons showed maximum orientation differences between neighboring subfields that were greater than 25 deg. The neurons preferring horizontal or vertical orientations showed less inhomogeneity in space than the neurons preferring oblique orientations. Over 50% of all units also exhibited suppressive profiles, and those were more heterogeneous than facilitatory profiles. The preferred orientation and spatial frequency of suppressive profiles differed substantially from those of facilitatory profiles, and the neurons with suppressive subfields had greater orientation selectivity than those without suppressive subfields. The peak suppression occurred with longer delays than the peak facilitation. These results suggest that the receptive field profiles of the majority of V2 neurons reflect the orderly convergence of V1 inputs over space, but that a subset of V2 neurons exhibit more complex response profiles having both suppressive and facilitatory subfields. These V2 neurons with heterogeneous subfield profiles could play an important role in the initial processing of complex stimulus features. PMID:22114163

Viral kinetics are associated with changes in cytokines and chemokines in serum and target organs of SSM-CVB3-infected macaques.

PubMed

Han, Tiesuo; Zhao, Kui; Wu, Chenchen; Lu, Huijun; Song, Deguang; He, Wenqi; Gao, Feng

2013-02-01

To determine the relationship between viral kinetics and the expression patterns for different cytokines and chemokines in the serum and organs of coxsackievirus B3 (SSM-CVB3)-infected macaques over the course of infection. SSM-CVB3 levels in serum and organs were measured using the Spearman-Karber 50% tissue culture infectious dose (TCID(50)) method. Cytokine and chemokine levels in the serum and organs were measured by indirect-ELISA. Low viral titers were detected in the serum samples on the first day post-inoculation (p.i.) and peaked at 6 to 10 days p.i. in the serum samples from five macaques. Serum levels of IL-1β, IL-2, IL-6, IL-12p40, IL-17α, IFN-γ, TNF-α, MCP-1 and MIP-1β were detected each day and, similar to the viral titers, peaked at 6 to 10 days. IL-10 was only detected on days 10 to 14 p.i. Additionally, higher viral titers and relative viral mRNA levels were associated with higher cytokine and chemokine levels in selected tissues from infected macaques including heart, liver, spleen, lung, kidney and brain. The results indicate that patterns of cytokine and chemokine response are associated with viral kinetics in the serum and target organs of SSM-CVB3-infected macaques, suggesting that the changes in cytokines and chemokines could help further our understanding of the progress of CVB3 infections in clinical settings. Copyright © 2012 Elsevier Inc. All rights reserved.

Sex differences in the stone tool-use behavior of a wild population of burmese long-tailed macaques (Macaca fascicularis aurea).

PubMed

Gumert, Michael D; Hoong, Low Kuan; Malaivijitnond, Suchinda

2011-12-01

We investigated sex differences in how Burmese long-tailed macaques (Macaca fascicularis aurea) used stone tools to open shelled food items along the shores of two islands in Laemson National Park, Thailand. Over a 2-week period in December 2009, we collected scan and focal samples on macaques when they were visible along the shores and mangroves. We found females used stones more often while feeding and used smaller tools than males. Females also processed sessile oysters more than males, whereas males processed unattached foods more than females. It was unclear which sex was overall more proficient at stone tool use, but males did perform significantly better at opening unattached food items with large pounding stones. Females also struck food items more times during tool-use bouts and at a faster rate, but no significant difference was found in average tool-use bout duration. Males processed foods slightly faster within a tool-use bout, but we were unable to detect a significant difference in the rate of food processing while foraging with tools. In summary females chipped open sessile oysters with an axing technique more than males, while males used larger stones to pound open unattached shelled food more often than females. Despite using pounding more than females, males also regularly utilized the axing technique on sessile oysters. Our results are the first assessment of sex differences in macaque stone tool use, providing a basis for comparison with tool use in other primates, and to nonfunctional forms of stone use in other macaques. © 2011 Wiley Periodicals, Inc.

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

PubMed

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.

Minimally Invasive Lumbar Port System for the Collection of Cerebrospinal Fluid from Rhesus Macaques (Macaca mulatta)

PubMed Central

MacAllister, Rhonda Pung; Lester McCully, Cynthia M; Bacher, John; Thomas, Marvin L; Cruz, Rafael; Wangari, Solomon; Warren, Katherine E

2016-01-01

Biomedical translational research frequently incorporates collection of CSF from NHP, because CSF drug levels are used as a surrogate for CNS tissue penetration in pharmacokinetic and dynamic studies. Surgical placement of a CNS ventricular catheter reservoir for CSF collection is an intensive model to create and maintain and thus may not be feasible or practical for short-term studies. Furthermore, previous NHP lumbar port models require laminectomy for catheter placement. The new model uses a minimally invasive technique for percutaneous placement of a lumbar catheter to create a closed, subcutaneous system for effective, repeated CSF sample collection. None of the rhesus macaques (Macaca mulatta; n = 10) implanted with our minimally invasive lumbar port (MILP) system experienced neurologic deficits, postoperative infection of the surgical site, or skin erosion around the port throughout the 21.7-mo study. Functional MILP systems were maintained in 70% of the macaques, with multiple, high-quality, 0.5- to 1.0-mL samples of CSF collected for an average of 3 mo by using aspiration or gravitational flow. Among these macaques, 57% had continuous functionality for a mean of 19.2 mo; 50% of the cohort required surgical repair for port repositioning and replacement during the study. The MILP was unsuccessful in 2 macaques, at an average of 9.5 d after surgery. Nonpatency in these animals was attributed to the position of the lumbar catheter. The MILP system is an appropriate replacement for temporary catheterization and previous models requiring laminectomy and is a short-term alternative for ventricular CSF collection systems in NHP. PMID:27538866

Recent advances in the development of vaccines against ricin.

PubMed

Brey, Robert N; Mantis, Nicholas J; Pincus, Seth H; Vitetta, Ellen S; Smith, Leonard A; Roy, Chad J

2016-05-03

Several promising subunit vaccines against ricin toxin (RT) have been developed during the last decade and are now being tested for safety and immunogenicity in humans and for efficacy in nonhuman primates. The incentive to develop a preventive vaccine as a countermeasure against RT use as a bioweapon is based on the high toxicity of RT after aerosol exposure, its environmental stability, abundance, and ease of purification. RT is the second most lethal biological toxin and is considered a "universal toxin" because it can kill all eukaryotic cells through binding to ubiquitous cell surface galactosyl residues. RT has two subunits conjoined by a single disulfide linkage: RTB, which binds galactosyl residues and RTA which enzymatically inactivates ribosomes intracellularly by cleavage ribosomal RNA. Attenuation of toxicity by elimination of the active site or introduction of other structural mutations of RTA has generated two similar clinical subunit vaccine candidates which induce antibodies in both humans and nonhuman primates. In rhesus macaques, inhaled RT causes rapid lung necrosis and fibrosis followed by death. After parenteral vaccination with RTA vaccine, macaques can be protected against aerosol RT exposure, suggesting that circulating antibodies can protect lung mucosa. Vaccination induces RT-neutralizing antibodies, the most likely correlate of protection. Macaques responded to conformational determinants in an RTA vaccine formulation, indicating preservation of RTA structure during initial manufacture. Comparative mapping studies have also demonstrated that macaques and humans recognize the same epitopes, significant in the study of macaques as a model during development of vaccines which cannot be tested for efficacy in humans.

Immunophenotypic Alterations in Resident Immune Cells and Myocardial Fibrosis in the Aging Rhesus Macaque (Macaca mulatta) Heart

PubMed Central

Macri, Sheila C.; Bailey, Charles C.; de Oca, Nicole Monts; Silva, Nilsa A.; Rosene, Douglas L.; Mansfield, Keith G.; Miller, Andrew D.

2012-01-01

The rhesus macaque (Macaca mulatta) is used extensively in translational biomedical research and drug development studies and is an important model of aging. Macaques often develop myocardial fibrosis with age which can result in the loss of normal cardiac architecture with the expansion of the extracellular matrix and deposition of collagen. The etiology and pathogenesis of this pernicious process is poorly understood. Cardiac fibrosis was assessed using histologic and immunohistochemical techniques in cardiac tissue sections from 34 rhesus macaques. Overall left ventricular and left ventricular mid-myocardial interstitial/perivascular fibrosis were positively correlated with age (r=0.6522, p<0.0001 and r=0.4704, p=0.005, respectively). When divided into young (mean=2.8 years), middle-aged (mean=17.5 years), and advanced age (mean=29.2 years) groups, immunophenotypic characterization of antigen presenting cells revealed differential expression of CD163 and DC-SIGN between the young and middle-aged groups compared to the advanced age group (p<0.0001). HAM-56 expression decreased significantly in the advanced age cohort (p=0.0021). The expression of CD8, CD163, and DCSIGN correlated positively with age (r=0.3999, p= 0.0191; r=0.5676, p=0.0005; r=0.5245, p=0.0014 respectively). These results show the importance of myocardial fibrosis as a common age-related pathology and additionally, alterations in T cell, macrophage, and dendritic cell phenotype in rhesus macaque myocardium are associated with age but unassociated with the fibrosis. PMID:22328408

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

PubMed

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.

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

PubMed

Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

2015-10-01

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86%) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2%, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques.

PubMed

Phuah, Jiayao; Wong, Eileen A; Gideon, Hannah P; Maiello, Pauline; Coleman, M Teresa; Hendricks, Matthew R; Ruden, Rachel; Cirrincione, Lauren R; Chan, John; Lin, Philana Ling; Flynn, JoAnne L

2016-05-01

Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses against Mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model of M. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells in M. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response in M. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Value of Extended Pedigrees for Next-Generation Analysis of Complex Disease in the Rhesus Macaque

PubMed Central

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. PMID:24174435

Human Immunodeficiency Virus Research Program

DTIC Science & Technology

1993-11-30

pluripotent hematopoietic stem cells ’- Description: This project exploits the proliferation and differentiation potential of hematopoietic stem cells and...if inactivated whole SIVme/elS generated in macaque cells when used as an immunogen in macaques induces a protective immunity following challenge with...antiviral strategies in hematopoeitic Mosca* stem cells (P) - Pending Protocol *Foundation Principal Investigator (PI) 95 OVERVIEW: The HIV Drugs and

Persistent babesiosis in a Rhesus macaque (Macaca mulatta) infected with a simian-human immunodeficiency virus

PubMed Central

Liu, David X.; Gill, Amy; Holman, Patricia J.; Didier, Peter J.; Blanchard, James L.; Veazey, Ronald S.; Lackner, Andrew A.

2014-01-01

A rhesus macaque developed persistent babesiosis following inoculation with a simian-human immunodeficiency virus. Blood smears demonstrated intraerythrocytic piroplasms and rare Maltese cross forms. Babesia microti-like protozoa were confirmed by PCR and gene sequence. With using nonhuman primates as models for human diseases, infection and complications from Babesia should be monitored. PMID:24517274

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

PubMed Central

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

2015-01-01

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

Dopamine Innervation in the Thalamus: Monkey versus Rat

PubMed Central

García-Cabezas, Miguel Ángel; Martínez-Sánchez, Patricia; Sánchez-González, Miguel Ángel; Garzón, Miguel

2009-01-01

We recently identified the thalamic dopaminergic system in the human and macaque monkey brains, and, based on earlier reports on the paucity of dopamine in the rat thalamus, hypothesized that this dopaminergic system was particularly developed in primates. Here we test this hypothesis using immunohistochemistry against the dopamine transporter (DAT) in adult macaque and rat brains. The extent and density of DAT-immunoreactive (-ir) axons were remarkably greater in the macaque dorsal thalamus, where the mediodorsal association nucleus and the ventral motor nuclei held the densest immunolabeling. In contrast, sparse DAT immunolabeling was present in the rat dorsal thalamus; it was mainly located in the mediodorsal, paraventricular, ventral medial, and ventral lateral nuclei. The reticular nucleus, zona incerta, and lateral habenular nucleus held numerous DAT-ir axons in both species. Ultrastructural analysis in the macaque mediodorsal nucleus revealed that thalamic interneurons are a main postsynaptic target of DAT-ir axons; this suggests that the marked expansion of the dopamine innervation in the primate in comparison to the rodent thalamus may be related to the presence of a sizable interneuron population in primates. We remark that it is important to be aware of brain species differences when using animal models of human brain disease. PMID:18550594

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2014-10-01

In this paper, we review research related to female homosexual behavior in Japanese macaques (Macaca fuscata), including our 20-year program of research on this species. Multiple lines of evidence indicate that female homosexual behavior in this species is sexually motivated. In contrast, many sociosexual hypotheses have been tested in relation to female homosexual behavior in Japanese macaques, but none have been supported. Female Japanese macaques sometimes engage in same-sex sexual activity even when motivated opposite-sex alternatives are available. Within this context of mate choice, males compete inter-sexually for opportunities to copulate with females above and beyond any intra-sexual competition that is required. Anecdotal evidence suggests that inter-sexual competition for female sexual partners has been observed in a number of other species, including humans. At present it is unclear whether inter-sexual competition for sexual partners influences patterns of reproduction. Our understanding of sexual selection and the evolution of mating systems may be improved by investigating whether inter-sexual mate competition influences the acquisition and maintenance of reproductive partners in those species in which such interactions occur. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aiding pest control management of long-tailed macaques (Macaca fascicularis fascicularis) in Malaysia by using molecular markers of mitochondrial DNA

NASA Astrophysics Data System (ADS)

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

2017-10-01

The long-tailed macaques (Macaca fascicularis fascicularis) has been the center of human wildlife conflict in Malaysia since 1970s. This well-adapted and opportunistic primates have been dominating wide range of habitat in Malaysia such as primary and secondary forest, mangrove, as well as human settlements. The conventional practices of translocation by the authorities are threatening the uniqueness of gene pool for this species and ironically contradicting with the ultimate purpose of genetic conservation of this species. The objectives of this study is to determine the level of genetic separation between populations of long-tailed macaques, primarily focusing on populations distributed in northern Peninsular Malaysia. A total of 954 base pairs of control regions mtDNA was sequenced and analyzed from 27 samples of M. fascicularis. The results exhibited a highly homogenous state of populations for long-tailed macaques genetically and this ultimately indicate unsuitable management and planning in terms of pest control management of the species. Authorities are suggested to translocate the species at least within the state boundaries to avoid homogeneity of gene pools for the particular species.

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

PubMed

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

2016-08-23

The Japanese macaque (Macaca fuscata) exhibits a species-specific communication sound called the "coo call" to locate group members and maintain within-group contact. Monkeys have been demonstrated to be capable of discriminating between individuals based only on their voices, but there is still debate regarding how the fundamental frequencies (F0) and filter properties of the vocal tract characteristics (VTC) contribute to individual discrimination in nonhuman primates. This study was performed to investigate the acoustic keys used by Japanese macaques in individual discrimination. Two animals were trained with standard Go/NoGo operant conditioning to distinguish the coo calls of two unfamiliar monkeys. The subjects were required to continue depressing a lever until the stimulus changed from one monkey to the other. The test stimuli were synthesized by combining the F0s and VTC from each individual. Both subjects released the lever when the VTC changed, whereas they did not when the F0 changed. The reaction times to the test stimuli were not significantly different from that to the training stimuli that shared the same VTC. Our data suggest that vocal tract characteristics are important for the identification of individuals by Japanese macaques.

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

PubMed Central

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

2010-01-01

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

Female orgasm rate increases with male dominance in Japanese macaques.

PubMed

Troisi; Carosi

1998-11-01

Under specific circumstances, nonhuman primate females may experience orgasm. The occurrence of female copulatory orgasm appears to be highly variable, however, and its proximate causation is poorly understood. We investigated the proximate mechanisms that control orgasmic response in female macaques. During 238 h of observation of sexual behaviour in a large captive group of Japanese macaques, Macaca fuscata, 240 copulations were recorded involving 68 different heterosexual pairs formed by 16 males and 26 females. Female orgasmic responses were observed in 80 of 240 copulations (33%). The frequency of orgasms was not correlated with female age or dominance rank, but it was higher for copulations lasting longer and involving a higher number of mounts and pelvic thrusts. When the level of physical stimulation experienced by females during copulation was statistically controlled, the highest frequency of female orgasms was found among pairs formed by high-ranking males and low-ranking females and the lowest frequency among pairs formed by low-ranking males and high-ranking females. These findings suggest that the proximate mechanisms that control orgasmic threshold in female macaques are more responsive to social stimuli and less constrained by physiological limitations than previously thought. Copyright 1998 The Association for the Study of Animal Behaviour.

Oxytocin and vasopressin flatten dominance hierarchy and enhance behavioral synchrony in part via anterior cingulate cortex.

PubMed

Jiang, Yaoguang; Platt, Michael L

2018-05-29

The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) influence social functions in many mammals. In humans and rhesus macaques, OT delivered intranasally can promote prosocial behavior in certain contexts. Yet the precise neural mechanisms mediating these behavioral effects remain unclear. Here we show that treating a group of male macaque monkeys intranasally with aerosolized OT relaxes their spontaneous social interactions with other monkeys. OT reduces differences in social behavior between dominant and subordinate monkeys, thereby flattening the status hierarchy. OT also increases behavioral synchrony within a pair. Intranasal delivery of aerosolized AVP reproduces the effects of OT with greater efficacy. Remarkably, all behavioral effects are replicated when OT or AVP is injected focally into the anterior cingulate gyrus (ACCg), a brain area linked to empathy and other-regarding behavior. ACCg lacks OT receptors but is rich in AVP receptors, suggesting exogenous OT may shape social behavior, in part, via nonspecific binding. Notably, OT and AVP alter behaviors of both the treated monkey and his untreated partner, consistent with enhanced feedback through reciprocal social interactions. These findings bear important implications for use of OT in both basic research and as a therapy for social impairments in neurodevelopmental disorders.

Callosally projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein

NASA Technical Reports Server (NTRS)

Hof, P. R.; Ungerleider, L. G.; Adams, M. M.; Webster, M. J.; Gattass, R.; Blumberg, D. M.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1997-01-01

Previous immunohistochemical studies combined with retrograde tracing in macaque monkeys have demonstrated that corticocortical projections can be differentiated by their content of neurofilament protein. The present study analyzed the distribution of nonphosphorylated neurofilament protein in callosally projecting neurons located at the V1/V2 border. All of the retrogradely labeled neurons were located in layer III at the V1/V2 border and at an immediately adjacent zone of area V2. A quantitative analysis showed that the vast majority (almost 95%) of these interhemispheric projection neurons contain neurofilament protein immunoreactivity. This observation differs from data obtained in other sets of callosal connections, including homotypical interhemispheric projections in the prefrontal, temporal, and parietal association cortices, that were found to contain uniformly low proportions of neurofilament protein-immunoreactive neurons. Comparably, highly variable proportions of neurofilament protein-containing neurons have been reported in intrahemispheric corticocortical pathways, including feedforward and feedback visual connections. These results indicate that neurofilament protein is a prominent neurochemical feature that identifies a particular population of interhemispheric projection neurons at the V1/V2 border and suggest that this biochemical attribute may be critical for the function of this subset of callosal neurons.

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

PubMed Central

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

2008-01-01

Background The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV) drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT) inhibitor tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl] adenine monohydrate), a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV) in a well-established and standardised macaque model. Methods and Findings A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50) of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC), quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA) load by sensitive quantitative competitive (qc) RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test) wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6) or had 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-γ)-secreting T cells were detected in the blood of four of seven protected animals tested, with frequencies ranging from 144 spot forming cells (SFC)/106 PBMC to 261 spot forming cells (SFC)/106 PBMC. Conclusions 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. PMID:18684007

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

PubMed

Zhang, Xiaodong; Yan, Yumei; Tong, Frank; Li, Chun-Xia; Jones, Benjamin; Wang, Silun; Meng, Yuguang; Muly, E Chris; Kempf, Doty; Howell, Leonard

2018-01-01

Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion. Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion. Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post-stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings. The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

Computed tomography or necropsy diagnosis of multiple bullae and the treatment of pneumothorax in rhesus macaques (Macaca mulatta).

PubMed

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.

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

PubMed

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.

Report on primate supply for biomedical scientific work in the UK. EUPREN UK Working Party.

PubMed

Owen, S; Thomas, C; West, P; Wolfensohn, S; Wood, M

1997-10-01

A Working Party of the UK group of European Primate Resources Network (EUPREN) considered primate supply for scientific work in the UK. Through a questionnaire, which achieved a very good response, it obtained details of primate use, sources and breeding in the UK and it put forward options to ensure that animal welfare is the best possible whilst ensuring continued supply. The questionnaire showed that contract research laboratories and pharmaceutical companies use about 80% of the 4233 primates used annually at the moment, with the rest accounted for by academic establishments and public sector laboratories. Fifty-four per cent are cynomolgus macaques (Macaca fascicularis), of which nearly 90% are captive-bred outside the European Union (EU), the remainder being bred in the UK. Nearly 90% of cynomolgus macaques are used by only five institutions. Thirty-seven per cent of primates used are marmosets (Callithrix jacchus jacchus), all of which are bred in the UK. Most of the rest are rhesus macaques (Macaca mulatta), about half of which are captive-bred outside the EU, the other half being bred in the UK. Overall primate use has increased from about 3000 per year in 1990 and users predict that requirements for all species except baboons (Papio sp.) will be maintained or increase. Marmoset breeding in the UK is already closely matched to use, and it could be increased reasonably easily if necessary. Some of the existing breeding centres of macaques in the UK would be prepared to consider expanding to supply others, although investment and imported breeding stock would be needed and it is likely that a large investment would be needed to breed a significant fraction of the macaque use in the UK. A further problem is that the users of only about 10% of the cynomolgus macaques said that they could replace this species by rhesus macaques, which are easier to breed in the UK. The questionnaire showed that much of the use of macaques would be transferred to other countries equally remote from the natural source countries of the animals, if constraints on primate use became more severe in the UK. Users felt that it is unlikely that much of the work could be transferred to the natural source countries themselves. A review of the literature revealed a paucity of information on the effects of transport on primate welfare. The importance of obtaining this information before making decisions about alternative means of supply is stressed. Current schemes for the accreditation of primate breeders were reviewed. A list of options is presented for discussion. Users vary so much in their requirements that it is unlikely that one means of supply will be applicable to all. Animal welfare will benefit and supply will be more certain if cooperation between those concerned (preferably through the UK group of EUPREN) is maintained.

Measles Vaccination of Nonhuman Primates Provides Partial Protection against Infection with Canine Distemper Virus

PubMed Central

de Vries, Rory D.; Ludlow, Martin; Verburgh, R. Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D. Tien; McQuaid, Stephen; Osterhaus, Albert D. M. E.; Duprex, W. Paul

2014-01-01

ABSTRACT Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150+ lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. IMPORTANCE Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to understand the zoonotic potential of animal morbilliviruses. Morbilliviruses are thought to have evolved from a common ancestral virus that jumped species and adapted to new hosts. Recently, canine distemper virus (CDV), a morbillivirus normally restricted to carnivores, caused disease outbreaks in nonhuman primates. Here, we report that experimental CDV infection of monkeys resulted in fever and leukopenia. The virus replicated to high levels in lymphocytes but did not spread to epithelial cells or the central nervous system. Importantly, like measles virus in macaques, the infections were self-limiting. In measles-vaccinated macaques CDV was cleared more rapidly, resulting in limited virus shedding from the upper respiratory tract. These studies demonstrate that although CDV can readily infect primates, measles immunity is protective, and CDV infection is self-limiting. PMID:24501402

Measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus.

PubMed

de Vries, Rory D; Ludlow, Martin; Verburgh, R Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D Tien; McQuaid, Stephen; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

2014-04-01

Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150(+) lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to understand the zoonotic potential of animal morbilliviruses. Morbilliviruses are thought to have evolved from a common ancestral virus that jumped species and adapted to new hosts. Recently, canine distemper virus (CDV), a morbillivirus normally restricted to carnivores, caused disease outbreaks in nonhuman primates. Here, we report that experimental CDV infection of monkeys resulted in fever and leukopenia. The virus replicated to high levels in lymphocytes but did not spread to epithelial cells or the central nervous system. Importantly, like measles virus in macaques, the infections were self-limiting. In measles-vaccinated macaques CDV was cleared more rapidly, resulting in limited virus shedding from the upper respiratory tract. These studies demonstrate that although CDV can readily infect primates, measles immunity is protective, and CDV infection is self-limiting.

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

PubMed

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.

Changes in the primate trade in indonesian wildlife markets over a 25-year period: Fewer apes and langurs, more macaques, and slow lorises.

PubMed

Nijman, Vincent; Spaan, Denise; Rode-Margono, Eva Johanna; Wirdateti; Nekaris, K A I

2017-11-01

Indonesia has amongst the highest primate species richness, and many species are included on the country's protected species list, partially to prevent over-exploitation. Nevertheless traders continue to sell primates in open wildlife markets especially on the islands of Java and Bali. We surveyed 13 wildlife markets in 2012-2014 and combined our results with previous surveys from 1990-2009 into a 122-survey dataset with 2,424 records of 17 species. These data showed that the diversity of species in trade decreased over time, shifting from rare rainforest-dwelling primates traded alongside more widespread species that are not confined to forest to the latter type only. In the 1990s and early 2000s orangutans, gibbons and langurs were commonly traded alongside macaques and slow lorises but in the last decade macaques and slow lorises comprised the bulk of the trade. In 2012-2014 we monitored six wildlife markets in Jakarta, Bandung and Garut (all on Java), and Denpasar (Bali). During 51 surveys we recorded 1,272 primates of eight species. Traders offered long-tailed macaque (total 1,007 individuals) and three species of slow loris (228 individuals) in five of the six markets, whereas they traded ebony langurs (18 individuals), and pig-tailed macaques (14 individuals) mostly in Jakarta. Pramuka and Jatinegara markets, both in Jakarta, stood out as important hubs for the primate trade, with a clear shift in importance over time from the former to the latter. Slow lorises, orangutans, gibbons and some langurs are protected under Indonesian law, which prohibits all trade in them; of these protected species, only the slow lorises remained common in trade throughout the 25-year period. Trade in non-protected macaques and langurs is subject to strict regulations-which market traders did not follow-making all the market trade in primates that we observed illegal. Trade poses a substantial threat to Indonesian primates, and without enforcement, the sheer volume of trade may mean that species of Least Concern or Near Threatened may rapidly decline. Am. J. Primatol. 79:e22517, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Identification of unique B virus (Macacine Herpesvirus 1) epitopes of zoonotic and macaque isolates using monoclonal antibodies

PubMed Central

Vasireddi, Mugdha; Patrusheva, Irina; Seoh, Hyuk-Kyu; Filfili, Chadi N.; Wildes, Martin J.; Oh, Jay

2017-01-01

Our overall aim is to develop epitope-based assays for accurate differential diagnosis of B virus zoonotic infections in humans. Antibodies to cross-reacting epitopes on human-simplexviruses continue to confound the interpretation of current assays where abundant antibodies exist from previous infections with HSV types 1 and 2. To find B virus-specific epitopes we cloned ten monoclonal antibodies (mAbs) from the hybridomas we produced. Our unique collection of rare human sera from symptomatic and asymptomatic patients infected with B virus was key to the evaluation and identification of the mAbs as reagents in competition ELISAs (mAb-CE). The analysis of the ten mAbs revealed that the target proteins for six mAbs was glycoprotein B of which two are reactive to simian simplexviruses and not to human simplexviruses. Two mAbs reacted specifically with B virus glycoprotein D, and two other mAbs were specific to VP13/14 and gE-gI complex respectively. The mAbs specific to VP13/14 and gE-gI are strain specific reacting with B virus isolates from rhesus and Japanese macaques and not with isolates from cynomolgus and pigtail macaques. The mAb-CE revealed that a high proportion of naturally B virus infected rhesus macaques and two symptomatic humans possess antibodies to epitopes of VP13/14 protein and on the gE-gI complex. The majority of sera from B virus infected macaques and simplexvirus-infected humans competed with the less specific mAbs. These experiments produced a novel panel of mAbs that enabled B virus strain identification and confirmation of B virus infected macaques by the mAb-CE. For human sera the mAb-CE could be used only for selected cases due to the selective B virus strain-specificity of the mAbs against VP13/14 and gE/gI. To fully accomplish our aim to provide reagents for unequivocal differential diagnosis of zoonotic B virus infections, additional mAbs with a broader range of specificities is critical. PMID:28783746

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

PubMed

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 depend on both individuals' direct connections and on secondary network pathways that define community structure. They lend support to the hypothesis that social network communities may act as bottlenecks to contain the spread of infectious agents, thereby encouraging disease control strategies to focus on multiple organizational scales. Future directions includeincreasing microbial sampling effort per individual to better-detect dyadic transmission events, and assessments of the co-evolutionary links between sociality, infectious agent risk, and host immune function.

Local attitudes and perceptions toward crop-raiding by orangutans (Pongo abelii) and other nonhuman primates in northern Sumatra, Indonesia.

PubMed

Campbell-Smith, Gail; Simanjorang, Hubert V P; Leader-Williams, Nigel; Linkie, Matthew

2010-09-01

Human-wildlife conflicts, such as crop-raiding, increase as people expand their agricultural activities into wildlife habitats. Crop-raiding can reduce tolerance toward species that are already threatened, whereas potential dangers posed by conflicts with large-bodied species may also negatively influence local attitudes. Across Asia, wild pigs and primates, such as macaques, tend to be the most commonly reported crop raiders. To date, reports of crop-raiding incidents involving great apes have been less common, but incidents involving orangutans are increasingly emerging in Indonesia. To investigate the interplay of factors that might explain attitudes toward crop-raiding by orangutans (Pongo abelii), focal group discussions and semi-structured interviews were conducted among 822 farmers from 2 contrasting study areas in North Sumatra. The first study area of Batang Serangan is an agroforest system containing isolated orangutans that crop-raid. In contrast, the second area of Sidikalang comprises farmlands bordering extensive primary forest where orangutans are present but not reported to crop-raid. Farmers living in Batang Serangan thought that orangutans were dangerous, irrespective of earlier experience of crop-raiding. Farmers placed orangutans as the third most frequent and fourth most destructive crop pest, after Thomas' leaf monkey (Presbytis thomasi), wild boar (Sus scrofa), and long-tailed macaque (Macaca fascicularis). Although most (57%) farmers across both study areas were not scared of wildlife species, more than a quarter (28%) of the farmers' feared orangutans. Farmers in Batang Serangan were generally more tolerant toward crop-raiding orangutans, if they did not perceive them to present a physical threat. Most (67%) Batang Serangan farmers said that the local Forestry Department staff should handle crop-raiding orangutans, and most (81%) said that these officials did not care about such problems. Our results suggest that efforts to mitigate human-orangutan conflict may not, per se, change negative perceptions of those who live with the species, because these perceptions are often driven by fear. 2010 Wiley-Liss, Inc.

Neurofilament protein defines regional patterns of cortical organization in the macaque monkey visual system: a quantitative immunohistochemical analysis

NASA Technical Reports Server (NTRS)

Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

Visual function in monkeys is subserved at the cortical level by a large number of areas defined by their specific physiological properties and connectivity patterns. For most of these cortical fields, a precise index of their degree of anatomical specialization has not yet been defined, although many regional patterns have been described using Nissl or myelin stains. In the present study, an attempt has been made to elucidate the regional characteristics, and to varying degrees boundaries, of several visual cortical areas in the macaque monkey using an antibody to neurofilament protein (SMI32). This antibody labels a subset of pyramidal neurons with highly specific regional and laminar distribution patterns in the cerebral cortex. Based on the staining patterns and regional quantitative analysis, as many as 28 cortical fields were reliably identified. Each field had a homogeneous distribution of labeled neurons, except area V1, where increases in layer IVB cell and in Meynert cell counts paralleled the increase in the degree of eccentricity in the visual field representation. Within the occipitotemporal pathway, areas V3 and V4 and fields in the inferior temporal cortex were characterized by a distinct population of neurofilament-rich neurons in layers II-IIIa, whereas areas located in the parietal cortex and part of the occipitoparietal pathway had a consistent population of large labeled neurons in layer Va. The mediotemporal areas MT and MST displayed a distinct population of densely labeled neurons in layer VI. Quantitative analysis of the laminar distribution of the labeled neurons demonstrated that the visual cortical areas could be grouped in four hierarchical levels based on the ratio of neuron counts between infragranular and supragranular layers, with the first (areas V1, V2, V3, and V3A) and third (temporal and parietal regions) levels characterized by low ratios and the second (areas MT, MST, and V4) and fourth (frontal regions) levels characterized by high to very high ratios. Such density trends may correspond to differential representation of corticocortically (and corticosubcortically) projecting neurons at several functional steps in the integration of the visual stimuli. In this context, it is possible that neurofilament protein is crucial for the unique capacity of certain subsets of neurons to perform the highly precise mapping functions of the monkey visual system.

Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model

PubMed Central

Araki, Susumu; Imai, Shinji; Ishigaki, Hirohito; Mimura, Tomohiro; Nishizawa, Kazuya; Ueba, Hiroaki; Kumagai, Kousuke; Kubo, Mitsuhiko; Mori, Kanji; Ogasawara, Kazumasa; Matsusue, Yoshitaka

2015-01-01

Background and purpose Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. Methods Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). Results The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. Interpretation Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice. PMID:25175660

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

PubMed

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.

Testing for links between face color and age, dominance status, parity, weight, and intestinal nematode infection in a sample of female Japanese macaques.

PubMed

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

2017-01-01

Studies of the role of secondary sexual ornaments in mate choice tend to focus on colorful traits in males, but females of many animal species express colorful ornamentation too. Among non-human primates, investigations into the role of female secondary sexual traits as indicators of life history characteristics, reproductive success, and health status have mostly focused on sexual swellings, whereas only few studies have been conducted on the role of facial color. Recent studies on rhesus macaques and mandrills suggested that female ornamentation might provide information about female life history characteristics, but not on disease resistance factors and parasite infection, which have been shown to affect male ornamentation in some non-primate species. In Japanese macaques (Macaca fuscata), females have brightly colored faces that are indicative of their reproductive status. Here, we aimed to determine whether female facial color might also convey information about age, dominance rank, parity, weight, and intestinal nematode infection in free-ranging individuals. We analyzed whether female facial parameters (luminance and redness) were linked to these individual characteristics, using digital photography and data on intestinal parasite infection collected systematically during 1 month for each of seven free-ranging females. We found no evidence to suggest that female facial color is an indicator of any of these measures in Japanese macaques. Considering our small data set, it is still preliminary to draft any clear conclusions. Future studies combining digital, hormonal, parasitological and behavioral data are needed to assess the possible role of female face color on male preferences and mating choice in Japanese macaques.

Retinal, functional, and morphological comparisons of two different macaque species, Macaca mulatta and Macaca fasicularis, for models of laser eye injury

NASA Astrophysics Data System (ADS)

DiCarlo, Cheryl D.; Hacker, Henry D.; Brown, Araceli; Cheramie, Rachael; Martinsen, Gary L.; Rockwell, Benjamin; Stuck, Bruce E.

2005-04-01

The past several years has seen a severe shortage of pathogen-free Indian origin rhesus macaques due to the increased requirement for this model in retroviral research. With greater than 30 years of research data accumulated using the Rhesus macaque as the model for laser eye injury there exists a need to bridge to a more readily available nonhuman primate model. Much of the data previously collected from the Rhesus monkey (Macaca mulatta) provided the basis for the American National Standards Institute (ANSI) standards for laser safety. Currently a Tri-service effort is underway to utilize the Cynomolgus monkey (Macaca fasicularis) as a replacement for the Rhesus macaque. Preliminary functional and morphological baseline data collected from multifocal electroretinography (mfERG), optical coherence tomography (OCT) and retinal cell counts were compared from a small group of monkeys and tissues to determine if significant differences existed between the species. Initial functional findings rom mfERG yielded only one difference for the n2 amplitude value which was greater in the Cynomolgus monkey. No significant differences were seen in retinal and foveal thickness, as determined by OCT scans and no significant differences were seen in ganglion cell and inner nuclear cell nuclei counts. A highly significant difference was seen in the numbers of photoreceptor nuclei with greater numbers in the Rhesus macaque. This indicates more studies should be performed to determine the impact that a model change would have on the laser bioeffects community and their ability to continue to provide minimal visible lesion data for laser safety standards. The continued goal of this project will be to provide that necessary baseline information for a seamless transition to a more readily available animal model.

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

PubMed

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.

Predictive Value of Parkinsonian Primates in Pharmacologic Studies: A Comparison between the Macaque, Marmoset, and Squirrel Monkey.

PubMed

Veyres, Nicolas; Hamadjida, Adjia; Huot, Philippe

2018-05-01

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism, and psychosis. Three species have been used in most studies-the macaque, marmoset, and squirrel monkey-the last much less so than the first two species; however, the predictive value of each species at forecasting clinical efficacy, or lack thereof, is poorly documented. Here, we have reviewed all the published literature detailing pharmacologic studies that assessed the effects of experimental drugs on dyskinesia, parkinsonism, and psychosis in each of these species and have calculated their predictive value of success and failure at the clinical level. We found that, for dyskinesia, the macaque has a positive predictive value of 87.5% and a false-positive rate of 38.1%, whereas the marmoset has a positive predictive value of 76.9% and a false-positive rate of 15.6%. For parkinsonism, the macaque has a positive predictive value of 68.2% and a false-positive rate of 44.4%, whereas the marmoset has a positive predictive value of 86.9% and a false-positive rate of 41.7%. No drug that alleviates psychosis in the clinic has shown efficacy at doing so in the macaque, whereas the marmoset has 100% positive predictive value. The small number of studies conducted in the squirrel monkey precluded us from calculating its predictive efficacy. We hope our results will help in the design of pharmacologic experiments and will facilitate the drug discovery and development process in PD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Sensitive Detection of Francisella tularensis Directly from Whole Blood by Use of the GeneXpert System.

PubMed

Banada, Padmapriya P; Deshpande, Srinidhi; Chakravorty, Soumitesh; Russo, Riccardo; Occi, James; Meister, Gabriel; Jones, Kelly J; Gelhaus, Carl H; Valderas, Michelle W; Jones, Martin; Connell, Nancy; Alland, David

2017-01-01

Francisella tularensis is a potential bioterrorism agent that is highly infectious at very low doses. Diagnosis of tularemia by blood culture and nucleic acid-based diagnostic tests is insufficiently sensitive. Here, we demonstrate a highly sensitive F. tularensis assay that incorporates sample processing and detection into a single cartridge suitable for point-of-care detection. The assay limit of detection (LOD) and dynamic range were determined in a filter-based cartridge run on the GeneXpert system. F. tularensis DNA in buffer or CFU of F. tularensis was spiked into human or macaque blood. To simulate detection in human disease, the assay was tested on blood drawn from macaques infected with F. tularensis Schu S4 at daily intervals. Assay detection was compared to that with a conventional quantitative PCR (qPCR) assay and blood culture. The assay LOD was 0.1 genome equivalents (GE) per reaction and 10 CFU/ml F. tularensis in both human and macaque blood. In infected macaques, the assay detected F. tularensis on days 1 to 4 postinfection in 21%, 17%, 60%, and 83% of macaques, respectively, compared to conventional qPCR positivity rates of 0%, 0%, 30%, and 100% and CFU detection of blood culture at 0%, 0%, 0%, and 10% positive, respectively. Assay specificity was 100%. The new cartridge-based assay can rapidly detect F. tularensis in bloodstream infections directly in whole blood at the early stages of infection with a sensitivity that is superior to that of other methods. The simplicity of the automated testing procedures may make this test suitable for rapid point-of-care detection. Copyright © 2016 American Society for Microbiology.

Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque1

PubMed Central

Sumigama, Shiho; Mansell, Steven; Miller, Melissa; Lishko, Polina V.; Cherr, Gary N.; Meyers, Stuart A.; Tollner, Theodore

2015-01-01

During transit through the female reproductive tract, mammalian spermatozoa are exposed to increasing concentrations of progesterone (P4) released by the cumulus oophorus. P4 triggers massive calcium influx into human sperm through activation of the sperm-specific calcium channel CatSper. These properties of human spermatozoa are thought to be unique since CatSper is not progesterone sensitive in rodent sperm. Here, by performing patch clamp recording from spermatozoa from rhesus macaque for the first time, we report that they express P4-sensitive CatSper channel identically to human sperm and react to P4 by inducing responsiveness to zona pellucida, unlike human sperm, which respond directly to P4. We have also determined the physiologic levels of P4 capable of inducing capacitation-associated changes in macaque sperm. Progesterone (1 μM) induced up to a 3-fold increase in the percentage of sperm undergoing the zona pellucida-induced acrosome reaction with the lowest threshold as low as 10 nM of P4. Submicromolar levels of P4 induced a dose-dependent increase in curvilinear velocity and lateral head displacement, while sperm protein tyrosine phosphorylation was not altered. Macaque spermatozoa exposed to 10 μM of P4 developed fully hyperactivated motility. Similar to human sperm, on approaching cumulus mass and binding to zona pellucida, macaque spermatozoa display hyperactivation and undergo an acrosome reaction that coincides with the rise in the sperm intracellular calcium. Taken together, these data indicate that P4 accelerates the completion of capacitation and provides evidence of spermatozoa “priming” as they move into a gradient of progesterone in search for the oocyte. PMID:26490839

Expression of m1-type muscarinic acetylcholine receptors by parvalbumin-immunoreactive neurons in the primary visual cortex: a comparative study of rat, guinea pig, ferret, macaque, and human.

PubMed

Disney, Anita A; Reynolds, John H

2014-04-01

Cholinergic neuromodulation is a candidate mechanism for aspects of arousal and attention in mammals. We have reported previously that cholinergic modulation in the primary visual cortex (V1) of the macaque monkey is strongly targeted toward GABAergic interneurons, and in particular that the vast majority of parvalbumin-immunoreactive (PV) neurons in macaque V1 express the m1-type (pirenzepine-sensitive, Gq-coupled) muscarinic ACh receptor (m1AChR). In contrast, previous physiological data indicates that PV neurons in rats rarely express pirenzepine-sensitive muscarinic AChRs. To examine further this apparent species difference in the cholinergic effectors for the primary visual cortex, we have conducted a comparative study of the expression of m1AChRs by PV neurons in V1 of rats, guinea pigs, ferrets, macaques, and humans. We visualize PV- and mAChR-immunoreactive somata by dual-immunofluorescence confocal microscopy and find that the species differences are profound; the vast majority (>75%) of PV-ir neurons in macaques, humans, and guinea pigs express m1AChRs. In contrast, in rats only ∼25% of the PV population is immunoreactive for m1AChRs. Our data reveal that while they do so much less frequently than in primates, PV neurons in rats do express Gq-coupled muscarinic AChRs, which appear to have gone undetected in the previous in vitro studies. Data such as these are critical in determining the species that represent adequate models for the capacity of the cholinergic system to modulate inhibition in the primate cortex. Copyright © 2013 Wiley Periodicals, Inc.

Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment.

PubMed

Bissel, Stephanie J; Gurnsey, Kate; Jedema, Hank P; Smith, Nicholas F; Wang, Guoji; Bradberry, Charles W; Wiley, Clayton A

2018-02-01

Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuropathological or cellular basis of HAND. We sought to study the potential contribution of aging to the pathogenesis of HAND. Aged (range = 14.7-24.8 year) rhesus macaques of Chinese origin (RM-Ch) (n = 23) were trained to perform cognitive tasks. Macaques were then divided into four groups to assess the impact of SIVmac251 infection (n = 12) and combined antiretroviral therapy (CART) (5 infected; 5 mock-infected) on the execution of these tasks. Aged SIV-infected RM-Ch demonstrated significant plasma viremia and modest CSF viral loads but showed few clinical signs, no elevations of systemic temperature, and no changes in activity levels, platelet counts or weight. Concentrations of biomarkers of acute and chronic inflammation such as soluble CD14, CXCL10, IL-6 and TNF-α are known to be elevated following SIV infection of young adult macaques of several species, but concentrations of these biomarkers did not shift after SIV infection in aged RM-Ch and remained similar to mock-infected macaques. Neither acute nor chronic SIV infection or CART had a significant impact on accuracy, speed or percent completion in a sensorimotor test. Viremia in the absence of a chronic elevated inflammatory response seen in some aged RM-Ch is reminiscent of SIV infection in natural disease resistant hosts. The absence of cognitive impairment during SIV infection in aged RM-Ch might be in part attributed to diminishment of some facets of the immunological response. Additional study encompassing species and age differences is necessary to substantiate this hypothesis.

Effect of ovarian aging on androgen biosynthesis in a cynomolgus macaque model

PubMed Central

Ethun, K. F.; Wood, C. E.; Parker, C. R.; Kaplan, J. R.; Chen, H.; Appt, S. E.

2013-01-01

Objective The role of androgens in chronic disease pathogenesis, cognitive function and libido during menopause is of increasing interest. The aim of this study was to characterize the distribution and expression of androgenic proteins in the macaque ovary and to investigate the relationship between serum androgen concentrations, follicle number, and the persistence of androgenesis in the aging macaque ovary. Methods The subjects were 26 adult female cynomolgus macaques. Ovaries were immunostained for cytochrome P450 17α-hydroxylase/17–20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3βHSD), and cytochrome b5 (cytb5). Based on primordial follicle counts, animals were divided into tertiles (low (≤200), intermediate (226–1232), and high (2372–4356)) to evaluate differences in androgen staining and changes in serum androgen concentrations following ovariectomy. Results Positive immunostaining for P450c17 and cytb5 within the theca interna layer of growing follicles persisted in advanced atretic follicles and secondary interstitial cells (residual stromal cells). Ovaries with low follicle numbers had less staining for all androgenic proteins compared to ovaries with higher numbers of growing follicles. Immunostaining for cytb5 was the most reliable marker for persistent androgenesis in ovaries with minimal primordial follicle numbers (<100) and residual stromal cells. Following ovariectomy, a significant decrease in testosterone (−27.7%, −30.8%, −27.5%; p < 0.01) and androstenedione (−33.4%, −35.7%, −46.0%; p < 0.01) was observed in monkeys with low, intermediate, and high primordial follicle counts, respectively. Conclusions Despite low follicle numbers, the aging macaque ovary retains the necessary proteins for androgenesis within residual stromal cells and contributes to peripheral androgen concentrations. PMID:21864136

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

PubMed

Shimada, Masaki

2006-10-01

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

Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

PubMed Central

Jensen, Kara; dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R.; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R.; Hudgens, Michael G.; Amedee, Angela; Kozlowski, Pamela A.; Estes, Jacob D.; Lifson, Jeffrey D.; Van Rompay, Koen K. A.; Larsen, Michelle

2016-01-01

ABSTRACT Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID:27655885

Next-Generation Sequence Analysis of the Genome of RFHVMn, the Macaque Homolog of Kaposi's Sarcoma (KS)-Associated Herpesvirus, from a KS-Like Tumor of a Pig-Tailed Macaque

PubMed Central

Bruce, A. Gregory; Ryan, Jonathan T.; Thomas, Mathew J.; Peng, Xinxia; Grundhoff, Adam; Tsai, Che-Chung

2013-01-01

The complete sequence of retroperitoneal fibromatosis-associated herpesvirus Macaca nemestrina (RFHVMn), the pig-tailed macaque homolog of Kaposi's sarcoma-associated herpesvirus (KSHV), was determined by next-generation sequence analysis of a Kaposi's sarcoma (KS)-like macaque tumor. Colinearity of genes was observed with the KSHV genome, and the core herpesvirus genes had strong sequence homology to the corresponding KSHV genes. RFHVMn lacked homologs of open reading frame 11 (ORF11) and KSHV ORFs K5 and K6, which appear to have been generated by duplication of ORFs K3 and K4 after the divergence of KSHV and RFHV. RFHVMn contained positional homologs of all other unique KSHV genes, although some showed limited sequence similarity. RFHVMn contained a number of candidate microRNA genes. Although there was little sequence similarity with KSHV microRNAs, one candidate contained the same seed sequence as the positional homolog, kshv-miR-K12-10a, suggesting functional overlap. RNA transcript splicing was highly conserved between RFHVMn and KSHV, and strong sequence conservation was noted in specific promoters and putative origins of replication, predicting important functional similarities. Sequence comparisons indicated that RFHVMn and KSHV developed in long-term synchrony with the evolution of their hosts, and both viruses phylogenetically group within the RV1 lineage of Old World primate rhadinoviruses. RFHVMn is the closest homolog of KSHV to be completely sequenced and the first sequenced RV1 rhadinovirus homolog of KSHV from a nonhuman Old World primate. The strong genetic and sequence similarity between RFHVMn and KSHV, coupled with similarities in biology and pathology, demonstrate that RFHVMn infection in macaques offers an important and relevant model for the study of KSHV in humans. PMID:24109218

Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques

PubMed Central

Amedee, Angela M.; Nichols, Whitney A.; LeCapitaine, Nicole J.; Stouwe, Curtis Vande; Birke, Leslie L.; Lacour, Nedra; Winsauer, Peter J.

2014-01-01

Abstract Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ9-THC dronabinol). Previously, we demonstrated that chronic Δ9-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ9-THC (0.18–0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by Δ9-THC compared to control females; however, females that received chronic Δ9-THC did not gain as much weight as control animals. In addition, Δ9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID:25113915

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

PubMed Central

Seltmann, Anne; Majolo, Bonaventura

2013-01-01

Social animals have to coordinate activities and collective movements to benefit from the advantages of group living. Animals in large groups maintain cohesion by self-organization processes whereas in smaller groups consensus decisions can be reached. Where consensus decisions are relevant leadership may emerge. Variation in the organization of collective movements has been linked to variation in female social tolerance among macaque species ranging from despotic to egalitarian. Here we investigated the processes underlying group movements in a wild macaque species characterized by a degree of social tolerance intermediate to previously studied congeneric species. We focused on processes before, during and after the departure of the first individual. To this end, we observed one group of wild Barbary macaques (Macaca sylvanus) in the Middle Atlas, Morocco using all-occurrence behaviour sampling of 199 collective movements. We found that initiators of a collective movement usually chose the direction in which more individuals displayed pre-departure behavior. Dominant individuals contributed to group movements more than subordinates, especially juveniles, measured as frequencies of successful initiations and pre-departure behaviour. Joining was determined by affiliative relationships and the number of individuals that already joined the movement (mimetism). Thus, in our study group partially shared consensus decisions mediated by selective mimetism seemed to be prevalent, overall supporting the suggestion that a species’ social style affects the organization of group movements. As only the most tolerant species show equally shared consensus decisions whereas in others the decision is partially shared with a bias to dominant individuals the type of consensus decisions seems to follow a stepwise relation. Joining order may also follow a stepwise, however opposite, relationship, because dominance only determined joining in highly despotic, but not in intermediate and tolerant species. PMID:23805305

Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

PubMed

Saunders, Kevin O; Santra, Sampa; Parks, Robert; Yates, Nicole L; Sutherland, Laura L; Scearce, Richard M; Balachandran, Harikrishnan; Bradley, Todd; Goodman, Derrick; Eaton, Amanda; Stanfield-Oakley, Sherry A; Tartaglia, James; Phogat, Sanjay; Pantaleo, Giuseppe; Esteban, Mariano; Gomez, Carmen E; Perdiguero, Beatriz; Jacobs, Bertram; Kibler, Karen; Korber, Bette; Montefiori, David C; Ferrari, Guido; Vandergrift, Nathan; Liao, Hua-Xin; Tomaras, Georgia D; Haynes, Barton F

2018-04-15

A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge. IMPORTANCE The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model. Copyright © 2018 American Society for Microbiology.

SIV/Macaque Model of HIV Infection in Cocaine Users: Minimal Effects of Cocaine on Behavior, Virus Replication, and CNS Inflammation

PubMed Central

Weed, Michael; Adams, Robert J.; Hienz, Robert D.; Meulendyke, Kelly A.; Linde, Michael E.; Clements, Janice E.; Mankowski, Joseph L.; Zink, M. Christine

2011-01-01

Studies of the effects of drugs of abuse on HIV immune status, disease progression, and neuroAIDS have produced conflicting data and have not definitively shown whether this combination promotes cognitive impairment or disease progression. Using a consistent SIV–macaque model, we investigated the effects of cocaine on behavior, virologic parameters, and CNS inflammation. Macaques received either vehicle or chronic administration of behaviorally active doses of cocaine (1.7 or 3.2 mg/kg/day). Chronic cocaine administration reduced CD8+ T cell counts during acute and late stage infection but had no effect on CD4+ T cell counts. Low-dose cocaine-treated animals had lower CSF vRNA levels late in infection, but cocaine did not alter plasma viral load or vRNA or protein in brain. There were no differences in CSF CCL-2 or interleukin (IL)-6 levels or severity of encephalitis in cocaine-treated as compared to vehicle-treated macaques. There were no differences in brain inflammation or neurodegeneration markers, as determined by interferon (IFN)-β, MxA, CCL2, IL-6, TNFα, IFNγ, and indolamine 2,3-deoxygenase mRNA levels. APP levels also were not altered. The executive function of inhibitory control was not impaired in cocaine-treated or control animals following SIV infection. However, animals receiving 3.2 mg/kg/day cocaine performed more slowly in a bimanual motor test. Thus, chronic administration of cocaine produced only minor changes in behavior, encephalitis severity, CNS inflammation/neurodegeneration, and virus replication in SIV-infected pigtailed macaques, suggesting that cocaine would have only modest effects on the progression of neuroAIDS in HIV-infected individuals. PMID:21626125

Of stones and monkeys: testing ecological constraints on stone handling, a behavioral tradition in Japanese macaques.

PubMed

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

2008-02-01

Japanese macaques are known to manipulate stones by displaying various seemingly functionless behavioral patterns, including carrying a stone, rubbing two stones together, or gathering several stones into a pile. This form of solitary object play called stone handling (SH) is a behavioral tradition in Japanese macaques, showing striking intertroop differences in frequency and form. Here, we evaluated two ecologically based hypotheses invoked to account for these differences. We hypothesized that the occurrence and form of SH would be affected by stone availability and the degree of terrestriality. We used standardized sampling methods to assess differences in SH and terrestriality among four captive and six free-ranging troops of Japanese macaques, and determine site-specific stone availability. Although we demonstrated that SH is almost exclusively a terrestrial activity, our comparative analyses showed that the number of stones readily available and the relative amount of time spent on the ground by the macaques were not associated with the intertroop differences in the occurrence of SH. Failure to accept the terrestriality and stone availability hypotheses suggests that the performance of SH and the motivation to engage in this activity are both more diverse and more complex than the direct links to time spent on the ground or the number of stones locally available. Other environmental influences and sociodemographic factors should be jointly considered to identify the sources of variation in SH, as a beginning to better understand the constraints on the appearance and subsequent diffusion of stone-use traditions in nonhuman primates. Am J Phys Anthropol, 2008. (c) 2007 Wiley-Liss, Inc. Copyright 2007 Wiley-Liss, Inc.

Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

PubMed Central

Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

2015-01-01

Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P < 0.001). Notably, ILC3 could be induced to undergo apoptosis by microbial products through the TLR2 (lipoteichoic acid) and/or TLR4 (LPS) pathway. These findings indicated that persistent microbial translocation may result in loss of ILC3 in lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

PubMed

Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

2018-06-01

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.