Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis).

PubMed

Colagross-Schouten, Angela M; Canfield, Don R

2015-12-01

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

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.

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

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

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

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.

The Laplacian spectrum of neural networks

PubMed Central

de Lange, Siemon C.; de Reus, Marcel A.; van den Heuvel, Martijn P.

2014-01-01

The brain is a complex network of neural interactions, both at the microscopic and macroscopic level. Graph theory is well suited to examine the global network architecture of these neural networks. Many popular graph metrics, however, encode average properties of individual network elements. Complementing these “conventional” graph metrics, the eigenvalue spectrum of the normalized Laplacian describes a network's structure directly at a systems level, without referring to individual nodes or connections. In this paper, the Laplacian spectra of the macroscopic anatomical neuronal networks of the macaque and cat, and the microscopic network of the Caenorhabditis elegans were examined. Consistent with conventional graph metrics, analysis of the Laplacian spectra revealed an integrative community structure in neural brain networks. Extending previous findings of overlap of network attributes across species, similarity of the Laplacian spectra across the cat, macaque and C. elegans neural networks suggests a certain level of consistency in the overall architecture of the anatomical neural networks of these species. Our results further suggest a specific network class for neural networks, distinct from conceptual small-world and scale-free models as well as several empirical networks. PMID:24454286

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.

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.

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

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.

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.

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.

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

Preclinical Assessment of CD171-Directed CAR T-cell Adoptive Therapy for Childhood Neuroblastoma: CE7 Epitope Target Safety and Product Manufacturing Feasibility.

PubMed

Künkele, Annette; Taraseviciute, Agne; Finn, Laura S; Johnson, Adam J; Berger, Carolina; Finney, Olivia; Chang, Cindy A; Rolczynski, Lisa S; Brown, Christopher; Mgebroff, Stephanie; Berger, Michael; Park, Julie R; Jensen, Michael C

2017-01-15

The identification and vetting of cell surface tumor-restricted epitopes for chimeric antigen receptor (CAR)-redirected T-cell immunotherapy is the subject of intensive investigation. We have focused on CD171 (L1-CAM), an abundant cell surface molecule on neuroblastomas and, specifically, on the glycosylation-dependent tumor-specific epitope recognized by the CE7 monoclonal antibody. CD171 expression was assessed by IHC using CE7 mAb in tumor microarrays of primary, metastatic, and recurrent neuroblastoma, as well as human and rhesus macaque tissue arrays. The safety of targeting the CE7 epitope of CD171 with CE7-CAR T cells was evaluated in a preclinical rhesus macaque trial on the basis of CD171 homology and CE7 cross reactivity. The feasibility of generating bioactive CAR T cells from heavily pretreated pediatric patients with recurrent/refractory disease was assessed. CD171 is uniformly and abundantly expressed by neuroblastoma tumor specimens obtained at diagnoses and relapse independent of patient clinical risk group. CD171 expression in normal tissues is similar in humans and rhesus macaques. Infusion of up to 1 × 10 8 /kg CE7-CAR + CTLs in rhesus macaques revealed no signs of specific on-target off-tumor toxicity. Manufacturing of lentivirally transduced CD4 + and CD8 + CE7-CAR T-cell products under GMP was successful in 4 out of 5 consecutively enrolled neuroblastoma patients in a phase I study. All four CE7-CAR T-cell products demonstrated in vitro and in vivo antitumor activity. Our preclinical assessment of the CE7 epitope on CD171 supports its utility and safety as a CAR T-cell target for neuroblastoma immunotherapy. Clin Cancer Res; 23(2); 466-77. ©2016 AACR. ©2016 American Association for Cancer Research.

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.

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

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

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.

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.

Attention and normalization circuits in macaque V1

PubMed Central

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

2015-01-01

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

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

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.

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

PubMed

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

2013-10-01

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

[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)].

PubMed

Toledano, A; Álvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

2014-01-01

In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;<30% in macaques). The differences between normal and pathological (Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

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

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

Abdominal Lipomatosis with Secondary Self-Strangulation of Masses in an Adult Rhesus Macaque (Macaca mulatta)

PubMed Central

Chum, Helen H; Long, C Tyler; McKeon, Gabriel P; Chang, Angela G; Luong, Richard H; Albertelli, Megan A

2014-01-01

An 10-y-old, intact male rhesus macaque (Macaca mulatta) presented for bilateral scrotal swelling and a distended abdomen. A soft mass in the left upper quadrant of the abdomen was palpated. A barium study did not reveal any gastrointestinal abnormalities. Exploratory laparotomy revealed a large (1.25 kg, 15.0 × 13.0 × 9.5 cm), red and tan, soft, circumscribed, spherical mass within the greater omentum and 10 to 20 smaller (diameter, 1 to 4 cm), soft to firm masses in the mesentery and greater omentum. The resected mass was a self-strangulating abdominal lipoma, a pedunculated neoplasm composed of white adipocytes arising from peritoneal adipose tissue undergoing secondary coagulation necrosis after strangulation of the blood supply due to twisting of the mass around the peduncle. The smaller masses were histologically consistent with simple or self-strangulating pedunculated abdominal lipomas. The macaque presented again 9 mo later with a firm, 5.0-cm mass in the midabdomen, with intestinal displacement visible on radiographs. Given this animal's medical history and questionable prognosis, euthanasia was elected. Necropsy revealed numerous, multifocal to coalescing, 1.0- to 15.0-cm, pale tan to yellow, circumscribed, soft to firm, spherical to ellipsoid, pedunculated masses that were scattered throughout the mesentery, greater omentum, lesser omentum, and serosal surfaces of the gastrointestinal tract. All of the masses were pedunculated abdominal lipomas, and most demonstrated coagulation necrosis due to self-strangulation of the blood supply. To our knowledge, this report is the first to describe abdominal lipomatosis with secondary self-strangulation of masses in a rhesus macaque. PMID:25402181

Reactive amyloidosis associated with ischial callosititis: a report with histology of ischial callosities in rhesus macaques (Macaca mulatta).

PubMed

Liu, David X; Gilbert, Margaret H; Wang, Xiaolei; Didier, Peter J; Veazey, Ronald S

2012-11-01

Ischial callosities have received little attention in veterinary medicine even though they are distinguishing anatomic organs. The organs are characterized by a pair of hairless pads of thickened epidermis, located bilaterally in the gluteal region, which overlay the tuberosities of the ischia of all Old World monkeys, gibbons, and siamangs. The current report describes a case of reactive amyloidosis associated with ischial callosititis in a rhesus macaque (Macaca mulatta). Amyloid A (AA) protein was found in the liver, spleen, small intestine, mesenteric lymph nodes, and ischial callosities by histology, Congo red stain, and immunohistochemistry. Confocal microscopy showed that many cluster of differentiation (CD)68-positive macrophages within the ischial callosities contained intracellular AA protein, which suggests that CD68-positive macrophages have an important role in the pathogenesis of reactive amyloidosis in nonhuman primates. The normal histology of ischial callosities of rhesus macaques is also documented in this report.

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

Attention and normalization circuits in macaque V1.

PubMed

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

2015-04-01

Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

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.

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

PubMed Central

Shooner, Christopher; Kelly, Jenna G.; García-Marín, Virginia; Movshon, J. Anthony; Kiorpes, Lynne

2017-01-01

In amblyopia, a visual disorder caused by abnormal visual experience during development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted by interocular suppression. We used 96-electrode arrays to record neurons and neuronal groups in areas V1 and V2 of six female macaque monkeys (Macaca nemestrina) made amblyopic by artificial strabismus or anisometropia in early life, as well as two visually normal female controls. To measure suppressive binocular interactions directly, we recorded neuronal responses to dichoptic stimulation. We stimulated both eyes simultaneously with large sinusoidal gratings, controlling their contrast independently with raised-cosine modulators of different orientations and spatial frequencies. We modeled each eye's receptive field at each cortical site using a difference of Gaussian envelopes and derived estimates of the strength of central excitation and surround suppression. We used these estimates to calculate ocular dominance separately for excitation and suppression. Excitatory drive from the FE dominated amblyopic visual cortex, especially in more severe amblyopes, but suppression from both the FE and AEs was prevalent in all animals. This imbalance created strong interocular suppression in deep amblyopes: increasing contrast in the AE decreased responses at binocular cortical sites. These response patterns reveal mechanisms that likely contribute to the interocular suppression that disrupts vision in amblyopes. SIGNIFICANCE STATEMENT Amblyopia is a developmental visual disorder that alters both monocular vision and binocular interaction. Using microelectrode arrays, we examined binocular interaction in primary visual cortex and V2 of six amblyopic macaque monkeys (Macaca nemestrina) and two visually normal controls. By stimulating the eyes dichoptically, we showed that, in amblyopic cortex, the binocular combination of signals is altered. The excitatory influence of the two eyes is imbalanced to a degree that can be predicted from the severity of amblyopia, whereas suppression from both eyes is prevalent in all animals. This altered balance of excitation and suppression reflects mechanisms that may contribute to the interocular perceptual suppression that disrupts vision in amblyopes. PMID:28743725

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

PubMed

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

2017-08-23

In amblyopia, a visual disorder caused by abnormal visual experience during development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted by interocular suppression. We used 96-electrode arrays to record neurons and neuronal groups in areas V1 and V2 of six female macaque monkeys ( Macaca nemestrina ) made amblyopic by artificial strabismus or anisometropia in early life, as well as two visually normal female controls. To measure suppressive binocular interactions directly, we recorded neuronal responses to dichoptic stimulation. We stimulated both eyes simultaneously with large sinusoidal gratings, controlling their contrast independently with raised-cosine modulators of different orientations and spatial frequencies. We modeled each eye's receptive field at each cortical site using a difference of Gaussian envelopes and derived estimates of the strength of central excitation and surround suppression. We used these estimates to calculate ocular dominance separately for excitation and suppression. Excitatory drive from the FE dominated amblyopic visual cortex, especially in more severe amblyopes, but suppression from both the FE and AEs was prevalent in all animals. This imbalance created strong interocular suppression in deep amblyopes: increasing contrast in the AE decreased responses at binocular cortical sites. These response patterns reveal mechanisms that likely contribute to the interocular suppression that disrupts vision in amblyopes. SIGNIFICANCE STATEMENT Amblyopia is a developmental visual disorder that alters both monocular vision and binocular interaction. Using microelectrode arrays, we examined binocular interaction in primary visual cortex and V2 of six amblyopic macaque monkeys ( Macaca nemestrina ) and two visually normal controls. By stimulating the eyes dichoptically, we showed that, in amblyopic cortex, the binocular combination of signals is altered. The excitatory influence of the two eyes is imbalanced to a degree that can be predicted from the severity of amblyopia, whereas suppression from both eyes is prevalent in all animals. This altered balance of excitation and suppression reflects mechanisms that may contribute to the interocular perceptual suppression that disrupts vision in amblyopes. Copyright © 2017 the authors 0270-6474/17/378216-11$15.00/0.

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.

Integrated network analysis reveals a novel role for the cell cycle in 2009 pandemic influenza virus-induced inflammation in macaque lungs

PubMed Central

2012-01-01

Background Annually, influenza A viruses circulate the world causing wide-spread sickness, economic loss, and death. One way to better defend against influenza virus-induced disease may be to develop novel host-based therapies, targeted at mitigating viral pathogenesis through the management of virus-dysregulated host functions. However, mechanisms that govern aberrant host responses to influenza virus infection remain incompletely understood. We previously showed that the pandemic H1N1 virus influenza A/California/04/2009 (H1N1; CA04) has enhanced pathogenicity in the lungs of cynomolgus macaques relative to a seasonal influenza virus isolate (A/Kawasaki/UTK-4/2009 (H1N1; KUTK4)). Results Here, we used microarrays to identify host gene sequences that were highly differentially expressed (DE) in CA04-infected macaque lungs, and we employed a novel strategy – combining functional and pathway enrichment analyses, transcription factor binding site enrichment analysis and protein-protein interaction data – to create a CA04 differentially regulated host response network. This network describes enhanced viral RNA sensing, immune cell signaling and cell cycle arrest in CA04-infected lungs, and highlights a novel, putative role for the MYC-associated zinc finger (MAZ) transcription factor in regulating these processes. Conclusions Our findings suggest that the enhanced pathology is the result of a prolonged immune response, despite successful virus clearance. Most interesting, we identify a mechanism which normally suppresses immune cell signaling and inflammation is ineffective in the pH1N1 virus infection; a dyregulatory event also associated with arthritis. This dysregulation offers several opportunities for developing strain-independent, immunomodulatory therapies to protect against future pandemics. PMID:22937776

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.

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.

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.

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.

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

Reactive amyloidosis associated with ischial callosititis: a report with histology of ischial callosities in rhesus macaques (Macaca mulatta)

PubMed Central

Liu, David X.; Gilbert, Margaret H.; Wang, Xiaolei; Didier, Peter J.; Veazey, Ronald S.

2014-01-01

Ischial callosities have received little attention in veterinary medicine even though they are distinguishing anatomic organs. The organs are characterized by a pair of hairless pads of thickened epidermis, located bilaterally in the gluteal region, which overlay the tuberosities of the ischia of all Old World monkeys, gibbons, and siamangs. The current report describes a case of reactive amyloidosis associated with ischial callosititis in a rhesus macaque (Macaca mulatta). Amyloid A (AA) protein was found in the liver, spleen, small intestine, mesenteric lymph nodes, and ischial callosities by histology, Congo red stain, and immunohistochemistry. Confocal microscopy showed that many cluster of differentiation (CD)68-positive macrophages within the ischial callosities contained intracellular AA protein, which suggests that CD68-positive macrophages have an important role in the pathogenesis of reactive amyloidosis in nonhuman primates. The normal histology of ischial callosities of rhesus macaques is also documented in this report. PMID:23104953

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.

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.

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

Ulcerative cheilitis in a rhesus macaque.

PubMed

Bailey, C C; Miller, A D

2012-03-01

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

Abdominal cysticercosis in a rhesus macaque (Macaca mulatta).

PubMed

Hobbs, Theodore R; Colgin, Lois M A; Maginnis, Gwendalyn M; Lewis, Anne D

2003-10-01

A mid-abdominal mass was discovered during routine physical examination of a rhesus macaque (Macaca mulatta). Further diagnostics and exploratory laparotomy were performed, revealing a fluid-filled cyst attached to the caudal free margin of the greater omentum. Formation and pulsatile movement of white-colored circumferential bands within the wall of the cyst were observed during surgery. The cyst was removed and later was dissected. The discovery of a single invaginated scolex identified the cyst as a cysticercus. The location and characteristics of the cysticercus were consistent with the larval form of Taenia hydatigena.

Ulcerative Cheilitis in a Rhesus Macaque

PubMed Central

Bailey, C. C.; Miller, A. D.

2011-01-01

A two-year-old, female, simian immunodeficiency virus E543-infected rhesus macaque (Macaca mulatta) was presented for necropsy following euthanasia due to a history of diarrhea, weight loss, and a small, round ulcer along the left labial commisure. Histopathologic examination of the ulcer revealed infiltration by large numbers of degenerate and non-degenerate neutrophils and macrophages admixed with syncytial epithelial cells. Rare epithelial cells contained herpetic inclusion bodies. These cells stained positive for Human herpesvirus 1 via immunohistochemistry and DNA sequencing confirmed the presence of closely related Macacine herpesvirus 1 (B virus). PMID:21383117

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.

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.

The influence of phylogeny, social style, and sociodemographic factors on macaque social network structure.

PubMed

Balasubramaniam, Krishna N; Beisner, Brianne A; Berman, Carol M; De Marco, Arianna; Duboscq, Julie; Koirala, Sabina; Majolo, Bonaventura; MacIntosh, Andrew J; McFarland, Richard; Molesti, Sandra; Ogawa, Hideshi; Petit, Odile; Schino, Gabriele; Sosa, Sebastian; Sueur, Cédric; Thierry, Bernard; de Waal, Frans B M; McCowan, Brenda

2018-01-01

Among nonhuman primates, the evolutionary underpinnings of variation in social structure remain debated, with both ancestral relationships and adaptation to current conditions hypothesized to play determining roles. Here we assess whether interspecific variation in higher-order aspects of female macaque (genus: Macaca) dominance and grooming social structure show phylogenetic signals, that is, greater similarity among more closely-related species. We use a social network approach to describe higher-order characteristics of social structure, based on both direct interactions and secondary pathways that connect group members. We also ask whether network traits covary with each other, with species-typical social style grades, and/or with sociodemographic characteristics, specifically group size, sex-ratio, and current living condition (captive vs. free-living). We assembled 34-38 datasets of female-female dyadic aggression and allogrooming among captive and free-living macaques representing 10 species. We calculated dominance (transitivity, certainty), and grooming (centrality coefficient, Newman's modularity, clustering coefficient) network traits as aspects of social structure. Computations of K statistics and randomization tests on multiple phylogenies revealed moderate-strong phylogenetic signals in dominance traits, but moderate-weak signals in grooming traits. GLMMs showed that grooming traits did not covary with dominance traits and/or social style grade. Rather, modularity and clustering coefficient, but not centrality coefficient, were strongly predicted by group size and current living condition. Specifically, larger groups showed more modular networks with sparsely-connected clusters than smaller groups. Further, this effect was independent of variation in living condition, and/or sampling effort. In summary, our results reveal that female dominance networks were more phylogenetically conserved across macaque species than grooming networks, which were more labile to sociodemographic factors. Such findings narrow down the processes that influence interspecific variation in two core aspects of macaque social structure. Future directions should include using phylogeographic approaches, and addressing challenges in examining the effects of socioecological factors on primate social structure. © 2017 Wiley Periodicals, Inc.

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.

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.

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.

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.

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

Daily Rhythm in Plasma N-Acetyltryptamine

PubMed Central

Backlund, Peter S.; Urbanski, Henryk F.; Doll, Mark A.; Hein, David W.; Bozinoski, Marjan; Mason, Christopher E.; Coon, Steven L.; Klein, David C.

2017-01-01

Normal physiology undergoes 24-hour changes in function, that include daily rhythms in circulating/hormones, most notably melatonin and cortical steroids. This study focuses on N-acetyltryptamine, a little-studied melatonin receptor mixed agonist/antagonist and the likely evolutionary precursor of melatonin. The central issue addressed was whether N-acetyltryptamine is physiologically present in the circulation. N-Acetyltrypamine was detected by LC-MS/MS in daytime plasma of three different mammals in subnanomolar levels (mean ± SEM: rat, 0.29 ± 0.05 nM, N=5; rhesus macaque, 0.54 ± 0.24 nM, N=4; human, 0.03 ± 0.01 nM, N=32). Twenty four hour blood collections from rhesus macaques revealed a nocturnal increase in plasma N-acetyltryptamine (P < 0.001), which varied from 2- to 15- fold over daytime levels among the four animals studied. Related RNA sequencing studies indicated that the transcript encoding the tryptamine acetylating enzyme arylalkylamine N-acetyltransferase (AANAT) is expressed at similar levels in the rhesus pineal gland and retina, thereby indicating that either tissue could contribute to circulating N-acetyltryptamine. The evidence that N-acetyltryptamine is a physiological component of mammalian blood and exhibits a daily rhythm, together with known effects as a melatonin receptor ligand shifts the status of N-acetyltryptamine from pharmacological tool to that of a candidate for a physiological role. This provides a new opportunity to extend our understanding of 24-hour biology. PMID:28466676

The Evolving MCART Multimodal Imaging Core: Establishing a protocol for Computed Tomography and Echocardiography in the Rhesus macaque to perform longitudinal analysis of radiation-induced organ injury

PubMed Central

de Faria, Eduardo B.; Barrow, Kory R.; Ruehle, Bradley T.; Parker, Jordan T.; Swartz, Elisa; Taylor-Howell, Cheryl; Kieta, Kaitlyn M.; Lees, Cynthia J.; Sleeper, Meg M.; Dobbin, Travis; Baron, Adam D.; Mohindra, Pranshu; MacVittie, Thomas J.

2015-01-01

Computed Tomography (CT) and Echocardiography (EC) are two imaging modalities that produce critical longitudinal data that can be analyzed for radiation-induced organ-specific injury to the lung and heart. The Medical Countermeasures Against Radiological Threats (MCART) consortium has a well-established animal model research platform that includes nonhuman primate (NHP) models of the acute radiation syndrome and the delayed effects of acute radiation exposure. These models call for a definition of the latency, incidence, severity, duration, and resolution of different organ-specific radiation-induced subsyndromes. The pulmonary subsyndromes and cardiac effects are a pair of inter-dependent syndromes impacted by exposure to potentially lethal doses of radiation. Establishing a connection between these will reveal important information about their interaction and progression of injury and recovery. Herein, we demonstrate the use of CT and EC data in the rhesus macaque models to define delayed organ injury thereby establishing: a) consistent and reliable methodology to assess radiation-induced damage to the lung and heart, b) an extensive database in normal age-matched NHP for key primary and secondary endpoints, c) identified problematic variables in imaging techniques and proposed solutions to maintain data integrity and d) initiated longitudinal analysis of potentially lethal radiation-induced damage to the lung and heart. PMID:26425907

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

PubMed

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

2017-11-01

The biogeographical history of Southeast Asia is complicated due to the continuous emergences and disappearances of land bridges throughout the Pleistocene. Here, we use long-tailed macaques (Macaca fascicularis), which are widely distributed throughout the mainland and islands of Southeast Asia, asa model for better understanding the biogeographical patterns of diversification in this geographically complex region. A reliable intraspecific phylogeny including individuals from localities on oceanic islands, continental islands, and the mainland is needed to trace relatedness along with the pattern and timing of colonization in this region. We used high-throughput sequencing techniques to sequence mitochondrial genomes (mitogenomes) from 95 Southeast Asian M. fascicularis specimens housed at natural history museums around the world. To achieve a comprehensive picture, we more than tripled the mitogenome sample size for M. fascicularis from previous studies, and for the first time included documented samples from the Philippines and several small Indonesian islands. Confirming the result from a previous, recent intraspecific phylogeny for M. fascicularis, the newly reconstructed phylogeny of 135 specimens divides the samples into two major clades: Clade A includes haplotypes from the mainland and some from northern Sumatra, while Clade B includes all insular haplotypes along with lineages from southern Sumatra. This study resolves a previous disparity by revealing a disjunction in the origin of Sumatran macaques, with separate lineages originating within the two major clades, suggesting that at least two major migrations to Sumatra occurred. However, our dated phylogeny reveals that the two major clades split ∼1.88Ma, which is earlier than in previously published phylogenies. Our new data reveal that most Philippine macaque lineages diverged from the Borneo stock within the last ∼0.06-0.43Ma. Finally, our study provides insight into successful sequencing of DNA across museums and shotgun sequencing of DNA specimens asa method to sequence the mitogenome. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

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. PMID:29372120

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection.

PubMed

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A; Veazey, Ronald S

2007-02-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)-infected adult macaques and human immunodeficiency virus (HIV)-infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that "activated" central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection

PubMed Central

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2007-01-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)–infected adult macaques and human immunodeficiency virus (HIV)–infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that “activated” central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques. PMID:17047153

Division of Labor in Hand Usage Is Associated with Higher Hand Performance in Free-Ranging Bonnet Macaques, Macaca radiata

PubMed Central

Mangalam, Madhur; Desai, Nisarg; Singh, Mewa

2015-01-01

A practical approach to understanding lateral asymmetries in body, brain, and cognition would be to examine the performance advantages/disadvantages associated with the corresponding functions and behavior. In the present study, we examined whether the division of labor in hand usage, marked by the preferential usage of the two hands across manual operations requiring maneuvering in three-dimensional space (e.g., reaching for food, grooming, and hitting an opponent) and those requiring physical strength (e.g., climbing), is associated with higher hand performance in free-ranging bonnet macaques, Macaca radiata. We determined the extent to which the macaques exhibit laterality in hand usage in an experimental unimanual and a bimanual food-reaching task, and the extent to which manual laterality is associated with hand performance in an experimental hand-performance-differentiation task. We observed negative relationships between (a) the latency in food extraction by the preferred hand in the hand-performance-differentiation task (wherein, lower latency implies higher performance), the preferred hand determined using the bimanual food-reaching task, and the normalized difference between the performance of the two hands, and (b) the normalized difference between the performance of the two hands and the absolute difference between the laterality in hand usage in the unimanual and the bimanual food-reaching tasks (wherein, lesser difference implies higher manual specialization). Collectively, these observations demonstrate that the division of labor between the two hands is associated with higher hand performance. PMID:25806511

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

PubMed

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

2013-01-01

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

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.

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

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

Multiple adaptable mechanisms early in the primate visual pathway

PubMed Central

Dhruv, Neel T.; Tailby, Chris; Sokol, Sach H.; Lennie, Peter

2011-01-01

We describe experiments that isolate and characterize multiple adaptable mechanisms that influence responses of orientation-selective neurons in primary visual cortex (V1) of anesthetized macaque (Macaca fascicularis). The results suggest that three adaptable stages of machinery shape neural responses in V1: a broadly-tuned early stage and a spatio-temporally tuned later stage, both of which provide excitatory input, and a normalization pool that is also broadly tuned. The early stage and the normalization pool are revealed by adapting gratings that themselves fail to evoke a response from the neuron: either low temporal frequency gratings at the null orientation or gratings of any orientation drifting at high temporal frequencies. When effective, adapting stimuli that altered the sensitivity of these two mechanisms caused reductions of contrast gain and often brought about a paradoxical increase in response gain due to a relatively greater desensitization of the normalization pool. The tuned mechanism is desensitized only by stimuli well-matched to a neuron’s receptive field. We could thus infer desensitization of the tuned mechanism by comparing effects obtained with adapting gratings of preferred and null orientation modulated at low temporal frequencies. PMID:22016535

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

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

PubMed Central

Baker, Kate; Lauder, Abigail; Kim, Dorothy; Bailey, Aubrey; Wu, Gary D.; Collman, Ronald G.; Doyle-Meyers, Lara; Russell-Lodrigue, Kasi; Blanchard, James; Bushman, Frederic D.; Bohm, Rudolf

2018-01-01

Idiopathic chronic enterocolitis (ICE) is one of the most commonly encountered and difficult to manage diseases of captive rhesus macaques (Macaca mulatta). The etiology is not well understood, but perturbations in gut microbial communities have been implicated. Here we evaluated the effects of a 14-day course of vancomycin, neomycin, and fluconazole on animals affected with ICE, comparing treated, untreated, and healthy animals. We performed microbiome analysis on duodenal and colonic mucosal samples and feces in order to probe bacterial and/or fungal taxa potentially associated with ICE. All treated animals showed a significant and long-lasting improvement in stool consistency over time when compared to untreated and healthy controls. Microbiome analysis revealed trends associating bacterial community composition with ICE, particularly lineages of the Lactobacillaceae family. Sequencing of DNA from macaque food biscuits revealed that fungal sequences recovered from stool were dominated by yeast-derived food additives; in contrast, bacteria in stool appeared to be authentic gut residents. In conclusion, while validation in larger cohorts is needed, the treatment described here was associated with significantly improved clinical signs; results suggested possible correlates of microbiome structure with disease, though no strong associations were detected between single microbes and ICE. PMID:29666764

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

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

PubMed

Tian, Guang; Qiu, Yefeng; Qi, Zhizhen; Wu, Xiaohong; Zhang, Qingwen; Bi, Yujing; Yang, Yonghai; Li, Yuchuan; Yang, Xiaoyan; Xin, Youquan; Li, Cunxiang; Cui, Baizhong; Wang, Zuyun; Wang, Hu; Yang, Ruifu; Wang, Xiaoyi

2011-04-29

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

Transduction of Photoreceptors With Equine Infectious Anemia Virus Lentiviral Vectors: Safety and Biodistribution of StarGen for Stargardt Disease

PubMed Central

Binley, Katie; Widdowson, Peter; Loader, Julie; Kelleher, Michelle; Iqball, Sharifah; Ferrige, Georgina; de Belin, Jackie; Carlucci, Marie; Angell-Manning, Diana; Hurst, Felicity; Ellis, Scott; Miskin, James; Fernandes, Alcides; Wong, Paul; Allikmets, Rando; Bergstrom, Christopher; Aaberg, Thomas; Yan, Jiong; Kong, Jian; Gouras, Peter; Prefontaine, Annick; Vezina, Mark; Bussieres, Martin; Naylor, Stuart; Mitrophanous, Kyriacos A.

2013-01-01

Purpose. StarGen is an equine infectious anemia virus (EIAV)-based lentiviral vector that expresses the photoreceptor-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STGD1), a juvenile macular dystrophy. EIAV vectors are able to efficiently transduce rod and cone photoreceptors in addition to retinal pigment epithelium in the adult macaque and rabbit retina following subretinal delivery. The safety and biodistribution of StarGen following subretinal delivery in macaques and rabbits was assessed. Methods. Regular ophthalmic examinations, IOP measurements, ERG responses, and histopathology were carried out in both species to compare control and vector-treated eyes. Tissue and fluid samples were obtained to evaluate the persistence, biodistribution, and shedding of the vector following subretinal delivery. Results. Ophthalmic examinations revealed a slightly higher level of inflammation in StarGen compared with control treated eyes in both species. However, inflammation was transient and no overt toxicity was observed in StarGen treated eyes and there were no abnormal clinical findings. There was no StarGen-associated rise in IOP or abnormal ERG response in either rabbits or macaques. Histopathologic examination of the eyes did not reveal any detrimental changes resulting from subretinal administration of StarGen. Although antibodies to StarGen vector components were detected in rabbit but not macaque serum, this immunologic response did not result in any long-term toxicity. Biodistribution analysis demonstrated that the StarGen vector was restricted to the ocular compartment. Conclusions. In summary, these studies demonstrate StarGen to be well tolerated and localized following subretinal administration. PMID:23620430

Latent variables affecting behavioral response to the human intruder test in infant rhesus macaques (Macaca mulatta).

PubMed

Gottlieb, Daniel H; Capitanio, John P

2013-04-01

The human intruder test is a testing paradigm designed to measure rhesus macaques' behavioral responses to a stressful and threatening situation. In the test, an unfamiliar human positions him/herself in various threatening positions relative to a caged macaque. This paradigm has been utilized for over 20 years to measure a variety of behavioral constructs, including fear and anxiety, behavioral inhibition, emotionality, and aggression. To date, there have been no attempts to evaluate comprehensively the structure of the behavioral responses to the test. Our first goal was to identify the underlying latent factors affecting the different responses among subjects, and our second goal was to determine if rhesus reared in different environments respond differently in this testing paradigm. To accomplish this, we first performed exploratory and confirmatory factor analyses on the behavioral responses of 3- to 4-month-old rhesus macaques, utilizing data from over 2,000 separate tests conducted between 2001-2007. Using the resulting model, we then tested to see whether early rearing experience affected responses in the test. Our first analyses suggested that most of the variation in infant behavioral responses to the human intruder test could be explained by four latent factors: "activity," "emotionality," "aggression," and "displacement." Our second analyses revealed a significant effect of rearing condition for each factor score (P < 0.001); most notable socially reared animals had the lowest activity score (P < 0.001), indoor mother-reared animals had the highest displacement score (P < 0.001), and nursery-reared animals had the highest emotionality (P < 0.001) and lowest aggression scores (P < 0.001). These results demonstrate that this standardized testing paradigm reveals multiple patterns of response, which are influenced by an animal's rearing history. © 2012 Wiley Periodicals, Inc.

Cross-Species Rhesus Cytomegalovirus Infection of Cynomolgus Macaques

PubMed Central

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

2016-01-01

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

Analysis of simian immunodeficiency virus sequence variation in tissues of rhesus macaques with simian AIDS.

PubMed Central

Kodama, T; Mori, K; Kawahara, T; Ringler, D J; Desrosiers, R C

1993-01-01

One rhesus macaque displayed severe encephalomyelitis and another displayed severe enterocolitis following infection with molecularly cloned simian immunodeficiency virus (SIV) strain SIVmac239. Little or no free anti-SIV antibody developed in these two macaques, and they died relatively quickly (4 to 6 months) after infection. Manifestation of the tissue-specific disease in these macaques was associated with the emergence of variants with high replicative capacity for macrophages and primary infection of tissue macrophages. The nature of sequence variation in the central region (vif, vpr, and vpx), the env gene, and the nef long terminal repeat (LTR) region in brain, colon, and other tissues was examined to see whether specific genetic changes were associated with SIV replication in brain or gut. Sequence analysis revealed strong conservation of the intergenic central region, nef, and the LTR. However, analysis of env sequences in these two macaques and one other revealed significant, interesting patterns of sequence variation. (i) Changes in env that were found previously to contribute to the replicative ability of SIVmac for macrophages in culture were present in the tissues of these animals. (ii) The greatest variability was located in the regions between V1 and V2 and from "V3" through C3 in gp120, which are different in location from the variable regions observed previously in animals with strong antibody responses and long-term persistent infection. (iii) The predominant sequence change of D-->N at position 385 in C3 is most surprising, since this change in both SIV and human immunodeficiency virus type 1 has been associated with dramatically diminished affinity for CD4 and replication in vitro. (iv) The nature of sequence changes at some positions (146, 178, 345, 385, and "V3") suggests that viral replication in brain and gut may be facilitated by specific sequence changes in env in addition to those that impart a general ability to replicate well in macrophages. These results demonstrate that complex selective pressures, including immune responses and varying cell and tissue specificity, can influence the nature of sequence changes in env. Images PMID:8411355

Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys.

PubMed

Muntané, Gerard; Santpere, Gabriel; Verendeev, Andrey; Seeley, William W; Jacobs, Bob; Hopkins, William D; Navarro, Arcadi; Sherwood, Chet C

2017-09-01

Handedness and language are two well-studied examples of asymmetrical brain function in humans. Approximately 90% of humans exhibit a right-hand preference, and the vast majority shows left-hemisphere dominance for language function. Although genetic models of human handedness and language have been proposed, the actual gene expression differences between cerebral hemispheres in humans remain to be fully defined. In the present study, gene expression profiles were examined in both hemispheres of three cortical regions involved in handedness and language in humans and their homologues in rhesus macaques: ventrolateral prefrontal cortex, posterior superior temporal cortex (STC), and primary motor cortex. Although the overall pattern of gene expression was very similar between hemispheres in both humans and macaques, weighted gene correlation network analysis revealed gene co-expression modules associated with hemisphere, which are different among the three cortical regions examined. Notably, a receptor-enriched gene module in STC was particularly associated with hemisphere and showed different expression levels between hemispheres only in humans.

Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: Clinical characterization and risk factors for severe disease

PubMed Central

Johnson, Reed F.; Dodd, Lori; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A.; Jett, Catherine; Bernbaum, John G.; Ragland, Dan R.; Claire, Marisa St.; Byrum, Russell; Paragas, Jason; Blaney, Joseph E.; Jahrling, Peter B.

2011-01-01

Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens. PMID:22014505

Differential Contribution of Low- and High-level Image Content to Eye Movements in Monkeys and Humans.

PubMed

Wilming, Niklas; Kietzmann, Tim C; Jutras, Megan; Xue, Cheng; Treue, Stefan; Buffalo, Elizabeth A; König, Peter

2017-01-01

Oculomotor selection exerts a fundamental impact on our experience of the environment. To better understand the underlying principles, researchers typically rely on behavioral data from humans, and electrophysiological recordings in macaque monkeys. This approach rests on the assumption that the same selection processes are at play in both species. To test this assumption, we compared the viewing behavior of 106 humans and 11 macaques in an unconstrained free-viewing task. Our data-driven clustering analyses revealed distinct human and macaque clusters, indicating species-specific selection strategies. Yet, cross-species predictions were found to be above chance, indicating some level of shared behavior. Analyses relying on computational models of visual saliency indicate that such cross-species commonalities in free viewing are largely due to similar low-level selection mechanisms, with only a small contribution by shared higher level selection mechanisms and with consistent viewing behavior of monkeys being a subset of the consistent viewing behavior of humans. © The Author 2017. Published by Oxford University Press.

Differential Contribution of Low- and High-level Image Content to Eye Movements in Monkeys and Humans

PubMed Central

Wilming, Niklas; Kietzmann, Tim C.; Jutras, Megan; Xue, Cheng; Treue, Stefan; Buffalo, Elizabeth A.; König, Peter

2017-01-01

Abstract Oculomotor selection exerts a fundamental impact on our experience of the environment. To better understand the underlying principles, researchers typically rely on behavioral data from humans, and electrophysiological recordings in macaque monkeys. This approach rests on the assumption that the same selection processes are at play in both species. To test this assumption, we compared the viewing behavior of 106 humans and 11 macaques in an unconstrained free-viewing task. Our data-driven clustering analyses revealed distinct human and macaque clusters, indicating species-specific selection strategies. Yet, cross-species predictions were found to be above chance, indicating some level of shared behavior. Analyses relying on computational models of visual saliency indicate that such cross-species commonalities in free viewing are largely due to similar low-level selection mechanisms, with only a small contribution by shared higher level selection mechanisms and with consistent viewing behavior of monkeys being a subset of the consistent viewing behavior of humans. PMID:28077512

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

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.

Video-induced yawning in stumptail macaques (Macaca arctoides)

PubMed Central

Paukner, Annika; Anderson, James R

2005-01-01

This study reports the first experimental exploration of possible contagious yawning in monkeys. Twenty-two stumptail macaques (Macaca arctoides) were presented with video clips of either yawns or control mouth movements by conspecifics. At a group level, monkeys yawned significantly more often during and just after the yawn tape than the control tape. Supplementary analysis revealed that the yawn tape also elicited significantly more self-directed scratching responses than the control tape, which suggests that yawning might have been caused by tension arising from viewing the yawn tape. Understanding to what extent the observed effect resembles contagious yawning as found in humans and chimpanzees requires more detailed experimentation. PMID:17148320

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

Sustained virologic control in SIV+ macaques after antiretroviral and α4β7 antibody therapy

PubMed Central

Byrareddy, Siddappa N.; Arthos, James; Cicala, Claudia; Villinger, Francois; Ortiz, Kristina T.; Little, Dawn; Sidell, Neil; Kane, Maureen A.; Yu, Jianshi; Jones, Jace W.; Santangelo, Philip J.; Zurla, Chiara; McKinnon, Lyle R.; Arnold, Kelly B.; Woody, Caroline E.; Walter, Lutz; Roos, Christian; Noll, Angela; Van Ryk, Donald; Jelicic, Katija; Cimbro, Raffaello; Gumber, Sanjeev; Reid, Michelle D.; Adsay, Volkan; Amancha, Praveen K.; Mayne, Ann E.; Parslow, Tristram G.; Fauci, Anthony S.; Ansari, Aftab A.

2017-01-01

Antiretroviral drug therapy (ART) effectively suppresses replication of both the immunodeficiency viruses, human (HIV) and simian (SIV); however, virus rebounds soon after ART is withdrawn. SIV-infected monkeys were treated with a 90-day course of ART initiated at 5 weeks post infection followed at 9 weeks post infection by infusions of a primatized monoclonal antibody against the α4β7 integrin administered every 3 weeks until week 32. These animals subsequently maintained low to undetectable viral loads and normal CD4+ T cell counts in plasma and gastrointestinal tissues for more than 9 months, even after all treatment was withdrawn. This combination therapy allows macaques to effectively control viremia and reconstitute their immune systems without a need for further therapy. PMID:27738167

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.

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

PubMed Central

2011-01-01

Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk. PMID:21999700

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.

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.'

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

PubMed

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

2014-11-01

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

Large-scale transcriptome sequencing and gene analyses in the crab-eating macaque (Macaca fascicularis) for biomedical research

PubMed Central

2012-01-01

Background As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use. Results Here, we sequenced the transcriptome of 16 tissues originated from two individuals of crab-eating macaque (male and female), and identified genes to resolve the main obstacles for understanding the biological response of the crab-eating macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS FLX sequencing method. Approximately 86% of human genes were represented among the genes sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed. Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally, investigation of TE exonization events and evolutionary analysis were conducted, revealing interesting phenomena of human-specific amplified trends in TE exonization events. Conclusions This report represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and could contribute to its utility for biomedical research and basic biology. PMID:22554259

Personality Structure in Brown Capuchin Monkeys: Comparisons with Chimpanzees, Orangutans, and Rhesus Macaques

PubMed Central

Morton, F. Blake; Lee, Phyllis C.; Buchanan-Smith, Hannah M.; Brosnan, Sarah F.; Thierry, Bernard; Paukner, Annika; de Waal, Frans B. M.; Widness, Jane; Essler, Jennifer L.; Weiss, Alexander

2013-01-01

Species comparisons of personality structure (i.e. how many personality dimensions and the characteristics of those dimensions) can facilitate questions about the adaptive function of personality in nonhuman primates. Here we investigate personality structure in the brown capuchin monkey (Sapajus apella), a New World primate species, and compare this structure to those of chimpanzees (Pan troglodytes), orangutans (Pongo spp.), and rhesus macaques (Macaca mulatta). Brown capuchins evolved behavioral and cognitive traits that are qualitatively similar to those of great apes, and individual differences in behavior and cognition are closely associated with differences in personality. Thus, we hypothesized that brown capuchin personality structure would overlap more with great apes than with rhesus macaques. We obtained personality ratings from seven sites on 127 brown capuchin monkeys. Principal-components analysis identified five personality dimensions (Assertiveness, Openness, Neuroticism, Sociability, and Attentiveness), which were reliable across raters and, in a subset of subjects, significantly correlated with relevant behaviors up to a year later. Comparisons between species revealed that brown capuchins and great apes overlapped in personality structure, particularly chimpanzees in the case of Neuroticism. However, in some respects (i.e. capuchin Sociability and Openness) the similarities between capuchins and great apes were not significantly greater than those between capuchins and rhesus macaques. We discuss the relevance of our results to brown capuchin behavior, and the evolution of personality structure in primates. PMID:23668695

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

PubMed

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

2017-01-01

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

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.

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

Executive decision-making in the domestic sheep.

PubMed

Morton, A Jennifer; Avanzo, Laura

2011-01-31

Two new large animal models of Huntington's disease (HD) have been developed recently, an old world monkey (macaque) and a sheep. Macaques, with their large brains and complex repertoire of behaviors are the 'gold-standard' laboratory animals for testing cognitive function, but there are many practical and ethical issues that must be resolved before HD macaques can be used for pre-clinical research. By contrast, despite their comparable brain size, sheep do not enjoy a reputation for intelligence, and are not used for pre-clinical cognitive testing. Given that cognitive decline is a major therapeutic target in HD, the feasibility of testing cognitive function in sheep must be explored if they are to be considered seriously as models of HD. Here we tested the ability of sheep to perform tests of executive function (discrimination learning, reversal learning and attentional set-shifting). Significantly, we found that not only could sheep perform discrimination learning and reversals, but they could also perform the intradimensional (ID) and extradimensional (ED) set-shifting tasks that are sensitive tests of cognitive dysfunction in humans. Their performance on the ID/ED shifts mirrored that seen in humans and macaques, with significantly more errors to reach criterion in the ED than the ID shift. Thus, sheep can perform 'executive' cognitive tasks that are an important part of the primate behavioral repertoire, but which have never been shown previously to exist in any other large animal. Sheep have great potential, not only for use as a large animal model of HD, but also for studying cognitive function and the evolution of complex behaviours in normal animals.

Distinct expression patterns of CD69 in mucosal and systemic lymphoid tissues in primary SIV infection of rhesus macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Alvarez, Xavier; Pahar, Bapi; Moroney-Rasmussen, Terri; Lackner, Andrew A; Veazey, Ronald S

2011-01-01

Although the intestinal tract plays a major role in early human immunodeficiency virus (HIV) infection, the role of immune activation and viral replication in intestinal tissues is not completely understood. Further, increasing evidence suggests the early leukocyte activation antigen CD69 may be involved in the development or regulation of important T cell subsets, as well as a major regulatory molecule of immune responses. Using the simian immunodeficiency virus (SIV) rhesus macaque model, we compared expression of CD69 on T cells from the intestine, spleen, lymph nodes, and blood of normal and SIV-infected macaques throughout infection. In uninfected macaques, the majority of intestinal lamina propria CD4+ T cells had a memory (CD95+) phenotype and co-expressed CD69, and essentially all intestinal CCR5+ cells co-expressed CD69. In contrast, systemic lymphoid tissues had far fewer CD69+ T cells, and many had a naïve phenotype. Further, marked, selective depletion of intestinal CD4+CD69+ T cells occurred in early SIV infection, and this depletion persisted throughout infection. Markedly increased levels of CD8+CD69+ T cells were detected after SIV infection in virtually all tissues, including the intestine. Further, confocal microscopy demonstrated selective, productive infection of CD3+CD69+ T cells in the intestine in early infection. Combined, these results indicate CD69+CD4+ T cells are a major early target for viral infection, and their rapid loss by direct infection may have profound effects on intestinal immune regulation in HIV infected patients.

Executive Decision-Making in the Domestic Sheep

PubMed Central

Morton, A. Jennifer; Avanzo, Laura

2011-01-01

Two new large animal models of Huntington's disease (HD) have been developed recently, an old world monkey (macaque) and a sheep. Macaques, with their large brains and complex repertoire of behaviors are the ‘gold-standard’ laboratory animals for testing cognitive function, but there are many practical and ethical issues that must be resolved before HD macaques can be used for pre-clinical research. By contrast, despite their comparable brain size, sheep do not enjoy a reputation for intelligence, and are not used for pre-clinical cognitive testing. Given that cognitive decline is a major therapeutic target in HD, the feasibility of testing cognitive function in sheep must be explored if they are to be considered seriously as models of HD. Here we tested the ability of sheep to perform tests of executive function (discrimination learning, reversal learning and attentional set-shifting). Significantly, we found that not only could sheep perform discrimination learning and reversals, but they could also perform the intradimensional (ID) and extradimensional (ED) set-shifting tasks that are sensitive tests of cognitive dysfunction in humans. Their performance on the ID/ED shifts mirrored that seen in humans and macaques, with significantly more errors to reach criterion in the ED than the ID shift. Thus, sheep can perform ‘executive’ cognitive tasks that are an important part of the primate behavioral repertoire, but which have never been shown previously to exist in any other large animal. Sheep have great potential, not only for use as a large animal model of HD, but also for studying cognitive function and the evolution of complex behaviours in normal animals. PMID:21305061

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

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.

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

PubMed

Putaporntip, Chaturong; Thongaree, Siriporn; Jongwutiwes, Somchai

2013-08-01

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

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

Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

NASA Technical Reports Server (NTRS)

Gazzaley, A. H.; Thakker, M. M.; Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1997-01-01

The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.

Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.

PubMed

Johnson, Reed F; Dodd, Lori E; Yellayi, Srikanth; Gu, Wenjuan; Cann, Jennifer A; Jett, Catherine; Bernbaum, John G; Ragland, Dan R; St Claire, Marisa; Byrum, Russell; Paragas, Jason; Blaney, Joseph E; Jahrling, Peter B

2011-12-20

Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens. Published by Elsevier Inc.

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

PubMed

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

2007-05-01

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

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

PubMed

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

2016-09-01

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

Mirror neurons and imitation: a computationally guided review.

PubMed

Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael

2006-04-01

Neurophysiology reveals the properties of individual mirror neurons in the macaque while brain imaging reveals the presence of 'mirror systems' (not individual neurons) in the human. Current conceptual models attribute high level functions such as action understanding, imitation, and language to mirror neurons. However, only the first of these three functions is well-developed in monkeys. We thus distinguish current opinions (conceptual models) on mirror neuron function from more detailed computational models. We assess the strengths and weaknesses of current computational models in addressing the data and speculations on mirror neurons (macaque) and mirror systems (human). In particular, our mirror neuron system (MNS), mental state inference (MSI) and modular selection and identification for control (MOSAIC) models are analyzed in more detail. Conceptual models often overlook the computational requirements for posited functions, while too many computational models adopt the erroneous hypothesis that mirror neurons are interchangeable with imitation ability. Our meta-analysis underlines the gap between conceptual and computational models and points out the research effort required from both sides to reduce this gap.

Simian immunodeficiency virus selectively infects proliferating CD4+ T cells in neonatal rhesus macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Pahar, Bapi; Alvarez, Xavier; Green, Linda C; Dufour, Jason; Moroney-Rasmussen, Terri; Lackner, Andrew A; Veazey, Ronald S

2010-11-18

Infants infected with HIV have a more severe course of disease and persistently higher viral loads than HIV-infected adults. However, the underlying pathogenesis of this exacerbation remains obscure. Here we compared the rate of CD4(+) and CD8(+) T-cell proliferation in intestinal and systemic lymphoid tissues of neonatal and adult rhesus macaques, and of normal and age-matched simian immunodeficiency virus (SIV)-infected neonates. The results demonstrate infant primates have much greater rates of CD4(+) T-cell proliferation than adult macaques, and that these proliferating, recently "activated" CD4(+) T cells are infected in intestinal and other lymphoid tissues of neonates, resulting in selective depletion of proliferating CD4(+) T cells in acute infection. This depletion is accompanied by a marked increase in CD8(+) T-cell activation and production, particularly in the intestinal tract. The data indicate intestinal CD4(+) T cells of infant primates have a markedly accelerated rate of proliferation and maturation resulting in more rapid and sustained production of optimal target cells (activated memory CD4(+) T cells), which may explain the sustained "peak" viremia characteristic of pediatric HIV infection. Eventual failure of CD4(+) T-cell turnover in intestinal tissues may indicate a poorer prognosis for HIV-infected infants.

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

Effects of Citalopram on Serotonin and CRF Systems in the Midbrain of Primates with Differences in Stress Sensitivity

PubMed Central

Bethea, Cynthia L.; Lima, Fernanda B.; Centeno, Maria L.; Weissheimer, Karin V.; Senashova, Olga; Reddy, Arubala P.; Cameron, Judy L.

2011-01-01

This chapter reviews the neurobiological effects of stress sensitivity and CIT treatment observed in our nonhuman primate model of Functional Hypothalamic Amenorrhea (FHA). This type of infertility, also known as stress-induced amenorrhea, is exhibited by cynomolgus macaques. In small populations, some individuals are stress sensitive (SS) and others are highly stress resilient (HSR). The SS macaques have suboptimal secretion of estrogen and progesterone during normal menstrual cycles. SS monkeys also have decreased serotonin gene expression and increased CRF expression compared to HSR monkeys. Recently, we found that s-citalopram (CIT) treatment improved ovarian steroid secretion in SS monkeys, but had no effect in HSR monkeys. Examination of the serotonin system revealed that SS monkeys had significantly lower Fev (fifth Ewing variant, rodent Pet1), TPH2 (tryptophan hydroxylase 2), 5HT1A autoreceptor and SERT (serotonin reuptake transporter) expression in the dorsal raphe than SR monkeys. However, CIT did not alter the expression of either Fev, TPH2, SERT or 5HT1A mRNAs. In contrast, SS monkeys tended to a higher density of CRF fiber innervation of the dorsal raphe than HSR monkeys, and CIT significantly decreased the CRF fiber density in SS animals. In addition, CIT increased CRF-R2 gene expression in the dorsal raphe. We speculate that in a 15-week time frame, the therapeutic effect of S-citalopram may be achieved through a mechanism involving extracellular serotonin inhibition of CRF and stimulation of CRF-R2, rather than alteration of serotonin-related gene expression. PMID:21683135

Genetics of the Shimokita macaque population suggest an ancient bottleneck.

PubMed

Kawamoto, Yoshi; Tomari, Ken-ichiro; Kawai, Shizuka; Kawamoto, Sakie

2008-01-01

The macaque population of the Shimokita Peninsula represents the northernmost distribution of this species and is isolated from other populations in the Tohoku region of Japan. A previous protein-based study revealed a high level of genetic variability in this population and considerable differentiation from other populations. In order to reassess the genetic features of the Shimokita macaques, we examined 11 autosomal microsatellite loci and three Y chromosomal microsatellite loci. We observed considerable differentiation from other Japanese populations of macaques, but in contrast to the previous results, we observed significantly lower genetic variability in this population. There was a weak indication of a population bottleneck, suggesting a decay over time from an excess of heterozygotes that might be expected in the initial stages of a bottleneck. This may indicate that an ancient bottleneck occurred during the warm period after the last glacial period rather than a recent bottleneck due to hunting in modern times. The frequencies of private alleles were exceptionally high in the Shimokita population, suggesting that the difference in variability as determined in various studies was due to accidental sampling of marker loci with low power to resolve genetic variations in the protein-based studies. The assessments of interpopulation differentiation as determined using autosomal and Y chromosomal markers were highly correlated, and using both types of markers the Shimokita population was found to be the most differentiated of the study populations, probably due to infrequent gene flow with surrounding populations.

Right Hemisphere Dominance for Emotion Processing in Baboons

ERIC Educational Resources Information Center

Wallez, Catherine; Vauclair, Jacques

2011-01-01

Asymmetries of emotional facial expressions in humans offer reliable indexes to infer brain lateralization and mostly revealed right hemisphere dominance. Studies concerned with oro-facial asymmetries in nonhuman primates largely showed a left-sided asymmetry in chimpanzees, marmosets and macaques. The presence of asymmetrical oro-facial…

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.

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

PubMed

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

2015-03-06

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

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

PubMed Central

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

2015-01-01

Celiac disease (CD) affects approximately 1% of the general population while an estimated additional 6% suffers from a recently characterized, rapidly emerging, similar disease, referred to as non-celiac gluten sensitivity (NCGS). The only effective treatment of CD and NCGS requires removal of gluten sources from the diet. Since required adherence to a gluten-free diet (GFD) is difficult to accomplish, efforts to develop alternative treatments have been intensifying in recent years. In this study, the non-human primate model of CD/NCGS, e.g., gluten-sensitive rhesus macaque, was utilized with the objective to evaluate the treatment potential of reduced gluten cereals using a reduced gluten (RG; 1% of normal gluten) barley mutant as a model. Conventional and RG barleys were used for the formulation of experimental chows and fed to gluten-sensitive (GS) and control macaques to determine if RG barley causes a remission of dietary gluten-induced clinical and immune responses in GS macaques. The impacts of the RG barley diet were compared with the impacts of the conventional barley-containing chow and the GFD. Although remission of the anti-gliadin antibody (AGA) serum responses and an improvement of clinical diarrhea were noted after switching the conventional to the RG barley diet, production of inflammatory cytokines, e.g., interferon-gamma (IFN-γ), tumor necrosis factor (TNF) and interleukin-8 (IL-8) by peripheral CD4+ T helper lymphocytes, persisted during the RG chow treatment and were partially abolished only upon re-administration of the GFD. It was concluded that the RG barley diet might be used for the partial improvement of gluten-induced disease but its therapeutic value still requires upgrading—by co-administration of additional treatments. PMID:25756783

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

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.

Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies.

PubMed

Fischer-Smith, Tracy; Bell, Christie; Croul, Sidney; Lewis, Mark; Rappaport, Jay

2008-08-01

Here the authors discuss evidence in human and animal models supporting two opposing views regarding the pathogenesis of human immunodeficiency virus (HIV) in the central nervous system (CNS): (1) HIV infection in the CNS is a compartmentalized infection, with the virus-infected macrophages entering the CNS early, infecting resident microglia and astrocytes, and achieving a state of latency with evolution toward a fulminant CNS infection late in the course of disease; or alternatively, (2) events in the periphery lead to altered monocyte/macrophage (MPhi) homeostasis, with increased CNS invasion of infected and/or uninfected MPhis. Here the authors have reevaluated evidence presented in the favor of the latter model, with a discussion of phenotypic characteristics distinguishing normal resident microglia with those accumulating in HIV encephalitis (HIVE). CD163 is normally expressed by perivascular MPhi s but not resident microglia in normal CNS of humans and rhesus macaques. In agreement with other studies, the authors demonstrate expression of CD163 by brain MPhi s in HIVE and simian immunodeficiency virus encephalitis (SIVE). CNS tissues from HIV-sero positive individuals with HIVE or HIV-associated progressive multifocal leukoencephalopathy (PML) were also examined. In HIVE, the authors further demonstrate colocalization of CD163 and CD16 (Fcgamma III recptor) gene expression, the latter marker associated with HIV infection of monocyte in vivo and permissivity of infection. Indeed, CD163(+) MPhis and microglia are often productively infected in HIVE CNS. In SIV infected rhesus macaques, CD163(+) cells accumulate perivascularly, within nodular lesions and the parenchyma in animals with encephalitis. Likewise, parenchymal microglia and perivascular MPhi s are CD163(+) in HIVE. In contrast to HIVE, CD163(+)perivascular and parenchymal MPhi s in HIV-associated PML were only associated with areas of demyelinating lesions. Interestingly, SIV-infected rhesus macaques whose viral burden was predominantly at 1 x 10(6) copies/ml or greater developed encephalitis. To further investigate the relationship between CD163(+)/CD16(+) MPhis/microglia in the CNS and altered homeostasis in the periphery, the authors performed flow-cytometric analyses of peripheral blood mononuclear cells (PBMCs) from SIV-infected rhesus macaques. The results demonstrate an increase in the percent frequency of CD163(+)/CD16(+) monocytes in animals with detectable virus that correlated significantly with increased viral burden and CD4(+) T-cell decline. These results suggest the importance of this monocyte subset in HIV/SIV CNS disease, and also in the immune pathogenesis of lentiviral infection. The authors further discuss the potential role of CD163(+)/CD16(+) monocyte/MPhi subset expansion, altered myeloid homeostasis, and potential consequences for immune polarization and suppression. The results and discussion here suggest new avenues for the development of acquired immunodeficiency syndrome (AIDS) therapeutics and vaccine design.

Activity and social factors affect cohesion among individuals in female Japanese macaques: A simultaneous focal-follow study.

PubMed

Nishikawa, Mari; Suzuki, Mariko; Sprague, David S

2014-07-01

Understanding cohesion among individuals within a group is necessary to reveal the social system of group-living primates. Japanese macaques (Macaca fuscata) are female-philopatric primates that reside in social groups. We investigated whether individual activity and social factors can affect spatio-temporal cohesion in wild female Japanese macaques. We conducted behavioral observation on a group, which contained 38 individuals and ranged over ca. 60 ha during the study period. Two observers carried out simultaneous focal-animal sampling of adult female pairs during full-day follows using global positioning system which enabled us to quantify interindividual distances (IIDs), group members within visual range (i.e., visual unit), and separation duration beyond visual range as indicators of cohesion among individuals. We found considerable variation in spatio-temporal group cohesion. The overall mean IID was 99.9 m (range = 0-618.2 m). The percentage of IIDs within visual range was 23.1%, within auditory range was 59.8%, and beyond auditory range was 17.1%. IIDs varied with activity; they were shorter during grooming and resting, and longer during foraging and traveling. Low-ranking females showed less cohesion than high-ranking ones. Kin females stayed nearly always within audible range. The macaques were weakly cohesive with small mean visual unit size (3.15 counting only adults, 5.99 counting all individuals). Both-sex units were the most frequently observed visual unit type when they were grooming/resting. Conversely, female units were the most frequently observed visual unit type when they were foraging. The overall mean visual separation duration was 25.7 min (range = 3-513 min). Separation duration was associated with dominance rank. These results suggest that Japanese macaques regulate cohesion among individuals depending on their activity and on social relationships; they were separated to adapt food distribution and aggregated to maintain social interactions. © 2014 Wiley Periodicals, Inc.

Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

PubMed

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

2018-03-28

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

Saccade Modulation by Optical and Electrical Stimulation in the Macaque Frontal Eye Field

PubMed Central

Grimaldi, Piercesare; Schweers, Nicole

2013-01-01

Recent studies have demonstrated that strong neural modulations can be evoked with optogenetic stimulation in macaque motor cortex without observing any evoked movements (Han et al., 2009, 2011; Diester et al., 2011). It remains unclear why such perturbations do not generate movements and if conditions exist under which they may evoke movements. In this study, we examine the effects of five optogenetic constructs in the macaque frontal eye field and use electrical microstimulation to assess whether optical perturbation of the local network leads to observable motor changes during optical, electrical, and combined stimulation. We report a significant increase in the probability of evoking saccadic eye movements when low current electrical stimulation is coupled to optical stimulation compared with when electrical stimulation is used alone. Experiments combining channelrhodopsin 2 (ChR2) and electrical stimulation with simultaneous fMRI revealed no discernible fMRI activity at the electrode tip with optical stimulation but strong activity with electrical stimulation. Our findings suggest that stimulation with current ChR2 optogenetic constructs generates subthreshold activity that contributes to the initiation of movements but, in most cases, is not sufficient to evoke a motor response. PMID:24133271

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.

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.

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…

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.

Selective reaching in macaques: evidence for action-centred attention.

PubMed

Bulgheroni, Maria; Camperio-Ciani, Andrea; Straulino, Elisa; Sartori, Luisa; D'Amico, Enrico; Castiello, Umberto

2017-03-01

When a monkey selects a piece of food lying on the ground from among other viable objects in the near vicinity, only the desired item governs the particular pattern and direction of the animal's reaching action. It would seem then that selection is an important component controlling the animal's action. But, we may ask, is the selection process in such cases impervious to the presence of other objects that could constitute potential obstacles to or constraints on movement execution? And if it is, in fact, pervious to other objects, do they have a direct influence on the organization of the response? The kinematics of macaques' reaching movements were examined by the current study that analysed some exemplars as they selectively reached to grasp a food item in the absence as well as in the presence of potential obstacles (i.e., stones) that could affect the arm trajectory. Changes in movement parameterization were noted in temporal measures, such as movement time, as well as in spatial ones, such as paths of trajectory. Generally speaking, the presence of stones in the vicinity of the acting hand stalled the reaching movement and affected the arm trajectory as the hand veered away from the stone even when it was not a physical obstacle. We concluded that nearby objects evoke a motor response in macaques, and the attentional mechanisms that allow for a successful action selection are revealed in the reaching path. The data outlined here concur with human studies indicating that potential obstacles are internally represented, a finding implying basic cognitive operations allowing for action selection in macaques.

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

PubMed

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

2015-01-01

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

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.

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.

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.

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

Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.

PubMed

Bauman, M D; Iosif, A-M; Ashwood, P; Braunschweig, D; Lee, A; Schumann, C M; Van de Water, J; Amaral, D G

2013-07-09

Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.

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.

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.

Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys

PubMed Central

Shooner, Christopher; Hallum, Luke E.; García-Marín, Virginia; Kiorpes, Lynne

2017-01-01

In amblyopia, abnormal visual experience leads to an extreme form of eye dominance, in which vision through the nondominant eye is degraded. A key aspect of this disorder is perceptual suppression: the image seen by the stronger eye often dominates during binocular viewing, blocking the image of the weaker eye from reaching awareness. Interocular suppression is the focus of ongoing work aimed at understanding and treating amblyopia, yet its physiological basis remains unknown. We measured binocular interactions in visual cortex of anesthetized amblyopic monkeys (female Macaca nemestrina), using 96-channel “Utah” arrays to record from populations of neurons in V1 and V2. In an experiment reported recently (Hallum et al., 2017), we found that reduced excitatory input from the amblyopic eye (AE) revealed a form of balanced binocular suppression that is unaltered in amblyopia. Here, we report on the modulation of the gain of excitatory signals from the AE by signals from its dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE responses to grating stimuli were attenuated by the presentation of a noise mask to the FE, as in a normal control animal. Responses to FE stimuli, by contrast, could not be masked from the AE. We conclude that a weakened ability of the amblyopic eye to modulate cortical response gain creates an imbalance of suppression that favors the dominant eye. SIGNIFICANCE STATEMENT In amblyopia, vision in one eye is impaired as a result of abnormal early visual experience. Behavioral observations in humans with amblyopia suggest that much of their visual loss is due to active suppression of their amblyopic eye. Here we describe experiments in which we studied binocular interactions in macaques with experimentally induced amblyopia. In normal monkeys, the gain of neuronal response to stimulation of one eye is modulated by contrast in the other eye, but in monkeys with amblyopia the balance of gain modulation is altered so that the weaker, amblyopic eye has little effect while the stronger fellow eye has a strong effect. This asymmetric suppression may be a key component of the perceptual losses in amblyopia. PMID:28760867

Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys.

PubMed

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

2017-09-06

In amblyopia, abnormal visual experience leads to an extreme form of eye dominance, in which vision through the nondominant eye is degraded. A key aspect of this disorder is perceptual suppression: the image seen by the stronger eye often dominates during binocular viewing, blocking the image of the weaker eye from reaching awareness. Interocular suppression is the focus of ongoing work aimed at understanding and treating amblyopia, yet its physiological basis remains unknown. We measured binocular interactions in visual cortex of anesthetized amblyopic monkeys (female Macaca nemestrina ), using 96-channel "Utah" arrays to record from populations of neurons in V1 and V2. In an experiment reported recently (Hallum et al., 2017), we found that reduced excitatory input from the amblyopic eye (AE) revealed a form of balanced binocular suppression that is unaltered in amblyopia. Here, we report on the modulation of the gain of excitatory signals from the AE by signals from its dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE responses to grating stimuli were attenuated by the presentation of a noise mask to the FE, as in a normal control animal. Responses to FE stimuli, by contrast, could not be masked from the AE. We conclude that a weakened ability of the amblyopic eye to modulate cortical response gain creates an imbalance of suppression that favors the dominant eye. SIGNIFICANCE STATEMENT In amblyopia, vision in one eye is impaired as a result of abnormal early visual experience. Behavioral observations in humans with amblyopia suggest that much of their visual loss is due to active suppression of their amblyopic eye. Here we describe experiments in which we studied binocular interactions in macaques with experimentally induced amblyopia. In normal monkeys, the gain of neuronal response to stimulation of one eye is modulated by contrast in the other eye, but in monkeys with amblyopia the balance of gain modulation is altered so that the weaker, amblyopic eye has little effect while the stronger fellow eye has a strong effect. This asymmetric suppression may be a key component of the perceptual losses in amblyopia. Copyright © 2017 the authors 0270-6474/17/378734-08$15.00/0.

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

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.

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.

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

Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems

PubMed Central

Ardeshir, Amir; Narayan, Nicole R.; Méndez-Lagares, Gema; Lu, Ding; Rauch, Marcus; Huang, Yong; Van Rompay, Koen K. A.; Lynch, Susan V.; Hartigan-O'Connor, Dennis J.

2015-01-01

Diet has a strong influence on the intestinal microbiota in both humans and animal models. It is well established that microbial colonization is required for normal development of the immune system and that specific microbial constituents prompt the differentiation or expansion of certain immune cell subsets. Nonetheless, it has been unclear how profoundly diet might shape the primate immune system or how durable the influence might be. We show that breast-fed and bottle-fed infant rhesus macaques develop markedly different immune systems, which remain different 6 months after weaning when the animals begin receiving identical diets. In particular, breast-fed infants develop robust populations of memory T cells as well as T helper 17 (TH17) cells within the memory pool, whereas bottle-fed infants do not. These findings may partly explain the variation in human susceptibility to conditions with an immune basis, as well as the variable protection against certain infectious diseases. PMID:25186175

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.

Isoform Evolution in Primates through Independent Combination of Alternative RNA Processing Events

PubMed Central

Zhang, Shi-Jian; Wang, Chenqu; Yan, Shouyu; Fu, Aisi; Luan, Xuke; Li, Yumei; Sunny Shen, Qing; Zhong, Xiaoming; Chen, Jia-Yu; Wang, Xiangfeng; Chin-Ming Tan, Bertrand; He, Aibin; Li, Chuan-Yun

2017-01-01

Abstract Recent RNA-seq technology revealed thousands of splicing events that are under rapid evolution in primates, whereas the reliability of these events, as well as their combination on the isoform level, have not been adequately addressed due to its limited sequencing length. Here, we performed comparative transcriptome analyses in human and rhesus macaque cerebellum using single molecule long-read sequencing (Iso-seq) and matched RNA-seq. Besides 359 million RNA-seq reads, 4,165,527 Iso-seq reads were generated with a mean length of 14,875 bp, covering 11,466 human genes, and 10,159 macaque genes. With Iso-seq data, we substantially expanded the repertoire of alternative RNA processing events in primates, and found that intron retention and alternative polyadenylation are surprisingly more prevalent in primates than previously estimated. We then investigated the combinatorial mode of these alternative events at the whole-transcript level, and found that the combination of these events is largely independent along the transcript, leading to thousands of novel isoforms missed by current annotations. Notably, these novel isoforms are selectively constrained in general, and 1,119 isoforms have even higher expression than the previously annotated major isoforms in human, indicating that the complexity of the human transcriptome is still significantly underestimated. Comparative transcriptome analysis further revealed 502 genes encoding selectively constrained, lineage-specific isoforms in human but not in rhesus macaque, linking them to some lineage-specific functions. Overall, we propose that the independent combination of alternative RNA processing events has contributed to complex isoform evolution in primates, which provides a new foundation for the study of phenotypic difference among primates. PMID:28957512

Latent Variables Affecting Behavioral Response to the Human Intruder Test in Infant Rhesus Macaques (Macaca mulatta)

PubMed Central

Gottlieb, Daniel H.; Capitanio, John P.

2012-01-01

The human intruder test is a testing paradigm designed to measure rhesus macaques’ behavioral responses to a stressful and threatening situation. In the test, an unfamiliar human positions him/herself in various threatening positions relative to a caged macaque. This paradigm has been utilized for over twenty years to measure a variety of behavioral constructs, including fear and anxiety, behavioral inhibition, emotionality, and aggression. To date there have been no attempts to evaluate comprehensively the structure of the behavioral responses to the test. Our first goal was to identify the underlying latent factors affecting the different responses among subjects, and our second goal was determine if rhesus reared in different environments respond differently in this testing paradigm. To accomplish this, we first performed exploratory and confirmatory factor analyses on the behavioral responses of 3–4 month-old rhesus macaques, utilizing data from over 2,000 separate tests conducted between 2001–2007. Using the resulting model, we then tested to see whether early rearing experience affected responses in the test. Our first analyses suggested that most of the variation in infant behavioral responses to the human intruder test could be explained by four latent factors: “Activity,” “Emotionality,” “Aggression,” and “Displacement.” Our second analyses revealed a significant effect of rearing condition for each factor score (P < 0.001); most notable socially-reared animals had the lowest Activity score (P < 0.001), indoor mother-reared animals had the highest Displacement score (P < 0.001), and nursery-reared animals had the highest Emotionality (P < 0.001) and lowest Aggression scores (P < 0.001). These results demonstrate that this standardized testing paradigm reveals multiple patterns of response, which are influenced by an animal’s rearing history. PMID:23229557

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

PubMed

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

2018-03-13

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

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

PubMed Central

Beisner, Brianne; Vandeleest, Jessica; Atwill, Edward; McCowan, Brenda

2016-01-01

In social animals, group living may impact the risk of infectious disease acquisition in two ways. On the one hand, social connectedness puts individuals at greater risk or susceptibility for acquiring enteric pathogens via contact-mediated transmission. Yet conversely, in strongly bonded societies like humans and some nonhuman primates, having close connections and strong social ties of support can also socially buffer individuals against susceptibility or transmissibility of infectious agents. Using social network analyses, we assessed the potentially competing roles of contact-mediated transmission and social buffering on the risk of infection from an enteric bacterial pathogen (Shigella flexneri) among captive groups of rhesus macaques (Macaca mulatta). Our results indicate that, within two macaque groups, individuals possessing more direct and especially indirect connections in their grooming and huddling social networks were less susceptible to infection. These results are in sharp contrast to several previous studies that indicate that increased (direct) contact-mediated transmission facilitates infectious disease transmission, including our own findings in a third macaque group in which individuals central in their huddling network and/or which initiated more fights were more likely to be infected. In summary, our findings reveal that an individual’s social connections may increase or decrease its chances of acquiring infectious agents. They extend the applicability of the social buffering hypothesis, beyond just stress and immune-function-related health benefits, to the additional health outcome of infectious disease resistance. Finally, we speculate that the circumstances under which social buffering versus contact-mediated transmission may occur could depend on multiple factors, such as living condition, pathogen-specific transmission routes, and/or an overall social context such as a group’s social stability. PMID:27812426

Induction of potent local cellular immunity with low dose X4 SHIV{sub SF33A} vaginal exposure

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

Tasca, Silvana; Tsai, Lily; Trunova, Nataliya

2007-10-10

Intravaginal inoculation of rhesus macaques with varying doses of the CXCR4 (X4)-tropic SHIV{sub SF33A} isolate revealed a threshold inoculum for establishment of systemic virus infection and a dose dependency in overall viral burden and CD4+ T cell depletion. While exposure to inoculum size of 1000 or greater 50% tissue infectious dose (TCID{sub 50}) resulted in high viremia and precipitous CD4+ T cell loss, occult infection was observed in seven of eight macaques exposed to 500 TCID{sub 50} of the same virus. The latter was characterized by intermittent detection of low level virus with no evidence of seroconversion or CD4+ Tmore » cell decline, but with signs of an ongoing antiviral T cell immune response. Upon vaginal re-challenge with the same limiting dose 11-12 weeks after the first, classic pathogenic X4 SHIV{sub SF33A} infection was established in four of the seven previously exposed seronegative macaques, implying enhanced susceptibility to systemic infection with prior exposure. Pre-existing peripheral SIV gag-specific CD4+ T cells were more readily demonstrable in macaques that became systemically infected following re-exposure than those that were not. In contrast, early presence of circulating polyfunctional cytokine secreting CD8+ T cells or strong virus-specific proliferative responses in draining lymph nodes and in the gut associated lymphoid tissue (GALT) following the first exposure was associated with protection from systemic re-infection. These studies identify the gut and lymphoid tissues proximal to the genital tract as sites of robust CD8 T lymphocyte responses that contribute to containment of virus spread following vaginal transmission.« less

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

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

Hodgen, G.D.; Wilks, J.W.; Vaitukaitis, J.L.

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

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

PubMed

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

2015-12-01

HIV acquisition in the female genital tract remains incompletely understood. Quantitative data on biological HIV risk factors, the influence of reproductive hormones, and infection risk are lacking. We evaluated vaginal epithelial thickness during the menstrual cycle in pigtail macaques (Macaca nemestrina). This model previously revealed increased susceptibility to vaginal infection during and after progesterone-dominated periods in the menstrual cycle. Nucleated and nonnucleated (superficial) epithelial layers were quantitated throughout the menstrual cycle of 16 macaques. We examined the relationship with previously estimated vaginal SHIVSF162P3 acquisition time points in the cycle of 43 different animals repeatedly exposed to low virus doses. In the luteal phase (days 17 to cycle end), the mean vaginal epithelium thinned to 66% of mean follicular thickness (days 1-16; P = 0.007, Mann-Whitney test). Analyzing 4-day segments, the epithelium was thickest on days 9 to 12 and thinned to 31% thereof on days 29 to 32, with reductions of nucleated and nonnucleated layers to 36% and 15% of their previous thickness, respectively. The proportion of animals with estimated SHIV acquisition in each cycle segment correlated with nonnucleated layer thinning (Pearson r = 0.7, P < 0.05, linear regression analysis), but not nucleated layer thinning (Pearson r = 0.6, P = 0.15). These data provide a detailed picture of dynamic cycle-related changes in the vaginal epithelium of pigtail macaques. Substantial thinning occurred in the superficial, nonnucleated layer, which maintains the vaginal microbiome. The findings support vaginal tissue architecture as susceptibility factor for infection and contribute to our understanding of innate resistance to SHIV infection.

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

A Novel Microbicide/Contraceptive Intravaginal Ring Protects Macaque Genital Mucosa against SHIV-RT Infection Ex Vivo.

PubMed

Villegas, Guillermo; Calenda, Giulia; Ugaonkar, Shweta; Zhang, Shimin; Kizima, Larisa; Mizenina, Olga; Gettie, Agegnehu; Blanchard, James; Cooney, Michael L; Robbiani, Melissa; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

2016-01-01

Women need multipurpose prevention products (MPTs) that protect against sexually transmitted infections (STIs) and provide contraception. The Population Council has developed a prototype intravaginal ring (IVR) releasing the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 (M), zinc acetate (ZA), carrageenan (CG) and levonorgestrel (LNG) (MZCL IVR) to protect against HIV, HSV-2, HPV and unintended pregnancy. Our objective was to evaluate the anti-SHIV-RT activity of MZCL IVR in genital mucosa. First, macaque vaginal tissues were challenged with SHIV-RT in the presence of (i) MIV-150 ± LNG or (ii) vaginal fluids (VF); available from studies completed earlier) collected at various time points post insertion of MZCL and MZC IVRs. Then, (iii) MZCL IVRs (vs. LNG IVRs) were inserted in non-Depo Provera-treated macaques for 24h and VF, genital biopsies, and blood were collected and tissues were challenged with SHIV-RT. Infection was monitored with one step SIV gag qRT-PCR or p27 ELISA. MIV-150 (LCMS/MS, RIA), LNG (RIA) and CG (ELISA) were measured in different compartments. Log-normal generalized mixed linear models were used for analysis. LNG did not affect the anti-SHIV-RT activity of MIV-150 in vitro. MIV-150 in VF from MZC/MZCL IVR-treated macaques inhibited SHIV-RT in vaginal mucosa in a dose-dependent manner (p<0.05). MIV-150 in vaginal tissue from MZCL IVR-treated animals inhibited ex vivo infection relative to baseline (96%; p<0.0001) and post LNG IVR group (90%, p<0.001). No MIV-150 dose-dependent protection was observed, likely because of high MIV-150 concentrations in all vaginal tissue samples. In cervical tissue, MIV-150 inhibited infection vs. baseline (99%; p<0.05). No cervical tissue was available for MIV-150 measurement. Exposure to LNG IVR did not change tissue infection level. These observations support further development of MZCL IVR as a multipurpose prevention technology to improve women's sexual and reproductive health.

Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: Lessons from human and nonhuman primate studies

PubMed Central

Fischer-Smith, Tracy; Bell, Christie; Croul, Sidney; Lewis, Mark; Rappaport, Jay

2009-01-01

Here the authors discuss evidence in human and animal models supporting two opposing views regarding the pathogenesis of human immunodeficiency virus (HIV) in the central nervous system (CNS): (1) HIV infection in the CNS is a compartmentalized infection, with the virus-infected macrophages entering the CNS early, infecting resident microglia and astrocytes, and achieving a state of latency with evolution toward a fulminant CNS infection late in the course of disease; or alternatively, (2) events in the periphery lead to altered monocyte/macrophage (MΦ) homeostasis, with increased CNS invasion of infected and/or uninfected MΦs. Here the authors have reevaluated evidence presented in the favor of the latter model, with a discussion of phenotypic characteristics distinguishing normal resident microglia with those accumulating in HIV encephalitis (HIVE). CD163 is normally expressed by perivascular MΦs but not resident microglia in normal CNS of humans and rhesus macaques. In agreement with other studies, the authors demonstrate expression of CD163 by brain MΦs in HIVE and simian immunodeficiency virus encephalitis (SIVE). CNS tissues from HIV-sero positive individuals with HIVE or HIV-associated progressive multifocal leukoencephalopathy (PML) were also examined. In HIVE, the authors further demonstrate colocalization of CD163 and CD16 (FcγIII recptor) gene expression, the latter marker associated with HIV infection of monocyte in vivo and permissivity of infection. Indeed, CD163+ MΦs and microglia are often productively infected in HIVE CNS. In SIV infected rhesus macaques, CD163+ cells accumulate perivascularly, within nodular lesions and the parenchyma in animals with encephalitis. Likewise, parenchymal microglia and perivascular MΦs are CD163+ in HIVE. In contrast to HIVE, CD163+perivascular and parenchymal MΦs in HIV-associated PML were only associated with areas of demyelinating lesions. Interestingly, SIV-infected rhesus macaques whose viral burden was predominantly at 1 × 106 copies/ml or greater developed encephalitis. To further investigate the relationship between CD163+/CD16+ MΦs/microglia in the CNS and altered homeostasis in the periphery, the authors performed flow-cytometric analyses of peripheral blood mononuclear cells (PBMCs) from SIV-infected rhesus macaques. The results demonstrate an increase in the percent frequency of CD163+/CD16+ monocytes in animals with detectable virus that correlated significantly with increased viral burden and CD4+ T-cell decline. These results suggest the importance of this monocyte subset in HIV/SIV CNS disease, and also in the immune pathogenesis of lentiviral infection. The authors further discuss the potential role of CD163+/CD16+ monocyte/MΦ subset expansion, altered myeloid homeostasis, and potential consequences for immune polarization and suppression. The results and discussion here suggest new avenues for the development of acquired immunodeficiency syndrome (AIDS) therapeutics and vaccine design. PMID:18780233

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.

A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig-tailed macaques has a limited number of amino acid substitutions in both SIVmac and HIV-1 regions of the genome and has offered cytotropism.

PubMed

Stephens, E B; Mukherjee, S; Sahni, M; Zhuge, W; Raghavan, R; Singh, D K; Leung, K; Atkinson, B; Li, Z; Joag, S V; Liu, Z Q; Narayan, O

1997-05-12

We have examined both the sequence changes in the LTR, gag, vif, vpr, vpx, tat, rev, vpu, env, and nef genes and the cell tropism of a cell-free stock of chimeric simian-human immunodeficiency virus (SHIV) isolated from the cerebrospinal fluid of a pig-tailed macaque (PNb) that developed AIDS. This virus (SHIVKU-1) is highly pathogenic when inoculated into other macaques. DNA sequence analysis of PCR-amplified products revealed a total of 5 nucleotide changes in the LTR while vif had 2 consensus amino acid changes. The gag, vif, and vpx had no consensus amino acid substitutions, whereas vpr had 1 consensus substitution. The tat and rev genes of the HXB2 region of SHIVKU-1 had 2 and 1 consensus amino acid changes, respectively. The vpu gene of the HXB2 region of SHIV, which originally had an ACG at the beginning of the gene, reverted to an initiation ATG codon and in addition contained a consensus amino acid substitution at position 69 of this protein. As expected, the majority of the nucleotide substitutions were found in the env and nef genes. Thirteen and 5 amino acid changes were predicted for the corresponding Env and Nef proteins, respectively. In addition, one-third of the env gene clones isolated from the SHIVKU-1 stock had a 5-amino-acid deletion in the V4 region. Using three independent assays, we determined that the changes in the SHIVKU-1 were associated with an increase in the efficiency of replication in macrophages. The strikingly few consensus changes in the virus suggest that conversion of this virus to one capable of causing AIDS in pig-tailed macaques was associated with relatively few changes in the viral envelope and/or accessory genes. These results will provide the basis for the development of a pathogenic, molecular clone of SHIV capable of causing AIDS in pig-tailed macaques.

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

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

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.

Locally infiltrative ameloblastic fibroma in a rhesus macaque (Macaca mulatta) with characterizations of its proliferating activity and biological behavior

PubMed Central

Liu, David X.; Doyle, Lara A.; Bouljihad, Mostafa T.; Didier, Peter J.; Gilbert, Margaret H.; Wang, Xiaolei; Pahar, Bapi; Bohm, Rudolf P.; Veazey, Ronald S.; Lackner, Andrew A.

2014-01-01

An 8-year-old male rhesus macaque (Macaca mulatta) presented with unilateral enlargement of the left mandible. Radiographs revealed a marked expansion of the left mandible with a multilocular radiolucent mass with abundant osteolysis. The mass was grossly firm, fleshy, and gelatinous on the cut surface. Histologically, the mass was locally infiltrative and composed of neoplastic epithelial and mesenchymal components that stained positive for cytokeratin and vimentin, respectively. Occasional densely spherical condensations of fibroblasts resembling the cap stage of odontogenesis were present in the mesenchyma. Immunohistochemical staining with Ki-67, S-100, and CD34 indicated that both epithelial and mesenchymal components of the neoplasm had low proliferation. Alcian blue, periodic acid–Schiff, and trichrome stains showed an immature stromal component with no collagen formation. Based on the clinical, histologic, and immunophenotypic features, the tumor was identified as a locally infiltrative ameloblastic fibroma. PMID:22529141

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 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.

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

PubMed Central

Hayashi, Takuya; Wakao, Shohei; Kitada, Masaaki; Ose, Takayuki; Watabe, Hiroshi; Kuroda, Yasumasa; Mitsunaga, Kanae; Matsuse, Dai; Shigemoto, Taeko; Ito, Akihito; Ikeda, Hironobu; Fukuyama, Hidenao; Onoe, Hirotaka; Tabata, Yasuhiko; Dezawa, Mari

2012-01-01

A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson’s disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [11C]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson’s disease. PMID:23202734

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.

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.

Economic Choices Reveal Probability Distortion in Macaque Monkeys

PubMed Central

Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

2015-01-01

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

Economic choices reveal probability distortion in macaque monkeys.

PubMed

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

2015-02-18

Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

Stimulus features coded by single neurons of a macaque body category selective patch.

PubMed

Popivanov, Ivo D; Schyns, Philippe G; Vogels, Rufin

2016-04-26

Body category-selective regions of the primate temporal cortex respond to images of bodies, but it is unclear which fragments of such images drive single neurons' responses in these regions. Here we applied the Bubbles technique to the responses of single macaque middle superior temporal sulcus (midSTS) body patch neurons to reveal the image fragments the neurons respond to. We found that local image fragments such as extremities (limbs), curved boundaries, and parts of the torso drove the large majority of neurons. Bubbles revealed the whole body in only a few neurons. Neurons coded the features in a manner that was tolerant to translation and scale changes. Most image fragments were excitatory but for a few neurons both inhibitory and excitatory fragments (opponent coding) were present in the same image. The fragments we reveal here in the body patch with Bubbles differ from those suggested in previous studies of face-selective neurons in face patches. Together, our data indicate that the majority of body patch neurons respond to local image fragments that occur frequently, but not exclusively, in bodies, with a coding that is tolerant to translation and scale. Overall, the data suggest that the body category selectivity of the midSTS body patch depends more on the feature statistics of bodies (e.g., extensions occur more frequently in bodies) than on semantics (bodies as an abstract category).

Stimulus features coded by single neurons of a macaque body category selective patch

PubMed Central

Popivanov, Ivo D.; Schyns, Philippe G.; Vogels, Rufin

2016-01-01

Body category-selective regions of the primate temporal cortex respond to images of bodies, but it is unclear which fragments of such images drive single neurons’ responses in these regions. Here we applied the Bubbles technique to the responses of single macaque middle superior temporal sulcus (midSTS) body patch neurons to reveal the image fragments the neurons respond to. We found that local image fragments such as extremities (limbs), curved boundaries, and parts of the torso drove the large majority of neurons. Bubbles revealed the whole body in only a few neurons. Neurons coded the features in a manner that was tolerant to translation and scale changes. Most image fragments were excitatory but for a few neurons both inhibitory and excitatory fragments (opponent coding) were present in the same image. The fragments we reveal here in the body patch with Bubbles differ from those suggested in previous studies of face-selective neurons in face patches. Together, our data indicate that the majority of body patch neurons respond to local image fragments that occur frequently, but not exclusively, in bodies, with a coding that is tolerant to translation and scale. Overall, the data suggest that the body category selectivity of the midSTS body patch depends more on the feature statistics of bodies (e.g., extensions occur more frequently in bodies) than on semantics (bodies as an abstract category). PMID:27071095

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

PubMed

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

2016-08-01

Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally infected with viral homologs of HHV-6 and HHV-7, which we provisionally named MneHV6 and MneHV7, respectively. In this study, we confirm that MneHV7 is genetically and biologically similar to its human counterpart, HHV-7. We determined the complete unique MneHV7 genome sequence and provide a comprehensive annotation of all genes. We also characterized viral transcription profiles in salivary glands from naturally infected macaques. We show that broad transcriptional activity across most of the viral genome is associated with high viral loads in infected parotid glands and that late viral protein expression is detected in salivary duct cells and peripheral nerve ganglia. Our study provides new insights into the natural behavior of an extremely prevalent virus and establishes a basis for subsequent investigations of the mechanisms that cause HHV-7 reactivation and associated disease. Copyright © 2016 Staheli et al.

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

PubMed Central

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

2016-01-01

ABSTRACT Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. IMPORTANCE Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally infected with viral homologs of HHV-6 and HHV-7, which we provisionally named MneHV6 and MneHV7, respectively. In this study, we confirm that MneHV7 is genetically and biologically similar to its human counterpart, HHV-7. We determined the complete unique MneHV7 genome sequence and provide a comprehensive annotation of all genes. We also characterized viral transcription profiles in salivary glands from naturally infected macaques. We show that broad transcriptional activity across most of the viral genome is associated with high viral loads in infected parotid glands and that late viral protein expression is detected in salivary duct cells and peripheral nerve ganglia. Our study provides new insights into the natural behavior of an extremely prevalent virus and establishes a basis for subsequent investigations of the mechanisms that cause HHV-7 reactivation and associated disease. PMID:27170755

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

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

Population Genetic Structure of the Cayo Santiago Colony of Rhesus Macaques (Macaca mulatta).

PubMed

Kanthaswamy, Sreetharan; Oldt, Robert F; Ng, Jillian; Ruiz-Lambides, Angelina V; Maldonado, Elizabeth; Martínez, Melween I; Sariol, Carlos A

2017-07-01

The rhesus macaque population at Cayo Santiago increases annually and is in urgent need of control. In-depth assessments of the colony's population genetic and pedigree structures provide a starting point for improving the colony's long-term management program. We evaluated the degree of genetic variation and coefficients of inbreeding and kinship of the Cayo Santiago colony by using pedigree and short tandem repeat (STR) data from 4738 rhesus macaques, which represent 7 extant social groups and a group of migrant males. Information on each animal's parentage, sex, birth date, and date of death or removal from the island were used to generate estimates of mean kinship, kinship value, gene value, genome uniqueness (GU), founder equivalents (fe), and founder genome equivalents (fg). Pedigree and STR analyses revealed that the social groups have not differentiated genetically from each other due to male-mediated gene flow (that is, FST estimates were in the negative range) and exhibit sufficient genetic variation, with mean estimates of allele numbers and observed and expected heterozygosity of 6.57, 0.72, and 0.70, respectively. Estimates of GU, fe, and fg show that a high effective number of founders has affected the colony's current genetic structure in a positive manner. As demographic changes occur, genetic and pedigree matrices need to be monitored consistently to ensure the health and wellbeing of the Cayo Santiago colony.

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

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

PubMed

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

2017-07-19

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

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

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.

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.

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.

A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots.

PubMed

Ye, Ling; Yong, Ken-Tye; Liu, Liwei; Roy, Indrajit; Hu, Rui; Zhu, Jing; Cai, Hongxing; Law, Wing-Cheung; Liu, Jianwei; Wang, Kai; Liu, Jing; Liu, Yaqian; Hu, Yazhuo; Zhang, Xihe; Swihart, Mark T; Prasad, Paras N

2012-05-20

Quantum dots have been used in biomedical research for imaging, diagnostics and sensing purposes. However, concerns over the cytotoxicity of their heavy metal constituents and conflicting results from in vitro and small animal toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates.

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

PubMed Central

Simmons, Heather A.; Salamat, M. Shahriar; Thoong, Troy H.; Weiler, Andrea M.; Barry, Gabrielle L.; Weisgrau, Kim L.; Vosler, Logan J.; Mohns, Mariel S.; Breitbach, Meghan E.; Stewart, Laurel M.; Newman, Christina M.; Graham, Michael E.; Turski, Patrick A.; Post, Jennifer; Hayes, Jennifer M.; Schotzko, Michele L.; Permar, Sallie R.; Rakasz, Eva G.; Capuano, Saverio; Tarantal, Alice F.; Osorio, Jorge E.; O’Connor, Shelby L.

2017-01-01

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals in a previous study contemporary with the current report clear viremia within 10–12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection. The results may also suggest that maternal-fetal ZIKV transmission in human pregnancy may be more frequent than currently appreciated. PMID:28542585

Permeability of blood-brain barrier in macaque model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson disease.

PubMed

Thiollier, Thibaud; Wu, Caisheng; Contamin, Hugues; Li, Qin; Zhang, Jinlan; Bezard, Erwan

2016-06-01

Brain bioavailability of drugs developed to address central nervous system diseases is classically documented through cerebrospinal fluid collected in normal animals, i.e., through an approximation as there are fundamental differences between cerebrospinal fluid and tissue contents. The fact that disease might affect brain availability of drugs is almost never considered at this stage although several conditions are associated with blood-brain barrier damage. Building upon our expertise in Parkinson's disease translational research, the present study addressed this gap comparing plasma and cerebrospinal fluid bioavailability of l-3,4-dihydroxyphenylalanine, carbamazepine, quinidine, lovastatin, and simvastatin, in healthy and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques, the gold standard model of Parkinson's disease. The drugs were selected based upon their differential transport across the blood-brain barrier. Interestingly, brain bioavailability of quinidine was decreased while others were unaffected. Pharmacokinetics and pharmacodynamics experiments of drugs addressing Parkinson's disease might thus be performed in healthy animals unless the drugs are known to interact with the organic cation transporter. © 2016 Wiley Periodicals, Inc.

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…

Measles Virus Infection of Epithelial Cells in the Macaque Upper Respiratory Tract Is Mediated by Subepithelial Immune Cells

PubMed Central

Ludlow, Martin; Lemon, Ken; de Vries, Rory D.; McQuaid, Stephen; Millar, Emma L.; van Amerongen, Geert; Yüksel, Selma; Verburgh, R. Joyce; Osterhaus, Albert D. M. E.; Duprex, W. Paul

2013-01-01

Measles virus (MV), one of the most contagious viruses infecting humans, causes a systemic infection leading to fever, immune suppression, and a characteristic maculopapular rash. However, the specific mechanism or mechanisms responsible for the spread of MV into the respiratory epithelium in the late stages of the disease are unknown. Here we show the crucial role of PVRL4 in mediating the spread of MV from immune to epithelial cells by generating a PVRL4 “blind” recombinant wild-type MV and developing a novel in vitro coculture model of B cells with primary differentiated normal human bronchial epithelial cells. We utilized the macaque model of measles to analyze virus distribution in the respiratory tract prior to and at the peak of MV replication. Expression of PVRL4 was widespread in both the lower and upper respiratory tract (URT) of macaques, indicating MV transmission can be facilitated by more than only epithelial cells of the trachea. Analysis of tissues collected at early time points after experimental MV infection demonstrated the presence of MV-infected lymphoid and myeloid cells contacting respiratory tract epithelium in the absence of infected epithelial cells, suggesting that these immune cells seed the infection in vivo. Thereafter, lateral cell-to-cell spread of MV led to the formation of large foci of infected cells in the trachea and high levels of MV infection in the URT, particularly in the nasal cavity. These novel findings have important implications for our understanding of the high transmissibility of measles. PMID:23365435

Herpes B Virus, Macacine Herpesvirus 1, Breaks Simplex Virus Tradition via Major Histocompatibility Complex Class I Expression in Cells from Human and Macaque Hosts

PubMed Central

Vasireddi, Mugdha

2012-01-01

B virus of the family Herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. Downregulation of major histocompatibility complex (MHC) class I in order to evade CD8+ T-cell activation is characteristic of most herpesviruses. Here we examined the cell surface presence and total protein expression of MHC class I molecules in B virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are representative of foreign and natural host initial target cells of B virus. Our results show <20% downregulation of surface MHC class I molecules in either type of host cells infected with B virus, which is statistically insignificantly different from that observed in uninfected cells. We also examined the surface expression of MHC class Ib molecules, HLA-E and HLA-G, involved in NK cell inhibition. Our results showed significant upregulation of HLA-E and HLA-G in host cells infected with B virus relative to the amounts observed in other herpesvirus-infected cells. These results suggest that B virus-infected cell surfaces maintain normal levels of MHC class Ia molecules, a finding unique among simplex viruses. This is a unique divergence in immune evasion for B virus, which, unlike human simplex viruses, does not inhibit the transport of peptides for loading onto MHC class Ia molecules because B virus ICP47 lacks a transporter-associated protein binding domain. The fact that MHC class Ib molecules were significantly upregulated has additional implications for host-pathogen interactions. PMID:22973043

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.

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

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

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

PubMed

Kajikawa, Yoshinao; Smiley, John F; Schroeder, Charles E

2017-10-18

Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. Copyright © 2017 the authors 0270-6474/17/3710139-15$15.00/0.

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

PubMed Central

Smiley, John F.; Schroeder, Charles E.

2017-01-01

Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed “local” (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. PMID:28924008

The Extracellular Domain of Myelin Oligodendrocyte Glycoprotein Elicits Atypical Experimental Autoimmune Encephalomyelitis in Rat and Macaque Species

PubMed Central

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

2014-01-01

Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund’s adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund’s adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6–7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and brainstem, and atypical disease induction. PMID:25303101

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

PubMed

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

2014-01-01

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

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

PubMed Central

Li, Xiao-Hong; Xu, Yu-Xin; Vance, Gill; Wang, Yun; Lv, Long-Bao; van Dam, Govert J.; Cao, Jian-Ping; Wilson, R. Alan

2015-01-01

Background Rhesus macaques are unusual among schistosome hosts, self-curing from an established infection and thereafter manifesting solid immunity against a challenge, an ideal model for vaccine development. Previously, the immunological basis of self-cure was confirmed; surviving worms had ceased feeding but how immunological pressure achieved this was unclear. The schistosome esophagus is not simply a conduit for blood but plays a central role in its processing. Secretions from the anterior and posterior esophageal glands mix with incoming blood causing erythrocyte lysis and tethering and killing of leucocytes. Methodology/Principal Findings We have analysed the self-cure process in rhesus macaques infected with Schistosoma japonicum. Faecal egg output and circulating antigen levels were used to chart the establishment of a mature worm population and its subsequent demise. The physiological stress of surviving females at perfusion was especially evident from their pale, shrunken appearance, while changes in the structure and function of the esophagus were observed in both sexes. In the anterior region electron microscopy revealed that the vesicle secretory process was disrupted, the tips of lining corrugations being swollen by greatly enlarged vesicles and the putative sites of vesicle release obscured by intense deposits of IgG. The lumen of the posterior esophagus in starving worms was occluded by cellular debris and the lining cytoplasmic plates were closely adherent, also potentially preventing secretion. Seven proteins secreted by the posterior gland were identified and IgG responses were detected to some or all of them. Intrinsic rhesus IgG colocalized with secreted SjMEGs 4.1, 8.2, 9, 11 and VAL-7 on cryosections, suggesting they are potential targets for disruption of function. Conclusions/Significance Our data suggest that rhesus macaques self-cure by blocking esophagus function with antibody; the protein products of the glands provide a new class of potential vaccine targets. PMID:26161644

Quaternary climate change and social behavior shaped the genetic differentiation of an endangered montane primate from the southern edge of the Tibetan Plateau.

PubMed

Chakraborty, Debapriyo; Ramakrishnan, Uma; Sinha, Anindya

2015-03-01

Multiple factors, including climate change, dispersal barriers, and social behavior influence the genetic structure of natural populations. While the effects of extrinsic factors such as historical climatic change and habitat topography have been well studied, mostly in temperate habitats, the simultaneous effects of intrinsic factors such as social behavior on genetic structure have rarely been explored. Such simultaneous effect, however, may particularly be common in social mammals such as many primates. Consequently, we studied the population structure of a rare and endangered social primate, the Arunachal macaque Macaca munzala, endemic to the northeastern Indian state of Arunachal Pradesh, located on the subtropical southern edge of the Tibetan Plateau and forming part of the Eastern Himalayan biodiversity hotspot. We studied a 534 bp-long mitochondrial DNA sequence and 22 autosomal microsatellite loci in individuals from three populations, Tawang, Upper Subansiri, and West Siang. The mtDNA data revealed three major divergence events: that between the Arunachal and bonnet macaques (ca. 1.61 mya), the founding of the West Siang population and the ancestral population of the present-day bonnet macaques (ca. 1.32 mya), and the divergence between the Tawang and Upper Subansiri populations (ca. 0.80 mya) that coincided with the major glacial events in the region. Comparing mitochondrial DNA with autosomal microsatellites, we also found evidence for female philopatry and male-driven long-distance gene flow. Arunachal macaques thus appear to be characterized by groups of philopatric females separated by geographical barriers and harsh climate but with dispersing males exerting a homogenizing effect on the nuclear gene pool. Given that severe population differentiation is of major concern in species conservation, we suggest that our study populations represent significant conservation units of this rare, endangered primate but, more importantly, emphasize the complex interplay of extrinsic and intrinsic factors in shaping the population structure of a social mammalian species. © 2014 Wiley Periodicals, Inc.

Mitochondrial DNA and retroviral RNA analyses of archival oral polio vaccine (OPV CHAT) materials: evidence of macaque nuclear sequences confirms substrate identity.

PubMed

Berry, Neil; Jenkins, Adrian; Martin, Javier; Davis, Clare; Wood, David; Schild, Geoffrey; Bottiger, Margareta; Holmes, Harvey; Minor, Philip; Almond, Neil

2005-02-25

Inoculation of live experimental oral poliovirus vaccines (OPV CHAT) during the 1950s in central Africa has been proposed to account for the introduction of HIV into human populations. For this to have occurred, it would have been necessary for chimpanzee rather than macaque kidney epithelial cells to have been included in the preparation of early OPV materials. Theoretically, this could have led to contamination with a progenitor of HIV-1 derived from a related simian immunodeficiency virus of chimpanzees (SIVCPZ). In this article we present further detailed analyses of two samples of OPV, CHAT 10A-11 and CHAT 6039/Yugo, which were used in early human trials of poliovirus vaccination. Recovery of poliovirus by culture techniques confirmed the biological viability of the vaccines and sequence analysis of poliovirus RNA specifically identified the presence of the CHAT strain. Independent nested sets of oligonucleotide primers specific for HIV-1/SIVCPZ and HIV-2/SIVMAC/SIVSM phylogenetic lineages, respectively, indicated no evidence of HIV/SIV RNA in either vaccine preparation, at a sensitivity of 100 RNA equivalents/ml. Analysis of cellular substrate by the amplification of two distinct regions of mitochondrial DNA (D-loop control region and 12S ribosomal sequences) revealed no evidence of chimpanzee cellular sequences. However, this approach positively identified rhesus and cynomolgus macaque DNA for the CHAT 10A-11 and CHAT 6039/Yugo vaccine preparations, respectively. Analysis of multiple clones of mtDNA 12S rDNA indicated a relatively high number of nuclear mitochondrial DNA sequences (numts) in the CHAT 10A-11 material, but confirmed the macaque origin of cellular substrate used in vaccine preparation. These data reinforce earlier findings on this topic providing no evidence to support the contention that poliovirus vaccination was responsible for the introduction of HIV into humans and sparking the AIDS pandemic.

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

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

FLB1, a human protein of epididymal origin that is involved in the sperm-oocyte recognition process.

PubMed

Boué, F; Duquenne, C; Lassalle, B; Lefèvre, A; Finaz, C

1995-02-01

CA6 antibody was selected out of a monoclonal antibody library raised against human sperm proteins primarily for its ability to recognize an epididymal antigen and to modify sperm adhesion to zona-free hamster oocytes. In the present study, CA6 was shown to decrease sperm binding to zona-free hamster and human oocytes by 40-92% and 38-48%, respectively. The corresponding protein, which was referred to as FLB1, was found to be secreted by the epididymis and to bind specifically to a human, macaque, and rodent subacrosomal sperm region. Western blotting revealed a molecular mass of 94 kDa in human epididymal extracts and of 100 kDa in human, macaque, mouse, rat, and hamster sperm, suggesting further modifications after its binding to sperm. An equivalent protein was not observed in human liver, ovary, testis, plasma, or epidermis. Two-dimensional electrophoresis showed that FLB1 is formed of two subunits with the same 47-kDa molecular mass and slightly different pI (5.8, 5.9). Microsequencing of the protein revealed a partial homology with human cytokeratins 1 and 10. These results suggest that FLB1 is an epididymis-specific cytokeratin-like protein that is involved in the sperm-oocyte recognition process.

Simian Homologues of Human Gamma-2 and Betaherpesviruses in Mandrill and Drill Monkeys

PubMed Central

Lacoste, Vincent; Mauclere, Philippe; Dubreuil, Guy; Lewis, John; Georges-Courbot, Marie-Claude; Rigoulet, Jacques; Petit, Thierry; Gessain, Antoine

2000-01-01

Recent serological and molecular surveys of different primate species allowed the characterization of several Kaposi's sarcoma-associated herpesvirus (KSHV) homologues in macaques, African green monkeys, chimpanzees, and gorillas. Identification of these new primate rhadinoviruses revealed the existence of two distinct genogroups, called RV1 and RV2. Using a degenerate consensus primer PCR method for the herpesvirus DNA polymerase gene, the presence of KSHV homologues has been investigated in two semi-free-ranging colonies of eight drill (Mandrillus leucophaeus), five mandrill (Mandrillus sphinx), and two hybrid (Mandrillus leucophaeus-Mandrillus sphinx) monkeys, living in Cameroon and Gabon, Central Africa. This search revealed the existence of not only two distinct KSHV homologues, each one belonging to one of the two rhadinovirus genogroups, but also of two new betaherpesvirus sequences, one being close to cytomegaloviruses and the other being related to human herpesviruses 6 and 7 (HHV-6 and -7). The latter viruses are the first simian HHV-6 and -7 homologues identified to date. These data show that mandrill and drill monkeys are the hosts of at least four novel distinct herpesviruses. Moreover, mandrills, like macaques and African green monkeys, harbor also two distinct gamma-2 herpesviruses, thus strongly suggesting that a second gamma-2 herpesvirus, belonging to the RV2 genogroup, may exist in humans. PMID:11090203

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

The Motivational Salience of Faces Is Related to Both Their Valence and Dominance.

PubMed

Wang, Hongyi; Hahn, Amanda C; DeBruine, Lisa M; Jones, Benedict C

2016-01-01

Both behavioral and neural measures of the motivational salience of faces are positively correlated with their physical attractiveness. Whether physical characteristics other than attractiveness contribute to the motivational salience of faces is not known, however. Research with male macaques recently showed that more dominant macaques' faces hold greater motivational salience. Here we investigated whether dominance also contributes to the motivational salience of faces in human participants. Principal component analysis of third-party ratings of faces for multiple traits revealed two orthogonal components. The first component ("valence") was highly correlated with rated trustworthiness and attractiveness. The second component ("dominance") was highly correlated with rated dominance and aggressiveness. Importantly, both components were positively and independently related to the motivational salience of faces, as assessed from responses on a standard key-press task. These results show that at least two dissociable components underpin the motivational salience of faces in humans and present new evidence for similarities in how humans and non-human primates respond to facial cues of dominance.

Social bonds affect anti-predator behaviour in a tolerant species of macaque, Macaca nigra.

PubMed

Micheletta, Jérôme; Waller, Bridget M; Panggur, Maria R; Neumann, Christof; Duboscq, Julie; Agil, Muhammad; Engelhardt, Antje

2012-10-07

Enduring positive social bonds between individuals are crucial for humans' health and well being. Similar bonds can be found in a wide range of taxa, revealing the evolutionary origins of humans' social bonds. Evidence suggests that these strong social bonds can function to buffer the negative effects of living in groups, but it is not known whether they also function to minimize predation risk. Here, we show that crested macaques (Macaca nigra) react more strongly to playbacks of recruitment alarm calls (i.e. calls signalling the presence of a predator and eliciting cooperative mobbing behaviour) if they were produced by an individual with whom they share a strong social bond. Dominance relationships between caller and listener had no effect on the reaction of the listener. Thus, strong social bonds may improve the coordination and efficiency of cooperative defence against predators, and therefore increase chances of survival. This result broadens our understanding of the evolution and function of social bonds by highlighting their importance in the anti-predator context.

Immunization-elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability

PubMed Central

Zhao, Xuelian; Howell, Katie A.; He, Shihua; Brannan, Jennifer M.; Wec, Anna Z.; Davidson, Edgar; Turner, Hannah L.; Chiang, Chi-I; Lei, Lin; Fels, J. Maximilian; Vu, Hong; Shulenin, Sergey; Turonis, Ashley N.; Kuehne, Ana I.; Liu, Guodong; Ta, Mi; Wang, Yimeng; Sundling, Christopher; Xiao, Yongli; Spence, Jennifer S.; Doranz, Benjamin J.; Holtsberg, Frederick W.; Ward, Andrew B.; Chandran, Kartik; Dye, John M.; Qiu, Xiangguo; Li, Yuxing; Aman, M. Javad

2018-01-01

Summary While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N-terminus of the ebolavirus glycoproteins (GP) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque suggests that elicitation of broadly neutralizing antibodies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones and their precursors. Unexpectedly, germline-reverted CA45, while exhibiting negligible binding to full-length GP, bound a proteolytically remodeled GP with picomolar affinity, suggesting that engineered ebolavirus vaccines could trigger rare bNAb precursors more robustly. These findings have important implications for developing pan-ebolavirus vaccine and immunotherapeutic cocktails. PMID:28525756

Full genome sequence analysis of a novel adenovirus of rhesus macaque origin indicates a new simian adenovirus type and species.

PubMed

Malouli, Daniel; Howell, Grant L; Legasse, Alfred W; Kahl, Christoph; Axthelm, Michael K; Hansen, Scott G; Früh, Klaus

2014-09-01

Multiple novel simian adenoviruses have been isolated over the past years and their potential to cross the species barrier and infect the human population is an ever present threat. Here we describe the isolation and full genome sequencing of a novel simian adenovirus (SAdV) isolated from the urine of two independent, never co-housed, late stage simian immunodeficiency virus (SIV)-infected rhesus macaques. The viral genome sequences revealed a novel type with a unique genome length, GC content, E3 region and DNA polymerase amino acid sequence that is sufficiently distinct from all currently known human- or simian adenovirus species to warrant classifying these isolates as a novel species of simian adenovirus. This new species, termed Simian mastadenovirus D (SAdV-D), displays the standard genome organization for the genus Mastadenovirus containing only one copy of the fiber gene which sets it apart from the old world monkey adenovirus species HAdV-G, SAdV-B and SAdV-C.

Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques.

PubMed

Stieh, Daniel J; Matias, Edgar; Xu, Huanbin; Fought, Angela J; Blanchard, James L; Marx, Preston A; Veazey, Ronald S; Hope, Thomas J

2016-04-13

The difficulty in detecting rare infected cells immediately after mucosal HIV transmission has hindered our understanding of the initial cells targeted by the virus. Working with the macaque simian immunodeficiency virus (SIV) vaginal challenge model, we developed methodology to identify discrete foci of SIV (mac239) infection 48 hr after vaginal inoculation. We find infectious foci throughout the reproductive tract, from labia to ovary. Phenotyping infected cells reveals that SIV has a significant bias for infection of CCR6+ CD4+ T cells. SIV-infected cells expressed the transcriptional regulator RORγt, confirming that the initial target cells are specifically of the Th17 lineage. Furthermore, we detect host responses to infection, as evidenced by apoptosis, cell lysis, and phagocytosis of infected cells. Thus, our analysis identifies Th17-lineage CCR6+ CD4+ T cells as primary targets of SIV during vaginal transmission. This opens new opportunities for interventions to protect these cells and prevent HIV transmission. Copyright © 2016 Elsevier Inc. All rights reserved.

Tuned Normalization Explains the Size of Attention Modulations

PubMed Central

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

2012-01-01

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

Tuned normalization explains the size of attention modulations.

PubMed

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

2012-02-23

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

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.

Visual responses of ganglion cells of a New-World primate, the capuchin monkey, Cebus apella.

PubMed

Lee, B B; Silveira, L C; Yamada, E S; Hunt, D M; Kremers, J; Martin, P R; Troy, J B; da Silva-Filho, M

2000-11-01

1. The genetic basis of colour vision in New-World primates differs from that in humans and other Old-World primates. Most New-World primate species show a polymorphism; all males are dichromats and most females trichromats. 2. In the retina of Old-World primates such as the macaque, the physiological correlates of trichromacy are well established. Comparison of the retinae in New- and Old-World species may help constrain hypotheses as to the evolution of colour vision and the pathways associated with it. 3. Ganglion cell behaviour was recorded from trichromatic and dichromatic members of a New-World species (the capuchin monkey, Cebus apella) and compared with macaque data. Despite some differences in quantitative detail (such as a temporal response extended to higher frequencies), results from trichromatic animals strongly resembled those from the macaque. 4. In particular, cells of the parvocellular (PC) pathway showed characteristic frequency-dependent changes in responsivity to luminance and chromatic modulation, cells of the magnocellular (MC) pathway showed frequency-doubled responses to chromatic modulation, and the surround of MC cells received a chromatic input revealed on changing the phase of heterochromatically modulated lights. 5. Ganglion cells of dichromats were colour-blind versions of those of trichromats. 6. This strong physiological homology is consistent with a common origin of trichromacy in New- and Old-World monkeys; in the New-World primate the presence of two pigments in the middle-to-long wavelength range permits full expression of the retinal mechanisms of trichromatic vision.

Identification of an Enterocytozoon bieneusi-like microsporidian parasite in simian-immunodeficiency-virus-inoculated macaques with hepatobiliary disease.

PubMed Central

Mansfield, K. G.; Carville, A.; Shvetz, D.; MacKey, J.; Tzipori, S.; Lackner, A. A.

1997-01-01

Enterocytozoon bieneusi is a common opportunistic pathogen of human patients with acquired immune deficiency syndrome (AIDS) causing significant morbidity and mortality. In a retrospective analysis utilizing conventional histochemical techniques, in situ hybridization, polymerase chain reaction, and ultrastructural examination, we identified 18 simian-immunodeficiency-virus-infected macaques (16 Macaca mulatta, 1 M. nemestrina, and 1 M. cyclopis) with Enterocytozoon infection of the hepatobiliary system and small intestine. The organisms were readily identified in the bile ducts and gall bladder by special stains and by in situ hybridization using a probe directed against the small subunit ribosomal RNA of human origin E. bieneusi. Infection of the biliary system was associated with a nonsuppurative and proliferative cholecystitis and choledochitis. Hepatic involvement was characterized by bridging portal fibrosis and nodular hepatocellular regeneration accompanied by marked bile ductular and septal duct hyperplasia. Ultrastructurally, all developmental stages of the organism were found in direct contact with the host cell cytoplasm; spores and sporoblasts contained a double layer of polar tubes. Sequencing of a 607-bp segment of the small subunit ribosomal RNA revealed 97 and 100% identity to two clones of small subunit ribosomal RNA derived from E. bieneusi of human origin. Extensive morphological and genetic similarities between the simian and human enterocytozoons suggest that experimentally infected macaques may serve as a useful model of microsporidial infection in AIDS. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9094995

FACIAL ASYMMETRY IS NEGATIVELY RELATED TO CONDITION IN FEMALE MACAQUE MONKEYS

PubMed Central

Little, Anthony C.; Paukner, Annika; Woodward, Ruth A.; Suomi, Stephen J.

2013-01-01

The face is an important visual trait in social communication across many species. In evolutionary terms there are large and obvious selective advantages in detecting healthy partners, both in terms of avoiding individuals with poor health to minimise contagion and in mating with individuals with high health to help ensure healthy offspring. Many models of sexual selection suggest that an individual’s phenotype provides cues to their quality. Fluctuating asymmetry is a trait that is proposed to be an honest indicator of quality and previous studies have demonstrated that rhesus monkeys gaze longer at symmetric faces, suggesting preferences for such faces. The current study examined the relationship between measured facial symmetry and measures of health in a captive population of female rhesus macaque monkeys. We measured asymmetry from landmarks marked on front-on facial photographs and computed measures of health based on veterinary health and condition ratings, number of minor and major wounds sustained, and gain in weight over the first four years of life. Analysis revealed that facial asymmetry was negatively related to condition related health measures, with symmetric individuals being healthier than more asymmetric individuals. Facial asymmetry appears to be an honest indicator of health in rhesus macaques and asymmetry may then be used by conspecifics in mate-choice situations. More broadly, our data support the notion that faces are valuable sources of information in non-human primates and that sexual selection based on facial information is potentially important across the primate lineage. PMID:23667290

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

PubMed

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

2018-02-01

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

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

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

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.

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.

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

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

Validating skinfold thickness as a proxy to estimate total body fat in wild toque macaques (Macaca sinica) using the mass of dissected adipose tissue.

PubMed

Dittus, Wolfgang P J; Gunathilake, K A Sunil

2015-06-01

Skinfold thickness (SFT) has been used often in non-human primates and humans as a proxy to estimate fatness (% body fat). We intended to validate the relation between SFT (in recently deceased specimens) and the mass of adipose tissue as determined from dissection of fresh carcasses of wild toque macaques (Macaca sinica). In adult male and female toque macaques body composition is normally 2% adipose tissue. Calipers for measuring SFT were suitable for measuring only some subcutaneous deposits of adipose tissue but were not suitable for measuring large fat deposits within the body cavity or minor intermuscular ones. The anatomical distribution of 13 different adipose deposits, in different body regions (subcutaneous, intra-abdominal and intermuscular) and their proportional size differences, were consistent in this species (as in other primates), though varying in total mass among individuals. These consistent allometric relationships were fundamental for estimating fatness of different body regions based on SFT. The best fit statistically significant correlations and regressions with the known masses of dissectible adipose tissue were evident between the SFT means of the seven sites measured, as well as with a single point on the abdomen anterior to the umbilicus. SFT related to total fat mass and intra-abdominal fat mass in curvilinear regressions and to subcutaneous fat mass in a linear relationship. To adjust for differences in body size among individuals, and to circumvent intangible variations in total body mass allocated, for example to the gastro-intestinal contents, dissected fat mass was estimated per unit body size (length of crown-rump)(3). SFT had greater coefficients of correlation and regressions with this Fat Mass Index (g/dm(3)) than with Percent Body Fat. © 2015 Wiley Periodicals, Inc.

Neurochemical evidence supporting dopamine D1-D2 receptor heteromers in the striatum of the long-tailed macaque: changes following dopaminergic manipulation.

PubMed

Rico, Alberto J; Dopeso-Reyes, Iria G; Martínez-Pinilla, Eva; Sucunza, Diego; Pignataro, Diego; Roda, Elvira; Marín-Ramos, David; Labandeira-García, José L; George, Susan R; Franco, Rafael; Lanciego, José L

2017-05-01

Although it has long been widely accepted that dopamine receptor types D1 and D2 form GPCR heteromers in the striatum, the presence of D1-D2 receptor heteromers has been recently challenged. In an attempt to properly characterize D1-D2 receptor heteromers, here we have used the in situ proximity ligation assay (PLA) in striatal sections comprising the caudate nucleus, the putamen and the core and shell territories of the nucleus accumbens. Experiments were carried out in control macaques as well as in MPTP-treated animals (with and without dyskinesia). Obtained data support the presence of D1-D2 receptor heteromers within all the striatal subdivisions, with the highest abundance in the accumbens shell. Dopamine depletion by MPTP resulted in an increase of D1-D2 density in caudate and putamen which was normalized by levodopa treatment. Two different sizes of heteromers were consistently found, thus suggesting that besides individual heteromers, D1-D2 receptor heteromers are sometimes organized in macromolecular complexes made of a number of D1-D2 heteromers. Furthermore, the PLA technique was combined with different neuronal markers to properly characterize the identities of striatal neurons expressing D1-D2 heteromers. We have found that striatal projection neurons giving rise to either the direct or the indirect basal ganglia pathways expressed D1-D2 heteromers. Interestingly, macromolecular complexes of D1-D2 heteromers were only found within cholinergic interneurons. In summary, here we provide overwhelming proof that D1 and D2 receptors form heteromeric complexes in the macaque striatum, thus representing a very appealing target for a number of brain diseases involving dopamine dysfunction.

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.

Profound loss of intestinal Tregs in acutely SIV-infected neonatal macaques.

PubMed

Wang, Xiaolei; Xu, Huanbin; Shen, Chanjuan; Alvarez, Xavier; Liu, David; Pahar, Bapi; Ratterree, Marion S; Doyle-Meyers, Lara A; Lackner, Andrew A; Veazey, Ronald S

2015-02-01

Impairment of the intestinal mucosal immune system is an early feature of HIV-infected children. Most infected children exhibit clinical gastrointestinal symptoms at some stage of infection, and persistent diarrhea is a marker for rapid disease progression. It is known that Tregs are especially important in mediating intestinal immune homeostasis and that loss of this subset may result in intestinal inflammation and associated clinical signs. Large numbers of FoxP3(+) T cells were found in all tissues in newborn macaques, which coexpressed high levels of CD25 and CD4, indicating that they were Tregs. Moreover, neonates had much greater percentages of Tregs in intestinal tissues compared with peripheral lymphoid tissues. After SIV infection, a significant loss of Tregs was detected in the intestine compared with age-matched normal infants. Finally, SIV-infected FoxP3(+) T cells were detected in tissues in neonates as early as 7 SIV dpi. These results demonstrate that Tregs constitute a significant fraction of CD4(+) T cells in neonatal intestinal tissues and that an early, profound loss of Tregs occurs in acute SIV infection, which may contribute to the intestinal disorders associated with neonatal HIV infection. © Society for Leukocyte Biology.

Acute and chronic T cell dynamics in the livers of simian immunodeficiency virus-infected macaques.

PubMed

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

2012-05-01

The mucosal immune system, particularly the gastrointestinal tract, is critically involved in the pathogenesis of human immunodeficiency virus (HIV) infection. Since the liver drains most of the substances coming from the intestinal tract, it may also play a role in the pathogenesis of HIV infection. Here we examined the percentages and absolute numbers of T cell subsets in the liver in normal and simian immunodeficiency virus (SIV)-infected macaques. Most of the T cells in the liver were CD8(+) memory cells, and most of these had an effector memory (CD95(+) CD28(-)) phenotype. CD4(+) T cells constituted approximately 20% of the liver T cell population, but the vast majority of these were also memory (CD95(+)) CCR5(+) cells, suggesting they were potential targets for viral infection. After SIV infection, CD4(+) T cells were markedly reduced, and increased proliferation and absolute numbers of CD8(+) T cells were detected in the liver. These data suggest that the liver is a major source of antigenic stimulation for promoting CD8(+) T cells and possibly a source for early CD4(+) T cell infection and destruction.

Acute and Chronic T Cell Dynamics in the Livers of Simian Immunodeficiency Virus-Infected Macaques

PubMed Central

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

2012-01-01

The mucosal immune system, particularly the gastrointestinal tract, is critically involved in the pathogenesis of human immunodeficiency virus (HIV) infection. Since the liver drains most of the substances coming from the intestinal tract, it may also play a role in the pathogenesis of HIV infection. Here we examined the percentages and absolute numbers of T cell subsets in the liver in normal and simian immunodeficiency virus (SIV)-infected macaques. Most of the T cells in the liver were CD8+ memory cells, and most of these had an effector memory (CD95+ CD28−) phenotype. CD4+ T cells constituted approximately 20% of the liver T cell population, but the vast majority of these were also memory (CD95+) CCR5+ cells, suggesting they were potential targets for viral infection. After SIV infection, CD4+ T cells were markedly reduced, and increased proliferation and absolute numbers of CD8+ T cells were detected in the liver. These data suggest that the liver is a major source of antigenic stimulation for promoting CD8+ T cells and possibly a source for early CD4+ T cell infection and destruction. PMID:22379078

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.

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.

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

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.

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.

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.

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

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

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.

The Role of Attention in Binocular Rivalry as Revealed through Optokinetic Nystagmus.

DTIC Science & Technology

1995-11-01

break down selectively when parts of the stri- ate and prestriate cortex is damaged. Speci cally, a group of patients su ering fromApperceptive Agnosia ...1981). Visual performance in cases of visual agnosia . In M. van- Ho , & G. Hohn (Eds.), Functional recovery from brain damage (pp. 275{286...macaques. Nature, 373, 609{611. Breese, B. (1899). On inhibition. Psychol.Rev., 3, 1{65. Campion, J., & Latto, R. (1985). Apperceptive agnosia due to

Strength of Gamma Rhythm Depends on Normalization

PubMed Central

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

2013-01-01

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

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

Phylogeography of Barbary macaques (Macaca sylvanus) and the origin of the Gibraltar colony.

PubMed

Modolo, Lara; Salzburger, Walter; Martin, Robert D

2005-05-17

The Barbary macaque (Macaca sylvanus) is the earliest offshoot of the genus Macaca and the only extant African representative, all other species being Asiatic. Once distributed throughout North Africa, M. sylvanus is now restricted to isolated forest fragments in Algeria and Morocco. The species is threatened; the maximum total wild population size is estimated at 10,000 individuals. Relationships among surviving wild subpopulations in Algeria (96 samples) and Morocco (116 samples) were examined by using 468-bp sequences from hypervariable region I of the mitochondrial DNA control region. Twenty-four different haplotypes were identified, differing by 1-26 mutational steps (0.2-5.6%) and 1 insertion. With one exception (attributable to secondary introduction in coastal Morocco), Algerian and Moroccan haplotypes are clearly distinct. However, whereas Moroccan subpopulations show little divergence in hypervariable region I sequences and little correspondence with geographical distribution, there is a deep division between two main subpopulations in Algeria and one marked secondary division, with haplotypes generally matching geographical distribution. Accepting an origin of the genus Macaca of 5.5 million years ago, the Moroccan population and the two main Algerian subpopulations diverged approximately 1.6 million years ago. Distinction between Moroccan and Algerian haplotypes permitted analysis of the origin of the Gibraltar colony of Barbary macaques (68 samples; 30% of the population). It is generally held that the present Gibraltar population descended from a dozen individuals imported during World War II. However, the Gibraltar sample was found to include Algerian and Moroccan haplotypes separated by at least 16 mutational steps, revealing a dual origin of the founding females.

Phylogeography of Barbary macaques (Macaca sylvanus) and the origin of the Gibraltar colony

PubMed Central

Modolo, Lara; Salzburger, Walter; Martin, Robert D.

2005-01-01

The Barbary macaque (Macaca sylvanus) is the earliest offshoot of the genus Macaca and the only extant African representative, all other species being Asiatic. Once distributed throughout North Africa, M. sylvanus is now restricted to isolated forest fragments in Algeria and Morocco. The species is threatened; the maximum total wild population size is estimated at 10,000 individuals. Relationships among surviving wild subpopulations in Algeria (96 samples) and Morocco (116 samples) were examined by using 468-bp sequences from hypervariable region I of the mitochondrial DNA control region. Twenty-four different haplotypes were identified, differing by 1-26 mutational steps (0.2-5.6%) and 1 insertion. With one exception (attributable to secondary introduction in coastal Morocco), Algerian and Moroccan haplotypes are clearly distinct. However, whereas Moroccan subpopulations show little divergence in hypervariable region I sequences and little correspondence with geographical distribution, there is a deep division between two main subpopulations in Algeria and one marked secondary division, with haplotypes generally matching geographical distribution. Accepting an origin of the genus Macaca of 5.5 million years ago, the Moroccan population and the two main Algerian subpopulations diverged ≈1.6 million years ago. Distinction between Moroccan and Algerian haplotypes permitted analysis of the origin of the Gibraltar colony of Barbary macaques (68 samples; 30% of the population). It is generally held that the present Gibraltar population descended from a dozen individuals imported during World War II. However, the Gibraltar sample was found to include Algerian and Moroccan haplotypes separated by at least 16 mutational steps, revealing a dual origin of the founding females. PMID:15870193

Molecular Smallpox Vaccine Delivered by Alphavirus Replicons Elicits Protective Immunity in Mice and Non-human Primates

PubMed Central

Hooper, Jay W.; Ferro, Anthony M.; Golden, Joseph W.; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F.; Kamrud, Kurt I.

2009-01-01

Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine. PMID:19833247

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

Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

PubMed Central

Lawler, James V; Endy, Timothy P; Hensley, Lisa E; Garrison, Aura; Fritz, Elizabeth A; Lesar, May; Baric, Ralph S; Kulesh, David A; Norwood, David A; Wasieloski, Leonard P; Ulrich, Melanie P; Slezak, Tom R; Vitalis, Elizabeth; Huggins, John W; Jahrling, Peter B; Paragas, Jason

2006-01-01

Background The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. Methods and Findings In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. Conclusions SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children. PMID:16605302

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.

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.

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.

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

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

Topically applied recombinant chemokine analogues fully protect macaques from vaginal simian-human immunodeficiency virus challenge.

PubMed

Veazey, Ronald S; Ling, Binhua; Green, Linda C; Ribka, Erin P; Lifson, Jeffrey D; Piatak, Michael; Lederman, Michael M; Mosier, Donald; Offord, Robin; Hartley, Oliver

2009-05-15

Effective strategies for preventing human immunodeficiency virus infection are urgently needed, but recent failures in key clinical trials of vaccines and microbicides highlight the need for new approaches validated in relevant animal models. Here, we show that 2 new chemokine (C-C motif) receptor 5 inhibitors, 5P12-RANTES (regulated on activation, normal T cell expressed and secreted) and 6P4-RANTES, fully protect against infection in the rhesus vaginal challenge model. These highly potent molecules, which are amenable to low-cost production, represent promising new additions to the microbicides pipeline.

Well-mixed plasma and tissue viral populations in RT-SHIV-infected macaques implies a lack of viral replication in the tissues during antiretroviral therapy.

PubMed

Kearney, Mary F; Anderson, Elizabeth M; Coomer, Charles; Smith, Luke; Shao, Wei; Johnson, Nicholas; Kline, Christopher; Spindler, Jonathan; Mellors, John W; Coffin, John M; Ambrose, Zandrea

2015-11-11

Determining the anatomic compartments that contribute to plasma HIV-1 is critical to understanding the sources of residual viremia during combination antiretroviral therapy (ART). We analyzed viral DNA and RNA populations in the plasma and tissues from macaques infected with SIV containing HIV-1 RT (RT-SHIV) to identify possible sources of persistent viremia and to investigate the effect of ART on viral replication in tissues. Tissues were collected at necropsy from four pigtailed macaques infected for 30 weeks with a diverse population of RT-SHIV. Two animals (6760 and 8232) were untreated and two animals (8030 and 8272) were treated with efavirenz, tenofovir, and emtricitabine for 20 weeks. A total of 1800 single-genome RT-SHIV pol and env DNA and RNA sequences were analyzed from the plasma, PBMCs, axillary and mesenteric lymph nodes, spleen, thymus, small intestine, bone marrow, lung, and brain. Analyses of intracellular DNA and RNA populations revealed that the majority of proviruses in tissues from untreated animal 8232 were not expressed, whereas a greater proportion of proviruses in tissues were expressed from 6760. Few intracellular RNA sequences were detected in treated animals and most contained inactivating mutations, such as frame shifts or large deletions. Phylogenetics showed that RT-SHIV DNA populations in tissues were not different from virus in contemporary plasma samples in the treated or untreated animals, demonstrating a lack of anatomic compartmentalization and suggesting that plasma viremia is derived from multiple tissue sources. No sequence divergence was detected in the plasma or between tissues in the treated animals after 20 weeks of ART indicating a lack of ongoing replication in tissues during treatment. Virus populations in plasma and tissues did not differ significantly in either treated or untreated macaques, suggesting frequent exchange of virus or infected cells between tissues and plasma, consistent with non-compartmentalized and widely disseminated infection. There was no genetic evidence of ongoing replication in tissues during suppressive ART.

Multilocus typing of Cryptosporidium spp. and Giardia duodenalis from non-human primates in China.

PubMed

Karim, Md Robiul; Zhang, Sumei; Jian, Fuchun; Li, Jiacheng; Zhou, Chunxiang; Zhang, Longxian; Sun, Mingfei; Yang, Guangyou; Zou, Fengcai; Dong, Haiju; Li, Jian; Rume, Farzana Islam; Qi, Meng; Wang, Rongjun; Ning, Changshen; Xiao, Lihua

2014-11-01

Non-human primates (NHPs) are commonly infected with Cryptosporidium spp. and Giardia duodenalis. However, molecular characterisation of these pathogens from NHPs remains scarce. In this study, 2,660 specimens from 26 NHP species in China were examined and characterised by PCR amplification of 18S rRNA, 70kDa heat shock protein (hsp70) and 60kDa glycoprotein (gp60) gene loci for Cryptosporidium; and 1,386 of the specimens by ssrRNA, triosephosphate isomerase (tpi) and glutamate dehydrogenase (gdh) gene loci for Giardia. Cryptosporidium was detected in 0.7% (19/2660) specimens of four NHP species including rhesus macaques (0.7%), cynomolgus monkeys (1.0%), slow lorises (10.0%) and Francois' leaf monkeys (6.7%), belonging to Cryptosporidium hominis (14/19) and Cryptosporidium muris (5/19). Two C. hominis gp60 subtypes, IbA12G3 and IiA17 were observed. Based on the tpi locus, G. duodenalis was identified in 2.2% (30/1,386) of specimens including 2.1% in rhesus macaques, 33.3% in Japanese macaques, 16.7% in Assam macaques, 0.7% in white-headed langurs, 1.6% in cynomolgus monkeys and 16.7% in olive baboons. Sequence analysis of the three targets indicated that all of the Giardia-positive specimens belonged to the zoonotic assemblage B. Highest sequence polymorphism was observed at the tpi locus, including 11 subtypes: three known and eight new ones. Phylogenetic analysis of the subtypes showed that most of them were close to the so-called subtype BIV. Intragenotypic variations at the gdh locus revealed six types of sequences (three known and three new), all of which belonged to so-called subtype BIV. Three specimens had co-infection with C. hominis (IbA12G3) and G. duodenalis (BIV). The presence of zoonotic genotypes and subtypes of Cryptosporidium spp. and G. duodenalis in NHPs suggests that these animals can potentially contribute to the transmission of human cryptosporidiosis and giardiasis. Copyright © 2014 Australian Society for Parasitology Inc. All rights reserved.

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.

High levels of diversity characterize mandrill (Mandrillus sphinx) Mhc-DRB sequences.

PubMed

Abbott, Kristin M; Wickings, E Jean; Knapp, Leslie A

2006-08-01

The major histocompatibility complex (MHC) is highly polymorphic in most primate species studied thus far. The rhesus macaque (Macaca mulatta) has been studied extensively and the Mhc-DRB region demonstrates variability similar to humans. The extent of MHC diversity is relatively unknown for other Old World monkeys (OWM), especially among genera other than Macaca. A molecular survey of the Mhc-DRB region in mandrills (Mandrillus sphinx) revealed extensive variability, suggesting that other OWMs may also possess high levels of Mhc-DRB polymorphism. In the present study, 33 Mhc-DRB loci were identified from only 13 animals. Eleven were wild-born and presumed to be unrelated and two were captive-born twins. Two to seven different sequences were identified for each individual, suggesting that some mandrills may have as many as four Mhc-DRB loci on a single haplotype. From these sequences, representatives of at least six Mhc-DRB loci or lineages were identified. As observed in other primates, some new lineages may have arisen through the process of gene conversion. These findings indicate that mandrills have Mhc-DRB diversity not unlike rhesus macaques and humans.

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

Brain aging in humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta): magnetic resonance imaging studies of macro- and microstructural changes

PubMed Central

Chen, Xu; Errangi, Bhargav; Li, Longchuan; Glasser, Matthew F.; Westlye, Lars T.; Fjell, Anders M.; Walhovd, Kristine B.; Hu, Xiaoping; Herndon, James G.; Preuss, Todd M.; Rilling, James K.

2013-01-01

Among primates, humans are uniquely vulnerable to many age-related neurodegenerative disorders. We used structural and diffusion magnetic resonance imaging (MRI) to examine the brains of chimpanzees and rhesus monkeys across each species' adult lifespan, and compared these results with published findings in humans. As in humans, gray matter volume decreased with age in chimpanzees and rhesus monkeys. Also like humans, chimpanzees showed a trend for decreased white matter volume with age, but this decrease occurred proportionally later in the chimpanzee lifespan than in humans. Diffusion MRI revealed widespread age-related decreases in fractional anisotropy and increases in radial diffusivity in chimpanzees and macaques. However, both the fractional anisotropy decline and the radial diffusivity increase started at a proportionally earlier age in humans than in chimpanzees. Thus, even though overall patterns of gray and white matter aging are similar in humans and chimpanzees, the longer lifespan of humans provides more time for white matter to deteriorate before death, with the result that some neurological effects of aging may be exacerbated in our species. PMID:23623601

Social bonds affect anti-predator behaviour in a tolerant species of macaque, Macaca nigra

PubMed Central

Micheletta, Jérôme; Waller, Bridget M.; Panggur, Maria R.; Neumann, Christof; Duboscq, Julie; Agil, Muhammad; Engelhardt, Antje

2012-01-01

Enduring positive social bonds between individuals are crucial for humans' health and well being. Similar bonds can be found in a wide range of taxa, revealing the evolutionary origins of humans' social bonds. Evidence suggests that these strong social bonds can function to buffer the negative effects of living in groups, but it is not known whether they also function to minimize predation risk. Here, we show that crested macaques (Macaca nigra) react more strongly to playbacks of recruitment alarm calls (i.e. calls signalling the presence of a predator and eliciting cooperative mobbing behaviour) if they were produced by an individual with whom they share a strong social bond. Dominance relationships between caller and listener had no effect on the reaction of the listener. Thus, strong social bonds may improve the coordination and efficiency of cooperative defence against predators, and therefore increase chances of survival. This result broadens our understanding of the evolution and function of social bonds by highlighting their importance in the anti-predator context. PMID:22859593

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

PubMed

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

1995-03-01

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

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

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.

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.

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

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

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

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.

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

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.

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.

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

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.

Glycerol Monolaurate Does Not Alter Rhesus Macaque (Macaca mulatta) Vaginal Lactobacilli and Is Safe for Chronic Use▿

PubMed Central

Schlievert, Patrick M.; Strandberg, Kristi L.; Brosnahan, Amanda J.; Peterson, Marnie L.; Pambuccian, Stefan E.; Nephew, Karla R.; Brunner, Kevin G.; Schultz-Darken, Nancy J.; Haase, Ashley T.

2008-01-01

Glycerol monolaurate (GML) is a fatty acid monoester that inhibits growth and exotoxin production of vaginal pathogens and cytokine production by vaginal epithelial cells. Because of these activities, and because of the importance of cytokine-mediated immune activation in human immunodeficiency virus type 1 (HIV-1) transmission to women, our laboratories are performing studies on the potential efficacy of GML as a topical microbicide to interfere with HIV-1 transmission in the simian immunodeficiency virus-rhesus macaque model. While GML is generally recognized as safe by the FDA for topical use, its safety for chronic use and effects on normal vaginal microflora in this animal model have not been evaluated. GML was therefore tested both in vitro for its effects on vaginal flora lactobacilli and in vivo as a 5% gel administered vaginally to monkeys. In vitro studies demonstrated that lactobacilli are not killed by GML; GML blocks the loss of their viability in stationary phase and does not interfere with lactic acid production. GML (5% gel) does not quantitatively alter monkey aerobic vaginal microflora compared to vehicle control gel. Lactobacilli and coagulase-negative staphylococci are the dominant vaginal aerobic microflora, with beta-hemolytic streptococci, Staphylococcus aureus, and yeasts sporadically present; gram-negative rods are not part of their vaginal flora. Colposcopy and biopsy studies indicate that GML does not alter normal mucosal integrity and does not induce inflammation; instead, GML reduces epithelial cell production of interleukin 8. The studies suggest that GML is safe for chronic use in monkeys when applied vaginally; it does not alter either mucosal microflora or integrity. PMID:18838587

Modeling man: the monkey colony at the Carnegie Institution of Washington's Department of Embryology, 1925-1971.

PubMed

Wilson, Emily K

2012-01-01

Though better recognized for its immediate endeavors in human embryo research, the Carnegie Department of Embryology also employed a breeding colony of rhesus macaques for the purposes of studying human reproduction. This essay follows the course of the first enterprise in maintaining a primate colony for laboratory research and the overlapping scientific, social, and political circumstances that tolerated and cultivated the colony's continued operation from 1925 until 1971. Despite a new-found priority for reproductive sciences in the United States, by the early 1920s an unfertilized human ovum had not yet been seen and even the timing of ovulation remained unresolved. Progress would require an organized research approach that could extend beyond the limitations of working with scant and inherently restrictive human subjects or with common lab mammals like mice. In response, the Department of Embryology, under the Carnegie Institution of Washington (CIW), instituted a novel methodology using a particular primate species as a surrogate in studying normal human reproductive physiology. Over more than 40 years the monkey colony followed an unpremeditated trajectory that would contribute fundamentally to discoveries in human reproduction, early embryo development, reliable birth control methods, and to the establishment of the rhesus macaque as a common model organism.

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.

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

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).

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.

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.

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

PubMed

Molesti, Sandra; Majolo, Bonaventura

2017-09-01

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

Restricted Replication of Xenotropic Murine Leukemia Virus-Related Virus in Pigtailed Macaques

PubMed Central

Del Prete, Gregory Q.; Kearney, Mary F.; Spindler, Jon; Wiegand, Ann; Chertova, Elena; Roser, James D.; Estes, Jacob D.; Hao, Xing Pei; Trubey, Charles M.; Lara, Abigail; Lee, KyeongEun; Chaipan, Chawaree; Bess, Julian W.; Nagashima, Kunio; Keele, Brandon F.; Macallister, Rhonda; Smedley, Jeremy; Pathak, Vinay K.; KewalRamani, Vineet N.; Coffin, John M.

2012-01-01

Although xenotropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic in vivo infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential that is able to replicate in human cells. Here we describe a comprehensive analysis of two male pigtailed macaques (Macaca nemestrina) experimentally infected with XMRV. Following intravenous inoculation with >1010 RNA copy equivalents of XMRV, viral replication was limited and transient, peaking at ≤2,200 viral RNA (vRNA) copies/ml plasma and becoming undetectable by 4 weeks postinfection, though viral DNA (vDNA) in peripheral blood mononuclear cells remained detectable through 119 days of follow-up. Similarly, vRNA was not detectable in lymph nodes by in situ hybridization despite detectable vDNA. Sequencing of cell-associated vDNA revealed extensive G-to-A hypermutation, suggestive of APOBEC-mediated viral restriction. Consistent with limited viral replication, we found transient upregulation of type I interferon responses that returned to baseline by 2 weeks postinfection, no detectable cellular immune responses, and limited or no spread to prostate tissue. Antibody responses, including neutralizing antibodies, however, were detectable by 2 weeks postinfection and maintained throughout the study. Both animals were healthy for the duration of follow-up. These findings indicate that XMRV replication and spread were limited in pigtailed macaques, predominantly by APOBEC-mediated hypermutation. Given that human APOBEC proteins restrict XMRV infection in vitro, human XMRV infection, if it occurred, would be expected to be characterized by similarly limited viral replication and spread. PMID:22238316

Integrated Clinical, Pathologic, Virologic, and Transcriptomic Analysis of H5N1 Influenza Virus-Induced Viral Pneumonia in the Rhesus Macaque

PubMed Central

Shinya, Kyoko; Gao, Yuwei; Cilloniz, Cristian; Suzuki, Yasuhiro; Fujie, Masahiro; Deng, Guohua; Zhu, Qiyun; Fan, Shufang; Makino, Akiko; Muramoto, Yukiko; Fukuyama, Satoshi; Tamura, Daisuke; Noda, Takeshi; Eisfeld, Amie J.; Katze, Michael G.

2012-01-01

Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced nonlethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic, and transcriptomic analyses. Anhui/2 efficiently replicated in the lung from 12 h to 3 days postinfection (p.i.) and caused temporal but severe pneumonia that began to resolve by day 14. Lung transcriptional changes were first observed at 6 h, and increased expression of vascular permeability regulators and neutrophil chemoattractants correlated with increased serum leakage and neutrophil infiltration in situ. Additional inflammatory, antiviral, and apoptotic genes were upregulated from 12 h, concurrent with viral antigen detection and increasing immune cell populations. A shift toward upregulation of acquired immunity was apparent after day 6. Expression levels of established immune cell molecular markers revealed remarkable similarity with pathological findings, indicating early and robust neutrophil infiltration, a slight delay in macrophage accumulation, and abundant late populations of T lymphocytes. We also characterized the putative mechanisms regulating a unique, pneumonia-associated biphasic fever pattern. Thus, this study is the first to use a comprehensive and integrative approach to delineate specific molecular mechanisms regulating influenza virus-induced pneumonia in nonhuman primates, an important first step toward better management of human influenza virus disease. PMID:22491448

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

Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects

PubMed Central

Roberts, Victoria HJ; Lo, Jamie O; Salati, Jennifer A; Lewandowski, Katherine S; Lindner, Jonathan R; Morgan, Terry K; Frias, Antonio E

2016-01-01

Background The utero-placental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. Objective Here we demonstrate the feasibility of utilizing contrast-enhanced ultrasound to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. Study design Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n=6/group). Human subjects were recruited immediately prior to scheduled first trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition using a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. Results In macaques, rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and HSP70 as markers of apoptosis, nitrative and oxidative stress respectively were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11wks gestation and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast following first trimester ultrasound studies. Conclusions Use of contrast-enhanced ultrasound did not result in placental structural damage, and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound may offer a safe clinical tool for the identification of pregnancies at-risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes. PMID:26928151

The 17,18-epoxyeicosatetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques.

PubMed

Nagatake, Takahiro; Shiogama, Yumiko; Inoue, Asuka; Kikuta, Junichi; Honda, Tetsuya; Tiwari, Prabha; Kishi, Takayuki; Yanagisawa, Atsushi; Isobe, Yosuke; Matsumoto, Naomi; Shimojou, Michiko; Morimoto, Sakiko; Suzuki, Hidehiko; Hirata, So-Ichiro; Steneberg, Pär; Edlund, Helena; Aoki, Junken; Arita, Makoto; Kiyono, Hiroshi; Yasutomi, Yasuhiro; Ishii, Masaru; Kabashima, Kenji; Kunisawa, Jun

2017-12-27

Metabolites of eicosapentaenoic acid exert various physiologic actions. 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated. We evaluated the effectiveness of 17,18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17,18-EpETE. Contact hypersensitivity was induced by topical application of 2,4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17,18-EpETE was identified by using the TGF-α shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17,18-EpETE was examined by using KO mice and specific inhibitor treatment. We found that preventive or therapeutic treatment with 17,18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17,18-EpETE was recognized by G protein-coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17,18-EpETE was abolished in the absence or inhibition of GPR40. 17,18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Spontaneous representations of small numbers of objects by rhesus macaques: examinations of content and format.

PubMed

Hauser, Marc D; Carey, Susan

2003-12-01

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 one experimental condition, watched as eggplants were placed behind a screen one at a time, after which the screen was removed revealing an outcome that either matched or did not match the number placed there. Subjects looked longer at impossible than possible outcomes in 1+1=2 or 3, 1 small+1 small=1 big or 2 small, 2+1=2 or 3, and 2+1=3 or 4 conditions. They failed in 2+1+1=4 or 3 or 5 and in 1+1+1=2 or 3 conditions. This pattern of results closely matches that observed across several previous studies of human infants. The data allow us to test among four different proposals concerning the format and content of the mental representations underlying looking in these experiments. Object file representations are favored over: (i) low-level perceptual representations, (ii) representations of continuous variables such as volume or surface area, and (iii) analog magnitude representations of number. We conclude by considering exactly how the object tracking system revealed in these and other related experiments does and does not represent number, and how it might be one evolutionary precursor of the human specific system of number representations.

Whole body positron emission tomography imaging of simian immunodeficiency virus-infected rhesus macaques.

PubMed Central

Scharko, A M; Perlman, S B; Hinds PW2nd; Hanson, J M; Uno, H; Pauza, C D

1996-01-01

Pathogenesis of simian immunodeficiency virus (SIV) infection in rhesus macaques begins with acute viremia and then progresses to a distributed infection in the solid lymphoid tissues, which is followed by a process of cellular destruction leading to terminal disease and death. Blood and tissue specimens show the progress of infection at the cellular level but do not reveal the pattern of infection and host responses occurring throughout the body. The purpose of this investigation was to determine whether positron emission tomography (PET) imaging with intravenous 2-18F-2-deoxyglucose (FDG) could identify activated lymphoid tissues in a living animal and whether this pattern would reflect the extent of SIV infection. PET images from SIV-infected animals were distinguishable from uninfected controls and revealed a pattern consistent with widespread lymphoid tissue activation. Significant FDG accumulation in colon along with mesenteric and ileocaecal lymph nodes was found in SIV infection, especially during terminal disease stages. Areas of elevated FDG uptake in the PET images were correlated with productive SIV infection using in situ hybridization as a test for virus replication. PET-FDG images of SIV-infected animals correlated sites of virus replication with high FDG accumulation. These data show that the method can be used to evaluate the distribution and activity of infected tissues in a living animal without biopsy. Fewer tissues had high FDG uptake in terminal animals than midstage animals, and both were clearly distinguishable from uninfected animal scans. Images Fig. 1 Fig. 2 Fig. 3 PMID:8692831

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

PubMed

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

2015-12-15

Spatial and temporal changes in brain tissue after acute ischemic stroke are still poorly understood. Aims of this study were three-fold: (1) to determine unique temporal magnetic resonance imaging (MRI) patterns at the acute, subacute and chronic stages after stroke in macaques by combining quantitative T2 and diffusion MRI indices into MRI 'tissue signatures', (2) to evaluate temporal differences in these signatures between transient (n = 2) and permanent (n = 2) middle cerebral artery occlusion, and (3) to correlate histopathology findings in the chronic stroke period to the acute and subacute MRI derived tissue signatures. An improved iterative self-organizing data analysis algorithm was used to combine T2, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) maps across seven successive timepoints (1, 2, 3, 24, 72, 144, 240 h) which revealed five temporal MRI signatures, that were different from the normal tissue pattern (P < 0.001). The distribution of signatures between brains with permanent and transient occlusions varied significantly between groups (P < 0.001). Qualitative comparisons with histopathology revealed that these signatures represented regions with different histopathology. Two signatures identified areas of progressive injury marked by severe necrosis and the presence of gitter cells. Another signature identified less severe but pronounced neuronal and axonal degeneration, while the other signatures depicted tissue remodeling with vascular proliferation and astrogliosis. These exploratory results demonstrate the potential of temporally and spatially combined voxel-based methods to generate tissue signatures that may correlate with distinct histopathological features. The identification of distinct ischemic MRI signatures associated with specific tissue fates may further aid in assessing and monitoring the efficacy of novel pharmaceutical treatments for stroke in a pre-clinical and clinical setting.

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.

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

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

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.

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.

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.

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.

Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive.

PubMed

O'Rand, Michael G; Hamil, Katherine G; Adevai, Tiffany; Zelinski, Mary

2018-01-01

Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75-80 mg/kg) followed by a recovery period and a subsequent high dose (125-130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.

Traditional Chinese medicine etiology and pathogenesis of acquired immune deficiency syndrome in simian immunodeficiency virus-infected Chinese rhesus macaques.

PubMed

Li, Maoqing; Fu, Linchun; Hu, Yinjie; Zhang, Miaomiao; He, Jinyang; Chen, Zhixi; Chen, Jinyan

2012-12-01

To investigate the traditional Chinese Medicine (TCM) etiology and pathogenesis of acquired immune deficiency syndrome (AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus (SIV) mac239. Thirty-five healthy Chinese rhesus macaques were divided into a model group (n = 30) and a control group (n = 5). The model was established by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV infection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lymphocyte subsets, plasma triiodothyronine (T3), tetraiodothyronine (T4), adrenocorticotropic hormone (ACTH) and cortisol (Cor) were tested periodically during the experiment. During the acute infection period of SIV, model monkeys temporarily showed clinical symptoms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4+ T-lymphocytes were observed but levels of T3, T4, Cor, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infection showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed normal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of T3 and Cor. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3 appeared. The results suggest that the rhesus monkey SIV/SAIDS model can be applied to research on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the invasion of SIV virus, incubation of the virus, balance between virus and healthy "Qi", damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.

Sirtuin 1-Chromatin-Binding Dynamics Points to a Common Mechanism Regulating Inflammatory Targets in SIV Infection and in the Aging Brain.

PubMed

Bortell, Nikki; Basova, Liana; Najera, Julia A; Morsey, Brenda; Fox, Howard S; Marcondes, Maria Cecilia Garibaldi

2018-06-01

Microglia and macrophages are the main non-neuronal subsets of myeloid origin in the brain, and are critical regulators in neurodegenerative disorders, where inflammation is a key factor. Since HIV infection results in neurological perturbations that are similar to those in aging, we examined microglial and infiltrating myeloid subsets in the search for changes that might resemble the ones in aging. For that, we used the SIV infection in rhesus macaques to model neuroAIDS. We found that Sirt-1, a molecule that impacts survival and health in many models, was decreased in cell preparations containing a majority of microglia and myeloid cells from the brain of infected macaques. The role of Sirt-1 in neuroAIDS is unknown. We hypothesized that Sirt-1 silencing functions are affected by SIV. Mapping of Sirt-1 binding patterns to chromatin revealed that the number of Sirt-1-bound genes was 29.6% increased in myeloid cells from infected animals with mild or no detectable neuropathology, but 51% was decreased in severe neuropathology, compared to controls. Importantly, Sirt-1-bound genes in controls largely participate in neuroinflammation. Promoters of type I IFN pathway genes IRF7, IRF1, IFIT1, and AIF1, showed Sirt-1 binding in controls, which was consistently lost after infection, together with higher transcription. Loss of Sirt-1 binding was also found in brains from old uninfected animals, suggesting a common regulation. The role of Sirt-1 in regulating these inflammatory markers was confirmed in two different in vitro models, where Sirt-1 blockage modulated IRF7, IRF1 and AIF1 levels both in human macrophage cell lines and in human blood-derived monocytes from various normal donors, stimulated with a TLR9 agonist. Our data suggests that Sirt-1-inflammatory gene silencing is disturbed by SIV infection, resembling aging in brains. These findings may impact our knowledge on the contribution of myeloid subsets to the neurological consequences of HIV infection, aggravated and overlapping with the aging process.

Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey.

PubMed

Jenkinson, Ned; Nandi, Dipankar; Miall, R Chris; Stein, John F; Aziz, Tipu Z

2004-12-03

We have studied the effects of stimulating the pedunculopontine nuclei through a fully implanted macroelectrode with a s.c. implantable pulse generator whose parameters can be programmed telemetrically, in a macaque before and after inducing Parkinsonian akinesia with MPTP. Our results show that in the normal monkey high frequency stimulation of the pedunculopontine nuclei reduces motor activity while low frequency stimulation increases it significantly over baseline. After making the monkey Parkinsonian with MPTP, unilateral low frequency stimulation of the pedunculopontine nuclei led to significant increases in activity. These results suggest that pedunculopontine nuclei stimulation could be clinically effective in treating advanced Parkinson's disease and other akinetic disorders.

Light Levels, Refractive Development, and Myopia – a Speculative Review

PubMed Central

Norton, Thomas T.; Siegwart, John T.

2013-01-01

Recent epidemiological evidence in children indicates that time spent outdoors is protective against myopia. Studies in animal models (chick, macaque, tree shrew) have found that light levels (similar to being in the shade outdoors) that are mildly elevated compared to indoor levels, slow form-deprivation myopia and (in chick and tree shrew) lens-induced myopia. Normal chicks raised in low light levels (50 lux) with a circadian light on/off cycle often develop spontaneous myopia. We propose a model in which the ambient illuminance levels produce a continuum of effects on normal refractive development and the response to myopiagenic stimuli such that low light levels favor myopia development and elevated levels are protective. Among possible mechanisms, elevation of retinal dopamine activity seems the most likely. Inputs from intrinsically-photosensitive retinal ganglion cells (ipRGCs) at elevated light levels may be involved, providing additional activation of retinal dopaminergic pathways. PMID:23680160

The INIA19 Template and NeuroMaps Atlas for Primate Brain Image Parcellation and Spatial Normalization

PubMed Central

Rohlfing, Torsten; Kroenke, Christopher D.; Sullivan, Edith V.; Dubach, Mark F.; Bowden, Douglas M.; Grant, Kathleen A.; Pfefferbaum, Adolf

2012-01-01

The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T1-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/). PMID:23230398

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.

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).

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

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.

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.

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).

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.

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

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.

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

Brain aging in humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta): magnetic resonance imaging studies of macro- and microstructural changes.

PubMed

Chen, Xu; Errangi, Bhargav; Li, Longchuan; Glasser, Matthew F; Westlye, Lars T; Fjell, Anders M; Walhovd, Kristine B; Hu, Xiaoping; Herndon, James G; Preuss, Todd M; Rilling, James K

2013-10-01

Among primates, humans are uniquely vulnerable to many age-related neurodegenerative disorders. We used structural and diffusion magnetic resonance imaging (MRI) to examine the brains of chimpanzees and rhesus monkeys across each species' adult lifespan, and compared these results with published findings in humans. As in humans, gray matter volume decreased with age in chimpanzees and rhesus monkeys. Also like humans, chimpanzees showed a trend for decreased white matter volume with age, but this decrease occurred proportionally later in the chimpanzee lifespan than in humans. Diffusion MRI revealed widespread age-related decreases in fractional anisotropy and increases in radial diffusivity in chimpanzees and macaques. However, both the fractional anisotropy decline and the radial diffusivity increase started at a proportionally earlier age in humans than in chimpanzees. Thus, even though overall patterns of gray and white matter aging are similar in humans and chimpanzees, the longer lifespan of humans provides more time for white matter to deteriorate before death, with the result that some neurological effects of aging may be exacerbated in our species. Copyright © 2013 Elsevier Inc. All rights reserved.

Distinctive receptive field and physiological properties of a wide-field amacrine cell in the macaque monkey retina

PubMed Central

Puller, Christian; Rieke, Fred; Neitz, Jay; Neitz, Maureen

2015-01-01

At early stages of visual processing, receptive fields are typically described as subtending local regions of space and thus performing computations on a narrow spatial scale. Nevertheless, stimulation well outside of the classical receptive field can exert clear and significant effects on visual processing. Given the distances over which they occur, the retinal mechanisms responsible for these long-range effects would certainly require signal propagation via active membrane properties. Here the physiology of a wide-field amacrine cell—the wiry cell—in macaque monkey retina is explored, revealing receptive fields that represent a striking departure from the classic structure. A single wiry cell integrates signals over wide regions of retina, 5–10 times larger than the classic receptive fields of most retinal ganglion cells. Wiry cells integrate signals over space much more effectively than predicted from passive signal propagation, and spatial integration is strongly attenuated during blockade of NMDA spikes but integration is insensitive to blockade of NaV channels with TTX. Thus these cells appear well suited for contributing to the long-range interactions of visual signals that characterize many aspects of visual perception. PMID:26133804

Brain Creatine Elevation and NAA Reduction Indicates Neuronal Dysfunction in the Setting of Enhanced Glial Energy Metabolism in a Macaque Model of neuroAIDS

PubMed Central

Ratai, Eva-Maria; Annamalai, Lakshmanan; Burdo, Tricia; Joo, Chan-Gyu; Bombardier, Jeffrey P.; Fell, Robert; Hakimelahi, Reza; He, Julian; Lentz, Margaret R.; Campbell, Jennifer; Curran, Elizabeth; Halpern, Elkan F.; Masliah, Eliezer; Westmoreland, Susan. V.; Williams, Kenneth C.; González, R. Gilberto

2011-01-01

Proton magnetic resonance spectroscopy (1H MRS) has emerged as one of the most informative neuroimaging modalities for studying the effect of HIV infection in the brain, providing surrogate markers by which to assess disease progression and monitor treatment. Reductions in the level of N-Acetylaspartate (NAA) and NAA/creatine (NAA/Cr) are established markers of neuronal injury or loss. However, the biochemical basis of altered creatine levels in neuroAIDS is not well understood. This study used a rapid progression macaque model of neuroAIDS to elucidate the changes in creatine. As the disease progressed 1H MRS revealed a decrease in NAA, indicative of neuronal injury, and an increase in creatine yet to be elucidated. Subsequently, immunohistochemistry and stereology measures of decreased synaptophysin, microtubule-associated protein 2, and neuronal density confirmed neuronal injury. Furthermore, increases in ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein indicated microglial and astroglial activation, respectively. Given these data, elevated creatine may reflect enhanced high-energy phosphate turnover in highly metabolizing activated astrocytes and microglia. PMID:21381104

Corticocortical feedback increases the spatial extent of normalization.

PubMed

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

2014-01-01

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

Corticocortical feedback increases the spatial extent of normalization

PubMed Central

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

2014-01-01

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

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…

Cortical Effects on Ipsilateral Hindlimb Muscles Revealed with Stimulus-Triggered Averaging of EMG Activity

PubMed Central

Messamore, William G.; Van Acker, Gustaf M.; Hudson, Heather M.; Zhang, Hongyu Y.; Kovac, Anthony; Nazzaro, Jules; Cheney, Paul D.

2016-01-01

While a large body of evidence supports the view that ipsilateral motor cortex may make an important contribution to normal movements and to recovery of function following cortical injury (Chollet et al. 1991; Fisher 1992; Caramia et al. 2000; Feydy et al. 2002), relatively little is known about the properties of output from motor cortex to ipsilateral muscles. Our aim in this study was to characterize the organization of output effects on hindlimb muscles from ipsilateral motor cortex using stimulus-triggered averaging of EMG activity. Stimulus-triggered averages of EMG activity were computed from microstimuli applied at 60–120 μA to sites in both contralateral and ipsilateral M1 of macaque monkeys during the performance of a hindlimb push–pull task. Although the poststimulus effects (PStEs) from ipsilateral M1 were fewer in number and substantially weaker, clear and consistent effects were obtained at an intensity of 120 μA. The mean onset latency of ipsilateral poststimulus facilitation was longer than contralateral effects by an average of 0.7 ms. However, the shortest latency effects in ipsilateral muscles were as short as the shortest latency effects in the corresponding contralateral muscles suggesting a minimal synaptic linkage that is equally direct in both cases. PMID:26088970

Comparative analysis of A-to-I editing in human and non-human primate brains reveals conserved patterns and context-dependent regulation of RNA editing.

PubMed

O'Neil, Richard T; Wang, Xiaojing; Morabito, Michael V; Emeson, Ronald B

2017-04-06

A-to-I RNA editing is an important process for generating molecular diversity in the brain through modification of transcripts encoding several proteins important for neuronal signaling. We investigated the relationships between the extent of editing at multiple substrate transcripts (5HT2C, MGLUR4, CADPS, GLUR2, GLUR4, and GABRA3) in brain tissue obtained from adult humans and rhesus macaques. Several patterns emerged from these studies revealing conservation of editing across primate species. Additionally, variability in the human population allows us to make novel inferences about the co-regulation of editing at different editing sites and even across different brain regions.

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.)

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.

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.

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

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

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

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.

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

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

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

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.

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.

Old World Monkeys Compare to Apes in the Primate Cognition Test Battery

PubMed Central

Schmitt, Vanessa; Pankau, Birte; Fischer, Julia

2012-01-01

Understanding the evolution of intelligence rests on comparative analyses of brain sizes as well as the assessment of cognitive skills of different species in relation to potential selective pressures such as environmental conditions and social organization. Because of the strong interest in human cognition, much previous work has focused on the comparison of the cognitive skills of human toddlers to those of our closest living relatives, i.e. apes. Such analyses revealed that apes and children have relatively similar competencies in the physical domain, while human children excel in the socio-cognitive domain; in particular in terms of attention sharing, cooperation, and mental state attribution. To develop a full understanding of the evolutionary dynamics of primate intelligence, however, comparative data for monkeys are needed. We tested 18 Old World monkeys (long-tailed macaques and olive baboons) in the so-called Primate Cognition Test Battery (PCTB) (Herrmann et al. 2007, Science). Surprisingly, our tests revealed largely comparable results between Old World monkeys and the Great apes. Single comparisons showed that chimpanzees performed only better than the macaques in experiments on spatial understanding and tool use, but in none of the socio-cognitive tasks. These results question the clear-cut relationship between cognitive performance and brain size and – prima facie – support the view of an accelerated evolution of social intelligence in humans. One limitation, however, is that the initial experiments were devised to tap into human specific skills in the first place, thus potentially underestimating both true nonhuman primate competencies as well as species differences. PMID:22485130

Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes

PubMed Central

Curnow, E. C.; Ryan, J. P.; Saunders, D. M.; Hayes, E. S.

2010-01-01

Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes. PMID:20591337

Hue-specific colour memory impairment in an individual with intact colour perception and colour naming.

PubMed

Jakobson, L S; Pearson, P M; Robertson, B

2008-01-15

Cases of hue-selective dyschomatopsias, together with the results of recent optical imaging studies [Xiao, Y., Casti, A. R. R., Xiao, J., & Kaplan, E. (2006). A spatially organized representation of colour in macaque primary visual cortex. Perception, 35, ECVP Abstract Supplement; Xiao, Y., Wang, Y., & Felleman, D. J. (2003). A spatially organized representation of colour in macaque cortical area V2. Nature, 421, 535-539], have provided support for the idea that different colours are processed in spatially distinct regions of extrastriate cortex. In the present report, we provide evidence suggesting that a similar, but distinct, map may exist for representations of colour in memory. This evidence comes from observations of a young woman (QP) who demonstrates an isolated deficit in colour memory secondary to a concussive episode. Despite having normal colour perception and colour naming skills, and above-average memory skills in other domains, QP's ability to recall visually encoded colour information over short retention intervals is dramatically impaired. Her long-term memory for colour and her colour imagery skills are also abnormal. Surprisingly, however, these impairments are not seen with all hues; specifically, her ability to remember or imagine blue shades is spared. This interesting case contributes to the literature suggesting that colour perception, naming, and memory can be clinically dissociated, and provides insights into the organization of colour information in memory.

Four Decades of Ground-Breaking Research in the Reproductive and Developmental Sciences: The Infant Primate Research Laboratory at the University of Washington National Primate Research Center

PubMed Central

Burbacher, Thomas M.; Grant, Kimberly S.; Worlein, Julie; Ha, James; Curnow, Eliza; Juul, Sandra; Sackett, Gene P.

2017-01-01

The Infant Primate Research Laboratory (IPRL) was established in the 1970s at the University of Washington as a visionary project of Dr. Gene (Jim) P. Sackett. Supported by a collaboration between the Washington National Primate Research Center and the Center on Human Health and Disability, the IPRL operates under the principle that learning more about the causes of abnormal development in macaque monkeys will provide important insights into mechanisms underlying childhood neurodevelopmental disorders. Over the past forty years, a broad range of research projects have been conducted at the IPRL. Some have described the normal expression of species-typical behaviors in nursery-reared macaques while others have focused on specific issues in perinatal medicine and research. This article will review the unique history of the IPRL and the scientific contributions produced by research conducted in the laboratory. Past and present investigations at the IPRL have explored the consequences of adverse early rearing, low-birth-weight, prematurity, epilepsy, chemical/drug exposure, viral infection, diarrheal disease, vaccine safety, assisted reproductive technologies and perinatal hypoxia on growth and development. New directions of investigation include the production of a transgenic primate model using our embryonic stem cell-based technology to better understand and treat heritable forms of human mental retardation such as fragile X. PMID:23873400

Oocyte glutathione and fertilisation outcome of Macaca nemestrina and Macaca fascicularis in in vivo- and in vitro-matured oocytes.

PubMed

Curnow, E C; Ryan, J P; Saunders, D M; Hayes, E S

2010-01-01

Fertilisation and development of IVM non-human primate oocytes is limited compared with that of in vivo-matured (IVO) oocytes. The present study describes the IVM of macaque oocytes with reference to oocyte glutathione (GSH). Timing of maturation, comparison of IVM media and cysteamine (CYS) supplementation as a modulator of GSH were investigated. A significantly greater proportion of oocytes reached MII after 30 h compared with 24 h of IVM. Following insemination, IVM oocytes had a significantly lower incidence of normal fertilisation (i.e. 2PN = two pronuclei and at least one polar body) and a higher rate of abnormal fertilisation (1PN = one pronucleus and at least one polar body) compared with IVO oocytes. Immunofluorescence of 1PN zygotes identified incomplete sperm head decondensation and failure of male pronucleus formation as the principal cause of abnormal fertilisation in IVM oocytes. The IVO oocytes had significantly higher GSH content than IVM oocytes. Cumulus-denuded oocytes had significantly lower GSH following IVM compared with immature oocytes at collection. Cysteamine supplementation of the IVM medium significantly increased the GSH level of cumulus-intact oocytes and reduced the incidence of 1PN formation, but did not improve GSH levels of the denuded oocyte. Suboptimal GSH levels in macaque IVM oocytes may be related to reduced fertilisation outcomes.

Intestinal double-positive CD4+CD8+ T cells of neonatal rhesus macaques are proliferating, activated memory cells and primary targets for SIVMAC251 infection

PubMed Central

Wang, Xiaolei; Das, Arpita; Lackner, Andrew A.; Veazey, Ronald S.

2008-01-01

Peripheral blood and thymic double-positive (DP) CD4+CD8+ T cells from neonates have been described earlier, but the function and immunophenotypic characteristics of other tissue-derived DP T cells are not clearly understood. Here, we demonstrate the functional and immunophenotypic characteristics of DP cells in 6 different tissues, including thymus from normal neonatal rhesus macaques (Macaca mulatta) between 0 and 21 days of age. In general, intestinal DP T cells of neonates have higher percentages of memory markers (CD28+CD95+CD45RAlowCD62Llow) and proliferation compared with single-positive (SP) CD4+ and CD8+ T cells. In addition, percentages of DP T cells increase and CD62L expression decreases as animals mature, suggesting that DP cells mature and proliferate with maturity and/or antigen exposure. Consistent with this, intestinal DP T cells in neonates express higher levels of CCR5 and are the primary targets in simian immunodeficiency virus (SIV) infection. Finally, DP T cells produce higher levels of cytokine in response to mitogen stimulation compared with SP CD4+ or CD8+ T cells. Collectively, these findings demonstrate that intestinal DP T cells of neonates are proliferating, activated memory cells and are likely involved in regulating immune responses, in contrast to immature DP T cells in the thymus. PMID:18820133

Rapid down-regulation of γc on T cells in early SIV infection correlates with impairment of T-cell function.

PubMed

Xu, Huanbin; Wang, Xiaolei; Pahar, Bapi; Alvarez, Xavier; Rasmussen, Kelsi K; Lackner, Andrew A; Veazey, Ronald S

2012-06-01

The common γ(c) subunit molecule is shared among all γ(c) cytokines and clearly involved in T-cell function, but its role in HIV infection and immunity is not well understood. Here, we examined expression and function of γ(c) on T cells during SIV infection in Rhesus macaques. Surface γ(c) distribution was differentially expressed on CD4(+) and CD8(+) T cells, and CD4(+) naive/memory cell populations in various lymphoid tissues of normal macaques. However, surface γ(c) expression was rapidly and significantly down-regulated on T cells in acute infection with pathogenic SIV, compared to infection with a less virulent SHIV or controls and did not recover on CD8(+) T cells in the chronic stage. Moreover, the peripheral and CD4(+)T cell loss was inversely correlated with γ(c)(+) CD8(+) T cells in individual tissues. γ(c)(+) T cells were mainly functional as evidenced by higher cytokine secretion and proliferative capacity. Further in vitro experiments found that surface γ(c) expression could be down-regulated following high level of IL-7 treatment by both internalization and shedding. Down-regulation of γ(c) during early HIV/SIV infection may inhibit T-cell function, particularly of CD8(+) T cells, and, may be linked with immune failure and loss of viral containment.

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

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.

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.

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.

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

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.

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