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Sample records for african nonhuman primates

  1. Property in Nonhuman Primates

    ERIC Educational Resources Information Center

    Brosnan, Sarah F.

    2011-01-01

    Property is rare in most nonhuman primates, most likely because their lifestyles are not conducive to it. Nonetheless, just because these species do not frequently maintain property does not mean that they lack the propensity to do so. Primates show respect for possession, as well as behaviors related to property, such as irrational decision…

  2. Polyomaviruses of Nonhuman Primates: Implications for Research

    PubMed Central

    Simon, Meredith A

    2008-01-01

    Polyomaviruses are a family of small nonenveloped DNA viruses that infect birds and mammals. At least 7 nonhuman primate polyomaviruses that occur in macaques, African green monkeys, marmosets baboons, and chimpanzees have been described, as well as 4 polyomaviruses that occur in humans. Simian virus 40 (SV40), which infects macaques, was the first nonhuman primate polyomavirus identified as a contaminant of early polio vaccines. Primate polyomaviruses cause inapparent primary infections but persist in the host and can cause severe disease in situations of immunocompromise. This review describes the primate polyomaviruses, and the diseases associated with the viruses of macaques. In macaques, the greatest current concerns are the potential confounding of study results by polyomavirus infections and the zoonotic potential of SV40. PMID:19793457

  3. Assessing anxiety in nonhuman primates.

    PubMed

    Coleman, Kristine; Pierre, Peter J

    2014-01-01

    Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates' biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates.

  4. Assessing Anxiety in Nonhuman Primates

    PubMed Central

    Coleman, Kristine; Pierre, Peter J.

    2014-01-01

    Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates’ biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates. PMID:25225310

  5. Optogenetics in the nonhuman primate

    PubMed Central

    Han, Xue

    2013-01-01

    The nonhuman primate brain, the model system closest to the human brain, plays a critical role in our understanding of neural computation, cognition, and behavior. The continued quest to crack the neural codes in the monkey brain would be greatly enhanced with new tools and technologies that can rapidly and reversibly control the activities of desired cells at precise times during specific behavioral states. Recent advances in adapting optogenetic technologies to monkeys have enabled precise control of specific cells or brain regions at the millisecond timescale, allowing for the investigation of the causal role of these neural circuits in this model system. Validation of optogenetic technologies in monkeys also represents a critical preclinical step on the translational path of new generation cell-type-specific neural modulation therapies. Here, I discuss the current state of the application of optogenetics in the nonhuman primate model system, highlighting the available genetic, optical and electrical technologies, and their limitations and potentials. PMID:22341328

  6. Serendipitous insights involving nonhuman primates.

    PubMed

    Morton, William R; Swindler, Kathryn

    2005-01-01

    Serendipity is discussed as a form of controlled chaos, a phenomenon in a class with synchronicity and other actions affecting research in terms of theory versus observation (e.g., "optional stopping"). Serendipity is a fundamental aspect of basic research, a profitable and normal outcome in the context of "informed observation." The serendipitous finding fits into the following pattern: it is unanticipated, anomalous, and strategic. All observations that have meaning must fit into some context in the observer's mind or suggest a revolutionary new context. It is critically important to maintain access to the resources provided by established primate centers and similar laboratories to capitalize in a timely way on serendipitous findings and to benefit from valuable discoveries made in more directly targeted development investments. Examples are given of serendipitous insights gained in experimentation and observation relative to nonhuman primate research, including both broad and narrow topics. Genomics, which uses comparison-based strategies and capitalizes on the DNA sequences of genetic information, presents what might seem the basis for endless serendipity because nonhuman primates are likely to share most genes present in the human genome. Other topics discussed include infant behavior, birth periodicity, leprosy, cystic fibrosis, environmental enrichment, endocrinology, drug development, and the rapidly expanding study of infectious diseases and pathogen-based bioterrorism. PMID:16179742

  7. Helminth and protozoan gastrointestinal tract parasites in captive and wild-trapped African non-human primates.

    PubMed

    Munene, E; Otsyula, M; Mbaabu, D A; Mutahi, W T; Muriuki, S M; Muchemi, G M

    1998-08-14

    The objective of this study was to investigate the gastro-intestinal (GIT) parasites commonly occurring in captive and wild-trapped (WT) non-human primates (baboons, vervets and Sykes) in Kenya and compare their prevalence. Three hundred and fifteen faecal samples were subjected to a battery of diagnostic tests, namely, direct smear, modified formal ether sedimentation, Kato thick smear, Harada-Mori techniques for parasite detection and culture to facilitate nematode larvae identification. Of these, 203 (64.4%) harboured helminths and 54 (17.1%) had protozoa. The helminth parasites comprised Strongyloides fulleborni 141 (44.8%), Trichuris trichuira 200 (63.5,%), Oesophagostomum sp. 48 (15.2%), Trichostrongylus sp. 73 (23.2%), Enterobius vermicularis 44 (14.0%), Schistosoma mansoni 4/92 (4.3%) and Streptopharagus sp. 68 (21.6%). Protozoan parasites consisted of Entamoeba coli 204 (64.8%), Balantidium coli 127 (40.3%) and Entamoeba histolytica 78 (24.8%). Both WT and colony-borne (CB) primates had similar species of parasites, but higher prevalences of protozoan infection were observed in CB baboons while helminth infections were relatively more common in WT primates. Some of the parasites observed in this study are reported to be zoonotic in various parasitological literatures. Chemoprophylaxis and other managerial practices were believed to be responsible for the lower worm prevalence in CB primates. Similar intervention against protozoa and other agents will not only improve primate health, but also increase safety to animal handlers and colony workers. PMID:9760061

  8. Biokinetics of Plutonium in Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Guilmette, Raymond A; Gesell, Thomas F; Harris, Jason T; Brey, Richard R

    2016-10-01

    A major source of data on metabolism, excretion and retention of plutonium comes from experimental animal studies. Although old world monkeys are one of the closest living relatives to humans, certain physiological differences do exist between these nonhuman primates and humans. The objective of this paper was to describe the metabolism of plutonium in nonhuman primates using the bioassay and retention data obtained from macaque monkeys injected with plutonium citrate. A biokinetic model for nonhuman primates was developed by adapting the basic model structure and adapting the transfer rates described for metabolism of plutonium in adult humans. Significant changes to the parameters were necessary to explain the shorter retention of plutonium in liver and skeleton of the nonhuman primates, differences in liver to bone partitioning ratio, and significantly higher excretion of plutonium in feces compared to that in humans. PMID:27575347

  9. Exposure to Nonhuman Primates in Rural Cameroon

    PubMed Central

    Prosser, A. Tassy; Carr, Jean K.; Tamoufe, Ubald; Mpoudi-Ngole, Eitel; Torimiro, J. Ndongo; LeBreton, Matthew; McCutchan, Francine E.; Birx, Deborah L.; Burke, Donald S.

    2004-01-01

    Exposure to nonhuman primates has led to the emergence of important diseases, including Ebola hemorrhagic fever, AIDS, and adult T-cell leukemia. To determine the extent of exposure to nonhuman primates, persons were examined in 17 remote villages in Cameroon that represented three habitats (savanna, gallery forest, and lowland forest). Questionnaire data were collected to assess whether persons kept wild animal pets; hunted and butchered wild game; had experienced bites, scratches, or injuries from live animals; or had been injured during hunting or butchering. While all villages had substantial exposure to nonhuman primates, higher rates of exposure were seen in lowland forest sites. The study demonstrates that exposure is not limited to small groups of hunters. A high percentage of rural villagers report exposure to nonhuman primate blood and body fluids and risk acquiring infectious diseases. PMID:15663844

  10. Biokinetics of Plutonium in Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Guilmette, Raymond A; Gesell, Thomas F; Harris, Jason T; Brey, Richard R

    2016-10-01

    A major source of data on metabolism, excretion and retention of plutonium comes from experimental animal studies. Although old world monkeys are one of the closest living relatives to humans, certain physiological differences do exist between these nonhuman primates and humans. The objective of this paper was to describe the metabolism of plutonium in nonhuman primates using the bioassay and retention data obtained from macaque monkeys injected with plutonium citrate. A biokinetic model for nonhuman primates was developed by adapting the basic model structure and adapting the transfer rates described for metabolism of plutonium in adult humans. Significant changes to the parameters were necessary to explain the shorter retention of plutonium in liver and skeleton of the nonhuman primates, differences in liver to bone partitioning ratio, and significantly higher excretion of plutonium in feces compared to that in humans.

  11. The use of nonhuman primates in space

    NASA Technical Reports Server (NTRS)

    Simmonds, R. C. (Editor); Bourne, G. H. (Editor)

    1977-01-01

    Space related biomedical research involving nonhuman primates is reviewed. The scientific assets of various species and the instruments used for monitoring physiological processes during long duration experimentations are described.

  12. Lipoprotein(a): nonhuman primate models.

    PubMed

    Makino, K; Scanu, A M

    1991-09-01

    Lipoprotein(a) [Lp(a)] is a low density lipoprotein which has apo(a) disulfide-linked to apoB100. Apo(a) has recently been shown to have a striking homology with plasminogen, a knowledge that has stimulated a lot of interest in the mechanism of atherogenicity and thrombogenicity of this lipoprotein particle. Several studies have documented the presence of Lp(a) in nonhuman primates with particular reference to the rhesus monkeys and baboons. The Lp(a) of rhesus monkey is structurally very similar to that of humans, except for the absence of kringle V and the amino acid composition of the catalytic region. The Lp(a) of nonhuman primates, like their human counterparts, exhibit a wide range of interindividual plasma levels and also a wide size polymorphism of apo(a). Nonhuman primates appear to represent a good model for the study of the structure and biology of Lp(a).

  13. Primacy and recency effects in nonhuman primates.

    PubMed

    Castro, C A; Larsen, T

    1992-10-01

    The reports of primacy and recency memory effects in nonhuman primates have been criticized because they have all used an initiating response. That is, the presentation of the to-be-remembered list of items was always contingent on a response being initiated by the nonhuman primate. It has been argued that this initiating response improves performance for early items in the list, resulting in the occurrence of the primacy effect, independent of any memory processing mechanism. This criticism was addressed in the present study by not using an initiating response prior to the presentation of the list. Nevertheless, both a primacy and a recency effect were observed in all 6 rhesus monkeys evaluated using a serial probe recognition task. Thus, the results are similar to those for humans, in that both primacy and recency effects can be obtained in nonhuman primates. A brief literature review is included, and it is proposed that the primacy and recency effects observed in humans, nonhuman primates, and infraprimates can be explained within the context of the configural-association theory.

  14. 42 CFR 71.53 - Nonhuman primates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... nonhuman primates that is suspected of being yellow fever, monkeypox, or Marburg/Ebola disease. (3... disease that may constitute a threat to public health, the Director may provide for or require examination... be required under other Federal regulations (50 CFR parts 17 and 23) protecting such...

  15. Nonhuman primate quarantine: its evolution and practice.

    PubMed

    Roberts, Jeffrey A; Andrews, Kirk

    2008-01-01

    Nonhuman primates (NHPs) are imported to the United States for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. During the past 60 years, individuals responsible for NHP importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. These outbreaks have included infectious agents such as tuberculosis, Herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the Ebola and Marburg viruses. Some outbreaks have affected both animal and human populations. These epizootics are attributable to a variety of factors, including increased population density, exposure of naïve populations to new infectious agents, and stress. The practice of quarantining animals arriving in the United States was first applied by individual research programs to improve animal health and ensure the quality of animals entering research programs. The development of government regulations for nonhuman primate quarantine accompanied the recognition that imported NHPs could pose a risk to public health. This article briefly reviews the history of US NHP importation and the factors behind the development of NHP quarantine regulations. The focus is on regulations concerned with infectious disease, public health, and the health of domestic primate colonies. These regulations have had the dual benefit of protecting public health as well as reducing animal morbidity and mortality during importation and quarantine. We review current practices and facilities for nonhuman primate quarantine and identify challenges for the future. PMID:18323577

  16. Nonhuman primate models of polycystic ovary syndrome

    PubMed Central

    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-01-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

  17. Nonhuman primate models of polycystic ovary syndrome.

    PubMed

    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-07-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction.

  18. Nonhuman primate dermatology: a literature review

    PubMed Central

    Bernstein, Joseph A.; Didier, Peter J.

    2015-01-01

    In general, veterinary dermatologists do not have extensive clinical experience of nonhuman primate (NHP) dermatoses. The bulk of the published literature does not provide an organized evidence-based approach to the NHP dermatologic case. The veterinary dermatologist is left to extract information from both human and veterinary dermatology, an approach that can be problematic as it forces the clinician to make diagnostic and therapeutic decisions based on two very disparate bodies of literature. A more cohesive approach to NHP dermatology – without relying on assumptions that NHP pathology most commonly behaves similarly to other veterinary and human disease – is required. This review of the dermatology of NHP species includes discussions of primary dermatoses, as well as diseases where dermatologic signs represent a significant secondary component, provides a first step towards encouraging the veterinary community to study and report the dermatologic diseases of nonhuman primates. PMID:19490576

  19. [Ecotourism disturbances to non-human primates].

    PubMed

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

    In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals. PMID:23389980

  20. [Ecotourism disturbances to non-human primates].

    PubMed

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

    In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals.

  1. Behavioral abnormalities in captive nonhuman primates.

    PubMed

    Mallapur, Avanti; Choudhury, B C

    2003-01-01

    In this study, we dealt with 11 species of nonhuman primates across 10 zoos in India. We recorded behavior as instantaneous scans between 9 a.m. and 5 p.m. In the study, we segregated behaviors for analyses into abnormal, undesirable, active, and resting. The 4 types of abnormal behavior exhibited included floating limb, self-biting, self-clasping, and stereotypic pacing. In the study, we recorded 2 types of undesirable behavior: autoerotic stimulation and begging. Langurs and group-housed macaques did not exhibit undesirable behaviors. A male lion-tailed macaque and a male gibbon exhibited begging behavior. autoerotic stimulation and self-biting occurred rarely. Males exhibited higher levels of undesirable behavior than did females. Animals confiscated from touring zoos, circuses, and animal traders exhibited higher levels of abnormal behaviors than did animals reared in larger, recognized zoos. The stump-tailed macaque was the only species to exhibit floating limb, autoerotic stimulation, self-biting, and self-clasping. Our results show that rearing experience and group composition influence the proportions of abnormal behavior exhibited by nonhuman primates in captivity. The history of early social and environmental deprivation in these species of captive nonhuman primates probably is critical in the development of behavioral pathologies. Establishing this will require further research.

  2. [Experimental whooping cough of nonhuman primate].

    PubMed

    Kubrava, D T; Medkova, A Iu; Siniashina, L N; Shevtsova, Z V; Matua, A Z; Kondzharia, I G; Barkaia, V S; Elistratova, Zh V; Karataev, G I; Mikvabia, Z Ia; Gintsburg, A L

    2013-01-01

    Despite considerable success in study of Bordetella pertussis virulence factors, pathogenesis of whooping cough, duration of B. pertussis bacteria persistence, types and mechanisms of immune response are still keep underinvestigated. It can be explained by the absence ofadequate experimental animal model for pertussis study. Our study estimates clinical and laboratory parameters of whooping cough in non-human primates of the Old World in the process of intranasan infection by virulent B. pertussis bacteria. Also the duration of B. pertussis bacteria persistence in animals was investigated. 14 animal units of 4 species of non-human primates of the Old World were used for intranasal infection. The examination of infect animals included: visual exploration of nasopharynx, thermometry, clinical and biochemical blood analyses, identification ofB. pertussis, using microbiologic and molecular genetic analyses, estimation of innate and adoptive immune factors. The development of infectious process was accompanied by generation of B. pertussis bacteria, catarrhal inflammation of nasopharyngeal mucosa, leucocytosis, hypoglycemia specific for pertussis, and activation of innate and adaptive immunity for all primates regardless of specie were seen. While repeated experimental infection in primates single bacterial colonies were registered during only first week after challenge. It occurs like the absence of inflammation of nasopharyngeal mucosa and the lack of laboratory marks of whooping cough, recorded after first challenge. The evident booster effect of humoral immunity was observed. As a model for investigation of B. pertussis bacteria persistence and immune response against whooping cough we suggest the usage of rhesus macaque as more available to experiments.

  3. Progress with nonhuman primate embryonic stem cells.

    PubMed

    Wolf, Don P; Kuo, Hung-Chih; Pau, K-Y Francis; Lester, Linda

    2004-12-01

    Embryonic stem cells hold potential in the fields of regenerative medicine, developmental biology, tissue regeneration, disease pathogenicity, and drug discovery. Embryonic stem (ES) cell lines are now available in primates, including man, rhesus, and cynomologous monkeys. Monkey ES cells serve as invaluable clinically relevant models for studies that can't be conducted in humans because of practical or ethical limitations, or in rodents because of differences in physiology and anatomy. Here, we review the current status of nonhuman primate research with ES cells, beginning with a description of their isolation, characterization, and availability. Substantial limitations still plague the use of primate ES cells, such as their required growth on feeder layers, poor cloning efficiency, and restricted availability. The ability to produce homogenous populations of both undifferentiated as well as differentiated phenotypes is an important challenge, and genetic approaches to achieving these objectives are discussed. Finally, safety, efficiency, and feasibility issues relating to the transplantation of ES-derived cells are considered.

  4. Induced Pluripotent Stem Cells from Nonhuman Primates.

    PubMed

    Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

    2016-01-01

    Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

  5. Nonhuman primate models in translational regenerative medicine.

    PubMed

    Daadi, Marcel M; Barberi, Tiziano; Shi, Qiang; Lanford, Robert E

    2014-12-01

    Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer unique opportunities to develop stem cell-based therapeutic interventions that directly address relevant and challenging translational aspects of cell transplantation therapy. These include the use of autologous induced pluripotent stem cell-derived cellular products, issues related to the immune response in autologous and allogeneic setting, pros and cons of delivery techniques in a clinical setting, as well as the safety and efficacy of candidate cell lines. The NHP model allows the assessment of complex physiological, biochemical, behavioral, and imaging end points, with direct relevance to human conditions. At the same time, the value of using primates in scientific research must be carefully evaluated and timed due to expense and the necessity for specialized equipment and highly trained personnel. Often it is more efficient and useful to perform initial proof-of-concept studies for new therapeutics in rodents and/or other species before the pivotal studies in NHPs that may eventually lead to first-in-human trials. In this report, we present how the Southwest National Primate Research Center, one of seven NIH-funded National Primate Research Centers, may help the global community in translating promising technologies to the clinical arena.

  6. Social inequalities in health in nonhuman primates.

    PubMed

    Shively, Carol A; Day, Stephen M

    2015-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum.

  7. Social inequalities in health in nonhuman primates

    PubMed Central

    Shively, Carol A.; Day, Stephen M.

    2014-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum. PMID:27589665

  8. Conditioned Sexual Arousal in a Nonhuman Primate

    PubMed Central

    Snowdon, Charles T.; Tannenbaum, Pamela L.; Schultz-Darken, Nancy J.; Ziegler, Toni E.; Ferris, Craig F.

    2010-01-01

    Conditioning of sexual arousal has been demonstrated in several species from fish to humans, but has not been demonstrated in nonhuman primates. Controversy exists over whether nonhuman primates produce pheromones that arouse sexual behavior. Although common marmosets copulate throughout the ovarian cycle and during pregnancy, males exhibit behavioral signs of arousal, demonstrate increased neural activation of anterior hypothalamus and medial preoptic area and have an increase in serum testosterone after exposure to odors of novel ovulating females suggestive of a sexually arousing pheromone. Males also have increased androgens prior to their mate’s ovulation. However, males presented with odors of ovulating females demonstrate activation of many other brain areas associated with motivation, memory and decision making. In this study we demonstrate that male marmosets can be conditioned to a novel, arbitrary odor (lemon) with observation of erections, and increased exploration of the location where they previously experienced a receptive female, and increased scratching in postconditioning test without a female present. This conditioned response was demonstrated up to a week after the end of conditioning trials, a much longer lasting effect of conditioning than reported in studies of other species. These results further suggest that odors of ovulating females are not pheromones, strictly speaking, and that marmoset males may learn specific characteristics of odors of females providing a possible basis for mate identification. PMID:21029736

  9. Social inequalities in health in nonhuman primates.

    PubMed

    Shively, Carol A; Day, Stephen M

    2015-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum. PMID:27589665

  10. Isolation of Pancreatic Islets from Nonhuman Primates.

    PubMed

    Berman, Dora M

    2016-01-01

    Nonhuman primates (NHP) constitute a highly relevant pre-clinical animal model to develop strategies for beta cell replacement. The close phylogenetic and immunologic relationship between NHP and humans results in cross-reactivity of various biological agents with NHP cells, as well as a very similar cytoarchitecture between islets from human and NHP that is strikingly different from that observed in rodent islets. The composition and location of endocrine cells in human or NHP islets, randomly distributed and associated with blood vessels, have functional consequences and a predisposition for paracrine interactions. Furthermore, translation of approaches that proved successful in rodent models to the clinic has been limited. Consequently, data collected from NHP studies can form the basis for an IND submission to the FDA. This chapter describes in detail the key aspects for isolation of islets from NHP, from organ procurement up to assessment of islet function, comparing and emphasizing the similarities between isolation procedures for human and NHP islets. PMID:27586422

  11. IACUC Review of Nonhuman Primate Research

    PubMed Central

    Tardif, Suzette D.; Coleman, Kristine; Hobbs, Theodore R.; Lutz, Corrine

    2013-01-01

    This article will detail some of the issues that must be considered as institutional animal care and use committees (IACUCs) review the use of nonhuman primates (NHPs) in research. As large, intelligent, social, long-lived, and non-domesticated animals, monkeys are amongst the most challenging species used in biomedical research and the duties of the IACUC in relation to reviewing research use of these species can also be challenging. Issues of specific concern for review of NHP research protocols that are discussed in this article include scientific justification, reuse, social housing requirements, amelioration of distress, surgical procedures, and humane endpoints. Clear institutional policies and procedures as regards NHP in these areas are critical, and the discussion of these issues presented here can serve as a basis for the informed establishment of such policies and procedures. PMID:24174445

  12. 78 FR 11521 - Control of Communicable Disease; Foreign-Requirements for Importers of Nonhuman Primates (NHP)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-15

    ... requiring a special permit for importing cynomolgus, African green, and rhesus monkeys (55 FR 15210, April... a final rule at 78 FR 9828 establishing a user fee for filovirus testing of all nonhuman primates... ``prospective'' recipients of NHPs. HHS/CDC routinely audits importer records to verify that distribution is...

  13. Contributions of Nonhuman Primates to Research on Aging

    PubMed Central

    Didier, E. S.; MacLean, A. G.; Mohan, M.; Didier, P. J.; Lackner, A. A.; Kuroda, M. J.

    2016-01-01

    Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. PMID:26869153

  14. Nonhuman Primate Models in the Genomic Era: A Paradigm Shift

    PubMed Central

    Vallender, Eric J.; Miller, Gregory M.

    2013-01-01

    Because of their strong similarities to humans across physiologic, developmental, behavioral, immunologic, and genetic levels, nonhuman primates are essential models for a wide spectrum of biomedical research. But unlike other animal models, nonhuman primates possess substantial outbred genetic variation, reducing statistical power and potentially confounding interpretation of results in research studies. Although unknown genetic variation is a hindrance in studies that allocate animals randomly, taking genetic variation into account in study design affords an opportunity to transform the way that nonhuman primates are used in biomedical research. New understandings of how the function of individual genes in rhesus macaques mimics that seen in humans are greatly advancing the rhesus macaques utility as research models, but epistatic interaction, epigenetic regulatory mechanisms, and the intricacies of gene networks limit model development. We are now entering a new era of nonhuman primate research, brought on by the proliferation and rapid expansion of genomic data. Already the cost of a rhesus macaque genome is dwarfed by its purchase and husbandry costs, and complete genomic datasets will inevitably encompass each rhesus macaque used in biomedical research. Advancing this outcome is paramount. It represents an opportunity to transform the way animals are assigned and used in biomedical research and to develop new models of human disease. The genetic and genomic revolution brings with it a paradigm shift for nonhuman primates and new mandates on how nonhuman primates are used in biomedical research. PMID:24174439

  15. Microgravity Flight - Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1994-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey, Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  16. Microgravity Flight - Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1994-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  17. Microgravity Flight: Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1995-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey, Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  18. Evolutionary Developmental Psychology: Contributions from Comparative Research with Nonhuman Primates

    ERIC Educational Resources Information Center

    Maestripieri, Dario; Roney, James R.

    2006-01-01

    Evolutionary developmental psychology is a discipline that has the potential to integrate conceptual approaches to the study of behavioral development derived from psychology and biology as well as empirical data from humans and animals. Comparative research with animals, and especially with nonhuman primates, can provide evidence of adaptation in…

  19. Distinct Lineages of Bufavirus in Wild Shrews and Nonhuman Primates.

    PubMed

    Sasaki, Michihito; Orba, Yasuko; Anindita, Paulina D; Ishii, Akihiro; Ueno, Keisuke; Hang'ombe, Bernard M; Mweene, Aaron S; Ito, Kimihito; Sawa, Hirofumi

    2015-07-01

    Viral metagenomic analysis identified a new parvovirus genome in the intestinal contents of wild shrews in Zambia. Related viruses were detected in spleen tissues from wild shrews and nonhuman primates. Phylogenetic analyses showed that these viruses are related to human bufaviruses, highlighting the presence and genetic diversity of bufaviruses in wildlife. PMID:26079728

  20. Molecular identification of Entamoeba spp. in captive nonhuman primates.

    PubMed

    Levecke, B; Dreesen, Leentje; Dorny, Pierre; Verweij, Jaco J; Vercammen, Francis; Casaert, Stijn; Vercruysse, Jozef; Geldhof, Peter

    2010-08-01

    This study describes the molecular identification of 520 Entamoeba-positive fecal samples from a large and diverse population of captive nonhuman primates (NHP). The results revealed the presence of Entamoeba histolytica (NHP variant only), E. dispar, E. moshkovskii, E. hartmanni, E. coli, and E. polecki-like organisms. PMID:20573870

  1. Nonhuman Primates Prefer Slow Tempos but Dislike Music Overall

    ERIC Educational Resources Information Center

    McDermott, Josh; Hauser, Marc D.

    2007-01-01

    Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21]…

  2. Nonhuman primate vocalizations support categorization in very young human infants.

    PubMed

    Ferry, Alissa L; Hespos, Susan J; Waxman, Sandra R

    2013-09-17

    Language is a signature of our species and our primary conduit for conveying the contents of our minds. The power of language derives not only from the exquisite detail of the signal itself but also from its intricate link to human cognition. To acquire a language, infants must identify which signals are part of their language and discover how these signals are linked to meaning. At birth, infants prefer listening to vocalizations of human and nonhuman primates; within 3 mo, this initially broad listening preference is tuned specifically to human vocalizations. Moreover, even at this early developmental point, human vocalizations evoke more than listening preferences alone: they engender in infants a heightened focus on the objects in their visual environment and promote the formation of object categories, a fundamental cognitive capacity. Here, we illuminate the developmental origin of this early link between human vocalizations and cognition. We document that this link emerges from a broad biological template that initially encompasses vocalizations of human and nonhuman primates (but not backward speech) and that within 6 mo this link to cognition is tuned specifically to human vocalizations. At 3 and 4 mo, nonhuman primate vocalizations promote object categorization, mirroring precisely the advantages conferred by human vocalizations, but by 6 mo, nonhuman primate vocalizations no longer exert this advantageous effect. This striking developmental shift illuminates a path of specialization that supports infants as they forge the foundational links between human language and the core cognitive processes that will serve as the foundations of meaning. PMID:24003164

  3. Comparison of Experimental Respiratory Tularemia in Three Nonhuman Primate Species

    PubMed Central

    Glynn, Audrey R.; Alves, Derron A.; Frick, Ondraya; Erwin-Cohen, Rebecca; Porter, Aimee; Norris, Sarah; Waag, David; Nalca, Aysegul

    2015-01-01

    Tularemia is a zoonotic disease caused by Francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. Left untreated, the pneumonic form has more than > 30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. This study compared tularemia disease progression across three species of nonhuman primates [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)] following aerosolized F. tularensis Schu S4 exposure. Groups of the animals exposed to various challenge doses were observed for clinical signs of infection and blood samples were analyzed to characterize the disease pathogenesis. Whereas the AGMs and CMs succumbed to disease following challenge doses of 40 and 32 colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU. Following all challenge doses that caused disease, the NHPs experienced weight loss, bacteremia, fever as early as 4 days post exposure, and tissue burden. Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung, lymph nodes, spleen, and bone marrow. Overall, the CM model consistently manifested pathological responses similar to those resulting from inhalation of F. tularensis in humans and thereby most closely emulates human tularemia disease. The RM model displayed a higher tolerance to infection and survived exposures of up to 15,593 CFU of aerosolized F. tularensis. PMID:25766142

  4. Comparison of experimental respiratory tularemia in three nonhuman primate species.

    PubMed

    Glynn, Audrey R; Alves, Derron A; Frick, Ondraya; Erwin-Cohen, Rebecca; Porter, Aimee; Norris, Sarah; Waag, David; Nalca, Aysegul

    2015-04-01

    Tularemia is a zoonotic disease caused by Francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. Left untreated, the pneumonic form has more than >30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. This study compared tularemia disease progression across three species of nonhuman primates [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)] following aerosolized F. tularensis Schu S4 exposure. Groups of the animals exposed to various challenge doses were observed for clinical signs of infection and blood samples were analyzed to characterize the disease pathogenesis. Whereas the AGMs and CMs succumbed to disease following challenge doses of 40 and 32 colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU. Following all challenge doses that caused disease, the NHPs experienced weight loss, bacteremia, fever as early as 4 days post exposure, and tissue burden. Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung, lymph nodes, spleen, and bone marrow. Overall, the CM model consistently manifested pathological responses similar to those resulting from inhalation of F. tularensis in humans and thereby most closely emulates human tularemia disease. The RM model displayed a higher tolerance to infection and survived exposures of up to 15,593 CFU of aerosolized F. tularensis.

  5. Chronic wasting disease agents in nonhuman primates.

    PubMed

    Race, Brent; Meade-White, Kimberly D; Phillips, Katie; Striebel, James; Race, Richard; Chesebro, Bruce

    2014-05-01

    Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic potential is critical. To evaluate primate susceptibility, we tested monkeys from 2 genera. We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

  6. Improving Genome Assemblies and Annotations for Nonhuman Primates

    PubMed Central

    Norgren, Robert B.

    2013-01-01

    The study of nonhuman primates (NHP) is key to understanding human evolution, in addition to being an important model for biomedical research. NHPs are especially important for translational medicine. There are now exciting opportunities to greatly increase the utility of these models by incorporating Next Generation (NextGen) sequencing into study design. Unfortunately, the draft status of nonhuman genomes greatly constrains what can currently be accomplished with available technology. Although all genomes contain errors, draft assemblies and annotations contain so many mistakes that they make currently available nonhuman primate genomes misleading to investigators conducting evolutionary studies; and these genomes are of insufficient quality to serve as references for NextGen studies. Fortunately, NextGen sequencing can be used in the production of greatly improved genomes. Existing Sanger sequences can be supplemented with NextGen whole genome, and exomic genomic sequences to create new, more complete and correct assemblies. Additional physical mapping, and an incorporation of information about gene structure, can be used to improve assignment of scaffolds to chromosomes. In addition, mRNA-sequence data can be used to economically acquire transcriptome information, which can be used for annotation. Some highly polymorphic and complex regions, for example MHC class I and immunoglobulin loci, will require extra effort to properly assemble and annotate. However, for the vast majority of genes, a modest investment in money, and a somewhat greater investment in time, can greatly improve assemblies and annotations sufficient to produce true, reference grade nonhuman primate genomes. Such resources can reasonably be expected to transform nonhuman primate research. PMID:24174438

  7. Alopecia: Possible Causes and Treatments, Particularly in Captive Nonhuman Primates

    PubMed Central

    Novak, Melinda A; Meyer, Jerrold S

    2009-01-01

    Alopecia (hair loss) occurs in some nonhuman primates housed in captivity and is of concern to colony managers and veterinarians. Here we review the characteristics, potential causes, and treatments for this condition. Although we focus on nonhuman primates, relevant research on other mammalian species is discussed also, due to the relative paucity of studies on alopecia in the primate literature. We first discuss the cycle of hair growth and explain how this cycle can be disrupted to produce alopecia. Numerous factors may be related to hair loss and range from naturally occurring processes (for example, seasonality, aging) to various biologic dysfunctions, including vitamin and mineral imbalances, endocrine disorders, immunologic diseases, and genetic mutations. We also address bacterial and fungal infections, infestation by parasites, and atopic dermatitis as possible causes of alopecia. Finally, we examine the role of psychogenic factors, such as stress. Depending on the presumed cause of the hair loss, various treatment strategies can be pursued. Alopecia in nonhuman primates is a multifaceted disorder with many potential sources. For this reason, appropriate testing for various disease conditions should be completed before alopecia is considered to be related to stress. PMID:19295051

  8. The origins of non-human primates' manual gestures

    PubMed Central

    Liebal, Katja; Call, Josep

    2012-01-01

    The increasing body of research into human and non-human primates' gestural communication reflects the interest in a comparative approach to human communication, particularly possible scenarios of language evolution. One of the central challenges of this field of research is to identify appropriate criteria to differentiate a gesture from other non-communicative actions. After an introduction to the criteria currently used to define non-human primates' gestures and an overview of ongoing research, we discuss different pathways of how manual actions are transformed into manual gestures in both phylogeny and ontogeny. Currently, the relationship between actions and gestures is not only investigated on a behavioural, but also on a neural level. Here, we focus on recent evidence concerning the differential laterality of manual actions and gestures in apes in the framework of a functional asymmetry of the brain for both hand use and language. PMID:22106431

  9. The origins of non-human primates' manual gestures.

    PubMed

    Liebal, Katja; Call, Josep

    2012-01-12

    The increasing body of research into human and non-human primates' gestural communication reflects the interest in a comparative approach to human communication, particularly possible scenarios of language evolution. One of the central challenges of this field of research is to identify appropriate criteria to differentiate a gesture from other non-communicative actions. After an introduction to the criteria currently used to define non-human primates' gestures and an overview of ongoing research, we discuss different pathways of how manual actions are transformed into manual gestures in both phylogeny and ontogeny. Currently, the relationship between actions and gestures is not only investigated on a behavioural, but also on a neural level. Here, we focus on recent evidence concerning the differential laterality of manual actions and gestures in apes in the framework of a functional asymmetry of the brain for both hand use and language.

  10. Justice- and fairness-related behaviors in nonhuman primates.

    PubMed

    Brosnan, Sarah F

    2013-06-18

    A distinctive feature across human societies is our interest in justice and fairness. People will sometimes invest in extremely costly behavior to achieve fair outcomes for themselves and others. Why do people care so much about justice? One way to address this is comparatively, exploring behaviors related to justice and fairness in other species. In this paper, I review work exploring responses to inequity, prosocial behavior, and other relevant behaviors in nonhuman primates in an effort to understand both the potential evolutionary function of these behaviors and the social and ecological reasons for the individual differences in behavior. I also consider how these behaviors relate to human behavior, particularly in the case of experimental studies using games derived from experimental economics to compare nonhuman primates' responses to those of humans in similar experimental conditions. These results emphasize the importance of a comparative approach to better understand the function and diversity of human behavior.

  11. Manzanita Wood: A Sanitizable Enrichment Option for Nonhuman Primates

    PubMed Central

    Luchins, Kerith R; Baker, Kate C; Gilbert, Margaret H; Blanchard, James L; Bohm, Rudolf P

    2011-01-01

    Wooden objects are often used as nonhuman primate enrichment to provide variety and novelty, promote exploratory behavior, and supply an outlet for curiosity. However, concerns have been raised regarding the ability to sanitize wood by using conventional cage-wash procedures. To address this concern, we examined sanitation outcomes between soiled plastic toys and manzanita wooden manipulanda immediately after a cage-wash cycle. Both an ATP luminometer device, which is capable of providing an immediate assessment of sanitation levels, and traditional bacterial culture were used, with the secondary goal of comparing these methods for sanitation monitoring. Results showed that the wooden objects did not differ from plastic toys with respect to the overall efficacy of cage-wash sanitization. Therefore, manzanita wood can be used as nonhuman primate enrichment without risking pathogen transmission when items are rotated among animals. PMID:22330781

  12. Biorhythms and space experiments with nonhuman primates

    NASA Technical Reports Server (NTRS)

    Winget, C. M.

    1977-01-01

    Man's response to exposure to spaceflight and weightlessness is expressed in physiological adjustments which involve his health and ability to function. The amplitude and periodicity of fluctuations in biological processes affect various functions and responses to provocative stimuli. Primates and other species are subjected to tests to determine the consequences of an altered biorhythm on work and performance, emotional stability, biomedical evaluation in space, the ability to cope with the unexpected, and susceptibility to infection, toxicity, radiation, drugs, and stress. Factors in the environment or operational setup which can change the physiological baseline must be determined and controlled.

  13. Analgesic Use in Nonhuman Primates Undergoing Neurosurgical Procedures

    PubMed Central

    DiVincenti, Louis

    2013-01-01

    Animals experiencing major invasive surgery during biomedical research must receive appropriate and sufficient analgesia. The concept of pain management in veterinary medicine has evolved over the past several decades, and a multimodal, preemptive approach to postoperative analgesia is the current standard of care. Here, the pathophysiology of pain and a multimodal approach to analgesia for neurosurgical procedures is discussed, with emphasis on those involving nonhuman primates. PMID:23562027

  14. Differences in auditory timing between human and nonhuman primates.

    PubMed

    Honing, Henkjan; Merchant, Hugo

    2014-12-01

    The gradual audiomotor evolution hypothesis is proposed as an alternative interpretation to the auditory timing mechanisms discussed in Ackermann et al.'s article. This hypothesis accommodates the fact that the performance of nonhuman primates is comparable to humans in single-interval tasks (such as interval reproduction, categorization, and interception), but shows differences in multiple-interval tasks (such as entrainment, synchronization, and continuation).

  15. Characterization of interleukin-8 receptors in non-human primates

    SciTech Connect

    Alvarez, V.; Coto, E.; Gonzalez-Roces, S.; Lopez-Larrea, C.

    1996-09-01

    Interleukin-8 is a chemokine with a potent neutrophil chemoatractant activity. In humans, two different cDNAs encoding human IL8 receptors designated IL8RA and IL8RB have been cloned. IL8RA binds IL8, while IL8RB binds IL8 as well as other {alpha}-chemokines. Both human IL8Rs are encoded by two genes physically linked on chromosome 2. The IL8RA and IL8RB genes have open reading frames (ORF) lacking introns. By direct sequencing of the polymerase chain reaction products, we sequenced the IL8R genes of cell lines from four non-human primates: chimpanzee, gorilla, orangutan, and macaca. The IL8RB encodes an ORF in the four non-human primates, showing 95%-99% similarity to the human IL8RB sequence. The IL8RA homologue in gorilla and chimpanzee consisted of two ORF 98%-99% identical to the human sequence. The macaca and orangutan IL8RA homologues are pseudogenes: a 2 base pair insertion generated a sequence with several stop codons. In addition, we describe the physical linkage of these genes in the four non-human primates and discuss the evolutionary implications of these findings. 25 refs., 5 figs., 3 tabs.

  16. Environmental enrichment for nonhuman primates: theory and application.

    PubMed

    Lutz, Corrine K; Novak, Melinda A

    2005-01-01

    Investigators have an obligation to promote the psychological well-being of nonhuman primates used in research. Considerable emphasis has been placed on providing nonhuman primates with enriched environments as a means to achieve this objective. A framework is provided that consists of a set of hypotheses about well-being, and the extent to which exposure to various enrichment devices and procedures actually promotes well-being is evaluated. Two hypotheses are concerned with fostering species-typical behavior: use (versus nonuse) of the enrichment, and whether use of enrichment helps normalize other aspects of the behavioral repertoire. Two additional hypotheses are concerned with abnormal behavior: whether currently existing enrichment lowers levels of abnormal behavior, and whether it prevents the behavior. This framework is applied to various enrichment strategies ranging from toys and foraging devices to social interaction. Most devices are used by nonhuman primates and thus constitute an important way to enrich the captive environment. However, enrichment devices vary as to their effectiveness in normalizing the behavioral repertoire and eliminating abnormal behavior. Only social contact satisfies the goal of promoting a wide variety of species-typical activities while at the same time reducing or preventing the development of abnormal behavior.

  17. A review of lateralization of spatial functioning in nonhuman primates.

    PubMed

    Oleksiak, Anna; Postma, Albert; van der Ham, Ineke J M; Klink, P Christiaan; van Wezel, Richard J A

    2011-06-24

    The majority of research on functional cerebral lateralization in primates revolves around vocal abilities, addressing the evolutionary origin of the human language faculty and its predominance in the left hemisphere of the brain. Right hemisphere specialization in spatial cognition is commonly reported in humans. This functional asymmetry is especially evident in the context of the unilateral neglect, a deficit in attention to and awareness of one side of space, that more frequently occurs after right-side rather than left-side brain damage. Since most of the research efforts are concentrated on vocalization in primates, much less is known about the presence or absence of spatial functions lateralization. Obtaining this knowledge can provide insight into the evolutionary aspect of the functionally lateralized brain of Homo sapiens and deliver refinement and validation of the nonhuman primate unilateral neglect model. This paper reviews the literature on functional brain asymmetries in processing spatial information, limiting the search to nonhuman primates, and concludes there is no clear evidence that monkeys process spatial information with different efficiency in the two hemispheres. We suggest that lateralization of spatial cognition in humans represents a relatively new feature on the evolutionary time scale, possibly developed as a by-product of the left hemisphere intrusion of language competence. Further, we argue that the monkey model of hemispatial neglect requires reconsideration. PMID:21059373

  18. Voice processing in human and non-human primates

    PubMed Central

    Belin, Pascal

    2006-01-01

    Humans share with non-human primates a number of voice perception abilities of crucial importance in social interactions, such as the ability to identify a conspecific individual from its vocalizations. Speech perception is likely to have evolved in our ancestors on the basis of pre-existing neural mechanisms involved in extracting behaviourally relevant information from conspecific vocalizations (CVs). Studying the neural bases of voice perception in primates thus not only has the potential to shed light on cerebral mechanisms that may be—unlike those involved in speech perception—directly homologous between species, but also has direct implications for our understanding of how speech appeared in humans. In this comparative review, we focus on behavioural and neurobiological evidence relative to two issues central to voice perception in human and non-human primates: (i) are CVs ‘special’, i.e. are they analysed using dedicated cerebral mechanisms not used for other sound categories, and (ii) to what extent and using what neural mechanisms do primates identify conspecific individuals from their vocalizations? PMID:17118926

  19. Why Primates? The Importance of Nonhuman Primates for Understanding Human Infancy

    ERIC Educational Resources Information Center

    Weiss, Daniel J.; Santos, Laurie R.

    2006-01-01

    We introduce the thematic collection by noting some striking similarities in the cognitive abilities of human infants and nonhuman primates. What are the implications of these similarities for our comprehension of human infant cognition? After providing a brief historical and conceptual background on comparative behavioral research, we discuss how…

  20. Whisper-like behavior in a non-human primate.

    PubMed

    Morrison, Rachel; Reiss, Diana

    2013-01-01

    In humans, whispering has evolved as a counteractive strategy against eavesdropping. Some evidence for whisper-like behavior exists in a few other species, but has not been reported in non-human primates. We discovered the first evidence of whisper-like behavior in a non-human primate, the cotton-top tamarin (Saguinus oedipus), in the course of investigating their use of human-directed mobbing calls. We exposed a family of captive cotton-top tamarins to a supervisor who previously elicited a strong mobbing response. Simultaneous audio-video recordings documented the animals' behavioral and vocal responses in the supervisor's presence and absence. Rather than exhibiting a mobbing response and producing loud human-directed mobbing calls, the tamarins exhibited other anti-predator behaviors and produced low amplitude vocalizations that initially eluded our detection. A post-hoc analysis of the data was conducted to test a new hypothesis-the tamarins were reducing the amplitude of their vocalizations in the context of exposure to a potential threat. Consistent with whisper-like behavior, the amplitude of the tamarins' vocalizations was significantly reduced only in the presence of the supervisor. Due to its subtle properties, this phenomenon may have eluded detection in this species. Increasing evidence of whisper-like behavior in non-human species suggests that such low amplitude signaling may represent a convergence in a communication strategy amongst highly social and cooperative species. PMID:24038444

  1. Nonhuman primates prefer slow tempos but dislike music overall.

    PubMed

    McDermott, Josh; Hauser, Marc D

    2007-09-01

    Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21] to test cotton-top tamarins and common marmosets, two new-World primates, for their spontaneous responses to stimuli that varied systematically with respect to tempo. Across several experiments, we found that both tamarins and marmosets preferred slow tempos to fast. It is possible that the observed preferences were due to arousal, and that this effect is homologous to the human response to tempo. In other respects, however, these two monkey species showed striking differences compared to humans. Specifically, when presented with a choice between slow tempo musical stimuli, including lullabies, and silence, tamarins and marmosets preferred silence whereas humans, when similarly tested, preferred music. Thus despite the possibility of homologous mechanisms for tempo perception in human and nonhuman primates, there appear to be motivational ties to music that are uniquely human.

  2. Justice- and fairness-related behaviors in nonhuman primates

    PubMed Central

    Brosnan, Sarah F.

    2013-01-01

    A distinctive feature across human societies is our interest in justice and fairness. People will sometimes invest in extremely costly behavior to achieve fair outcomes for themselves and others. Why do people care so much about justice? One way to address this is comparatively, exploring behaviors related to justice and fairness in other species. In this paper, I review work exploring responses to inequity, prosocial behavior, and other relevant behaviors in nonhuman primates in an effort to understand both the potential evolutionary function of these behaviors and the social and ecological reasons for the individual differences in behavior. I also consider how these behaviors relate to human behavior, particularly in the case of experimental studies using games derived from experimental economics to compare nonhuman primates’ responses to those of humans in similar experimental conditions. These results emphasize the importance of a comparative approach to better understand the function and diversity of human behavior. PMID:23754407

  3. Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates

    PubMed Central

    Farese, Ann M.; Cohen, Melanie V.; Katz, Barry P.; Smith, Cassandra P.; Gibbs, Allison; Cohen, Daniel M.; MacVittie, Thomas J.

    2015-01-01

    Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n =22) or filgrastim-treated (n =24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome. PMID:23210705

  4. Manganese Neurotoxicity: Lessons Learned from Longitudinal Studies in Nonhuman Primates

    PubMed Central

    Burton, Neal C.; Guilarte, Tomás R.

    2009-01-01

    Background Exposure to excess levels of the essential trace element manganese produces cognitive, psychiatric, and motor abnormalities. The understanding of Mn neurotoxicology is heavily governed by pathologic and neurochemical observations derived from rodent studies that often employ acute Mn exposures. The comparatively sparse studies incorporating in vivo neuroimaging in nonhuman primates provide invaluable insights on the effects of Mn on brain chemistry. Objectives The purpose of this review is to discuss important aspects of Mn neurotoxicology and to synthesize recent findings from one of the largest cohorts of nonhuman primates used to study the neurologic effects of chronic Mn exposure. Discussion We reviewed our recent in vivo and ex vivo studies that have significantly advanced the understanding of Mn-induced neurotoxicity. In those studies, we administered weekly doses of 3.3–5.0 (n = 4), 5.0–6.7 (n = 5), or 8.3–10.0 mg Mn/kg (n = 3) for 7–59 weeks to cynomolgus macaque monkeys. Animals expressed subtle deficits in cognition and motor function and decreases in the N-acetylaspartate-to-creatine ratio in the parietal cortex measured by magnetic resonance spectroscopy reflective of neuronal dysfunction. Impaired striatal dopamine release measured by positron emission tomography was observed in the absence of changes in markers of dopamine neuron degeneration. Neuropathology indicated decreased glutamine synthetase expression in the globus pallidus with otherwise normal markers of glutamatergic and GABAergic neurotransmission. Increased amyloid beta (A4) precursor-like protein 1 gene expression with multiple markers of neurodegeneration and glial cell activation was observed in the frontal cortex. Conclusions These findings provide new information on mechanisms by which Mn affects behavior, neurotransmitter function, and neuropathology in nonhuman primates. PMID:19337503

  5. Instrumentation for space flight experiments. [using nonhuman primates

    NASA Technical Reports Server (NTRS)

    Mccutcheon, E. P.

    1977-01-01

    The selection of measurement systems for experiments conducted in the context of a space flight must be guided by the criteria applicable to any scientific study requiring objective measurements of physiological variables. Steps fundamental to the process of choosing the best instrumentation system are identified and the key factors in matching the operational characteristics of the instrumentation to its intended use are discussed. Special problems in obtaining data from nonhuman primates, whether restrained or unrestrained, are explored. Choices for data processing are evaluated as well as the use of prototype flight tests and simulations to assess future life science experiments for spacelab or payloads for the space shuttle biomedical scientific satellite.

  6. Nonhuman gamblers: lessons from rodents, primates, and robots

    PubMed Central

    Paglieri, Fabio; Addessi, Elsa; De Petrillo, Francesca; Laviola, Giovanni; Mirolli, Marco; Parisi, Domenico; Petrosino, Giancarlo; Ventricelli, Marialba; Zoratto, Francesca; Adriani, Walter

    2014-01-01

    The search for neuronal and psychological underpinnings of pathological gambling in humans would benefit from investigating related phenomena also outside of our species. In this paper, we present a survey of studies in three widely different populations of agents, namely rodents, non-human primates, and robots. Each of these populations offers valuable and complementary insights on the topic, as the literature demonstrates. In addition, we highlight the deep and complex connections between relevant results across these different areas of research (i.e., cognitive and computational neuroscience, neuroethology, cognitive primatology, neuropsychiatry, evolutionary robotics), to make the case for a greater degree of methodological integration in future studies on pathological gambling. PMID:24574984

  7. Social consequences of disability in a nonhuman primate.

    PubMed

    Turner, Sarah E; Fedigan, Linda M; Matthews, H Damon; Nakamichi, Masayuki

    2014-03-01

    Debates about the likelihood of conspecific care for disabled individuals in ancestral hominins rely on evidence from extant primates, yet little is known about social treatment (positive, neutral or negative) of physically disabled individuals in nonhuman primates. A group of free-ranging Japanese macaques (Macaca fuscata) at the Awajishima Monkey Center (AMC) in Japan presents a unique opportunity to investigate the relationships between physical impairment and social behavior, in the context of congenital limb malformation in adult nonhuman primates. We collected behavioral data on 23 focal animals, taking 30-minute continuous time samples on disabled and nondisabled adult female Japanese macaques during three consecutive birth seasons (May-August 2005, 2006, and 2007). Disabled females were less social overall compared with nondisabled controls, a pattern that was evident from a variety of measures. Disabled females rested significantly more and socialized significantly less compared with controls, had fewer adult female affiliates, fewer adult female grooming partners, and spent less time engaged in grooming with adult females. Some measures suggested that the social differences were the result of behavioral flexibility on the part of disabled females compensating for their disabilities with lower levels of social involvement and more rest. Disabled females were as successful at groom solicitations as were nondisabled females and the ratio of disabled and nondisabled affiliates was similar among focal animals; there was no strong preference related to the disability status of affiliates. Disabled females were also bitten and chased less frequently. Overall, there was little evidence either for conspecific care or for social selection against disability. In general, there was a socially neutral response to disability, and while neutral social context allows for the possibility of care behaviors, our findings emphasize the self-reliant abilities of these

  8. Social consequences of disability in a nonhuman primate.

    PubMed

    Turner, Sarah E; Fedigan, Linda M; Matthews, H Damon; Nakamichi, Masayuki

    2014-03-01

    Debates about the likelihood of conspecific care for disabled individuals in ancestral hominins rely on evidence from extant primates, yet little is known about social treatment (positive, neutral or negative) of physically disabled individuals in nonhuman primates. A group of free-ranging Japanese macaques (Macaca fuscata) at the Awajishima Monkey Center (AMC) in Japan presents a unique opportunity to investigate the relationships between physical impairment and social behavior, in the context of congenital limb malformation in adult nonhuman primates. We collected behavioral data on 23 focal animals, taking 30-minute continuous time samples on disabled and nondisabled adult female Japanese macaques during three consecutive birth seasons (May-August 2005, 2006, and 2007). Disabled females were less social overall compared with nondisabled controls, a pattern that was evident from a variety of measures. Disabled females rested significantly more and socialized significantly less compared with controls, had fewer adult female affiliates, fewer adult female grooming partners, and spent less time engaged in grooming with adult females. Some measures suggested that the social differences were the result of behavioral flexibility on the part of disabled females compensating for their disabilities with lower levels of social involvement and more rest. Disabled females were as successful at groom solicitations as were nondisabled females and the ratio of disabled and nondisabled affiliates was similar among focal animals; there was no strong preference related to the disability status of affiliates. Disabled females were also bitten and chased less frequently. Overall, there was little evidence either for conspecific care or for social selection against disability. In general, there was a socially neutral response to disability, and while neutral social context allows for the possibility of care behaviors, our findings emphasize the self-reliant abilities of these

  9. Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV

    PubMed Central

    Wilkins, Jordan; Zheng, Yi-Min; Yu, Jingyou; Liang, Chen

    2016-01-01

    Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis. PMID:27257969

  10. Enumeration of Objects and Substances in Non-Human Primates: Experiments with Brown Lemurs ("Eulemur Fulvus")

    ERIC Educational Resources Information Center

    Mahajan, Neha; Barnes, Jennifer L.; Blanco, Marissa; Santos, Laurie R.

    2009-01-01

    Both human infants and adult non-human primates share the capacity to track small numbers of objects across time and occlusion. The question now facing developmental and comparative psychologists is whether similar mechanisms give rise to this capacity across the two populations. Here, we explore whether non-human primates' object tracking…

  11. Pollical oblique ligament in humans and non-human primates.

    PubMed

    Shrewsbury, Marvin

    2003-04-01

    A morphological study of the oblique ligament in the thumb is presented. The ligament was consistently described in human specimens and compared with dissections of non-human primates from different species. The oblique ligament was found in some, but not all, specimens in each of the following species examined: chimpanzee, orangutan, gibbon, anubis baboon, hamadryas baboon, squirrel monkey, lemur and marmoset. A revised identity of the oblique ligament is proposed as a reinforced distal border of a fibro-osseous annular pollical flexor sheath and whose function is not independent of the flexor sheath. The constant presence and tendinous trait of the pollical oblique ligament in humans, when compared with non-human primates, supports the notion that the oblique ligament strengthens the pollical flexor sheath in humans for restraint of the flexor pollicis longus tendon during forceful precision pinching. A derivation of the pollical oblique ligament is considered as representing a vestigial radial limb of a flexor pollicis superficialis tendon in the thumb.

  12. Suffixation influences receivers' behaviour in non-human primates

    PubMed Central

    Coye, Camille; Ouattara, Karim; Zuberbühler, Klaus; Lemasson, Alban

    2015-01-01

    Compared to humans, non-human primates have very little control over their vocal production. Nonetheless, some primates produce various call combinations, which may partially offset their lack of acoustic flexibility. A relevant example is male Campbell's monkeys (Cercopithecus campbelli), which give one call type (‘Krak’) to leopards, while the suffixed version of the same call stem (‘Krak-oo’) is given to unspecific danger. To test whether recipients attend to this suffixation pattern, we carried out a playback experiment in which we broadcast naturally and artificially modified suffixed and unsuffixed ‘Krak’ calls of male Campbell's monkeys to 42 wild groups of Diana monkeys (Cercopithecus diana diana). The two species form mixed-species groups and respond to each other's vocalizations. We analysed the vocal response of male and female Diana monkeys and overall found significantly stronger vocal responses to unsuffixed (leopard) than suffixed (unspecific danger) calls. Although the acoustic structure of the ‘Krak’ stem of the calls has some additional effects, subject responses were mainly determined by the presence or the absence of the suffix. This study indicates that suffixation is an evolved function in primate communication in contexts where adaptive responses are particularly important. PMID:25925101

  13. Field endocrinology of nonhuman primates: past, present, and future.

    PubMed

    Higham, James P

    2016-08-01

    In the past few decades, research on nonhuman primate endocrinology has moved from the lab to the field, leading to a huge increase in both the breadth and depth of primate field studies. Here, I discuss the past, present, and future of primate field endocrinology. I review the history of the field, and go on to discuss methodological developments and the issues that they sometimes entail. Next, I consider ways in which we might conceptualize the role of hormones, and focus on the need to distinguish proximate from ultimate levels of explanation. Current potentially problematic issues in the field include: 1) an inability to obtain noninvasive measurements of Central Nervous System (CNS) rather than peripheral hormone concentrations; 2) research questions that become stuck (e.g., questions regarding sexual swelling expression mechanisms); 3) data dredging and post-hoc linking of hormones to any plausible variable, leading to a lack of clarity on their role in animal ecology and behavior. I finish by discussing several unanswered questions that might benefit from further research. These are how we might: 1) best obtain measurements for CNS hormone concentrations non-invasively; 2) measure hormone receptor expression alongside hormone concentrations; 3) consider the human endocrinology literature more thoroughly and perhaps take more multimarker approaches; 4) better consider the social environment, including audience and dyadic familiarity effects; and 5) apply our findings to conservation issues. PMID:27469069

  14. Meeting Report: Spontaneous Lesions and Diseases in Wild, Captive-Bred, and Zoo-Housed Nonhuman Primates and in Nonhuman Primate Species Used in Drug Safety Studies

    PubMed Central

    Sasseville, V. G.; Mansfield, K. G.; Mankowski, J. L.; Tremblay, C.; Terio, K. A.; Mätz-Rensing, K.; Gruber-Dujardin, E.; Delaney, M. A.; Schmidt, L. D.; Liu, D.; Markovits, J. E.; Owston, M.; Harbison, C.; Shanmukhappa, S.; Miller, A. D.; Kaliyaperumal, S.; Assaf, B. T.; Kattenhorn, L.; Macri, S. Cummings; Simmons, H. A.; Baldessari, A.; Sharma, P.; Courtney, C.; Bradley, A.; Cline, J. M.; Reindel, J. F.; Hutto, D. L.; Montali, R. J.; Lowenstine, L. J.

    2014-01-01

    The combination of loss of habitat, human population encroachment, and increased demand of select nonhuman primates for biomedical research has significantly affected populations. There remains a need for knowledge and expertise in understanding background findings as related to the age, source, strain, and disease status of nonhuman primates. In particular, for safety/biomedical studies, a broader understanding and documentation of lesions would help clarify background from drug-related findings. A workshop and a minisymposium on spontaneous lesions and diseases in nonhuman primates were sponsored by the concurrent Annual Meetings of the American College of Veterinary Pathologists and the American Society for Veterinary Clinical Pathology held December 3–4, 2011, in Nashville, Tennessee. The first session had presentations from Drs Lowenstine and Montali, pathologists with extensive experience in wild and zoo populations of nonhuman primates, which was followed by presentations of 20 unique case reports of rare or newly observed spontaneous lesions in nonhuman primates (see online files for access to digital whole-slide images corresponding to each case report at http://www.scanscope.com/ACVP%20Slide%20 Seminars/2011/Primate%20Pathology/view.apml). The minisymposium was composed of 5 nonhuman-primate researchers (Drs Bradley, Cline, Sasseville, Miller, Hutto) who concentrated on background and spontaneous lesions in nonhuman primates used in drug safety studies. Cynomolgus and rhesus macaques were emphasized, with some material presented on common marmosets. Congenital, acquired, inflammatory, and neoplastic changes were highlighed with a focus on clinical, macroscopic, and histopathologic findings that could confound the interpretation of drug safety studies. PMID:23135296

  15. The unique value of primate models in translational research. Nonhuman primate models of women's health: introduction and overview.

    PubMed

    Shively, Carol A; Clarkson, Thomas B

    2009-09-01

    This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that have proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and

  16. Application of the genome editing tool CRISPR/Cas9 in non-human primates.

    PubMed

    Luo, Xin; Li, Min; Su, Bing

    2016-07-18

    In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates. PMID:27469252

  17. Role of non-human primates in malaria vaccine development: Memorandum from a WHO Meeting*

    PubMed Central

    1988-01-01

    This Memorandum discusses the coordination and standardization of malaria vaccine research in non-human primates to encourage optimum use of the available animals in experiments that are fully justified both scientifically and ethically. The requirements for experimentation in non-human primates, the availability of suitable animals for malaria vaccine studies, and the criteria for testing candidate vaccines are considered. The policy and legislation relevant to the use of non-human primates in biomedical research are also briefly discussed. The Memorandum concludes with eight recommendations. PMID:3266112

  18. Application of the genome editing tool CRISPR/Cas9 in non-human primates

    PubMed Central

    LUO, Xin; LI, Min; SU, Bing

    2016-01-01

    In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates. PMID:27469252

  19. Application of the genome editing tool CRISPR/Cas9 in non-human primates.

    PubMed

    Luo, Xin; Li, Min; Su, Bing

    2016-07-18

    In the past three years, RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system has been used to facilitate efficient genome editing in many model and non-model animals. However, its application in nonhuman primates is still at the early stage, though in view of the similarities in anatomy, physiology, behavior and genetics, closely related nonhuman primates serve as optimal models for human biology and disease studies. In this review, we summarize the current proceedings of gene editing using CRISPR/Cas9 in nonhuman primates.

  20. Chromobacterium violaceum infections in 13 non-human primates

    PubMed Central

    Liu, David X.; Didier, Peter J.; Plauche, Gail B.

    2015-01-01

    Background Recently, an Indian-origin macaque was found dead and Chromobacterium violaceum was isolated from the skin wound, and hepatic and pulmonary abscesses. Methods By searching the database, a total of thirteen cases of C. violaceum infection in pigtail macaques (n = 8), rhesus macaques (n = 4), and one baboon were identified from 2001 to 2010 at Tulane National Primate Research Center. Medical records were reviewed for breed, sex, age, clinical findings, treatment, outcome, bacteriology, and gross and histological findings. Results Seven pigtail macaques and one Indian-origin rhesus macaque died of chromobacterial septicemia. All chromobacterial septicemic pigtail macaques were adult with higher incidence in female. Hepatic abscess and thrombosis were typical findings along with pulmonary abscess and thrombosis, renal venous thromboembolism, and necrosuppurative pleuritis, peritonitis, splenitis, myocarditis, pericarditis, and meningoencephalitis. Skin wound, uterine infection, and oral and respiratory exposure were considered the points of entry for these animals. Conclusions This represents the first report of chromobacteriosis in pigtail, rhesus macaque, and baboon. Our experience suggests that chromobacterial infections may be more common in non-human primates than previously recognized. PMID:22211858

  1. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    PubMed Central

    Benveniste, Helene; Fowler, Joanna S.; Rooney, William D.; Scharf, Bruce A.; Backus, W. Walter; Izrailtyan, Igor; Knudsen, Gitte M.; Hasselbalch, Steen G.; Volkow, Nora D.

    2010-01-01

    Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (∼100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine’s effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine are influenced by the state of pregnancy. Our findings have clinical implications because they imply that the adverse effects of prenatal cocaine exposure to the newborn child include not only cocaine’s deleterious effects to the placental circulation, but also cocaine’s direct pharmacological effect to the developing fetal brain. PMID:20080687

  2. Effects of 60 Hz electric fields on operant and social stress behaviors of nonhuman primates

    SciTech Connect

    Rogers, W.R.; Lucas, J.H.; Moore, G.T.; Orr, J.L.

    1985-01-01

    An overall description of this research program is presented. The objectives are to investigate using nonhuman primates, possible behavioral effects associated with exposure to high-intensity, 60 Hz, electric fields. 6 tabs.

  3. Accelerated Diversification of Nonhuman Primate Malarias in Southeast Asia: Adaptive Radiation or Geographic Speciation?

    PubMed Central

    Muehlenbein, Michael P.; Pacheco, M. Andreína; Taylor, Jesse E.; Prall, Sean P.; Ambu, Laurentius; Nathan, Senthilvel; Alsisto, Sylvia; Ramirez, Diana; Escalante, Ananias A.

    2015-01-01

    Although parasitic organisms are found worldwide, the relative importance of host specificity and geographic isolation for parasite speciation has been explored in only a few systems. Here, we study Plasmodium parasites known to infect Asian nonhuman primates, a monophyletic group that includes the lineage leading to the human parasite Plasmodium vivax and several species used as laboratory models in malaria research. We analyze the available data together with new samples from three sympatric primate species from Borneo: The Bornean orangutan and the long-tailed and the pig-tailed macaques. We find several species of malaria parasites, including three putatively new species in this biodiversity hotspot. Among those newly discovered lineages, we report two sympatric parasites in orangutans. We find no differences in the sets of malaria species infecting each macaque species indicating that these species show no host specificity. Finally, phylogenetic analysis of these data suggests that the malaria parasites infecting Southeast Asian macaques and their relatives are speciating three to four times more rapidly than those with other mammalian hosts such as lemurs and African apes. We estimate that these events took place in approximately a 3–4-Ma period. Based on the genetic and phenotypic diversity of the macaque malarias, we hypothesize that the diversification of this group of parasites has been facilitated by the diversity, geographic distributions, and demographic histories of their primate hosts. PMID:25389206

  4. Comparative sequence analysis of cytokine genes from human and nonhuman primates

    SciTech Connect

    Villinger, F.; Brar, S.S.; Mayne, A.

    1995-10-15

    Two major issues severely limit the studies of human recombinant cytokines/growth factors in nonhuman primates. First, assays and reagents specific for the detection and quantitation of human cytokines do not all function when utilized to detect/quantitate the nonhuman primate cytokines. Second, although most of the human cytokines appear to induce similar, if not identical, biologic function when used with cells from nonhuman primates in vitro or in vivo, they invariably induce Ab responses in vivo, precluding their repeated and/or continued use in vivo. Our laboratory has thus initiated studies to clone, sequence, and prepare recombinant cytokines from nonhuman primates and to define assays and reagents for their detection and quantitation at the nucleic acid and protein level. The data that were derived from such studies show that the nonhuman primate cytokines IL-1{alpha}, IL-1{beta}, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12{alpha}, IL-12{beta}, IL-15, IFN-{alpha}, IFN-{gamma}, and TNF-{alpha} share 93 to 99% homology at the nucleic acid and protein level with the human equivalents. The most prominent differences between human and nonhuman primate cytokine sequences were noted for IL-1{alpha}/{beta}, IL-2, IL-8, IFN-{alpha}, IFN-{gamma}, and IL-12{beta}. The aligned sequences of cytokines for human and several nonhuman primate species are provided herein, and a phylogenetic analysis of the published sequences of select cytokines from other species, along with those of the nonhuman primates, are described. In addition, comparative analysis of the relative bioactivity of our immunoaffinity-purified recombinant rhesus macaque IL-4, IL-15, and IFN-{gamma} with commercially available human recombinant cytokines is described herein. 40 refs., 5 figs., 2 tabs.

  5. Ultra-rapid categorisation in non-human primates.

    PubMed

    Girard, P; Jouffrais, C; Kirchner, C H

    2008-07-01

    The visual system of primates is remarkably efficient for analysing information about objects present in complex natural scenes. Recent work has demonstrated that they perform this at very high speeds. In a choice saccade task, human subjects can initiate a first reliable saccadic eye movement response to a target (the image containing an animal) in only 120 ms after image onset. Such fast responses impose severe time constraints if one considers neuronal responses latencies in high-level ventral areas of the macaque monkey. The question then arises: are non-human primates able to perform the task? Two rhesus macaque monkeys (Macaca mulatta) were trained to perform the same forced-choice categorization task as the one used in humans. Both animals performed the task with a high accuracy and generalized to new stimuli that were introduced everyday: accuracy levels were comparable both with new and well-known images (84% vs. 94%). More importantly, reaction times were extremely fast (minimum reaction time 100 ms and median reaction time 152 ms). Given that typical single units onset times in Inferotemporal cortex (IT) are about as long as the shortest behavioural responses measured here, we conclude that visual processing involved in ultra rapid categorizations might be based on rather simple shape cue analysis that can be achieved in areas such as extrastriate cortical area V4. The present paper demonstrates for the first time, that rhesus macaque monkeys (Macaca mulatta) are able to match human performance in a forced-choice saccadic categorisation task of animals in natural scenes.

  6. Sex differences in energy expenditure in non-human primates.

    PubMed Central

    Key, C; Ross, C

    1999-01-01

    Female mammals bear the energetic costs of gestation and lactation. Therefore, it is often assumed that the overall energetic costs are greater for females than they are for males. However, the energetic costs to males of intrasex competition may also be considerable, particularly if males maintain a much larger body size than females. Using data from 19 non-human primates, this paper examines the relationship between male and female energetic costs both in the short term (daily energy expenditure) and the long term (the energetic cost of producing a single offspring). It is shown that the major determinant of sex differences in energetic costs is body size dimorphism. In the long term, the energetic costs are often greater for females, but, when male body size exceeds female body size by 60% or more, male energetic costs are greater than those for females. That is, in highly sexually dimorphic species the energetic costs of gestation and lactation for the females are matched by the energetic costs to the males of maintaining a large body size. PMID:10693818

  7. Can nonhuman primates use tokens to represent and sum quantities?

    PubMed

    Evans, Theodore A; Beran, Michael J; Addessi, Elsa

    2010-11-01

    It is unclear whether nonhuman animals can use physical tokens to flexibly represent various quantities by combining token values. Previous studies showed that chimpanzees (Pan troglodytes) and a macaque (Macaca mulatta) were only partly successful in tests involving sets of different-looking food containers representing different food quantities, while some capuchin monkeys (Cebus apella) have shown greater success in tests involving sets of various concrete objects representing different food quantities. Some of the discrepancy in results between these studies may be attributed to the different methods used. In an effort to reconcile these discrepancies, we presented two primates species, chimpanzees and capuchin monkeys, with two token tasks. The critical test in each task involved summing the value of multiple tokens of different types to make accurate quantity judgments. We found that, using either method, individuals of both species learned to associate individual tokens with specific quantities, as well as successfully compare individual tokens to one another or to sets of visible food items. However, regardless of method, only a few individuals exhibited the capacity to sum multiple tokens of different types and then use those summed values to make an optimal response. This suggests that flexible combination of symbolic stimuli in quantity judgments tasks is within the abilities of chimpanzees and capuchins but does not characterize the majority of individuals. Furthermore, the results suggest the need to carefully examine specific methodological details that may promote or hinder such possible representation. PMID:20836596

  8. The non-human primate experimental glaucoma model.

    PubMed

    Burgoyne, Claude F

    2015-12-01

    The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic intraocular pressure (IOP) elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model.

  9. Modified toolbox for optogenetics in the nonhuman primate

    PubMed Central

    Dai, Ji; Ozden, Ilker; Brooks, Daniel I.; Wagner, Fabien; May, Travis; Agha, Naubahar S.; Brush, Benjamin; Borton, David; Nurmikko, Arto V.; Sheinberg, David L.

    2015-01-01

    Abstract. Attracted by the appealing advantages of optogenetics, many nonhuman primate labs are attempting to incorporate this technique in their experiments. Despite some reported successes by a few groups, many still find it difficult to develop a reliable way to transduce cells in the monkey brain and subsequently monitor light-induced neuronal activity. Here, we describe a methodology that we have developed and successfully deployed on a regular basis with multiple monkeys. All devices and accessories are easy to obtain and results using these have been proven to be highly replicable. We developed the “in-chair” viral injection system and used tapered and thinner fibers for optical stimulation, which significantly improved the efficacy and reduced tissue damage. With these methods, we have successfully transduced cells in multiple monkeys in both deep and shallow cortical areas. We could reliably obtain neural modulation for months after injection, and no light-induced artifacts were observed during recordings. Further experiments using these methods have shown that optogenetic stimulation can be used to bias spatial attention in a visual choice discrimination task in a way comparable to electrical microstimulation, which demonstrates the potential use of our methods in both fundamental research and clinical applications. PMID:26158011

  10. Optogenetics through windows on the brain in the nonhuman primate

    PubMed Central

    Ruiz, Octavio; Lustig, Brian R.; Nassi, Jonathan J.; Cetin, Ali; Reynolds, John H.; Albright, Thomas D.; Callaway, Edward M.; Stoner, Gene R.

    2013-01-01

    Optogenetics combines optics and genetics to control neuronal activity with cell-type specificity and millisecond temporal precision. Its use in model organisms such as rodents, Drosophila, and Caenorhabditis elegans is now well-established. However, application of this technology in nonhuman primates (NHPs) has been slow to develop. One key challenge has been the delivery of viruses and light to the brain through the thick dura mater of NHPs, which can only be penetrated with large-diameter devices that damage the brain. The opacity of the NHP dura prevents visualization of the underlying cortex, limiting the spatial precision of virus injections, electrophysiological recordings, and photostimulation. Here, we describe a new optogenetics approach in which the native dura is replaced with an optically transparent artificial dura. This artificial dura can be penetrated with fine glass micropipettes, enabling precisely targeted injections of virus into brain tissue with minimal damage to cortex. The expression of optogenetic agents can be monitored visually over time. Most critically, this optical window permits targeted, noninvasive photostimulation and concomitant measurements of neuronal activity via intrinsic signal imaging and electrophysiological recordings. We present results from both anesthetized-paralyzed (optical imaging) and awake-behaving NHPs (electrophysiology). The improvements over current methods made possible by the artificial dura should enable the widespread use of optogenetic tools in NHP research, a key step toward the development of therapies for neuropsychiatric and neurological diseases in humans. PMID:23761700

  11. Nonhuman primate models for HIV/AIDS vaccine development.

    PubMed

    Sui, Yongjun; Gordon, Shari; Franchini, Genoveffa; Berzofsky, Jay A

    2013-10-01

    The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the simian immunodeficiency viruses (SIVs) that cause disease in macaques, which also closely mimic HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here we examine the multiple variables and considerations that must be taken into account in order to use this nonhuman primate (NHP) model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration, and macaque genetics, including the major histocompatibility complex molecules that affect immune responses, and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues that could not easily be performed on human volunteers. Furthermore, macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

  12. Detection thresholds for 60 Hz electric fields by nonhuman primates

    SciTech Connect

    Orr, J.L.; Rogers, W.R.; Smith, H.D.

    1995-12-31

    Because responses of animals to detection of the presence of an electric field (EF) are a possible mechanism for production of biological effects, it is important to know what EF intensities are detectable. Operant methods were used to train six baboons (Papio cynocephalus) to perform a psychophysical task involving detection of EF presence. During the response phase of a trial, a subject responded on one push button to report the presence of the EF and on a different push button to report the absence of the EF. Correct reports of EF presence or absence produced delivery of food rewards. The subjects became proficient at performing this psychophysical detection task; during 35 days of testing, false alarm rates averaged 9%. The average EF detection threshold was 12 kV/m; the range of means among subjects was 5--15 kV/m. Two special test procedures confirmed that the subjects were responding directly to EF presence or absence and not to artifacts that might be associated with EF generation. The EF detection threshold of nonhuman primates is similar to thresholds reported for rats and humans.

  13. Consequences of prenatal cocaine exposure in nonhuman primates.

    PubMed

    Lidow, Michael S

    2003-12-30

    The extent to which cocaine abuse by pregnant women can affect development of their offspring remains a matter of significant debate. In large part, this is due to difficulties in accurate determination of the type, dose, and pattern of cocaine administration by drug abusing women as well as to difficulties in controlling for a wide range of potentially confounding variables, such as other drugs used, race, socioeconomic status, and level of prenatal care. On this background, examination of the effects of prenatal cocaine exposure in highly controlled nonhuman primate models represents an important complement to the human research. The present review summarizes the data obtained in several different rhesus monkey models of cocaine exposure in utero. These data demonstrate the potential of prenatal cocaine exposure to interfere with structural and biochemical development of the brain leading to behavioral deficits at birth and/or during adulthood. However, the differences in the outcomes between individual models also suggest that the specific types and severity of cocaine effects are likely dependent on the route, dose, gestational period, and daily pattern of administration. PMID:14741748

  14. Foodborne transmission of bovine spongiform encephalopathy to nonhuman primates.

    PubMed

    Holznagel, Edgar; Yutzy, Barbara; Schulz-Schaeffer, Walter; Kruip, Carina; Hahmann, Uwe; Bierke, Pär; Torres, Juan-Maria; Kim, Yong-Sun; Thomzig, Achim; Beekes, Michael; Hunsmann, Gerhard; Loewer, Johannes

    2013-05-01

    Risk for human exposure to bovine spongiform encephalopathy (BSE)-inducing agent was estimated in a nonhuman primate model. To determine attack rates, incubation times, and molecular signatures, we orally exposed 18 macaques to 1 high dose of brain material from cattle with BSE. Several macaques were euthanized at regular intervals starting at 1 year postinoculation, and others were observed until clinical signs developed. Among those who received ≥5 g BSE-inducing agent, attack rates were 100% and prions could be detected in peripheral tissues from 1 year postinoculation onward. The overall median incubation time was 4.6 years (3.7-5.3). However, for 3 macaques orally exposed on multiple occasions, incubation periods were at least 7-10 years. Before clinical signs were noted, we detected a non-type 2B signature, indicating the existence of atypical prion protein during the incubation period. This finding could affect diagnosis of variant Creutzfeldt-Jakob disease in humans and might be relevant for retrospective studies of positive tonsillectomy or appendectomy specimens because time of infection is unknown.

  15. Optogenetics through windows on the brain in the nonhuman primate.

    PubMed

    Ruiz, Octavio; Lustig, Brian R; Nassi, Jonathan J; Cetin, Ali; Reynolds, John H; Albright, Thomas D; Callaway, Edward M; Stoner, Gene R; Roe, Anna W

    2013-09-01

    Optogenetics combines optics and genetics to control neuronal activity with cell-type specificity and millisecond temporal precision. Its use in model organisms such as rodents, Drosophila, and Caenorhabditis elegans is now well-established. However, application of this technology in nonhuman primates (NHPs) has been slow to develop. One key challenge has been the delivery of viruses and light to the brain through the thick dura mater of NHPs, which can only be penetrated with large-diameter devices that damage the brain. The opacity of the NHP dura prevents visualization of the underlying cortex, limiting the spatial precision of virus injections, electrophysiological recordings, and photostimulation. Here, we describe a new optogenetics approach in which the native dura is replaced with an optically transparent artificial dura. This artificial dura can be penetrated with fine glass micropipettes, enabling precisely targeted injections of virus into brain tissue with minimal damage to cortex. The expression of optogenetic agents can be monitored visually over time. Most critically, this optical window permits targeted, noninvasive photostimulation and concomitant measurements of neuronal activity via intrinsic signal imaging and electrophysiological recordings. We present results from both anesthetized-paralyzed (optical imaging) and awake-behaving NHPs (electrophysiology). The improvements over current methods made possible by the artificial dura should enable the widespread use of optogenetic tools in NHP research, a key step toward the development of therapies for neuropsychiatric and neurological diseases in humans.

  16. Can nonhuman primates use tokens to represent and sum quantities?

    PubMed

    Evans, Theodore A; Beran, Michael J; Addessi, Elsa

    2010-11-01

    It is unclear whether nonhuman animals can use physical tokens to flexibly represent various quantities by combining token values. Previous studies showed that chimpanzees (Pan troglodytes) and a macaque (Macaca mulatta) were only partly successful in tests involving sets of different-looking food containers representing different food quantities, while some capuchin monkeys (Cebus apella) have shown greater success in tests involving sets of various concrete objects representing different food quantities. Some of the discrepancy in results between these studies may be attributed to the different methods used. In an effort to reconcile these discrepancies, we presented two primates species, chimpanzees and capuchin monkeys, with two token tasks. The critical test in each task involved summing the value of multiple tokens of different types to make accurate quantity judgments. We found that, using either method, individuals of both species learned to associate individual tokens with specific quantities, as well as successfully compare individual tokens to one another or to sets of visible food items. However, regardless of method, only a few individuals exhibited the capacity to sum multiple tokens of different types and then use those summed values to make an optimal response. This suggests that flexible combination of symbolic stimuli in quantity judgments tasks is within the abilities of chimpanzees and capuchins but does not characterize the majority of individuals. Furthermore, the results suggest the need to carefully examine specific methodological details that may promote or hinder such possible representation.

  17. Radioprotective Efficacy of Gamma-Tocotrienol in Nonhuman Primates.

    PubMed

    Singh, Vijay K; Kulkarni, Shilpa; Fatanmi, Oluseyi O; Wise, Stephen Y; Newman, Victoria L; Romaine, Patricia L P; Hendrickson, Howard; Gulani, Jatinder; Ghosh, Sanchita P; Kumar, K Sree; Hauer-Jensen, Martin

    2016-03-01

    The search for treatments to counter potentially lethal radiation-induced injury over the past several decades has led to the development of multiple classes of radiation countermeasures. However, to date only granulocyte colony-stimulating factor (G-CSF; filgrastim, Neupogen)and pegylated G-CSF (pegfilgrastim, Neulasta) have been approved by the United States Food and Drug Administration (FDA) for the treatment of hematopoietic acute radiation syndrome (ARS). Gamma-tocotrienol (GT3) has demonstrated strong radioprotective efficacy in the mouse model, indicating the need for further evaluation in a large animal model. In this study, we evaluated GT3 pharmacokinetics (PK) and efficacy at different doses of cobalt-60 gamma radiation (0.6 Gy/min) using the nonhuman primate (NHP) model. The PK results demonstrated increased area under the curve with increasing drug dose and half-life of GT3. GT3 treatment resulted in reduced group mean neutropenia by 3-5 days and thrombocytopenia by 1-5 days. At 5.8 and 6.5 Gy total-body irradiation, GT3 treatment completely prevented thrombocytopenia. The capability of GT3 to reduce severity and duration of neutropenia and thrombocytopenia was dose dependent; 75 mg/kg treatment was more effective than 37.5 mg/kg treatment after a 5.8 Gy dose. However, the higher GT3 dose (75 mg/kg) was associated with higher frequency of adverse skin effects (small abscess) at the injection site. GT3 treatment of irradiated NHPs caused no significant difference in animal survival at 60 days postirradiation, however, low mortality was observed in irradiated, vehicle-treated groups as well. The data from this pilot study further elucidate the role and pharmacokinetics of GT3 in hematopoietic recovery after irradiation in a NHP model, and demonstrate the potential of GT3 as a promising radioprotector. PMID:26930378

  18. Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

    PubMed Central

    Silva, Tanielly Cristina Raiol; Andrade Junior, Edilson Ferreira; Rezende, Alexandre Pingarilho; Carneiro Muniz, José Augusto Pereira; Lacreta Junior, Antonio Carlos Cunha; Assumpção, Paulo Pimentel; Calcagno, Danielle Queiroz; Demachki, Samia; Rabenhorst, Silvia Helena Barem; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodriguez

    2011-01-01

    The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU). Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9th day though on the 14th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the tolerability and

  19. Biokinetics of 90Sr in Male Nonhuman Primates.

    PubMed

    Krage, Eric S; Poudel, Deepesh; Swanson, Jasen; Guilmette, Raymond A; Brey, Richard R

    2016-06-01

    The current study tests the hypothesis that the biokinetics of Sr can be represented by simplification of the ICRP publication 78 Sr model. Default and proposed models were evaluated by their ability to predict injected activity and more thoroughly define the activity residing in the skeleton of rhesus monkeys. The data obtained from studies done by Patricia Durbin and her colleagues at the Lawrence Berkley National Laboratory were used to create a profile of the activity residing in the skeleton at the time of sacrifice. Post mortem data along with periodic whole body count data were used to optimize the biokinetic parameters using the Integrated Modules for Bioassay Analysis (IMBA), Weighted Likelihood Monte-Carlo Sampling (WeLMoS) program to better predict the intake and fit of the bioassay data. Analysis of the default ICRP 78 parameters resulted in an overprediction of activity in the skeleton for a male cohort by as much as 180%. Using Monte Carlo sampling methods, three models were developed and optimized for a composite cohort of male monkeys. Of the three developed models, one model proved to have the best predictive capabilities. The optimized model C obtained for the male cohort was then tested on a validation cohort to test predictive capabilities. Using the optimized model C parameters, the ability to predict activity in the skeleton was improved in comparison to ICRP 78. Prediction of the intake from bioassay data was also improved by a factor of 2 in comparison to ICRP 78. The results suggest that the modified transfer rates of model C could be used as default parameters for biokinetic nonhuman primate modeling and potentially extrapolated to humans. PMID:27115225

  20. Structural analysis of the RH-like blood group gene products in nonhuman primates

    SciTech Connect

    Salvignol, I.; Calvas, P.; Blancher, A.; Socha, W.W.; Colin, Y.; Le Van Kim, C.; Bailly, P.; Cartron, J.P.; Ruffie, J.; Blancher, A.

    1995-03-01

    Rh-related transcripts present in bone marrow samples from several species of nonhuman primates (chimpanzee, gorilla, gibbon, crab-eating macaque) have been amplified by RT-polymerase chain reaction using primers deduced from the sequence of human RH genes. Nucleotide sequence analysis of the nonhuman transcripts revealed a high degree of similarity to human blood group Rh sequences, suggesting a great conservation of the RH genes throughout evolution. Full-length transcripts, potentially encoding 417 amino acid long proteins homologous to Rh polypeptides, were characterized, as well as mRNA isoforms which harbored nucleotide deletions or insertions and potentially encode truncated proteins. Proteins of 30-40,000 M{sub r}, immunologically related to human Rh proteins, were detected by western blot analysis with antipeptide antibodies, indicating that Rh-like transcripts are translated into membrane proteins. Comparison of human and nonhuman protein sequences was pivotal in clarifying the molecular basis of the blood group C/c polymorphism, showing that only the Pro103Ser substitution was correlated with C/c polymorphism. In addition, it was shown that a proline residue at position 102 was critical in the expression of C and c epitopes, most likely by providing an appropriate conformation of Rh polypeptides. From these data a phylogenetic reconstruction of the RH locus evolution has been calculated from which an unrooted phylogenetic tree could be proposed, indicating that African ape Rh-like genes would be closer to the human RhD gene than to the human RhCE gene. 55 refs., 4 figs., 1 tab.

  1. Control of communicable disease; foreign--requirements for importers of nonhuman primates (NHP). Final rule.

    PubMed

    2013-02-15

    The Centers for Disease Control and Prevention (CDC), located within the Department of Health and Human Services (HHS), is amending regulations for the importation of live nonhuman primates (NHPs) by extending existing requirements for the importation of Macaca fascicularis (cynomolgus), Chlorocebus aethiops (African green), and Macaca mulatta (rhesus) monkeys to all NHPs with the exception of the filovirus testing requirement. Filovirus testing will only be required for Old World NHPs in quarantine that have illness consistent with filovirus infection or that die for any reason other than trauma during quarantine. HHS/CDC is also finalizing a provision to reduce the frequency at which importers of cynomolgus, African green, and rhesus monkeys are required to renew their special permits (from every 180 days to every 2 years). HHS/CDC is incorporating existing guidelines into the regulations and adding new provisions to address the following: NHPs imported as part of an animal act; NHPs imported or transferred by zoological societies; the transfer of NHPs from approved laboratories; and non-live imported NHP products. Finally, HHS/CDC is also requiring that all NHPs be imported only through ports of entry where a HHS/CDC quarantine station is located.

  2. PET Studies in Nonhuman Primate Models of Cocaine Abuse: Translational Research Related to Vulnerability and Neuroadaptations

    PubMed Central

    Gould, Robert W.; Duke, Angela N.; Nader, Michael A.

    2013-01-01

    The current review highlights the utility of positron emission tomography (PET) imaging to study the neurobiological substrates underlying vulnerability to cocaine addiction and subsequent adaptations following chronic cocaine self-administration in nonhuman primate models of cocaine abuse. Environmental (e.g., social rank) and sex-specific influences on dopaminergic function and sensitivity to the reinforcing effects of cocaine are discussed. Cocaine-related cognitive deficits have been hypothesized to contribute to high rates of relapse and are described in nonhuman primate models. Lastly, the long-term consequences of cocaine on neurobiology are discussed. PET imaging and longitudinal, within-subject behavioral studies in nonhuman primates have provided a strong framework for designing pharmacological and behavioral treatment strategies to aid drug-dependent treatment seekers. Non-invasive PET imaging will allow for individualized treatment strategies. Recent advances in radiochemistry of novel PET ligands and other imaging modalities can further advance our understanding of stimulant use on the brain. PMID:23458573

  3. Stereotypic Behavior in Nonhuman Primates as a Model for the Human Condition

    PubMed Central

    Lutz, Corrine K.

    2014-01-01

    Stereotypies that develop spontaneously in nonhuman primates can provide an effective model for repetitive stereotyped behavior in people with neurodevelopmental or obsessive-compulsive disorders. The behaviors are similar in form, are similarly affected by environmental conditions, and are improved with similar treatment methods such as enrichment, training, and drug therapy. However, because of a greater number of commonalities in these factors, nonhuman primates may serve as a better model for stereotyped behavior in individuals with autism or intellectual disability than for compulsions in individuals with obsessive-compulsive disorder. Because animal models may not be exact in all features of the disorder being studied, it is important to investigate the strengths and weaknesses of using a nonhuman primate model for stereotyped behavior in people with psychological disorders. PMID:25225307

  4. Control, choice, and assessments of the value of behavioral management to nonhuman primates in captivity.

    PubMed

    Schapiro, Steven J; Lambeth, Susan P

    2007-01-01

    Many people have devoted considerable effort to enhancing the environments of nonhuman primates in captivity. There is substantial motivation to develop experimental, analytical, and interpretational frameworks to enable objective measurements of the value of environmental enrichment/behavioral management efforts. The consumer-demand approach is a framework not frequently implemented in studies of nonhuman primate welfare but profitably used in studies of the welfare of nonhuman animals in agriculture. Preference studies, in which primates can voluntarily choose to socialize or to participate in training, may be the best current examples of a consumer-demand-like approach to assessing the effects of captive management strategies on primate welfare. Additional work in this area would be beneficial; however, there are potential ethical constraints on purposefully subjecting primates to adverse circumstances to measure their demand for a resource. Primate welfare researchers need to design consumer-demand studies with obstacles that will help measure the relative value of resources to captive primates without compromising the welfare they are attempting to evaluate and enhance.

  5. Macular Structure and Function in Nonhuman Primate Experimental Glaucoma

    PubMed Central

    Wilsey, Laura J.; Reynaud, Juan; Cull, Grant; Burgoyne, Claude F.; Fortune, Brad

    2016-01-01

    Purpose To evaluate structure and function of macular retinal layers in nonhuman primate (NHP) experimental glaucoma (EG). Methods Twenty-one NHP had longitudinal imaging of macular structure by SDOCT, 16 also had recordings of function by multifocal ERG. The average thickness over 15° was derived for seven individual SDOCT layers: macular nerve fiber layer (m-NFL), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer+inner segments combined (ONL+IS), and outer segments (OS). Peripapillary RNFL thickness (ppRNFLT) was measured from a single circular B-scan with 12° diameter. Responses to a slow-sequence multifocal ERG (mfERG) stimulus (7F) were filtered (at 75 Hz) into low- and high-frequency components (LFC, HFC). Results At final follow-up, significant structural loss occurred only in EG eyes and only for ppRNFLT (−29 ± 23%), m-NFL (−17 ± 16%), RGCL (−22 ± 15%), and IPL (−19 ± 14%); though there was also a small increase in OPL (+6 ± 7%) and ONL+IS (4 ± 4%) and a similar tendency for INL. Macular structural loss was correlated with ppRNFLT only for the NFL, RGCL and IPL (R = 0.95, 0.93 and 0.95, respectively, P < 0.0001). Significant functional loss occurred only for HFC and N2 in EG eyes. Significant longitudinal structure–function correlations (P < 0.01) were observed only in EG eyes and only for mfERG HFC and N2: HFC was correlated with ppRNFLT (R = 0.69), macular NFL (R = 0.67), RGCL (R = 0.74), and IPL (R = 0.72); N2 was correlated with RGCL (R = 0.54) and IPL (R = 0.48). High-frequency components amplitude change was inversely correlated with outer retinal thickness change (= −0.66). Conclusions Macular structural and functional losses are correlated and specific to ganglion cells over a wide range of EG severity. Outer retinal changes are likely due to inner retinal loss. PMID:27082305

  6. Guidelines for developing and managing an environmental enrichment program for nonhuman primates.

    PubMed

    Bloomsmith, M A; Brent, L Y; Schapiro, S J

    1991-08-01

    Before implementing an environmental enrichment program for nonhuman primates, several issues should be considered. The assignment of enrichment tasks can be made to caretakers, a dedicated "enrichment technician," volunteers, students or individuals with training in behavioral science. Determining the enrichment techniques to be used must take into account personnel time available; the species, age, sex, and individual histories of the nonhuman primates; and experimental protocols for which animals are being maintained. Identifying the most beneficial way to use the available personnel time must be tailored for each institution. To meet federal regulations, records must be kept of the environmental enhancements available to each nonhuman primate. Good record-keeping will allow appropriate evaluation of the program. This evaluation should involve the animals' responses to the enrichment opportunity, cost and durability of enrichment items, human and nonhuman safety considerations, and personnel required. The well-being of captive nonhuman primates will be most improved if well-informed decisions are made in developing and managing environmental enrichment programs.

  7. Plasticity and Recovery After Dorsal Column Spinal Cord Injury in Nonhuman Primates.

    PubMed

    Reed, Jamie L; Liao, Chia-Chi; Qi, Hui-Xin; Kaas, Jon H

    2016-01-01

    Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in nonhuman primates. Plasticity in the adult central nervous system has been established and studied for the past several decades; however, capacities and limits of plasticity are still under investigation. Studies of plasticity include assessing multiple measures before and after injury in animal models. Such studies are particularly important for improving recovery after injury in patients. In summarizing work by our research team and others, we suggest how the findings from plasticity studies in nonhuman primate models may affect therapeutic interventions for conditions involving sensory loss due to spinal cord injury. PMID:27578996

  8. Plasticity and Recovery After Dorsal Column Spinal Cord Injury in Nonhuman Primates

    PubMed Central

    Reed, Jamie L.; Liao, Chia-Chi; Qi, Hui-Xin; Kaas, Jon H.

    2016-01-01

    Here, we review recent work on plasticity and recovery after dorsal column spinal cord injury in nonhuman primates. Plasticity in the adult central nervous system has been established and studied for the past several decades; however, capacities and limits of plasticity are still under investigation. Studies of plasticity include assessing multiple measures before and after injury in animal models. Such studies are particularly important for improving recovery after injury in patients. In summarizing work by our research team and others, we suggest how the findings from plasticity studies in nonhuman primate models may affect therapeutic interventions for conditions involving sensory loss due to spinal cord injury. PMID:27578996

  9. Rabies Postexposure Prophylaxis for Travelers Injured by Nonhuman Primates, Marseille, France, 2001–2014

    PubMed Central

    Blaise, Agathe; Parola, Philippe; Brouqui, Philippe

    2015-01-01

    Most exposures of residents of Marseille to nonhuman primates occurred among unvaccinated adult travelers to Southeast Asia within the first 10 days of their arrival at 2 major tourist locations in Thailand and 1 in Indonesia. A small proportion of travelers received rabies immunoglobulin in the country of exposure. PMID:26196180

  10. 77 FR 7109 - Establishment of User Fees for Filovirus Testing of Nonhuman Primate Liver Samples

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... collection or record keeping requirements. E. National Environmental Policy Act (NEPA) Pursuant to 48 FR 9374...: (404) 639-1600. 3. 55 FR 10288, March 20, 1990, ``Importation of Nonhuman Primates: Meeting.'' 4... Mortality Weekly Report MMWR 1990; 39(13):221. 5. 55 FR 15210, April 20, 1990, Requirement for a...

  11. Birth intervention and non-maternal infant-handling during parturition in a nonhuman primate.

    PubMed

    Pan, Wenshi; Gu, Tieliu; Pan, Yue; Feng, Chunguang; Long, Yu; Zhao, Yi; Meng, Hao; Liang, Zuhong; Yao, Meng

    2014-10-01

    Direct intervention in infant delivery by non-parturient individuals is a rare phenomenon in nonhuman primates. In contrast, birth assistance by other individuals, or the practice of midwifery, is universal among human societies and generally believed to be a behavior unique to our species. It has been proposed that the enlarged head of the human fetus and the relatively narrow birth canal constrained by bipedalism has made human parturition more difficult than in nonhuman primates, and these anatomic challenges have led to the rotation of the fetus in the birth canal and an occiput anterior (i.e., backward-facing) orientation of emergence. These characteristics have hindered the mother's ability to self-assist the delivery of the infant, therefore necessitating assistance by other individuals or midwives for successful birth. Here we report the first high-definition video recordings of birth intervention behavior in a wild nonhuman primate, the white-headed langur (Trachypithecus leucocephalus). We observed that while a primiparous female gave birth to an infant in an occiput posterior (i.e., forward-facing) orientation, a multiparous female intervened in the delivery by manually pulling the infant out of the birth canal and cared for it in the following hours. Our finding shows extensive social interactions throughout parturition, and presents an unequivocal case of non-maternal intervention with infant birth in a nonhuman primate.

  12. Molecular Identification of Entamoeba spp. in Captive Nonhuman Primates ▿ †

    PubMed Central

    Levecke, B.; Dreesen, Leentje; Dorny, Pierre; Verweij, Jaco J.; Vercammen, Francis; Casaert, Stijn; Vercruysse, Jozef; Geldhof, Peter

    2010-01-01

    This study describes the molecular identification of 520 Entamoeba-positive fecal samples from a large and diverse population of captive nonhuman primates (NHP). The results revealed the presence of Entamoeba histolytica (NHP variant only), E. dispar, E. moshkovskii, E. hartmanni, E. coli, and E. polecki-like organisms. PMID:20573870

  13. 9 CFR 3.87 - Primary enclosures used to transport nonhuman primates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... transport nonhuman primates. Any person subject to the Animal Welfare regulations (9 CFR parts 1, 2, and 3... normal rigors of transportation; (2) The interior of the enclosure has no sharp points or edges and no... manner and to sit in an upright, hands down position without its head touching the top of the...

  14. Neurophysiology and Neuroanatomy of Reflexive and Voluntary Saccades in Non-Human Primates

    ERIC Educational Resources Information Center

    Johnston, Kevin; Everling, Stefan

    2008-01-01

    A multitude of cognitive functions can easily be tested by a number of relatively simple saccadic eye movement tasks. This approach has been employed extensively with patient populations to investigate the functional deficits associated with psychiatric disorders. Neurophysiological studies in non-human primates performing the same tasks have…

  15. Rabies Postexposure Prophylaxis for Travelers Injured by Nonhuman Primates, Marseille, France, 2001-2014.

    PubMed

    Blaise, Agathe; Parola, Philippe; Brouqui, Philippe; Gautret, Philippe

    2015-08-01

    Most exposures of residents of Marseille to nonhuman primates occurred among unvaccinated adult travelers to Southeast Asia within the first 10 days of their arrival at 2 major tourist locations in Thailand and 1 in Indonesia. A small proportion of travelers received rabies immunoglobulin in the country of exposure.

  16. 9 CFR 3.87 - Primary enclosures used to transport nonhuman primates.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... transport nonhuman primates. Any person subject to the Animal Welfare regulations (9 CFR parts 1, 2, and 3... physical contact with the animal contained inside; (7) Any material, treatment, paint, preservative, or other chemical used in or on the enclosure is nontoxic to the animal and not harmful to the health...

  17. 9 CFR 3.87 - Primary enclosures used to transport nonhuman primates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... transport nonhuman primates. Any person subject to the Animal Welfare regulations (9 CFR parts 1, 2, and 3... physical contact with the animal contained inside; (7) Any material, treatment, paint, preservative, or other chemical used in or on the enclosure is nontoxic to the animal and not harmful to the health...

  18. 9 CFR 3.87 - Primary enclosures used to transport nonhuman primates.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... transport nonhuman primates. Any person subject to the Animal Welfare regulations (9 CFR parts 1, 2, and 3... physical contact with the animal contained inside; (7) Any material, treatment, paint, preservative, or other chemical used in or on the enclosure is nontoxic to the animal and not harmful to the health...

  19. 9 CFR 3.87 - Primary enclosures used to transport nonhuman primates.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... transport nonhuman primates. Any person subject to the Animal Welfare regulations (9 CFR parts 1, 2, and 3... physical contact with the animal contained inside; (7) Any material, treatment, paint, preservative, or other chemical used in or on the enclosure is nontoxic to the animal and not harmful to the health...

  20. Epidemiology of invasive Klebsiella pneumoniae with hypermucoviscosity phenotype in a research colony of nonhuman primates.

    PubMed

    Burke, Robin L; Whitehouse, Chris A; Taylor, Justin K; Selby, Edward B

    2009-12-01

    Invasive Klebsiella pneumoniae with hypermucoviscosity phenotype (HMV K. pneumoniae) is an emerging human pathogen that, over the past 20 y, has resulted in a distinct clinical syndrome characterized by pyogenic liver abscesses sometimes complicated by bacteremia, meningitis, and endophthalmitis. Infections occur predominantly in Taiwan and other Asian countries, but HMV K. pneumoniae is considered an emerging infectious disease in the United States and other Western countries. In 2005, fatal multisystemic disease was attributed to HMV K. pneumoniae in African green monkeys (AGM) at our institution. After identification of a cluster of subclinically infected macaques in March and April 2008, screening of all colony nonhuman primates by oropharyngeal and rectal culture revealed 19 subclinically infected rhesus and cynomolgus macaques. PCR testing for 2 genes associated with HMV K. pneumoniae, rmpA and magA, suggested genetic variability in the samples. Random amplified polymorphic DNA analysis on a subset of clinical isolates confirmed a high degree of genetic diversity between the samples. Environmental testing did not reveal evidence of aerosol or droplet transmission of the organism in housing areas. Further research is needed to characterize HMV K. pneumoniae, particularly with regard to genetic differences among bacterial strains and their relationship to human disease and to the apparent susceptibility of AGM to this organism. PMID:20034435

  1. Morphine Produces Immunosuppressive Effects in Nonhuman Primates at the Proteomic and Cellular Levels*

    PubMed Central

    Brown, Joseph N.; Ortiz, Gabriel M.; Angel, Thomas E.; Jacobs, Jon M.; Gritsenko, Marina; Chan, Eric Y.; Purdy, David E.; Murnane, Robert D.; Larsen, Kay; Palermo, Robert E.; Shukla, Anil K.; Clauss, Theresa R.; Katze, Michael G.; McCune, Joseph M.; Smith, Richard D.

    2012-01-01

    Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. To explore how these changes interact with lentiviral infections in vivo, animals from two nonhuman primate species (African green monkeys and pigtailed macaques) were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g. lymph node, colon, cerebrospinal fluid, and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an interorgan, interindividual, and interspecies basis. In both species, morphine was associated with decreased levels of Ki-67+ T-cell activation but with only minimal changes in overall T-cell counts, neutrophil counts, and NK cell counts. Although changes in T-cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in lymph nodes, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have direct relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the potential interplay between opioid abuse and the immunological response to an infective agent. PMID:22580588

  2. Evidence for Conversion of Methanol to Formaldehyde in Nonhuman Primate Brain

    PubMed Central

    Zhai, Rongwei; Zheng, Na; Rizak, Joshua; Hu, Xintian

    2016-01-01

    Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain. Levels of FA in cerebrospinal fluid (CSF) were then assessed at different time points. A significant increase of FA levels was found at the 18th hour following a methanol injection. Moreover, the FA level returned to a normal physiological level at the 30th hour after the injection. These findings provide direct evidence that methanol is oxidized to FA in nonhuman primate brain and that a portion of the FA generated is released out of the brain cells. This study suggests that FA is produced from methanol metabolic processes in the nonhuman primate brain and that FA may play a significant role in methanol neurotoxicology. PMID:27066393

  3. Cryopreservation of non-human primate sperm: priorities for future research.

    PubMed

    Morrell, J M; Hodges, J K

    1998-10-01

    Wild populations of many non-human primate species have declined alarmingly due to habitat destruction, hunting and genetic isolation. Captive breeding programmes to aid species survival could be enhanced by the use of assisted reproductive techniques, such as artificial insemination (AI), if a source of viable sperm was readily accessible. Cryobanks of primate sperm could provide such a supply if techniques for freezing sperm could be developed. Although sporadic attempts to cryopreserve primate sperm have been reported for some of the more frequently encountered zoo-maintained species, there is limited information available on techniques for sperm collection and storage. It is vital that adequate reporting of all cryopreservation attempts be made to avoid repetition of inappropriate methodologies and wastage of valuable genetic material from rare or endangered animals. An integrated approach to the cryobanking of non-human primate sperm is considered to be essential for species conservation. In this review, the factors affecting the success of sperm cryopreservation are outlined, existing information is compiled from previous reported attempts at cryopreservation, and suggestions are made for cryopreserving sperm in further non-human primate species. Moreover, recommendations are given for additional studies to augment existing data. It is intended that this information should serve as a guide for developing cryopreservation protocols in the future, particularly for endangered species. PMID:9835366

  4. A tail of two monkeys: social housing for nonhuman primates in the research laboratory setting.

    PubMed

    Seelig, David

    2007-01-01

    Despite great adaptability, most nonhuman primates require regular tactile contact with conspecifics for their psychological well being. By illustrating the inherent value of social contact and by providing clues to the best ways of satisfying this need, behavioral studies are useful in designing social enrichment programs. Although group housing is ideal for most gregarious primates, space constraints and protocol requirements may preclude such environments for macaques housed indoors. Pair housing is an effective and practical alternative. Furthermore, such social experience facilitates integration into future social groups, including those in postresearch retirement facilities. This article references common research protocols that accommodate pair housing and includes scientific recommendations for institutional animal care and use committees (IACUCs) to facilitate providing physical social contact for nonhuman primates in laboratories.

  5. Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

    PubMed Central

    Kim, Jong R.; Holbrook, Beth C.; Hayward, Sarah L.; Blevins, Lance K.; Jorgensen, Matthew J.; Kock, Nancy D.; De Paris, Kristina; D'Agostino, Ralph B.; Aycock, S. Tyler; Mizel, Steven B.; Parks, Griffith D.

    2015-01-01

    ABSTRACT Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates. IMPORTANCE Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation

  6. Are non-human primates capable of rhythmic entrainment? Evidence for the gradual audiomotor evolution hypothesis

    PubMed Central

    Merchant, Hugo; Honing, Henkjan

    2014-01-01

    We propose a decomposition of the neurocognitive mechanisms that might underlie interval-based timing and rhythmic entrainment. Next to reviewing the concepts central to the definition of rhythmic entrainment, we discuss recent studies that suggest rhythmic entrainment to be specific to humans and a selected group of bird species, but, surprisingly, is not obvious in non-human primates. On the basis of these studies we propose the gradual audiomotor evolution hypothesis that suggests that humans fully share interval-based timing with other primates, but only partially share the ability of rhythmic entrainment (or beat-based timing). This hypothesis accommodates the fact that non-human primates (i.e., macaques) performance is comparable to humans in single interval tasks (such as interval reproduction, categorization, and interception), but show differences in multiple interval tasks (such as rhythmic entrainment, synchronization, and continuation). Furthermore, it is in line with the observation that macaques can, apparently, synchronize in the visual domain, but show less sensitivity in the auditory domain. And finally, while macaques are sensitive to interval-based timing and rhythmic grouping, the absence of a strong coupling between the auditory and motor system of non-human primates might be the reason why macaques cannot rhythmically entrain in the way humans do. PMID:24478618

  7. Are non-human primates capable of rhythmic entrainment? Evidence for the gradual audiomotor evolution hypothesis.

    PubMed

    Merchant, Hugo; Honing, Henkjan

    2013-01-01

    We propose a decomposition of the neurocognitive mechanisms that might underlie interval-based timing and rhythmic entrainment. Next to reviewing the concepts central to the definition of rhythmic entrainment, we discuss recent studies that suggest rhythmic entrainment to be specific to humans and a selected group of bird species, but, surprisingly, is not obvious in non-human primates. On the basis of these studies we propose the gradual audiomotor evolution hypothesis that suggests that humans fully share interval-based timing with other primates, but only partially share the ability of rhythmic entrainment (or beat-based timing). This hypothesis accommodates the fact that non-human primates (i.e., macaques) performance is comparable to humans in single interval tasks (such as interval reproduction, categorization, and interception), but show differences in multiple interval tasks (such as rhythmic entrainment, synchronization, and continuation). Furthermore, it is in line with the observation that macaques can, apparently, synchronize in the visual domain, but show less sensitivity in the auditory domain. And finally, while macaques are sensitive to interval-based timing and rhythmic grouping, the absence of a strong coupling between the auditory and motor system of non-human primates might be the reason why macaques cannot rhythmically entrain in the way humans do. PMID:24478618

  8. Continuities in Emotion Lateralization in Human and Non-Human Primates

    PubMed Central

    Lindell, Annukka K.

    2013-01-01

    Where hemispheric lateralization was once considered an exclusively human trait, it is increasingly recognized that hemispheric asymmetries are evident throughout the animal kingdom. Emotion is a prime example of a lateralized function: given its vital role in promoting adaptive behavior and hence survival, a growing body of research in affective neuroscience is working to illuminate the cortical bases of emotion processing. Presuming that human and non-human primates evolved from a shared ancestor, one would anticipate evidence of organizational continuity in the neural substrate supporting emotion processing. This paper thus reviews research examining the patterns of lateralization for the expression and perception of facial emotion in non-human primates, aiming to determine whether the patterns of hemispheric asymmetry that characterize the human brain are similarly evident in other primate species. As such, this review seeks to enhance understanding of the evolution of hemispheric specialization for emotion, using emotion lateralization in non-human primates as a window through which to view emotion lateralization in humans. PMID:23964230

  9. Are non-human primates capable of rhythmic entrainment? Evidence for the gradual audiomotor evolution hypothesis.

    PubMed

    Merchant, Hugo; Honing, Henkjan

    2013-01-01

    We propose a decomposition of the neurocognitive mechanisms that might underlie interval-based timing and rhythmic entrainment. Next to reviewing the concepts central to the definition of rhythmic entrainment, we discuss recent studies that suggest rhythmic entrainment to be specific to humans and a selected group of bird species, but, surprisingly, is not obvious in non-human primates. On the basis of these studies we propose the gradual audiomotor evolution hypothesis that suggests that humans fully share interval-based timing with other primates, but only partially share the ability of rhythmic entrainment (or beat-based timing). This hypothesis accommodates the fact that non-human primates (i.e., macaques) performance is comparable to humans in single interval tasks (such as interval reproduction, categorization, and interception), but show differences in multiple interval tasks (such as rhythmic entrainment, synchronization, and continuation). Furthermore, it is in line with the observation that macaques can, apparently, synchronize in the visual domain, but show less sensitivity in the auditory domain. And finally, while macaques are sensitive to interval-based timing and rhythmic grouping, the absence of a strong coupling between the auditory and motor system of non-human primates might be the reason why macaques cannot rhythmically entrain in the way humans do.

  10. Noise-Induced Frequency Modifications of Tamarin Vocalizations: Implications for Noise Compensation in Nonhuman Primates

    PubMed Central

    2015-01-01

    Previous research suggests that nonhuman primates have limited flexibility in the frequency content of their vocalizations, particularly when compared to human speech. Consistent with this notion, several nonhuman primate species have demonstrated noise-induced changes in call amplitude and duration, with no evidence of changes to spectral content. This experiment used broad- and narrow-band noise playbacks to investigate the vocal control of two call types produced by cotton-top tamarins (Saguinus Oedipus). In ‘combination long calls’ (CLCs), peak fundamental frequency and the distribution of energy between low and high frequency harmonics (spectral tilt) changed in response to increased noise amplitude and bandwidth. In chirps, peak and maximum components of the fundamental frequency increased with increasing noise level, with no changes to spectral tilt. Other modifications included the Lombard effect and increases in chirp duration. These results provide the first evidence for noise-induced frequency changes in nonhuman primate vocalizations and suggest that future investigations of vocal plasticity in primates should include spectral parameters. PMID:26107515

  11. Is somnambulism a distinct disorder of humans and not seen in non-human primates?

    PubMed

    Kantha, S S

    2003-01-01

    Though somnambulism (sleepwalking) is a well-recognized sleep disorder in humans, a biomedical literature search in Medline and Primate Literature bibliographic databases showed no publications on sleepwalking in non-human primates. From this finding, two inferences can be made. First is that somnambulism may be present in non-human primates; but due to limitations in expertise and methodological resources as well as narrow focus of research interest, until now researchers have not detected it in wild and/or captive conditions. Second, somnambulism does not exist in non-human primates including apes (chimpanzee, gorilla, orang-utan and gibbon); and thus, it is a unique behavioral disorder present only in humans. It is premature to conclude which of these two inferences is correct. In Jane Goodall's view, sleepwalking behavior is absent in chimpanzees. If further field observations can confirm Goodall's assertion that somnambulism is indeed absent in chimpanzees, it will be of evolutionary and medical interest to know why this parasomnic behavior became established in humans during the past 5.5 million years or so.

  12. Enhancing nonhuman primate care and welfare through the use of positive reinforcement training.

    PubMed

    Laule, Gail; Whittaker, Margaret

    2007-01-01

    Nonhuman primates are excellent subjects for the enhancement of care and welfare through training. The broad range of species offers tremendous behavioral diversity, and individual primates show varying abilities to cope with the stressors of captivity, which differ depending on the venue. Biomedical facilities include small single cages, pair housing, and breeding corrals with large social groups. Zoos have social groupings of differing sizes, emphasizing public display and breeding. Sanctuaries have nonbreeding groups of varying sizes and often of mixed species. In every venue, the primary objective is to provide good quality care, with minimal stress. Positive reinforcement training improves care and reduces stress by enlisting a primate's voluntary cooperation with targeted activities, including both husbandry and medical procedures. It can also improve socialization, reduce abnormal behaviors, and increase species-typical behaviors. This article reviews the results already achieved with positive reinforcement training and suggests further possibilities for enhancing primate care and welfare.

  13. Curing color blindness--mice and nonhuman primates.

    PubMed

    Neitz, Maureen; Neitz, Jay

    2014-11-01

    It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. PMID:25147187

  14. Curing Color Blindness—Mice and Nonhuman Primates

    PubMed Central

    Neitz, Maureen; Neitz, Jay

    2014-01-01

    It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function. PMID:25147187

  15. Curing color blindness--mice and nonhuman primates.

    PubMed

    Neitz, Maureen; Neitz, Jay

    2014-08-21

    It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function.

  16. Lineage-Specific Loss of Function of Bitter Taste Receptor Genes in Humans and Nonhuman Primates

    PubMed Central

    Go, Yasuhiro; Satta, Yoko; Takenaka, Osamu; Takahata, Naoyuki

    2005-01-01

    Since the process of becoming dead genes or pseudogenes (pseudogenization) is irreversible and can occur rather rapidly under certain environmental circumstances, it is one plausible determinant for characterizing species specificity. To test this evolutionary hypothesis, we analyzed the tempo and mode of duplication and pseudogenization of bitter taste receptor (T2R) genes in humans as well as in 12 nonhuman primates. The results show that primates have accumulated more pseudogenes than mice after their separation from the common ancestor and that lineage-specific pseudogenization becomes more conspicuous in humans than in nonhuman primates. Although positive selection has operated on some amino acids in extracellular domains, functional constraints against T2R genes are more relaxed in primates than in mice and this trend has culminated in the rapid deterioration of the bitter-tasting capability in humans. Since T2R molecules play an important role in avoiding generally bitter toxic and harmful substances, substantial modification of the T2R gene repertoire is likely to reflect different responses to changes in the environment and to result from species-specific food preference during primate evolution. PMID:15744053

  17. Primate Drum Kit: A System for Studying Acoustic Pattern Production by Non-Human Primates Using Acceleration and Strain Sensors

    PubMed Central

    Ravignani, Andrea; Olivera, Vicente Matellán; Gingras, Bruno; Hofer, Riccardo; Hernández, Carlos Rodríguez; Sonnweber, Ruth-Sophie; Fitch, W. Tecumseh

    2013-01-01

    The possibility of achieving experimentally controlled, non-vocal acoustic production in non-human primates is a key step to enable the testing of a number of hypotheses on primate behavior and cognition. However, no device or solution is currently available, with the use of sensors in non-human animals being almost exclusively devoted to applications in food industry and animal surveillance. Specifically, no device exists which simultaneously allows: (i) spontaneous production of sound or music by non-human animals via object manipulation, (ii) systematical recording of data sensed from these movements, (iii) the possibility to alter the acoustic feedback properties of the object using remote control. We present two prototypes we developed for application with chimpanzees (Pan troglodytes) which, while fulfilling the aforementioned requirements, allow to arbitrarily associate sounds to physical object movements. The prototypes differ in sensing technology, costs, intended use and construction requirements. One prototype uses four piezoelectric elements embedded between layers of Plexiglas and foam. Strain data is sent to a computer running Python through an Arduino board. A second prototype consists in a modified Wii Remote contained in a gum toy. Acceleration data is sent via Bluetooth to a computer running Max/MSP. We successfully pilot tested the first device with a group of chimpanzees. We foresee using these devices for a range of cognitive experiments. PMID:23912427

  18. Primate drum kit: a system for studying acoustic pattern production by non-human primates using acceleration and strain sensors.

    PubMed

    Ravignani, Andrea; Matellán Olivera, Vicente; Gingras, Bruno; Hofer, Riccardo; Rodríguez Hernández, Carlos; Sonnweber, Ruth-Sophie; Fitch, W Tecumseh

    2013-01-01

    The possibility of achieving experimentally controlled, non-vocal acoustic production in non-human primates is a key step to enable the testing of a number of hypotheses on primate behavior and cognition. However, no device or solution is currently available, with the use of sensors in non-human animals being almost exclusively devoted to applications in food industry and animal surveillance. Specifically, no device exists which simultaneously allows: (i) spontaneous production of sound or music by non-human animals via object manipulation, (ii) systematical recording of data sensed from these movements, (iii) the possibility to alter the acoustic feedback properties of the object using remote control. We present two prototypes we developed for application with chimpanzees (Pan troglodytes) which, while fulfilling the aforementioned requirements, allow to arbitrarily associate sounds to physical object movements. The prototypes differ in sensing technology, costs, intended use and construction requirements. One prototype uses four piezoelectric elements embedded between layers of Plexiglas and foam. Strain data is sent to a computer running Python through an Arduino board. A second prototype consists in a modified Wii Remote contained in a gum toy. Acceleration data is sent via Bluetooth to a computer running Max/MSP. We successfully pilot tested the first device with a group of chimpanzees. We foresee using these devices for a range of cognitive experiments. PMID:23912427

  19. Primate drum kit: a system for studying acoustic pattern production by non-human primates using acceleration and strain sensors.

    PubMed

    Ravignani, Andrea; Matellán Olivera, Vicente; Gingras, Bruno; Hofer, Riccardo; Rodríguez Hernández, Carlos; Sonnweber, Ruth-Sophie; Fitch, W Tecumseh

    2013-07-31

    The possibility of achieving experimentally controlled, non-vocal acoustic production in non-human primates is a key step to enable the testing of a number of hypotheses on primate behavior and cognition. However, no device or solution is currently available, with the use of sensors in non-human animals being almost exclusively devoted to applications in food industry and animal surveillance. Specifically, no device exists which simultaneously allows: (i) spontaneous production of sound or music by non-human animals via object manipulation, (ii) systematical recording of data sensed from these movements, (iii) the possibility to alter the acoustic feedback properties of the object using remote control. We present two prototypes we developed for application with chimpanzees (Pan troglodytes) which, while fulfilling the aforementioned requirements, allow to arbitrarily associate sounds to physical object movements. The prototypes differ in sensing technology, costs, intended use and construction requirements. One prototype uses four piezoelectric elements embedded between layers of Plexiglas and foam. Strain data is sent to a computer running Python through an Arduino board. A second prototype consists in a modified Wii Remote contained in a gum toy. Acceleration data is sent via Bluetooth to a computer running Max/MSP. We successfully pilot tested the first device with a group of chimpanzees. We foresee using these devices for a range of cognitive experiments.

  20. Evaluation of Flow Biosensor Technology in a Chronically-Instrumented Non-Human Primate Model

    NASA Technical Reports Server (NTRS)

    Koenig, S. C.; Reister, C.; Schaub, J.; Muniz, G.; Ferguson, T.; Fanton, J. W.

    1995-01-01

    The Physiology Research Branch of Brooks AFB conducts both human and non-human primate experiments to determine the effects of microgravity and hypergravity on the cardiovascular system and to indentify the particular mechanisms that invoke these responses. Primary investigative research efforts in a non-human primate model require the calculation of total peripheral resistance (TPR), systemic arterial compliance (SAC), and pressure-volume loop characteristics. These calculations require beat-to-beat measurement of aortic flow. We have evaluated commercially available electromagnetic (EMF) and transit-time flow measurement techniques. In vivo and in vitro experiments demonstrated that the average error of these techniques is less than 25 percent for EMF and less than 10 percent for transit-time.

  1. Nonhuman primate event-related potentials indexing covert shifts of attention.

    PubMed

    Woodman, Geoffrey F; Kang, Min-Suk; Rossi, Andrew F; Schall, Jeffrey D

    2007-09-18

    A half-century's worth of research has established the existence of numerous event-related potential components measuring different cognitive operations in humans including the selection of stimuli by covert attention mechanisms. Surprisingly, it is unknown whether nonhuman primates exhibit homologous electrophysiological signatures of selective visual processing while viewing complex scenes. We used an electrophysiological technique with macaque monkeys analogous to procedures for recording scalp event-related potentials from humans and found that monkeys exhibit short-latency visual components sensitive to sensory processing demands and lateralizations related to shifting of covert attention similar to the human N2pc component. These findings begin to bridge the gap between the disparate literatures by using electrophysiological measurements to study the deployment of visual attention in the brains of humans and nonhuman primates.

  2. Evolution of Multilevel Social Systems in Nonhuman Primates and Humans.

    PubMed

    Grueter, Cyril C; Chapais, Bernard; Zinner, Dietmar

    2012-10-01

    Multilevel (or modular) societies are a distinct type of primate social system whose key features are single-male-multifemale, core units nested within larger social bands. They are not equivalent to fission-fusion societies, with the latter referring to routine variability in associations, either on an individual or subunit level. The purpose of this review is to characterize and operationalize multilevel societies and to outline their putative evolutionary origins. Multilevel societies are prevalent in three primate clades: papionins, Asian colobines, and hominins. For each clade, we portray the most parsimonious phylogenetic pathway leading to a modular system and then review and discuss likely socioecological conditions promoting the establishment and maintenance of these societies. The multilevel system in colobines (most notably Rhinopithecus and Nasalis) has likely evolved as single-male harem systems coalesced, whereas the multilevel system of papionins (Papio hamadryas, Theropithecus gelada) and hominins most likely arose as multimale-multifemale groups split into smaller units. We hypothesize that, although ecological conditions acted as preconditions for the origin of multilevel systems in all three clades, a potentially important catalyst was intraspecific social threat, predominantly bachelor threat in colobines and female coercion/infanticide in papionins and humans. We emphasize that female transfers within bands or genetic relationships among leader males help to maintain modular societies by facilitating interunit tolerance. We still lack a good or even basic understanding of many facets of multilevel sociality. Key remaining questions are how the genetic structure of a multilevel society matches the observed social effort of its members, to what degree cooperation of males of different units is manifest and contributes to band cohesion, and how group coordination, communication, and decision making are achieved. Affiliative and cooperative

  3. Evaluation of the neural function of nonhuman primates with spinal cord injury using an evoked potential-based scoring system.

    PubMed

    Ye, Jichao; Ma, Mengjun; Xie, Zhongyu; Wang, Peng; Tang, Yong; Huang, Lin; Chen, Keng; Gao, Liangbin; Wu, Yanfeng; Shen, Huiyong; Zeng, Yuanshan

    2016-01-01

    Nonhuman primate models of spinal cord injury (SCI) have been widely used in evaluation of the efficacy and safety of experimental restorative interventions before clinical trials. However, no objective methods are currently available for the evaluation of neural function in nonhuman primates. In our long-term clinical practice, we have used evoked potential (EP) for neural function surveillance during operation and accumulated extensive experience. In the present study, a nonhuman primate model of SCI was established in 6 adult cynomologus monkeys through spinal cord contusion injury at T8-T9. The neural function before SCI and within 6 months after SCI was evaluated based on EP recording. A scoring system including somatosensory evoked potentials (SSEPs) and transcranial electrical stimulation-motor evoked potentials (TES-MEPs) was established for the evaluation of neural function of nonhuman primates with SCI. We compared the motor function scores of nonhuman primates before and after SCI. Our results showed that the EP below the injury level significantly changed during the 6 months after SCI. In addition, a positive correlation was identified between the EP scores and motor function. The EP-based scoring system is a reliable approach for evaluating the motor function changes in nonhuman primates with SCI. PMID:27629352

  4. From Sweeping to the Caress: Similarities and Discrepancies between Human and Non-Human Primates' Pleasant Touch.

    PubMed

    Grandi, Laura C

    2016-01-01

    Affective touch plays a key role in affiliative behavior, offering a mechanism for the formation and maintenance of social bonds among conspecifics, both in humans and non-human primates. Furthermore, it has been speculated that the CT fiber system is a specific coding channel for affiliative touch that occurs during skin-to-skin interactions with conspecifics. In humans, this touch is commonly referred to as the caress, and its correlation with the CT fiber system has been widely demonstrated. It has been hypothesized that the sweeping touch that occurs during grooming in non-human primates may modulate the CT fibers, with recent preliminary studies on rhesus monkeys supporting this hypothesis. The present mini-review proposes a comparison between the pleasant touch, caress and sweeping of humans and non-human primates, respectively. The currently available data was therefore reviewed regarding (i) the correlation between pleasant touch and CT fibers both in humans and non-human primates, (ii) the autonomic effects, (iii) the encoding at the central nervous system, (iv) the development from early life to adulthood, and (v) the potential applications of pleasant touch in the daily lives of both humans and non-human primates. Moreover, by considering both the similarities and discrepancies between the human caress and non-human primate sweeping, a possible evolutionary mechanism can be proposed that has developed from sweeping as a utilitarian action with affiliative meaning among monkeys, to the caress as a purely affective gesture associated with humans. PMID:27660620

  5. Evaluation of the neural function of nonhuman primates with spinal cord injury using an evoked potential-based scoring system

    PubMed Central

    Ye, Jichao; Ma, Mengjun; Xie, Zhongyu; Wang, Peng; Tang, Yong; Huang, Lin; Chen, Keng; Gao, Liangbin; Wu, Yanfeng; Shen, Huiyong; Zeng, Yuanshan

    2016-01-01

    Nonhuman primate models of spinal cord injury (SCI) have been widely used in evaluation of the efficacy and safety of experimental restorative interventions before clinical trials. However, no objective methods are currently available for the evaluation of neural function in nonhuman primates. In our long-term clinical practice, we have used evoked potential (EP) for neural function surveillance during operation and accumulated extensive experience. In the present study, a nonhuman primate model of SCI was established in 6 adult cynomologus monkeys through spinal cord contusion injury at T8–T9. The neural function before SCI and within 6 months after SCI was evaluated based on EP recording. A scoring system including somatosensory evoked potentials (SSEPs) and transcranial electrical stimulation-motor evoked potentials (TES-MEPs) was established for the evaluation of neural function of nonhuman primates with SCI. We compared the motor function scores of nonhuman primates before and after SCI. Our results showed that the EP below the injury level significantly changed during the 6 months after SCI. In addition, a positive correlation was identified between the EP scores and motor function. The EP-based scoring system is a reliable approach for evaluating the motor function changes in nonhuman primates with SCI. PMID:27629352

  6. Lessons in Nonhuman Primate Models for AIDS Vaccine Research: From Minefields to Milestones

    PubMed Central

    Lifson, Jeffrey D.; Haigwood, Nancy L.

    2012-01-01

    Nonhuman primate (NHP) disease models for AIDS have made important contributions to the search for effective vaccines for AIDS. Viral diversity, persistence, capacity for immune evasion, and safety considerations have limited development of conventional approaches using killed or attenuated vaccines, necessitating the development of novel approaches. Here we highlight the knowledge gained and lessons learned in testing vaccine concepts in different virus/NHP host combinations. PMID:22675663

  7. Balancing the welfare: the use of non-human primates in research.

    PubMed

    Zhou, Qi

    2014-11-01

    Until now, there have been no ideal alternatives to replace non-human primates (NHPs) in biomedical research, yet the debate on whether it is appropriate to sacrifice NHPs for research never stops. With recent advances in genomics and the appearance of new technologies, the time is right to return to the problem of finding solutions to balance the welfare of both humans and NHPs.

  8. Technical advance: liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease.

    PubMed

    Burwitz, Benjamin J; Reed, Jason S; Hammond, Katherine B; Ohme, Merete A; Planer, Shannon L; Legasse, Alfred W; Ericsen, Adam J; Richter, Yoram; Golomb, Gershon; Sacha, Jonah B

    2014-09-01

    Nonhuman primates are critical animal models for the study of human disorders and disease and offer a platform to assess the role of immune cells in pathogenesis via depletion of specific cellular subsets. However, this model is currently hindered by the lack of reagents that safely and specifically ablate myeloid cells of the monocyte/macrophage Lin. Given the central importance of macrophages in homeostasis and host immunity, development of a macrophage-depletion technique in nonhuman primates would open new avenues of research. Here, using LA at i.v. doses as low as 0.1 mg/kg, we show a >50% transient depletion of circulating monocytes and tissue-resident macrophages in RMs by an 11-color flow cytometric analysis. Diminution of monocytes was followed rapidly by emigration of monocytes from the bone marrow, leading to a rebound of monocytes to baseline levels. Importantly, LA was well-tolerated, as no adverse effects or changes in gross organ function were observed during depletion. These results advance the ex vivo study of myeloid cells by flow cytometry and pave the way for in vivo studies of monocyte/macrophage biology in nonhuman primate models of human disease. PMID:24823811

  9. Technical Advance: Liposomal alendronate depletes monocytes and macrophages in the nonhuman primate model of human disease

    PubMed Central

    Burwitz, Benjamin J.; Reed, Jason S.; Hammond, Katherine B.; Ohme, Merete A.; Planer, Shannon L.; Legasse, Alfred W.; Ericsen, Adam J.; Richter, Yoram; Golomb, Gershon; Sacha, Jonah B.

    2014-01-01

    Nonhuman primates are critical animal models for the study of human disorders and disease and offer a platform to assess the role of immune cells in pathogenesis via depletion of specific cellular subsets. However, this model is currently hindered by the lack of reagents that safely and specifically ablate myeloid cells of the monocyte/macrophage Lin. Given the central importance of macrophages in homeostasis and host immunity, development of a macrophage-depletion technique in nonhuman primates would open new avenues of research. Here, using LA at i.v. doses as low as 0.1 mg/kg, we show a >50% transient depletion of circulating monocytes and tissue-resident macrophages in RMs by an 11-color flow cytometric analysis. Diminution of monocytes was followed rapidly by emigration of monocytes from the bone marrow, leading to a rebound of monocytes to baseline levels. Importantly, LA was well-tolerated, as no adverse effects or changes in gross organ function were observed during depletion. These results advance the ex vivo study of myeloid cells by flow cytometry and pave the way for in vivo studies of monocyte/macrophage biology in nonhuman primate models of human disease. PMID:24823811

  10. Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts.

    PubMed

    Hautz, Theresa; Zelger, Bettina G; Nasr, Isam W; Mundinger, Gerhard S; Barth, Rolf N; Rodriguez, Eduardo D; Brandacher, Gerald; Weissenbacher, Annemarie; Zelger, Bernhard; Cavadas, Pedro; Margreiter, Raimund; Lee, W P Andrew; Pratschke, Johann; Lakkis, Fadi G; Schneeberger, Stefan

    2014-09-01

    The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T- and B-cell infiltration.

  11. Detection of Optogenetic Stimulation in Somatosensory Cortex by Non-Human Primates - Towards Artificial Tactile Sensation

    PubMed Central

    Brush, Benjamin; Borton, David; Wagner, Fabien; Agha, Naubahar; Sheinberg, David L.; Nurmikko, Arto V.

    2014-01-01

    Neuroprosthesis research aims to enable communication between the brain and external assistive devices while restoring lost functionality such as occurs from stroke, spinal cord injury or neurodegenerative diseases. In future closed-loop sensorimotor prostheses, one approach is to use neuromodulation as direct stimulus to the brain to compensate for a lost sensory function and help the brain to integrate relevant information for commanding external devices via, e.g. movement intention. Current neuromodulation techniques rely mainly of electrical stimulation. Here we focus specifically on the question of eliciting a biomimetically relevant sense of touch by direct stimulus of the somatosensory cortex by introducing optogenetic techniques as an alternative to electrical stimulation. We demonstrate that light activated opsins can be introduced to target neurons in the somatosensory cortex of non-human primates and be optically activated to create a reliably detected sensation which the animal learns to interpret as a tactile sensation localized within the hand. The accomplishment highlighted here shows how optical stimulation of a relatively small group of mostly excitatory somatosensory neurons in the nonhuman primate brain is sufficient for eliciting a useful sensation from data acquired by simultaneous electrophysiology and from behavioral metrics. In this first report to date on optically neuromodulated behavior in the somatosensory cortex of nonhuman primates we do not yet dissect the details of the sensation the animals exerience or contrast it to those evoked by electrical stimulation, issues of considerable future interest. PMID:25541938

  12. From vice to virtue: insights from sensitization in the nonhuman primate.

    PubMed

    Castner, Stacy A; Williams, Graham V

    2007-11-15

    Repeated, intermittent administration of psychomotor stimulants, or D1 agonists in dopamine-deficient states, induces behavioral sensitization, characterized by an enhanced response to a subsequent acute low dose challenge, which may be manifested in form of altered behavior or cognitive function. Amphetamine sensitization in the nonhuman primate encompasses profound and enduring changes to similar neuronal and neurochemical substrates that occur in rodents. The process of sensitization in the monkey also results in a long-lasting depression in baseline behavioral responding, as well as emergence of hallucinatory-like behaviors reminiscent of human psychosis in response to an acute challenge. Nonhuman primates show a reduction in spine density and dendritic length in prefrontal neurons and a marked reduction in basal dopamine turnover in both prefrontal cortex and striatum. A major hallmark of amphetamine sensitization in both nonhuman primates and rodents is the manifestation of deficits in executive function and working memory which rely upon the integrity of prefrontal cortex and thereby, may yield significant insights into the cognitive dysfunction associated with addiction. Together with evidence from human and rodent studies, it can be concluded that repeated exposure to psychomotor stimulants can lead to a corruption of neuroadaptive systems in the brain by an extraordinary influence on synaptic plasticity, learning, and memory. Actively harnessing this same process by repeated, intermittent D1 agonist administration may be the key to improved working memory and decision making in addiction and other dopamine dysfunctional states, such as schizophrenia.

  13. Early blood plutonium retention in nonhuman primates compared to the NCRP 156 wound biokinetic model.

    PubMed

    Konzen, Kevin; Brey, Richard; Guilmette, Raymond

    2015-03-01

    Data from animal experiments are relied upon for understanding the biokinetics of contaminant retention and excretion where insufficient human data exist. Records involving nonhuman primate experiments performed from 1973 to 1987 were collected and compiled by researchers at the Lawrence Berkeley Laboratory. These records included early blood samples that were taken after soluble plutonium was administered via intramuscular, subcutaneous, or intravenous injection. Samples were collected as early as 5 min post injection with several samples collected during the first few weeks. The NCRP 156 biokinetic model was developed primarily from animal experiments due to insufficient human data not influenced by chelation therapy. This work compared the NCRP 156 biokinetic model default transfer rate constants to the early blood excretion data from nonhuman primate experiments for 238Pu. These results indicated that the blood content of nonhuman primates exhibited "moderate" retention properties for simulated wound conditions. Additionally, there was no evidence of long-term retention of plutonium in the whole blood samples, confirming that plutonium was not incorporated within blood cells. Particle solubility characteristics should be considered for wounds when using the NCRP 156 wound biokinetic model.

  14. Glutamate neurons are intermixed with midbrain dopamine neurons in nonhuman primates and humans

    PubMed Central

    Root, David H.; Wang, Hui-Ling; Liu, Bing; Barker, David J.; Mód, László; Szocsics, Péter; Silva, Afonso C.; Maglóczky, Zsófia; Morales, Marisela

    2016-01-01

    The rodent ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) contain dopamine neurons intermixed with glutamate neurons (expressing vesicular glutamate transporter 2; VGluT2), which play roles in reward and aversion. However, identifying the neuronal compositions of the VTA and SNC in higher mammals has remained challenging. Here, we revealed VGluT2 neurons within the VTA and SNC of nonhuman primates and humans by simultaneous detection of VGluT2 mRNA and tyrosine hydroxylase (TH; for identification of dopamine neurons). We found that several VTA subdivisions share similar cellular compositions in nonhuman primates and humans; their rostral linear nuclei have a high prevalence of VGluT2 neurons lacking TH; their paranigral and parabrachial pigmented nuclei have mostly TH neurons, and their parabrachial pigmented nuclei have dual VGluT2-TH neurons. Within nonhuman primates and humans SNC, the vast majority of neurons are TH neurons but VGluT2 neurons were detected in the pars lateralis subdivision. The demonstration that midbrain dopamine neurons are intermixed with glutamate or glutamate-dopamine neurons from rodents to humans offers new opportunities for translational studies towards analyzing the roles that each of these neurons play in human behavior and in midbrain-associated illnesses such as addiction, depression, schizophrenia, and Parkinson’s disease. PMID:27477243

  15. Validation of Serological Tests for the Detection of Antibodies Against Treponema pallidum in Nonhuman Primates

    PubMed Central

    Knauf, Sascha; Dahlmann, Franziska; Batamuzi, Emmanuel K.; Frischmann, Sieghard; Liu, Hsi

    2015-01-01

    There is evidence to suggest that the yaws bacterium (Treponema pallidum ssp. pertenue) may exist in non-human primate populations residing in regions where yaws is endemic in humans. Especially in light of the fact that the World Health Organizaiton (WHO) recently launched its second yaws eradication campaign, there is a considerable need for reliable tools to identify treponemal infection in our closest relatives, African monkeys and great apes. It was hypothesized that commercially available serological tests detect simian anti-T. pallidum antibody in serum samples of baboons, with comparable sensitivity and specificity to their results on human sera. Test performances of five different treponemal tests (TTs) and two non-treponemal tests (NTTs) were evaluated using serum samples of 57 naturally T. pallidum-infected olive baboons (Papio anubis) from Lake Manyara National Park in Tanzania. The T. pallidum particle agglutination assay (TP-PA) was used as a gold standard for comparison. In addition, the overall infection status of the animals was used to further validate test performances. For most accurate results, only samples that originated from baboons of known infection status, as verified in a previous study by clinical inspection, PCR and immunohistochemistry, were included. All tests, TTs and NTTs, used in this study were able to reliably detect antibodies against T. pallidum in serum samples of infected baboons. The sensitivity of TTs ranged from 97.7-100%, while specificity was between 88.0-100.0%. The two NTTs detected anti-lipoidal antibodies in serum samples of infected baboons with a sensitivity of 83.3% whereas specificity was 100%. For screening purposes, the TT Espline TP provided the highest sensitivity and specificity and at the same time provided the most suitable format for use in the field. The enzyme immune assay Mastblot TP (IgG), however, could be considered as a confirmatory test. PMID:25803295

  16. Morphine Produces Immunosuppressive Effects in Non-human Primates at the Proteomic and Cellular Levels

    SciTech Connect

    Brown, Joseph N.; Ortiz, Gabriel M.; Angel, Thomas E.; Jacobs, Jon M.; Gritsenko, Marina A.; Chan, Eric Y.; Purdy, David E.; Murnane, Robert D.; Larsen, Kay; Palermo, Robert E.; Shukla, Anil K.; Clauss, Therese RW; Katze, Michael G.; McCune, Joseph M.; Smith, Richard D.

    2012-05-11

    Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. As a prelude to understanding how these changes might interact with lentiviral infection in vivo, animals from two non-human primate (NHP) species [African green monkey (AGMs) and pigtailed macaque (PTs)] were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g., lymph node, colon, cerebrospinal fluid (CSF), and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an inter-organ, inter-individual, and inter-species basis. In both species, morphine was associated with decreased levels of (Ki-67+) T cell activation but with only minimal changes in overall T cell counts, neutrophil counts, and NK cells counts. While changes in T cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in the lymph node, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the interplay between opioid abuse and the response to infection with agents such as the human immunodeficiency virus, type 1 (HIV).

  17. Carcinogenicity and hepatotoxicity of cycasin and its aglycone methylazoxymethanol acetate in nonhuman primates.

    PubMed

    Sieber, S M; Correa, P; Dalgard, D W; McIntire, K R; Adamson, R H

    1980-07-01

    The carcinogenic potential of cycasin and methylazoxymethanol (MAM) acetate was investigated in nonhuman primates. Old-world monkeys (rhesus, cynomolgus, and African green monkeys) received cycasin and/or MAM acetate by oral or ip routes up to 11 years. Eighteen monkeys survived longer than 2 months after initiation of treatment with cycasin (50-75 mg/kg) or MAM acetate (1.5-3.0 mg/kg) given orally 5 days/week; 9 of the animals were necropsied. Histopathologic examination of a liver tumor from 1 of these monkeys revealed well-differentiated hepatocellular carcinoma. A second monkey had multiple tumors, including hepatocellular carcinoma, intrahepatic bile duct adenocarcinoma, renal carcinoma and adenomas, and adenomatous polyps of the colon. Although liver tumors were not observed in the other monkeys, all but 1 monkey had hepatic lesions such as toxic hepatitis and cirrhosis. These monkeys had received cycasin and/or MAM acetate for an average of 57 months (range, 2-133 mo). A group of 10 monkeys received MAM acetate by weekly ip injections (3-10 mg/kg). Six of these animals developed tumors after receiving an average of 6.14 g (range, 3.58-9.66 g) of MAM acetate for an average of 75 months (range, 50-89 mo). Four of the monkeys developed hepatocellular carcinomas, and 2 had multiple primary tumors including hepatocellular carcinomas, renal carcinomas, squamous cell carcinomas of the esophagus, and adenocarcinomas of the small intestine. Our results showed that long-term administration of cycasin and/or MAM acetate by oral and ip routes was hepatotoxic and carcinogenic in old-world monkeys.

  18. Toward a nonhuman primate model of fetal programming: phenotypic plasticity of the common marmoset fetoplacental complex

    PubMed Central

    Rutherford, Julienne N.

    2012-01-01

    Nonhuman primate models offer unique opportunities as animal models in the study of developmental programming and the role of the placenta in developmental processes. All primates share fundamental similarities in life history and reproductive biology. Thus, insights gleaned from studies of nonhuman primates have a higher degree of biological salience to human biology than do studies of rodents or agricultural animals. The common marmoset monkey is a small-bodied primate from South America that produces litters of dizygotic fetuses that share a single placental mass. This natural variation allows us to model different intrauterine conditions and associated fetoplacental phenotypes. The marmoset placenta is phenotypically plastic according to litter size. Triplet litters are characterized by low individual fetal weights and significantly more efficient placentas and attendant alterations to the microscopic architecture and endocrine function, thus modeling a nutrient restricted intrauterine environment. Consistent with this model, triplet neonates experience a higher risk of perinatal mortality and an increased likelihood of elevated adult weight. Recent evidence has shown that the intrauterine experience of females has an impact on their own pregnancy outcomes in adulthood: triplet females experience significantly greater pregnancy loss than do twin females. The marmoset monkey thus represents a potential powerful nonhuman primate model of multiple pregnancies, restrictive prenatal experiences, and differential reproductive outcomes in adulthood, which may have important implications for studying the impact of in vitro fertilization on adult reproductive health. It is still too early to determine exactly what developmental pathways lead to this disparity or what specific role the placenta plays; future work on this front will be critical to establish the marmoset as an important model of fetal programming of reproductive function in adulthood and across generations

  19. Impact of visual context on public perceptions of non-human primate performers.

    PubMed

    Leighty, Katherine A; Valuska, Annie J; Grand, Alison P; Bettinger, Tamara L; Mellen, Jill D; Ross, Stephen R; Boyle, Paul; Ogden, Jacqueline J

    2015-01-01

    Prior research has shown that the use of apes, specifically chimpanzees, as performers in the media negatively impacts public attitudes of their conservation status and desirability as a pet, yet it is unclear whether these findings generalize to other non-human primates (specifically non-ape species). We evaluated the impact of viewing an image of a monkey or prosimian in an anthropomorphic or naturalistic setting, either in contact with or in the absence of a human. Viewing the primate in an anthropomorphic setting while in contact with a person significantly increased their desirability as a pet, which also correlated with increased likelihood of believing the animal was not endangered. The majority of viewers felt that the primates in all tested images were "nervous." When shown in contact with a human, viewers felt they were "sad" and "scared", while also being less "funny." Our findings highlight the potential broader implications of the use of non-human primate performers by the entertainment industry.

  20. Social processes and disease in nonhuman primates: introduction to the special section.

    PubMed

    Capitanio, John P

    2012-06-01

    Most nonhuman primate species are remarkably social, but their social nature presents many challenges, including increased opportunities for pathogen transmission and development of disease (both physical and psychological). An interdisciplinary symposium was convened at the 2010 annual meeting of the American Society of Primatologists on the topic of social processes and disease in nonhuman primates, and four articles from that session, as well as a fifth that was separately solicited, appear in this special section. The articles reflect a variety of disciplines and perspectives that highlight the many ways that social processes can impact disease processes (and vice versa) in this highly social taxon. This is an increasingly active area of research interest as a consequence of technological developments and the availability of long-term field data. The continuing loss of primate habitat in the wild, climate change, and the need to manage high densities of primates in captivity, however, all add urgency to our need to better understand the bidirectional relationship between social factors and disease processes. PMID:22539268

  1. Impact of visual context on public perceptions of non-human primate performers.

    PubMed

    Leighty, Katherine A; Valuska, Annie J; Grand, Alison P; Bettinger, Tamara L; Mellen, Jill D; Ross, Stephen R; Boyle, Paul; Ogden, Jacqueline J

    2015-01-01

    Prior research has shown that the use of apes, specifically chimpanzees, as performers in the media negatively impacts public attitudes of their conservation status and desirability as a pet, yet it is unclear whether these findings generalize to other non-human primates (specifically non-ape species). We evaluated the impact of viewing an image of a monkey or prosimian in an anthropomorphic or naturalistic setting, either in contact with or in the absence of a human. Viewing the primate in an anthropomorphic setting while in contact with a person significantly increased their desirability as a pet, which also correlated with increased likelihood of believing the animal was not endangered. The majority of viewers felt that the primates in all tested images were "nervous." When shown in contact with a human, viewers felt they were "sad" and "scared", while also being less "funny." Our findings highlight the potential broader implications of the use of non-human primate performers by the entertainment industry. PMID:25714101

  2. Impact of Visual Context on Public Perceptions of Non-Human Primate Performers

    PubMed Central

    Leighty, Katherine A.; Valuska, Annie J.; Grand, Alison P.; Bettinger, Tamara L.; Mellen, Jill D.; Ross, Stephen R.; Boyle, Paul; Ogden, Jacqueline J.

    2015-01-01

    Prior research has shown that the use of apes, specifically chimpanzees, as performers in the media negatively impacts public attitudes of their conservation status and desirability as a pet, yet it is unclear whether these findings generalize to other non-human primates (specifically non-ape species). We evaluated the impact of viewing an image of a monkey or prosimian in an anthropomorphic or naturalistic setting, either in contact with or in the absence of a human. Viewing the primate in an anthropomorphic setting while in contact with a person significantly increased their desirability as a pet, which also correlated with increased likelihood of believing the animal was not endangered. The majority of viewers felt that the primates in all tested images were “nervous.” When shown in contact with a human, viewers felt they were “sad” and “scared”, while also being less “funny.” Our findings highlight the potential broader implications of the use of non-human primate performers by the entertainment industry. PMID:25714101

  3. Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates

    PubMed Central

    Jackson, Kasey L.; Dayton, Robert D.; Fisher-Perkins, Jeanne M.; Didier, Peter J.; Baker, Kate C.; Weimer, Maria; Gutierrez, Amparo; Cain, Cooper D.; Mathis, J. Michael; Gitcho, Michael A.; Bunnell, Bruce A.; Klein, Ronald L.

    2015-01-01

    Background Most amyotrophic lateral sclerosis (ALS) research has focused on mice, but there are distinct differences in the functional neuroanatomy of the corticospinal pathway in primates vs. rodents. A non-human primate model may be more sensitive and more predictive for therapeutic efficacy. Methods Rhesus macaques received recombinant adeno-associated virus (AAV9) encoding either the ALS-related pathological protein TDP-43 or a green fluorescent protein (GFP) control by intravenous administration. Motor function and electromyography were assessed over a nine-month expression interval followed by post-mortem analyses. Results Recombinant TDP-43 or GFP was stably expressed long term. Although the TDP-43 subjects did not manifest severe paralysis and atrophy, there were trends of a partial disease state in the TDP-43 subjects relative to the control. Conclusions These data indicate that a higher gene vector dose will likely be necessary for more robust effects, yet augur that a relevant primate model is feasible. PMID:25639184

  4. Phylogenetic evidence that two distinct Trichuris genotypes infect both humans and non-human primates.

    PubMed

    Ravasi, Damiana F; O'Riain, Mannus J; Davids, Faezah; Illing, Nicola

    2012-01-01

    Although there has been extensive debate about whether Trichuris suis and Trichuris trichiura are separate species, only one species of the whipworm T. trichiura has been considered to infect humans and non-human primates. In order to investigate potential cross infection of Trichuris sp. between baboons and humans in the Cape Peninsula, South Africa, we sequenced the ITS1-5.8S-ITS2 region of adult Trichuris sp. worms isolated from five baboons from three different troops, namely the Cape Peninsula troop, Groot Olifantsbos troop and Da Gama Park troop. This region was also sequenced from T. trichiura isolated from a human patient from central Africa (Cameroon) for comparison. By combining this dataset with Genbank records for Trichuris isolated from other humans, non-human primates and pigs from several different countries in Europe, Asia, and Africa, we confirmed the identification of two distinct Trichuris genotypes that infect primates. Trichuris sp. isolated from the Peninsula baboons fell into two distinct clades that were found to also infect human patients from Cameroon, Uganda and Jamaica (named the CP-GOB clade) and China, Thailand, the Czech Republic, and Uganda (named the DG clade), respectively. The divergence of these Trichuris clades is ancient and precedes the diversification of T. suis which clustered closely to the CP-GOB clade. The identification of two distinct Trichuris genotypes infecting both humans and non-human primates is important for the ongoing treatment of Trichuris which is estimated to infect 600 million people worldwide. Currently baboons in the Cape Peninsula, which visit urban areas, provide a constant risk of infection to local communities. A reduction in spatial overlap between humans and baboons is thus an important measure to reduce both cross-transmission and zoonoses of helminthes in Southern Africa.

  5. Biokinetics of plutonium-238 injected in non-human primates

    NASA Astrophysics Data System (ADS)

    Chelidze, Nino

    Seventeen intravenously injected monkey data were analyzed using PowerBasic and SAAM II softwares. The study was divided into three parts. In the first part SAAM II predictions were compared with those calculated by Birchall algorithm based on the ICRP 67 systemic model for plutonium. In the second part SAAM II simulations were performed and compared for two representations of systemic model for plutonium: the ICRP 67 model and the Leggett model. In the third part, optimization of transfer rates suggested by ICRP 67 and Leggett models were attempted by solving each monkey case independently. The Birchall algorithm and SAAM II predicted values coincide with each other for all data presented: blood, urine and feces. Unfortunately, these predictions do not coincide with the measurement values. Plutonium activity in liver is about 50% of the injected activity. The uptake of plutonium in liver in primates seems to be close to the assumption of equal distribution of 45% plutonium in liver and skeleton in humans. For longer sacrificed monkeys we have prolonged liver retention compared to plutonium liver retention in humans. Pu retention in urine and blood has been simulated based on the ICRP 67 and Leggett models respectively and plotted against the measured data points to acquire the understanding of the models with respect to reality. Pu activity was also evaluated in liver and skeleton at the time of the sacrifice for both models and compared with the autopsy measurements for individual cases. Optimization of transfer rates suggested in the ICRP 67 and Leggett models was attempted. Default transfer rates were varied to improve the fits to the data and predict activities in the liver and skeleton at the time of death has been carried out in SAAM II. Good fits for the individual cases were obtained successfully, however, consistency among parameters from case to case was not observed.

  6. Secondary expansion of the transient subplate zone in the developing cerebrum of human and nonhuman primates.

    PubMed

    Duque, Alvaro; Krsnik, Zeljka; Kostović, Ivica; Rakic, Pasko

    2016-08-30

    The subplate (SP) was the last cellular compartment added to the Boulder Committee's list of transient embryonic zones [Bystron I, Blakemore C, Rakic P (2008) Nature Rev Neurosci 9(2):110-122]. It is highly developed in human and nonhuman primates, but its origin, mode, and dynamics of development, resolution, and eventual extinction are not well understood because human postmortem tissue offers only static descriptive data, and mice cannot serve as an adequate experimental model for the distinct regional differences in primates. Here, we take advantage of the large and slowly developing SP in macaque monkey to examine the origin, settling pattern, and subsequent dispersion of the SP neurons in primates. Monkey embryos exposed to the radioactive DNA replication marker tritiated thymidine ([(3)H]dT, or TdR) at early embryonic ages were killed at different intervals postinjection to follow postmitotic cells' positional changes. As expected in primates, most SP neurons generated in the ventricular zone initially migrate radially, together with prospective layer 6 neurons. Surprisingly, mostly during midgestation, SP cells become secondarily displaced and widespread into the expanding SP zone, which becomes particularly wide subjacent to the association cortical areas and underneath the summit of its folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and corticocortical axons is mainly responsible for this region-dependent passive dispersion of the SP cells. Histologic and immunohistochemical comparison with the human SP at corresponding fetal ages indicates that the same developmental events occur in both primate species. PMID:27503885

  7. Secondary expansion of the transient subplate zone in the developing cerebrum of human and nonhuman primates.

    PubMed

    Duque, Alvaro; Krsnik, Zeljka; Kostović, Ivica; Rakic, Pasko

    2016-08-30

    The subplate (SP) was the last cellular compartment added to the Boulder Committee's list of transient embryonic zones [Bystron I, Blakemore C, Rakic P (2008) Nature Rev Neurosci 9(2):110-122]. It is highly developed in human and nonhuman primates, but its origin, mode, and dynamics of development, resolution, and eventual extinction are not well understood because human postmortem tissue offers only static descriptive data, and mice cannot serve as an adequate experimental model for the distinct regional differences in primates. Here, we take advantage of the large and slowly developing SP in macaque monkey to examine the origin, settling pattern, and subsequent dispersion of the SP neurons in primates. Monkey embryos exposed to the radioactive DNA replication marker tritiated thymidine ([(3)H]dT, or TdR) at early embryonic ages were killed at different intervals postinjection to follow postmitotic cells' positional changes. As expected in primates, most SP neurons generated in the ventricular zone initially migrate radially, together with prospective layer 6 neurons. Surprisingly, mostly during midgestation, SP cells become secondarily displaced and widespread into the expanding SP zone, which becomes particularly wide subjacent to the association cortical areas and underneath the summit of its folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and corticocortical axons is mainly responsible for this region-dependent passive dispersion of the SP cells. Histologic and immunohistochemical comparison with the human SP at corresponding fetal ages indicates that the same developmental events occur in both primate species.

  8. Prenatal dexamethasone exposure induces changes in nonhuman primate offspring cardiometabolic and hypothalamic-pituitary-adrenal axis function

    PubMed Central

    de Vries, Annick; Holmes, Megan C.; Heijnis, Areke; Seier, Jürgen V.; Heerden, Joritha; Louw, Johan; Wolfe-Coote, Sonia; Meaney, Michael J.; Levitt, Naomi S.; Seckl, Jonathan R.

    2007-01-01

    Prenatal stress or glucocorticoid administration has persisting “programming” effects on offspring in rodents and other model species. Multiple doses of glucocorticoids are in widespread use in obstetric practice. To examine the clinical relevance of glucocorticoid programming, we gave 50, 120, or 200 μg/kg/d of dexamethasone (dex50, dex120, or dex200) orally from mid-term to a singleton-bearing nonhuman primate, Chlorocebus aethiops (African vervet). Dexamethasone dose-dependently reduced maternal cortisol levels without effecting maternal blood pressure, glucose, electrolytes, or weight gain. Birth weight was unaffected by any dexamethasone dose, although postnatal growth was attenuated after dex120 and dex200. At 8 months of age, dex120 and dex200 offspring showed impaired glucose tolerance and hyperinsulinemia, with reduced (approximately 25%) pancreatic β cell number at 12 months. Dex120 and dex200 offspring had increased systolic and diastolic blood pressures at 12 months. Mild stress produced an exaggerated cortisol response in dex200 offspring, implying hypothalamic-pituitary-adrenal axis programming. The data are compatible with the extrapolation of the glucocorticoid programming hypothesis to primates and indicate that repeated glucocorticoid therapy and perhaps chronic stress in humans may have long-term effects. PMID:17380204

  9. Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

    PubMed

    Amato, Katherine R

    2016-01-01

    The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. PMID:26808106

  10. Tissue-specific transcriptome sequencing analysis expands the non-human primate reference transcriptome resource (NHPRTR)

    PubMed Central

    Peng, Xinxia; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Nishida, Andrew; Pipes, Lenore; Bozinoski, Marjan; Thomas, Matthew J.; Kelly, Sara; Weiss, Jeffrey M.; Raveendran, Muthuswamy; Muzny, Donna; Gibbs, Richard A.; Rogers, Jeffrey; Schroth, Gary P.; Katze, Michael G.; Mason, Christopher E.

    2015-01-01

    The non-human primate reference transcriptome resource (NHPRTR, available online at http://nhprtr.org/) aims to generate comprehensive RNA-seq data from a wide variety of non-human primates (NHPs), from lemurs to hominids. In the 2012 Phase I of the NHPRTR project, 19 billion fragments or 3.8 terabases of transcriptome sequences were collected from pools of ∼20 tissues in 15 species and subspecies. Here we describe a major expansion of NHPRTR by adding 10.1 billion fragments of tissue-specific RNA-seq data. For this effort, we selected 11 of the original 15 NHP species and subspecies and constructed total RNA libraries for the same ∼15 tissues in each. The sequence quality is such that 88% of the reads align to human reference sequences, allowing us to compute the full list of expression abundance across all tissues for each species, using the reads mapped to human genes. This update also includes improved transcript annotations derived from RNA-seq data for rhesus and cynomolgus macaques, two of the most commonly used NHP models and additional RNA-seq data compiled from related projects. Together, these comprehensive reference transcriptomes from multiple primates serve as a valuable community resource for genome annotation, gene dynamics and comparative functional analysis. PMID:25392405

  11. Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

    PubMed

    Amato, Katherine R

    2016-01-01

    The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research.

  12. Experimental primates and non-human primate (NHP) models of human diseases in China: current status and progress

    PubMed Central

    ZHANG, Xiao-Liang; PANG, Wei; HU, Xin-Tian; LI, Jia-Li; YAO, Yong-Gang; ZHENG, Yong-Tang

    2014-01-01

    Non-human primates (NHPs) are phylogenetically close to humans, with many similarities in terms of physiology, anatomy, immunology, as well as neurology, all of which make them excellent experimental models for biomedical research. Compared with developed countries in America and Europe, China has relatively rich primate resources and has continually aimed to develop NHPs resources. Currently, China is a leading producer and a major supplier of NHPs on the international market. However, there are some deficiencies in feeding and management that have hampered China’s growth in NHP research and materials. Nonetheless, China has recently established a number of primate animal models for human diseases and achieved marked scientific progress on infectious diseases, cardiovascular diseases, endocrine diseases, reproductive diseases, neurological diseases, and ophthalmic diseases, etc. Advances in these fields via NHP models will undoubtedly further promote the development of China’s life sciences and pharmaceutical industry, and enhance China’s position as a leader in NHP research. This review covers the current status of NHPs in China and other areas, highlighting the latest developments in disease models using NHPs, as well as outlining basic problems and proposing effective countermeasures to better utilize NHP resources and further foster NHP research in China. PMID:25465081

  13. An ethnoprimatological approach to assessing levels of tolerance between human and commensal non-human primates in Sri Lanka.

    PubMed

    Nekaris, Anne-Isola; Boulton, Alex; Nijman, Vincent

    2013-01-01

    Human and non-human primates increasingly are forced to live commensally, and understanding the human-nonhuman interconnections are paramount in understanding tolerance and conflict. In our study area, the heavily deforested parts of southern Sri Lanka humans and primates live side by side and prevalent religious tenets encourage a peaceful co-existence. We quantify the attitudes of rural communities towards three resident primate species (red slender loris, purple-faced langur, toque macaque) and wildlife conservation through semi-structured interviews with 301 people. Presence of the three primates on people' s land or farms was not related to the distance to the nearest forest but for langurs the incidence of crop-raiding was negatively related to distance to the forest. Despite Buddhist' s beliefs about 10% of interviewees indicated having killed primates (in the past) but levels of killing was not related to awareness of protective status of the primates. Overall however positive attitudes towards primates prevailed, without noticeable influence of sex, education or employment type. There was overwhelming support for forest protection measures - not because of the primates but mainly for water preservation and for ensuring a steady timber supply. We found that despite high levels of deforestation, and an increase of encroachment of humans into primate habitats, attitudes has led only to a limited increased level of tension between humans and primates. PMID:23836757

  14. Optimization of a Novel Non-invasive Oral Sampling Technique for Zoonotic Pathogen Surveillance in Nonhuman Primates

    PubMed Central

    Smiley Evans, Tierra; Barry, Peter A.; Gilardi, Kirsten V.; Goldstein, Tracey; Deere, Jesse D.; Fike, Joseph; Yee, JoAnn; Ssebide, Benard J; Karmacharya, Dibesh; Cranfield, Michael R.; Wolking, David; Smith, Brett; Mazet, Jonna A. K.; Johnson, Christine K.

    2015-01-01

    Free-ranging nonhuman primates are frequent sources of zoonotic pathogens due to their physiologic similarity and in many tropical regions, close contact with humans. Many high-risk disease transmission interfaces have not been monitored for zoonotic pathogens due to difficulties inherent to invasive sampling of free-ranging wildlife. Non-invasive surveillance of nonhuman primates for pathogens with high potential for spillover into humans is therefore critical for understanding disease ecology of existing zoonotic pathogen burdens and identifying communities where zoonotic diseases are likely to emerge in the future. We developed a non-invasive oral sampling technique using ropes distributed to nonhuman primates to target viruses shed in the oral cavity, which through bite wounds and discarded food, could be transmitted to people. Optimization was performed by testing paired rope and oral swabs from laboratory colony rhesus macaques for rhesus cytomegalovirus (RhCMV) and simian foamy virus (SFV) and implementing the technique with free-ranging terrestrial and arboreal nonhuman primate species in Uganda and Nepal. Both ubiquitous DNA and RNA viruses, RhCMV and SFV, were detected in oral samples collected from ropes distributed to laboratory colony macaques and SFV was detected in free-ranging macaques and olive baboons. Our study describes a technique that can be used for disease surveillance in free-ranging nonhuman primates and, potentially, other wildlife species when invasive sampling techniques may not be feasible. PMID:26046911

  15. Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates.

    PubMed

    Stephens, Shannon B Z; Wallen, Kim

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Puberty is the developmental period when the hypothalamic-pituitary-gonadal (HPG) axis is activated, following a juvenile quiescent period, and reproductive capacity matures. Although pubertal events occur in a consistent sequence, there is considerable variation between individuals in the onset and timing of pubertal events, with puberty onset occurring earlier in girls than in boys. Evidence in humans demonstrates that social and environmental context influences the timing of puberty onset and may account for some of the observed variation. This review analyzes the nonhuman primate literature, focusing primarily on rhesus macaques (Macaca mulatta), to examine the social and environmental influences on puberty onset, how these factors influence puberty in males and females, and to review the relationship between puberty onset of adult neuroendocrine function and sexual behavior. Social and environmental factors influence the timing of puberty onset and pubertal events in nonhuman primates, as in humans, and the influences of these factors differ for males and females. In nonhuman primates, gonadal hormones are not required for sexual behavior, but modulate the frequency of occurrence of behavior, with social context influencing the relationship between gonadal hormones and sexual behavior. Thus, the onset of sexual behavior is independent of neuroendocrine changes at puberty; however, there are distinct behavioral changes that occur at puberty, which are modulated by social context. Puberty is possibly the developmental period when hormonal modulation of sexual behavior is organized, and thus, when social context interacts with hormonal state to strongly influence the expression of sexual behavior.

  16. Proceedings of a workshop on Lighting Requirements in Microgravity: Rodents and Nonhuman Primates

    NASA Technical Reports Server (NTRS)

    Holley, Daniel C. (Editor); Winget, Charles M. (Editor); Leon, Henry A. (Editor)

    1988-01-01

    A workshop, sponsored by Ames Research Center, was held at San Jose State University, San Jose, California, July 16-17, 1987, to discuss and correlate observations and theories relating to lighting requirements in animal habitats for rodents and nonhuman primates in microgravity (near space). This volume represents the results of the workshop. It contains a summary of the conclusions reached and recommendations for lighting animal housing modules used in microgravity related projects. The recommendations cover various aspects of habitat lighting including engineering standards for intensity, spectral properties, and light cycle controls.

  17. Evaluation of [11C]metergoline as a PET radiotracer for 5HTR in nonhuman primates

    SciTech Connect

    Hooker, J.M.; Hooker, J.M.; Kim, S.W.; Reibel, A.T.; Alexoff, D.; Xu, Y.; Shea, C.

    2010-04-20

    Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.

  18. Safety Evaluation and Imaging Properties of Gadolinium-Based Nanoparticles in nonhuman primates

    PubMed Central

    Kotb, Shady; Piraquive, Joao; Lamberton, Franck; Lux, François; Verset, Michael; Di Cataldo, Vanessa; Contamin, Hugues; Tillement, Olivier; Canet-Soulas, Emmanuelle; Sancey, Lucie

    2016-01-01

    In this article, we report the safety evaluation of gadolinium-based nanoparticles in nonhuman primates (NHP) in the context of magnetic resonance imaging (MRI) studies in atherosclerosis bearing animals and healthy controls. In healthy NHP, the pharmacokinetics and toxicity profiles demonstrated the absence of dose, time, and sex-effects, as well as a suitable tolerance of intravenous administration of the nanoparticles. We investigated their imaging properties for arterial plaque imaging in a standard diet or a high cholesterol diet NHP, and compared their characteristics with clinically applied Gd-chelate. This preliminary investigation reports the efficient and safe imaging of atherosclerotic plaques. PMID:27725693

  19. Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth

    PubMed Central

    Adams Waldorf, Kristina M.; Rubens, Craig E.; Gravett, Michael G.

    2010-01-01

    Preterm birth is the most important direct cause of neonatal mortality and remains a major challenge for obstetrics and global health. Intrauterine infection causes approximately 50% of early preterm births. Animal models using pregnant mice, rabbits, or sheep, demonstrate the key link between infection and premature birth, but differ in mechanisms of parturition and placental structure from humans. The nonhuman primate (NHP) is a powerful model which emulates many features of human placentation and parturition. The contributions of the NHP model to preterm birth research are reviewed emphasizing the role of infections, and potential development of preventative and therapeutic strategies. PMID:21040390

  20. The Ethics of Using Transgenic Non-Human Primates to Study What Makes Us Human

    PubMed Central

    Coors, Marilyn E.; Glover, Jacqueline J.; Juengst, Eric T.; Sikela, James M.

    2010-01-01

    An ongoing flood of comparative genomic data is identifying human lineage specific (HLS) sequences of unknown function, and there is strong interest in investigating their functional effects. Transgenic apes, our closest evolutionary relative, have the highest potential to express HLS sequences as they are expressed in Homo sapiens and likewise experience harm from such transgenic research. These harms render the conduct of this research ethically unacceptable in apes, justifying regulatory barriers between these species and all other non-human primates for transgenic research. PMID:20717156

  1. Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates.

    PubMed

    Geisbert, Thomas W; Daddario-DiCaprio, Kathleen M; Williams, Kinola J N; Geisbert, Joan B; Leung, Anders; Feldmann, Friederike; Hensley, Lisa E; Feldmann, Heinz; Jones, Steven M

    2008-06-01

    Recombinant vesicular stomatitis virus (VSV) vectors expressing homologous filoviral glycoproteins can completely protect rhesus monkeys against Marburg virus when administered after exposure and can partially protect macaques after challenge with Zaire ebolavirus. Here, we administered a VSV vector expressing the Sudan ebolavirus (SEBOV) glycoprotein to four rhesus macaques shortly after exposure to SEBOV. All four animals survived SEBOV challenge, while a control animal that received a nonspecific vector developed fulminant SEBOV hemorrhagic fever and succumbed. This is the first demonstration of complete postexposure protection against an Ebola virus in nonhuman primates and provides further evidence that postexposure vaccination may have utility in treating exposures to filoviruses.

  2. Non-human primate models of SIV infection and CNS neuropathology.

    PubMed

    Williams, Kenneth; Lackner, Andrew; Mallard, Jaclyn

    2016-08-01

    Non-human primate models of AIDS and neuroAIDS are the premiere model of HIV infection of the CNS and neuropathogenesis. This review discusses current SIV infection models of neuroAIDS emphasizing findings in the last two years. Consistent in these findings is the interplay between host factors that regulate immune responses to virus and viral replication. Several rapid models of AIDS with consistent CNS pathogenesis exist, each of which modulates by antibody treatment or viruses that cause rapid immune suppression and replicate well in macrophages. Consistent in all of these models are data underscoring the importance of monocyte and macrophage activation, infection and accumulation in the CNS. PMID:27544476

  3. Adenovirus-Vectored Vaccine Provides Postexposure Protection to Ebola Virus–Infected Nonhuman Primates

    PubMed Central

    Wong, Gary; Richardson, Jason S.; Pillet, Stéphane; Racine, Trina; Patel, Ami; Soule, Geoff; Ennis, Jane; Turner, Jeffrey; Qiu, Xiangguo; Kobinger, Gary P.

    2015-01-01

    Ebola virus (EBOV) causes lethal disease in up to 90% of EBOV-infected humans. Among vaccines, only the vesicular stomatitis virus platform has been successful in providing postexposure protection in nonhuman primates. Here, we show that an adjuvanted human adenovirus serotype 5 (Ad5)–vectored vaccine (Ad5–Zaire EBOV glycoprotein) protected 67% (6 of 9) and 25% (1 of 4) of cynomolgus macaques when administered 30 minutes and 24 hours following EBOV challenge, respectively. The treatment also protected 33% of rhesus macaques (1 of 3) when given at 24 hours. The results highlight the utility of adjuvanted Ad5 vaccines for rapid immunization against EBOV PMID:25957963

  4. Oral and Conjunctival Exposure of Nonhuman Primates to Low Doses of Ebola Makona Virus

    PubMed Central

    Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Deer, Daniel J.; Fenton, Karla A.; Geisbert, Thomas W.

    2016-01-01

    Nonhuman primate (NHP) models of Ebola virus (EBOV) infection primarily use parenteral or aerosol routes of exposure. Uniform lethality can be achieved in these models at low doses of EBOV (≤100 plaque-forming units [PFU]). Here, we exposed NHPs to low doses of EBOV (Makona strain) by the oral or conjunctival routes. Surprisingly, animals exposed to 10 PFU by either route showed no signs of disease. Exposure to 100 PFU resulted in illness and/or lethal infection. These results suggest that these more natural routes require higher doses of EBOV to produce disease or that there may be differences between Makona and historical strains. PMID:27284090

  5. Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

    PubMed Central

    Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in intact, awake monkeys (Macaca mulatta). We recorded action potentials within ~1 ms after 0.4 ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared to sham stimulation. The methodology is compatible with standard equipment in primate laboratories, allowing for easy implementation. Application of these new tools will facilitate the refinement of next generation TMS devices, experiments, and treatment protocols. PMID:24974797

  6. Species specific exome probes reveal new insights in positively selected genes in nonhuman primates

    PubMed Central

    Su, Zheng; Zhang, Junjie; Kumar, Chanchal; Molony, Cliona; Lu, Hongchao; Chen, Ronghua; Stone, David J.; Ling, Fei; Liu, Xiao

    2016-01-01

    Nonhuman primates (NHP) are important biomedical animal models for the study of human disease. Of these, the most widely used models in biomedical research currently are from the genus Macaca. However, evolutionary genetic divergence between human and NHP species makes human-based probes inefficient for the capture of genomic regions of NHP for sequencing and study. Here we introduce a new method to resequence the exome of NHP species by a designed capture approach specifically targeted to the NHP, and demonstrate its superior performance on four NHP species or subspecies. Detailed investigation on biomedically relevant genes demonstrated superior capture by the new approach. We identified 28 genes that appeared to be pseudogenized and inactivated in macaque. Finally, we identified 187 genes showing strong evidence for positive selection across all branches of the primate phylogeny including many novel findings. PMID:27659771

  7. Behavioural, hormonal and neurobiological mechanisms of aggressive behaviour in human and nonhuman primates.

    PubMed

    de Almeida, Rosa Maria Martins; Cabral, João Carlos Centurion; Narvaes, Rodrigo

    2015-05-01

    Aggression is a key component for social behaviour and can have an adaptive value or deleterious consequences. Here, we review the role of sex-related differences in aggressive behaviour in both human and nonhuman primates. First, we address aggression in primates, which varies deeply between species, both in intensity and in display, ranging from animals that are very aggressive, such as chimpanzees, to the nonaggressive bonobos. Aggression also influences the hierarchical structure of gorillas and chimpanzees, and is used as the main tool for dealing with other groups. With regard to human aggression, it can be considered a relevant adaptation for survival or can have negative impacts on social interaction for both sexes. Gender plays a critical role in aggressive and competitive behaviours, which are determined by a cascade of physiological changes, including GABAergic and serotonergic systems, and sex neurosteroids. The understanding of the neurobiological bases and behavioural determinants of different types of aggression is fundamental for minimising these negative impacts.

  8. Tolerance of Lung Allografts Achieved in Nonhuman Primates via Mixed Hematopoietic Chimerism.

    PubMed

    Tonsho, M; Lee, S; Aoyama, A; Boskovic, S; Nadazdin, O; Capetta, K; Smith, R-N; Colvin, R B; Sachs, D H; Cosimi, A B; Kawai, T; Madsen, J C; Benichou, G; Allan, J S

    2015-08-01

    While the induction of transient mixed chimerism has tolerized MHC-mismatched renal grafts in nonhuman primates and patients, this approach has not been successful for more immunogenic organs. Here, we describe a modified delayed-tolerance-induction protocol resulting in three out of four monkeys achieving long-term lung allograft survival without ongoing immunosuppression. Two of the tolerant monkeys displayed stable mixed lymphoid chimerism, and the other showed transient chimerism. Serial biopsies and post-mortem specimens from the tolerant monkeys revealed no signs of chronic rejection. The tolerant recipients also exhibited T cell unresponsiveness and a lack of alloantibody. This is the first report of durable mixed chimerism and successful tolerance induction of MHC-mismatched lungs in primates.

  9. Socialization Strategies and Disease Transmission in Captive Colonies of Nonhuman Primates

    PubMed Central

    Schapiro, Steven J.; Bernacky, Bruce J.

    2011-01-01

    In captive research environments for nonhuman primates (NHP), social housing strategies are often in conflict with protocols designed to minimize disease transmission. This is particularly true in breeding colonies, and is especially relevant when attempting to eliminate specific pathogens from a population of primates. Numerous strategies have been used to establish such specific pathogen free (SPF) breeding colonies (primarily of macaques), ranging from nursery rearing of neonates to single housing of socially-reared yearlings to the rearing of infants in large social groups. All of these strategies attempt to balance the effects of the chosen socialization strategy on parameters related to disease transmission, including the ultimate elimination of the target pathogens. Such strategies may affect the overall disease states of NHP breeding colonies through selective breeding processes. This can occur either by creating subpopulations of animals that do not have target diseases (SPF colonies), but may have other issues; or by creating situations in which the ‘best’ animals are sold and the breeding colony is stocked with animals that may be more disease susceptible than those that were sold. The disease states of NHP research colonies also may be affected by selective utilization programs, in which animals removed from the breeding colony for health/behavior reasons, are preferentially chosen for use in scientific investigations. Such utilization criteria raise the question of whether ideal subjects are being chosen for use in research. Finally, captive primate colonies, where both socialization and disease states are intensely managed, may provide opportunities for those testing predictions from models of the interactions of socialization and disease transmission in the evolution of wild populations of NHP. This would be especially true for some extreme conditions of these disease ecology models, given the exceedingly high social densities and levels of

  10. The role of nonhuman primates in the development of an AIDS vaccine.

    PubMed

    Nathanson, N; Hirsch, V M; Mathieson, B J

    1999-01-01

    Over the past decade, a substantial research investment has generated a vast body of knowledge relevant to the development of an effective AIDS vaccine. Furthermore, studies in nonhuman primates have demonstrated that a number of candidate immunogens can confer a significant degree of protection against a potentially pathogenic SIV or SHIV. Currently, there exists a robust program that supports discovery of new HIV immunogens and a proven successful program for collaborative human trials of promising vaccine candidates. However, we believe that there is a gap between discovery and clinical trials. An orderly process for screening of candidate immunogens prior to human trials would facilitate the vaccine development program. We suggest that nonhuman primates can fill this strategic gap and could accelerate vaccine development. Recognizing that there is considerable controversy about the potential usefulness of the primate models, we have attempted to set forth the relevant practical and biological issues as a series of questions for discussion. The most important biological problem is the absence of a single immune response correlate that will predict vaccine efficacy. Data from primate models indicate that such a single predictive correlate may not exist. In turn, this argues for a vaccine screening protocol that includes a pathogenic virus challenge, an approach only available in the nonhuman primate model. The further assumption is that nonprimate models can be used to predict the relative protective efficacy of diverse immunization protocols, a hypothesis that can only be tested by comparative studies yet to be conducted. A 'standard' set of virus challenges must be selected for comparison of different immunization protocols, and this effort has been initiated. At the practical level, it appears that the large number of candidate immunogens now being developed requires a screening process of the kind proposed, since it would not be practical to test all new

  11. Search for CEA-like molecules in polymorphonuclear leukocytes of non-human primates using monoclonal antibodies.

    PubMed

    Jantscheff, P; Indzhiia, L V; Micheel, B

    1986-01-01

    The monoclonal anti-CEA antibody ZIK-A42-A/C1 which reacts with NCA of human polymorphonuclear leukocytes was found to bind also to polymorphonuclear blood leukocytes of the following non-human primates tested: hamadryas baboon (Papio hamadryas), stump-tailed monkey (Macaca arctoides), pig-tailed monkey (Macaca nemestrina), and rhesus monkey (Macaca mulata). No binding was observed to mononuclear blood leukocytes. It was concluded that non-human primates contain CEA-like substances in their polymorphonuclear leukocytes as humans do and that these substances carry some identical epitopes.

  12. The behavioral pharmacology of anorexigenic drugs in nonhuman primates: 30 years of progress

    PubMed Central

    Foltin, Richard W.

    2013-01-01

    Comparatively few studies over the past 30 years have used pharmacological manipulations as a means of understanding processes underlying feeding behavior of nonhuman primates. In the 1970s and early 1980s, four laboratories provided data on the anorexigenic effects of a range of drugs on rhesus monkeys and baboons, and a fifth laboratory studied the effects of neuropeptides on feeding behavior of baboons. There were differences in the way anorexigenic drugs altered eating topography, and those that increased dopamine levels had greater abuse liability than those that increased serotonin levels. Studies in the 1980s and 1990s used foraging models and principles of behavioral economics to understand food–drug interactions. Experimenter-given anorexigenic drugs did not function as economic substitutes for food. Recent studies have examined the effects of a range of drugs on consumption of highly palatable food and model diet-induced obesity. Although some drugs, including stimulants, N-methyl-D-aspartate antagonists, and a cannabinoid antagonist increased the latency to standard food consumption, there was little evidence for a selective effect of any drug on highly palatable food consumption. Results obtained in nonhuman primates did not always confirm those observed in rodents. Future studies looking at sex differences and social factors may provide insight into factors related to human obesity. PMID:22772334

  13. Homologous and Heterologous Protection of Nonhuman Primates by Ebola and Sudan Virus-Like Particles

    PubMed Central

    Warfield, Kelly L.; Dye, John M.; Wells, Jay B.; Unfer, Robert C.; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Swenson, Dana L.; Bavari, Sina; Aman, M. Javad

    2015-01-01

    Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components. PMID:25793502

  14. Dopamine Reuptake Inhibitors in Parkinson's Disease: A Review of Nonhuman Primate Studies and Clinical Trials.

    PubMed

    Huot, Philippe; Fox, Susan H; Brotchie, Jonathan M

    2016-06-01

    Striatal dopamine deficiency is the core feature of the pathology of Parkinson's disease (PD), and dopamine replacement with l-3,4-dihydroxyphenylalanine (l-DOPA) is the mainstay of PD treatment. Unfortunately, chronic l-DOPA administration is marred by the emergence of dyskinesia and wearing-off. Alternatives to l-DOPA for alleviation of parkinsonism are of interest, although none can match the efficacy of l-DOPA to date. Catechol-O-methyltransferase and monoamine oxidase inhibitors are currently used to alleviate wearing-off, but they do not increase "on-time" without exacerbating dyskinesia. Alternate approaches to dopamine replacement in parkinsonism generally (and to wearing-off and dyskinesia, specifically) are therefore urgently needed. Inasmuch as they increase synaptic dopamine levels, dopamine transporter (DAT) inhibitors, whether they are selective or have actions on noradrenaline or serotonin transporters, theoretically represent an attractive way to alleviate parkinsonism per se and potentially enhance l-DOPA antiparkinsonian action (provided that sufficient dopamine terminals remain within the striatum). Several nonhuman primate studies and clinical trials have been performed to evaluate the potential of DAT inhibitors for PD. In this article, we review nonhuman primate studies and clinical trials, we summarize the current knowledge of DAT inhibitors in PD, and we propose a hypothesis as to how tailoring the selectivity of DAT inhibitors might maximize the benefits of DAT inhibition in PD. PMID:27190169

  15. Homologous and heterologous protection of nonhuman primates by Ebola and Sudan virus-like particles.

    PubMed

    Warfield, Kelly L; Dye, John M; Wells, Jay B; Unfer, Robert C; Holtsberg, Frederick W; Shulenin, Sergey; Vu, Hong; Swenson, Dana L; Bavari, Sina; Aman, M Javad

    2015-01-01

    Filoviruses cause hemorrhagic fever resulting in significant morbidity and mortality in humans. Several vaccine platforms that include multiple virus-vectored approaches and virus-like particles (VLPs) have shown efficacy in nonhuman primates. Previous studies have shown protection of cynomolgus macaques against homologous infection for Ebola virus (EBOV) and Marburg virus (MARV) following a three-dose vaccine regimen of EBOV or MARV VLPs, as well as heterologous protection against Ravn Virus (RAVV) following vaccination with MARV VLPs. The objectives of the current studies were to determine the minimum number of vaccine doses required for protection (using EBOV as the test system) and then demonstrate protection against Sudan virus (SUDV) and Taï Forest virus (TAFV). Using the EBOV nonhuman primate model, we show that one or two doses of VLP vaccine can confer protection from lethal infection. VLPs containing the SUDV glycoprotein, nucleoprotein and VP40 matrix protein provide complete protection against lethal SUDV infection in macaques. Finally, we demonstrate protective efficacy mediated by EBOV, but not SUDV, VLPs against TAFV; this is the first demonstration of complete cross-filovirus protection using a single component heterologous vaccine within the Ebolavirus genus. Along with our previous results, this observation provides strong evidence that it will be possible to develop and administer a broad-spectrum VLP-based vaccine that will protect against multiple filoviruses by combining only three EBOV, SUDV and MARV components.

  16. Evaluation of transit-time and electromagnetic flow measurement in a chronically instrumented nonhuman primate model

    NASA Technical Reports Server (NTRS)

    Koenig, S. C.; Reister, C. A.; Schaub, J.; Swope, R. D.; Ewert, D.; Fanton, J. W.; Convertino, V. A. (Principal Investigator)

    1996-01-01

    The Physiology Research Branch at Brooks AFB conducts both human and nonhuman primate experiments to determine the effects of microgravity and hypergravity on the cardiovascular system and to identify the particular mechanisms that invoke these responses. Primary investigative efforts in our nonhuman primate model require the determination of total peripheral resistance, systemic arterial compliance, and pressure-volume loop characteristics. These calculations require beat-to-beat measurement of aortic flow. This study evaluated accuracy, linearity, biocompatability, and anatomical features of commercially available electromagnetic (EMF) and transit-time flow measurement techniques. Five rhesus monkeys were instrumented with either EMF (3 subjects) or transit-time (2 subjects) flow sensors encircling the proximal ascending aorta. Cardiac outputs computed from these transducers taken over ranges of 0.5 to 2.0 L/min were compared to values obtained using thermodilution. In vivo experiments demonstrated that the EMF probe produced an average error of 15% (r = .896) and 8.6% average linearity per reading, and the transit-time flow probe produced an average error of 6% (r = .955) and 5.3% average linearity per reading. Postoperative performance and biocompatability of the probes were maintained throughout the study. The transit-time sensors provided the advantages of greater accuracy, smaller size, and lighter weight than the EMF probes. In conclusion, the characteristic features and performance of the transit-time sensors were superior to those of the EMF sensors in this study.

  17. Brain hemispheric structural efficiency and interconnectivity rightward asymmetry in human and nonhuman primates.

    PubMed

    Iturria-Medina, Yasser; Pérez Fernández, Alejandro; Morris, David M; Canales-Rodríguez, Erick J; Haroon, Hamied A; García Pentón, Lorna; Augath, Mark; Galán García, Lídice; Logothetis, Nikos; Parker, Geoffrey J M; Melie-García, Lester

    2011-01-01

    Evidence for interregional structural asymmetries has been previously reported for brain anatomic regions supporting well-described functional lateralization. Here, we aimed to investigate whether the two brain hemispheres demonstrate dissimilar general structural attributes implying different principles on information flow management. Common left hemisphere/right hemisphere structural network properties are estimated and compared for right-handed healthy human subjects and a nonhuman primate, by means of 3 different diffusion-weighted magnetic resonance imaging fiber tractography algorithms and a graph theory framework. In both the human and the nonhuman primate, the data support the conclusion that, in terms of the graph framework, the right hemisphere is significantly more efficient and interconnected than the left hemisphere, whereas the left hemisphere presents more central or indispensable regions for the whole-brain structural network than the right hemisphere. From our point of view, in terms of functional principles, this pattern could be related with the fact that the left hemisphere has a leading role for highly demanding specific process, such as language and motor actions, which may require dedicated specialized networks, whereas the right hemisphere has a leading role for more general process, such as integration tasks, which may require a more general level of interconnection.

  18. Biosafety in Ex Vivo Gene Therapy and Conditional Ablation of Lentivirally Transduced Hepatocytes in Nonhuman Primates

    PubMed Central

    Menzel, Olivier; Birraux, Jacques; Wildhaber, Barbara E; Jond, Caty; Lasne, Françoise; Habre, Walid; Trono, Didier; Nguyen, Tuan H; Chardot, Christophe

    2009-01-01

    Ex vivo gene therapy is an interesting alternative to orthotopic liver transplantation (OLT) for treating metabolic liver diseases. In this study, we investigated its efficacy and biosafety in nonhuman primates. Hepatocytes isolated from liver lobectomy were transduced in suspension with a bicistronic liver-specific lentiviral vector and immediately autotransplanted (SLIT) into three cynomolgus monkeys. The vector encoded cynomolgus erythropoietin (EPO) and the conditional suicide gene herpes simplex virus-thymidine kinase (HSV-TK). Survival of transduced hepatocytes and vector dissemination were evaluated by detecting transgene expression and vector DNA. SLIT was safely performed within a day in all three subjects. Serum EPO and hematocrit rapidly increased post-SLIT and their values returned to baseline within about 1 month. Isoforms of EPO detected in monkeys' sera differed from the physiological renal EPO. In liver biopsies at months 8 and 15, we detected EPO protein, vector mRNA and DNA, demonstrating long-term survival and functionality of transplanted lentivirally transduced hepatocytes. Valganciclovir administration resulted in complete ablation of the transduced hepatocytes. We demonstrated the feasibility and biosafety of SLIT, and the long term (>1 year) functionality of lentivirally transduced hepatocytes in nonhuman primates. The HSV-TK/valganciclovir suicide strategy can increase the biosafety of liver gene therapy protocols by safely and completely ablating transduced hepatocytes on demand. PMID:19568222

  19. Social isolation disrupts hippocampal neurogenesis in young non-human primates.

    PubMed

    Cinini, Simone M; Barnabe, Gabriela F; Galvão-Coelho, Nicole; de Medeiros, Magda A; Perez-Mendes, Patrícia; Sousa, Maria B C; Covolan, Luciene; Mello, Luiz E

    2014-01-01

    Social relationships are crucial for the development and maintenance of normal behavior in non-human primates. Animals that are raised in isolation develop abnormal patterns of behavior that persist even when they are later reunited with their parents. In rodents, social isolation is a stressful event and is associated with a decrease in hippocampal neurogenesis but considerably less is known about the effects of social isolation in non-human primates during the transition from adolescence to adulthood. To investigate how social isolation affects young marmosets, these were isolated from other members of the colony for 1 or 3 weeks and evaluated for alterations in their behavior and hippocampal cell proliferation. We found that anxiety-related behaviors like scent-marking and locomotor activity increased after social isolation when compared to baseline levels. In agreement, grooming-an indicative of attenuation of tension-was reduced among isolated marmosets. These results were consistent with increased cortisol levels after 1 and 3 weeks of isolation. After social isolation (1 or 3 weeks), reduced proliferation of neural cells in the subgranular zone of dentate granule cell layer was identified and a smaller proportion of BrdU-positive cells underwent neuronal fate (doublecortin labeling). Our data is consistent with the notion that social deprivation during the transition from adolescence to adulthood leads to stress and produces anxiety-like behaviors that in turn might affect neurogenesis and contribute to the deleterious consequences of prolonged stressful conditions.

  20. Primate cognition: attention, episodic memory, prospective memory, self-control, and metacognition as examples of cognitive control in nonhuman primates.

    PubMed

    Beran, Michael J; Menzel, Charles R; Parrish, Audrey E; Perdue, Bonnie M; Sayers, Ken; Smith, J David; Washburn, David A

    2016-09-01

    Primate Cognition is the study of cognitive processes, which represent internal mental processes involved in discriminations, decisions, and behaviors of humans and other primate species. Cognitive control involves executive and regulatory processes that allocate attention, manipulate and evaluate available information (and, when necessary, seek additional information), remember past experiences to plan future behaviors, and deal with distraction and impulsivity when they are threats to goal achievement. Areas of research that relate to cognitive control as it is assessed across species include executive attention, episodic memory, prospective memory, metacognition, and self-control. Executive attention refers to the ability to control what sensory stimuli one attends to and how one regulates responses to those stimuli, especially in cases of conflict. Episodic memory refers to memory for personally experienced, autobiographical events. Prospective memory refers to the formation and implementation of future-intended actions, such as remembering what needs to be done later. Metacognition consists of control and monitoring processes that allow individuals to assess what information they have and what information they still need, and then if necessary to seek information. Self-control is a regulatory process whereby individuals forego more immediate or easier to obtain rewards for more delayed or harder to obtain rewards that are objectively more valuable. The behavioral complexity shown by nonhuman primates when given tests to assess these capacities indicates psychological continuities with human cognitive control capacities. However, more research is needed to clarify the proper interpretation of these behaviors with regard to possible cognitive constructs that may underlie such behaviors. WIREs Cogn Sci 2016, 7:294-316. doi: 10.1002/wcs.1397 For further resources related to this article, please visit the WIREs website. PMID:27284790

  1. Primate cognition: attention, episodic memory, prospective memory, self-control, and metacognition as examples of cognitive control in nonhuman primates.

    PubMed

    Beran, Michael J; Menzel, Charles R; Parrish, Audrey E; Perdue, Bonnie M; Sayers, Ken; Smith, J David; Washburn, David A

    2016-09-01

    Primate Cognition is the study of cognitive processes, which represent internal mental processes involved in discriminations, decisions, and behaviors of humans and other primate species. Cognitive control involves executive and regulatory processes that allocate attention, manipulate and evaluate available information (and, when necessary, seek additional information), remember past experiences to plan future behaviors, and deal with distraction and impulsivity when they are threats to goal achievement. Areas of research that relate to cognitive control as it is assessed across species include executive attention, episodic memory, prospective memory, metacognition, and self-control. Executive attention refers to the ability to control what sensory stimuli one attends to and how one regulates responses to those stimuli, especially in cases of conflict. Episodic memory refers to memory for personally experienced, autobiographical events. Prospective memory refers to the formation and implementation of future-intended actions, such as remembering what needs to be done later. Metacognition consists of control and monitoring processes that allow individuals to assess what information they have and what information they still need, and then if necessary to seek information. Self-control is a regulatory process whereby individuals forego more immediate or easier to obtain rewards for more delayed or harder to obtain rewards that are objectively more valuable. The behavioral complexity shown by nonhuman primates when given tests to assess these capacities indicates psychological continuities with human cognitive control capacities. However, more research is needed to clarify the proper interpretation of these behaviors with regard to possible cognitive constructs that may underlie such behaviors. WIREs Cogn Sci 2016, 7:294-316. doi: 10.1002/wcs.1397 For further resources related to this article, please visit the WIREs website.

  2. Stress, the HPA axis, and nonhuman primate well-being: A review

    PubMed Central

    Novak, Melinda A.; Hamel, Amanda F.; Kelly, Brian J.; Dettmer, Amanda M.; Meyer, Jerrold S.

    2012-01-01

    Numerous stressors are routinely encountered by wild-living primates (e.g., food scarcity, predation, aggressive interactions, and parasitism). Although many of these stressors are eliminated in laboratory environments, other stressors may be present in that access to space and social partners is often restricted. Stress affects many physiological systems including the hypothalamic-pituitary-adrenocortical (HPA) axis, which is the focus of this review. The glucocorticoid, cortisol, is the ultimate output of this system in nonhuman primates, and levels of this hormone are used as an index of stress. Researchers can measure cortisol from several sampling matrices that include blood, saliva, urine, faeces, and hair. A comparison of the advantages and disadvantages of each sampling matrix is provided to aid researchers in selecting an optimal strategy for their research. Stress and its relationship to welfare have been examined in nonhuman primates using two complimentary approaches: comparing baseline cortisol levels under different conditions, or determining the reactivity of the system through exposure to a stressor. Much of this work is focused on colony management practices and developmental models of abnormal behaviour. Certain colony practices are known to increase stress at least temporarily. Both blood sampling and relocation are examples of this effect, and efforts have been made to reduce some of the more stressful aspects of these procedures. In contrast, other colony management practices such as social housing and environmental enrichment are hypothesized to reduce stress. Testing this hypothesis by comparing baseline cortisol levels has not proved useful, probably due to “floor” effects; however, social buffering studies have shown the powerful role of social housing in mitigating reactions of nonhuman primates to stressful events. Models of abnormal behaviour come from two sources: experimentally induced alterations in early experience (e.g., nursery

  3. Comparative studies on the topical administration of mucopolysaccharide and heparin ointments in nonhuman primates.

    PubMed

    Hoppensteadt, Debra A; Neville, Brian; Schultz, Christopher; Jeske, Walter; Raake, Wolfram; Fareed, Jawed

    2010-02-01

    Mucopolysaccharide polysulfate (MPS) represents a mammalian-derived sulfated polysaccharide. Because the origin and structure of heparins is similar to MPS, this study was conducted to compare 2 ointment formulations containing MPS or heparin with a placebo ointment on tissue factor pathway inhibitor (TFPI) released in nonhuman primates (Macaca mulatta). A primate colony composed of 18 animals, housed at Loyola University Medical Center, was used in compliance with an Institutional Animal Care and Use Committee (IACUC)-approved protocol. Mucopolysaccharide polysulfate (4.5%), heparin (4.5%), and a placebo ointment were topically applied to individual groups of primates in a crossover study for periods of up to 2 weeks. Blood samples were drawn on days 1, 2, 5, 7, and 10. The anticoagulant effects (activated partial thromboplastin time [APTT], Heptest, thrombin time [TT]), TFPI antigen and functional levels, thrombin activatable fibrinolytic inhibitor (TAFI), and antiheparin platelet factor 4 antibodies (AHPF4 abs) were measured in citrated plasma. All data were compiled as mean +/- 1 standard deviation and compared in groups. Topical administration of both the MPS and heparin ointments resulted in no measurable anticoagulant effects in the primate model; however, MPS produced a concentration-dependent release of TFPI antigen and a functional activity that was stronger than the effects observed with heparin. A decrease in TAFI activation was also observed in the MPS-treated primates. In addition, in the heparin-treated group, a slight increase in AHPF4 abs was observed. In conclusion, MPS showed a stronger release of TFPI than heparin that was not associated with a strong anticoagulant effect. Moreover, MPS downregulated TAFI, resulting in an enhanced fibrinolytic effect.

  4. Nicotinic receptors in non-human primates: Analysis of genetic and functional conservation with humans.

    PubMed

    Shorey-Kendrick, Lyndsey E; Ford, Matthew M; Allen, Daicia C; Kuryatov, Alexander; Lindstrom, Jon; Wilhelm, Larry; Grant, Kathleen A; Spindel, Eliot R

    2015-09-01

    Nicotinic acetylcholine receptors (nAChRs) are highly conserved between humans and non-human primates. Conservation exists at the level of genomic structure, protein structure and epigenetics. Overall homology of nAChRs at the protein level is 98% in macaques versus 89% in mice, which is highly relevant for evaluating subtype-specific ligands that have different affinities in humans versus rodents. In addition to conservation at the protein level, there is high conservation of genomic structure in terms of intron and exon size and placement of CpG sites that play a key role in epigenetic regulation. Analysis of single nucleotide polymorphisms (SNPs) shows that while the majority of SNPs are not conserved between humans and macaques, some functional polymorphisms are. Most significantly, cynomolgus monkeys express a similar α5 nAChR Asp398Asn polymorphism to the human α5 Asp398Asn polymorphism that has been linked to greater nicotine addiction and smoking related disease. Monkeys can be trained to readily self-administer nicotine, and in an initial study we have demonstrated that cynomolgus monkeys bearing the α5 D398N polymorphism show a reduced behavioral sensitivity to oral nicotine and tend to consume it in a different pattern when compared to wild-type monkeys. Thus the combination of highly homologous nAChR, higher cortical functions and capacity for complex training makes non-human primates a unique model to study in vivo functions of nicotinic receptors. In particular, primate studies on nicotine addiction and evaluation of therapies to prevent or overcome nicotine addiction are likely to be highly predictive of treatment outcomes in humans. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. PMID:25661700

  5. Models of stress in nonhuman primates and their relevance for human psychopathology and endocrine dysfunction.

    PubMed

    Meyer, Jerrold S; Hamel, Amanda F

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction.

  6. Models of stress in nonhuman primates and their relevance for human psychopathology and endocrine dysfunction.

    PubMed

    Meyer, Jerrold S; Hamel, Amanda F

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction. PMID:25225311

  7. Nicotinic receptors in non-human primates: analysis of genetic and functional conservation with humans

    PubMed Central

    Shorey-Kendrick, Lyndsey E.; Ford, Matthew M.; Allen, Daicia C.; Kuryatov, Alexander; Lindstrom, Jon; Wilhelm, Larry; Grant, Kathleen A.; Spindel, Eliot R.

    2015-01-01

    Nicotinic acetylcholine receptors (nAChRs) are highly conserved between humans and non-human primates. Conservation exists at the level of genomic structure, protein structure and epigenetics. Overall homology of nAChRs at the protein level is 98% in macaques versus 89% in mice, which is highly relevant for evaluating subtype-specific ligands that have different affinities in humans versus rodents. In addition to conservation at the protein level, there is high conservation of genomic structure in terms of intron and exon size and placement of CpG sites that play a key role in epigenetic regulation. Analysis of single nucleotide polymorphisms (SNPs) shows that while the majority of SNPs are not conserved between humans and macaques, some functional polymorphisms are. Most significantly, cynomolgus monkeys express a similar α5 nAChR Asp398Asn polymorphism to the human α5 Asp398Asn polymorphism that has been linked to greater nicotine addiction and smoking related disease. Monkeys can be trained to readily self-administer nicotine, and in an initial study we have demonstrated that cynomolgus monkeys bearing the α5 D398N polymorphism show a reduced behavioral sensitivity to oral nicotine and tend to consume it in a different pattern when compared to wild-type monkeys. Thus the combination of highly homologous nAChR, higher cortical functions and capacity for complex training makes non-human primates a unique model to study in vivo functions of nicotinic receptors. In particular, primate studies on nicotine addiction and evaluation of therapies to prevent or overcome nicotine addiction are likely to be highly predictive of treatment outcomes in humans. PMID:25661700

  8. Models of Stress in Nonhuman Primates and Their Relevance for Human Psychopathology and Endocrine Dysfunction

    PubMed Central

    Meyer, Jerrold S.; Hamel, Amanda F.

    2014-01-01

    Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction. PMID:25225311

  9. The non-human primate reference transcriptome resource (NHPRTR) for comparative functional genomics

    PubMed Central

    Pipes, Lenore; Li, Sheng; Bozinoski, Marjan; Palermo, Robert; Peng, Xinxia; Blood, Phillip; Kelly, Sara; Weiss, Jeffrey M.; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Zumbo, Paul; Chen, Ronghua; Schroth, Gary P.; Mason, Christopher E.; Katze, Michael G.

    2013-01-01

    RNA-based next-generation sequencing (RNA-Seq) provides a tremendous amount of new information regarding gene and transcript structure, expression and regulation. This is particularly true for non-coding RNAs where whole transcriptome analyses have revealed that the much of the genome is transcribed and that many non-coding transcripts have widespread functionality. However, uniform resources for raw, cleaned and processed RNA-Seq data are sparse for most organisms and this is especially true for non-human primates (NHPs). Here, we describe a large-scale RNA-Seq data and analysis infrastructure, the NHP reference transcriptome resource (http://nhprtr.org); it presently hosts data from12 species of primates, to be expanded to 15 species/subspecies spanning great apes, old world monkeys, new world monkeys and prosimians. Data are collected for each species using pools of RNA from comparable tissues. We provide data access in advance of its deposition at NCBI, as well as browsable tracks of alignments against the human genome using the UCSC genome browser. This resource will continue to host additional RNA-Seq data, alignments and assemblies as they are generated over the coming years and provide a key resource for the annotation of NHP genomes as well as informing primate studies on evolution, reproduction, infection, immunity and pharmacology. PMID:23203872

  10. Simian foamy virus in non-human primates and cross-species transmission to humans in Gabon: an emerging zoonotic disease in central Africa?

    PubMed

    Mouinga-Ondémé, Augustin; Kazanji, Mirdad

    2013-06-19

    It is now known that all human retroviruses have a non-human primate counterpart. It has been reported that the presence of these retroviruses in humans is the result of interspecies transmission. Several authors have described the passage of a simian retrovirus, simian foamy virus (SFV), from primates to humans. To better understand this retroviral "zoonosis" in natural settings, we evaluated the presence of SFV in both captive and wild non-human primates and in humans at high risk, such as hunters and people bitten by a non-human primate, in Gabon, central Africa. A high prevalence of SFV was found in blood samples from non-human primates and in bush meat collected across the country. Mandrills were found to be highly infected with two distinct strains of SFV, depending on their geographical location. Furthermore, samples collected from hunters and non-human primate laboratory workers showed clear, extensive cross-species transmission of SFV. People who had been bitten by mandrills, gorillas and chimpanzees had persistent SFV infection with low genetic drift. Thus, SFV is presumed to be transmitted from non-human primates mainly through severe bites, involving contact between infected saliva and blood. In this review, we summarize and discuss our five-year observations on the prevalence and dissemination of SFV in humans and non-human primates in Gabon.

  11. Absence of mutations associated with sulfa resistance in Pneumocystis carinii dihydropteroate synthase gene from non-human primates.

    PubMed

    Demanche, C; Guillot, J; Berthelemy, M; Petitt, T; Roux, P; Wakefield, A E

    2002-06-01

    The dihydropteroate synthase (DHPS) gene from Pneumocystis carinii isolated from non-human primates was amplified using a polymerase chain reaction (PCR) and sequenced to analyse point mutations associated with sulfa resistance. P. carinii DHPS gene amplification was obtained from eight lung samples from five New World primate species and one Old World primate species. None of the animals had been exposed to sulfa drugs and only the wild-type P. carinii DHPS sequence at codons 55 and 57 was observed. These data support the hypothesis that high rates of DHPS mutants in P. carinii f. sp. hominis have arisen with increased use of sulfa drugs for P. carinii pneumonia prophylaxis.

  12. Neurochemistry Study of Spinal Cord in Non-Human Primate (Sapajus Spp.)

    PubMed Central

    Torres-da-Silva, K.R.; da Silva, A.V.; Barioni, N.O.; Tessarin, G.W.L.; de Oliveira, J.A.; Ervolino, E.; Horta-Júnior, J.A.C.; Casatti, C.A.

    2016-01-01

    The spinal cord is involved in local, ascending and descending neural pathways. Few studies analyzed the distribution of neuromediators in the laminae of non-human primates along all segments. The present study described the classic neuromediators in the spinal cord of the non-human primate Sapajus spp. through histochemical and immunohistochemical methods. Nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) method showed neuronal somata in the intermediolateral column (IML), central cervical nucleus (CCN), laminae I, II, III, IV, V, VI, VII, VIII and X, besides dense presence of nerve fibers in laminae II and IX. Acetylcholinesterase (AChE) activity was evident in the neuronal somata in laminae V, VI, VII, VIII, IX, CCN, IML and in the Clarke’s column (CC). Immunohistochemistry data revealed neuronal nitric oxide synthase (nNOS) immunoreactivity in neuronal somata and in fibers of laminae I, II, III, VII, VIII, X and IML; choline acetyltransferase (ChAT) in neuronal somata and in fibers of laminae VII, VIII and IX; calcitonin gene-related peptide (CGRP) was noticed in neuronal somata of lamina IX and in nerve fibers of laminae I, II, III, IV, V, VI and VII; substance P (SP) in nerve fibers of laminae I, II, III, IV, V, VI, VII, VIII, IX, X, CCN, CC and IML; serotonin (5-HT) and vesicular glutamate transporter-1 (VGLUT1) was noticed in nerve fibers of all laminae; somatostatin (SOM) in neuronal somata of laminae III, IV, V, VI, VII, VIII and IX and nerve fibers in laminae I, II, V, VI, VII, X and IML; calbindin (Cb) in neuronal somata of laminae I, II, VI, VII, IX and X; parvalbumin (PV) was found in neuronal somata and in nerve fibers of laminae III, IV, V, VI, VII, VIII, IX and CC; finally, gamma-amino butyric acid (GABA) was present in neuronal somata of laminae V, VI, VII, VIII, IX and X. This study revealed interesting results concerning the chemoarchitecture of the Sapajus spp. spinal cord with a distribution pattern mostly similar to

  13. Personality in nonhuman primates: a review and evaluation of past research.

    PubMed

    Freeman, Hani D; Gosling, Samuel D

    2010-08-01

    Scientific reports of personality in nonhuman primates are now appearing with increasing frequency across a wide range of disciplines, including psychology, anthropology, endocrinology, and zoo management. To identify general patterns of research and summarize the major findings to date, we present a comprehensive review of the literature, allowing us to pinpoint the major gaps in knowledge and determine what research challenges lay ahead. An exhaustive search of five scientific databases identified 210 relevant research reports. These articles began to appear in the 1930s, but it was not until the 1980s that research on primate personality began to gather pace, with more than 100 articles published in the last decade. Our analyses of the literature indicate that some domains (e.g., sex, age, rearing conditions) are more evenly represented in the literature than are others (e.g., species, research location). Studies examining personality structure (e.g., with factor analysis) have identified personality dimensions that can be divided into 14 broad categories, with Sociability, Confidence/Aggression, and Fearfulness receiving the most research attention. Analyses of the findings pertaining to inter-rater agreement, internal consistency, test-retest reliability, generally support not only the reliability of primate personality ratings scales but also point to the need for more psychometric studies and greater consistency in how the analyses are reported. When measured at the level of broad dimensions, Extraversion and Dominance generally demonstrated the highest levels of inter-rater reliability, with weaker findings for the dimensions of Agreeableness, Emotionality, and Conscientiousness. Few studies provided data with regard to convergent and discriminant validity; Excitability and Dominance demonstrated the strongest validity coefficients when validated against relevant behavioral criterion measures. Overall, the validity data present a somewhat mixed picture

  14. 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

  15. Reward and decision processes in the brains of humans and nonhuman primates.

    PubMed

    Sirigu, Angela; Duhamel, Jean-René

    2016-03-01

    Choice behavior requires weighing multiple decision variables, such as utility, uncertainty, delay, or effort, that combine to define a subjective value for each considered option or course of action. This capacity is based on prior learning about potential rewards (and punishments) that result from prior actions. When made in a social context, decisions can involve strategic thinking about the intentions of others and about the impact of others' behavior on one's own outcome. Valuation is also influenced by different emotions that serve to adaptively regulate our choices in order to, for example, stay away from excessively risky gambles, prevent future regrets, or avoid personal rejection or conflicts. Drawing on economic theory and on advances in the study of neuronal mechanisms, we review relevant recent experiments in nonhuman primates and clinical observations made in neurologically impaired patients suffering from impaired decision-making capacities. PMID:27069379

  16. Reward and decision processes in the brains of humans and nonhuman primates

    PubMed Central

    Sirigu, Angela; Duhamel, Jean-René

    2016-01-01

    Choice behavior requires weighing multiple decision variables, such as utility, uncertainty, delay, or effort, that combine to define a subjective value for each considered option or course of action. This capacity is based on prior learning about potential rewards (and punishments) that result from prior actions. When made in a social context, decisions can involve strategic thinking about the intentions of others and about the impact of others' behavior on one's own outcome. Valuation is also influenced by different emotions that serve to adaptively regulate our choices in order to, for example, stay away from excessively risky gambles, prevent future regrets, or avoid personal rejection or conflicts. Drawing on economic theory and on advances in the study of neuronal mechanisms, we review relevant recent experiments in nonhuman primates and clinical observations made in neurologically impaired patients suffering from impaired decision-making capacities. PMID:27069379

  17. Protection of non-human primates against rabies with an adenovirus recombinant vaccine

    SciTech Connect

    Xiang, Z.Q.; Greenberg, L.; Ertl, H.C.; Rupprecht, C.E.

    2014-02-15

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.

  18. Evaluation of a Burkholderia pseudomallei Outer Membrane Vesicle Vaccine in Nonhuman Primates.

    PubMed

    Petersen, Hailey; Nieves, Wildaliz; Russell-Lodrigue, Kasi; Roy, Chad J; Morici, Lisa A

    2014-01-01

    Burkholderia pseudomallei (Bps)is the causative agent of melioidosis and is endemic in regions of northern Australia and Southeast Asia. Bps is inherently resistant to multiple antibiotics and is considered a potential biological warfare agent by the U.S. DHHS. Therefore, effective vaccines are necessary to prevent natural infection and to safeguard against biological attack with this organism. In our previous work we have shown that immunization with naturally derived outer membrane vesicles (OMVs) from Bps provides significant protection against lethal aerosol and systemic infection in BALB/c mice. In this work, we evaluated the safety and immunogenicity of escalating doses of OMV vaccine in rhesus macaques. We show that immunization of rhesus macaques with Bps OMVs generates humoral immuneresponses to protective protein and polysaccharide antigens without any associated toxicity or reactogenicity. These results lay the groundwork for evaluation of protective efficacy of the OMV vaccine in the nonhuman primate model of melioidosis.

  19. Evaluation of a Burkholderia pseudomallei Outer Membrane Vesicle Vaccine in Nonhuman Primates

    PubMed Central

    Petersen, Hailey; Nieves, Wildaliz; Russell-Lodrigue, Kasi; Roy, Chad J.; Morici, Lisa A.

    2014-01-01

    Burkholderia pseudomallei (Bps)is the causative agent of melioidosis and is endemic in regions of northern Australia and Southeast Asia. Bps is inherently resistant to multiple antibiotics and is considered a potential biological warfare agent by the U.S. DHHS. Therefore, effective vaccines are necessary to prevent natural infection and to safeguard against biological attack with this organism. In our previous work we have shown that immunization with naturally derived outer membrane vesicles (OMVs) from Bps provides significant protection against lethal aerosol and systemic infection in BALB/c mice. In this work, we evaluated the safety and immunogenicity of escalating doses of OMV vaccine in rhesus macaques. We show that immunization of rhesus macaques with Bps OMVs generates humoral immuneresponses to protective protein and polysaccharide antigens without any associated toxicity or reactogenicity. These results lay the groundwork for evaluation of protective efficacy of the OMV vaccine in the nonhuman primate model of melioidosis. PMID:25165491

  20. Spontaneous lesions in the reproductive tract and mammary gland of female non-human primates.

    PubMed

    Cooper, Timothy K; Gabrielson, Kathleen L

    2007-04-01

    Because of their close phylogenic relationship with humans, the use of non-human primates (NHP) as experimental subjects has a long history in biomedical research. Although research topics have shifted focus and species used have changed, NHP remain vital as models in basic and applied research. While there is a wealth of information available on the spontaneous lesions of NHP, most of this information is fragmented, dated, or narrow in focus, often limited to single case reports. This review attempts to integrate this information to illustrate and enumerate the spectrum of spontaneous pathology of the reproductive tract and mammary gland of NHP. Although not the focus of this review, steroid-related changes are inextricably linked to these tissues, and brief consideration is given to this subject as well. PMID:17342758

  1. In vivo whole brain, cellular and molecular imaging in nonhuman primate models of neuropathology.

    PubMed

    Huang, Lieven; Merson, Tobias D; Bourne, James A

    2016-07-01

    Rodents have been the principal model to study brain anatomy and function due to their well-mapped brain architecture, rapid reproduction and amenability to genetic modification. However, there are clear limitations, for example their simpler neocortex, necessitating the need to adopt a model that is closer to humans in order to understand human cognition and brain conditions. Nonhuman primates (NHPs) are ideally suited as they are our closest relatives in the animal kingdom but in vivo imaging technologies to study brain structure and function in these species can be challenging. With the surge in NHP research in recent years, scientists have begun adapting imaging technologies, such as two-photon microscopy, for these species. Here we review the various NHP models that exist as well as their use in advanced microscopic and mesoscopic studies. We discuss the challenges in the field and investigate the opportunities that lie ahead. PMID:27151822

  2. Does the mastery of center-embedded linguistic structures distinguish humans from nonhuman primates?

    PubMed

    Perruchet, Pierre; Rey, Arnaud

    2005-04-01

    In a recent Science article, Fitch and Hauser (2004; hereafter, F&H) claimed to have demonstrated that cotton-top tamarins fail to learn an artificial language produced by a phrase structure grammar (Chomsky, 1957) generating center-embedded sentences, whereas adult humans easily learn such a language. We report an experiment replicating the results of F&H in humans but also showing that subjects learned the language without exploiting in any way the center-embedded structure. When the procedure was modified to make the processing of this structure mandatory, the subjects no longer showed evidence of learning. We propose a simple interpretation for the difference in performance observed in F&H's task between humans and tamarins and argue that, beyond the specific drawbacks inherent in F&H's study, researching the source of the inability of nonhuman primates to master language within a framework built around Chomsky's hierarchy of grammars is a conceptual dead end. PMID:16082811

  3. Residual effects of polychlorinated biphenyls on adult nonhuman primates and their offspring

    SciTech Connect

    Allen, J.R.; Barsotti, D.A.; Carstens, L.A.

    1980-01-01

    After 18 months of consuming a diet containing 2.5 and 5.0 ppM PCB (Aroclor 1248), during which they and their offspring experienced marked alterations in physical status, female rhesus monkeys were placed on a control diet for 1 y. During this year there was a decided improvement in their general body health and reproductive capabilities. Infants born to these animals were small at birth and during their postnatal life developed signs of PCB intoxication similar to those observed in their siblings born during the period of PCB exposure. These data indicate that the residual effects of low-level ingestion of PCBs by nonhuman primates persist for over 1 y after discontinuation of exposure. There are also indications that the fetal and neonatal monkeys born to PCB-exposed mothers are more severely affected for a longer period than are the adult female monkeys.

  4. Reward and decision processes in the brains of humans and nonhuman primates.

    PubMed

    Sirigu, Angela; Duhamel, Jean-René

    2016-03-01

    Choice behavior requires weighing multiple decision variables, such as utility, uncertainty, delay, or effort, that combine to define a subjective value for each considered option or course of action. This capacity is based on prior learning about potential rewards (and punishments) that result from prior actions. When made in a social context, decisions can involve strategic thinking about the intentions of others and about the impact of others' behavior on one's own outcome. Valuation is also influenced by different emotions that serve to adaptively regulate our choices in order to, for example, stay away from excessively risky gambles, prevent future regrets, or avoid personal rejection or conflicts. Drawing on economic theory and on advances in the study of neuronal mechanisms, we review relevant recent experiments in nonhuman primates and clinical observations made in neurologically impaired patients suffering from impaired decision-making capacities.

  5. Functional definitions of parietal areas in human and non-human primates

    PubMed Central

    Orban, Guy A.

    2016-01-01

    Establishing homologies between cortical areas in animal models and humans lies at the heart of translational neuroscience, as it demonstrates how knowledge obtained from these models can be applied to the human brain. Here, we review progress in using parallel functional imaging to ascertain homologies between parietal areas of human and non-human primates, species sharing similar behavioural repertoires. The human homologues of several areas along monkey IPS involved in action planning and observation, such as AIP, LIP and CIP, as well as those of opercular areas (SII complex), have been defined. In addition, uniquely human areas, such as the tool-use area in left anterior supramarginal gyrus, have also been identified. PMID:27053755

  6. Brains, innovations, tools and cultural transmission in birds, non-human primates, and fossil hominins

    PubMed Central

    Lefebvre, Louis

    2013-01-01

    Recent work on birds and non-human primates has shown that taxonomic differences in field measures of innovation, tool use and social learning are associated with size of the mammalian cortex and avian mesopallium and nidopallium, as well as ecological traits like colonization success. Here, I review this literature and suggest that many of its findings are relevant to hominin intelligence. In particular, our large brains and increased intelligence may be partly independent of our ape phylogeny and the result of convergent processes similar to those that have molded avian and platyrrhine intelligence. Tool use, innovativeness and cultural transmission might be linked over our past and in our brains as operations of domain-general intelligence. Finally, colonization of new areas may have accompanied increases in both brain size and innovativeness in hominins as they have in other mammals and in birds, potentially accelerating hominin evolution via behavioral drive. PMID:23761751

  7. Effects of 60 Hz electrical fields on operant and social stress behaviors of nonhuman primates: Summary

    SciTech Connect

    Rogers, W.R.; Coelho, A.M. Jr.; Easley, S.P.; Orr, J.L.

    1988-04-06

    The objective of this program is to investigate, using the baboon as a nonhuman primate surrogate for the human, behavioral effects associated with exposure to 60-Hz electric fields. Results from this program, along with information from experiments conducted elsewhere, could be used to estimate and evaluate the likelihood of deleterious consequences resulting from exposure of humans to the electric fields associated with power transmission over high voltage lines. This program is being conducted at Southwest Research Institute as part of an international collaborative information exchange and scientific research effort involving the United State Department of Energy, Japan's Ministry of International Trade and Industry, and Japan's Central Research Institute of the Electric Power Industry. Since August of 1984, four major research projects were successfully completed. 48 refs., 12 figs., 2 tabs.

  8. Abstract Knowledge in the Broken-String Problem: Evidence from Nonhuman Primates and Pre-Schoolers

    PubMed Central

    Mayer, Carolina; Call, Josep; Albiach-Serrano, Anna; Visalberghi, Elisabetta; Sabbatini, Gloria; Seed, Amanda

    2014-01-01

    There is still large controversy about whether abstract knowledge of physical problems is uniquely human. We presented 9 capuchin monkeys, 6 bonobos, 6 chimpanzees and 48 children with two versions of a broken-string problem. In the standard condition, participants had to choose between an intact and a broken string as means to a reward. In the critical condition, the functional parts of the strings were covered up and replaced by perceptually similar, but non-functional cues. Apes, monkeys and young children performed significantly better in the standard condition in which the cues played a functional role, indicating knowledge of the functional properties involved. Moreover, a control experiment with chimpanzees and young children ruled out that this difference in performance could be accounted for by differences of perceptual feedback in the two conditions. We suggest that, similar to humans, nonhuman primates partly rely on abstract concepts in physical problem-solving. PMID:25272161

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

    PubMed

    Riley, Erin P; Priston, Nancy E C

    2010-09-01

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

  10. Nonhuman primate models of encephalitic alphavirus infection: historical review and future perspectives.

    PubMed

    Dupuy, Lesley C; Reed, Douglas S

    2012-06-01

    Venezuelan, western, and eastern equine encephalitis viruses are New World alphaviruses that are recognized as potential agents of biowarfare and bioterrorism owing to their morbidity and mortality in humans, ease of production, considerable stability, and high infectivity in aerosols. As a result, these encephalitic alphaviruses are defined as category B select agents. Studies involving infection of nonhuman primates have been instrumental in gaining an understanding of the in vivo pathogenesis of these viruses and have provided relevant models to evaluate the efficacy of candidate human vaccines. Recent advances have led to refinement and further characterization of these models toward the goal of utility in the licensure of next-generation alphavirus vaccines and therapeutics for use in humans by the Animal Rule. PMID:22709522

  11. An enhanced model of middle cerebral artery occlusion in nonhuman primates using an endovascular trapping technique

    PubMed Central

    Tong, Frank C.; Zhang, Xiaodong; Kempf, Doty J.; Yepes, Manuel S.; Connor-Stroud, Fawn R.; Zola, Stuart; Howell, Leonard

    2015-01-01

    Background and Purpose Current nonhuman primate stroke models are limited by either stroke variability or survivability. A new nonhuman primate stroke model was developed using endovascular trapping techniques to limit collateral vessels with serial MRI and neurological assessments. Methods Eight adult rhesus monkeys (female, 7–13 years old) underwent MRI scanning and Spetzler neurological assessment followed by endovascular stroke induction consisting of superselective endovascular placement of surgical silk suture into the right MCA using a trapping technique. Two initial subjects were euthanized immediately following post occlusion MRI scanning. The subsequent six subjects were recovered and underwent follow up MRI and Spetzler neurological assessments at 48 hours, with four being followed to 96 hours. Stroke infarct volumes were measured and the longitudinal Spetzler clinical neurological scores were assessed. The brain tissues were harvested and prepared with H&E staining. Results Focal permanent cerebral ischemia was induced in the targeted right MCA territory in all subjects. The volumes of the ischemic lesions at 6, 48 and 96-hours were 3.18 cc +/− 1.007 SEM (n=8), 6.70 +/− 1.666 SEM (n=6), and 7.23 +/− 1.371 SEM (n=4). For the survival animals, the immediate post surgical Spetzler Grading score improved from 60.7 at 24 hours to 68.7 at 48 hours. Conclusion We report a trapping modification to an established endovascular suture stroke model that yielded reproducible ischemia and clinically quantifiable neurological deficits with no strokes in non-target areas. This technique may be useful in evaluating translational stroke and penumbral imaging research in addition to preclinical testing of neuroprotective therapies. PMID:26381560

  12. Study of the gastrointestinal parasitic fauna of captive non-human primates (Macaca fascicularis).

    PubMed

    Zanzani, Sergio Aurelio; Gazzonis, Alessia Libera; Epis, Sara; Manfredi, Maria Teresa

    2016-01-01

    The aim of this study was to examine helminths and protozoans in cynomolgus macaques (Macaca fascicularis) imported from registered breeding facilities in China and their relation to health risks for non-human primate handlers in biomedical research centers and in breeding facilities. Fresh fecal samples were collected from a total of 443 M. fascicularis and analyzed by copromicroscopical analysis, immunoenzymatic, or molecular assays. As to helminths, whose eggs were shed in 2.03% of the samples, Trichuris and Oesophagostomum were the only two taxa found, with low prevalence and low eggs per gram (EPG) values. Protozoans were more frequently detected (87.40%), with Entamoeba coli (85.19%) and Endolimax nana (79.26%) as the most prevalent species shed. Other parasites found by fecal smear examination were uninucleated-cyst-producing Entamoebas (78.52%), Iodamoeba bütschlii (42.96%), and Chilomastix mesnili (24.44%), while cysts of Balantidium coli (22.2%) were only observed by sedimentation. No coproantigens of Giardia duodenalis, Cryptosporidium spp., and Entamoeba histolytica complex were detected. Blastocystis sp. infection was noticed in 87.63% of macaques by PCR. These cynomolgus monkeys were infected with many subtypes (ST1, ST2, ST3, ST5, and ST7), where the predominant Blastocystis sp. subtypes were ST2 (77.5%), followed by ST1 (63.5%). Data collected confirmed the presence of potentially zoonotic parasites and a high parasite diversity, suggesting the need for appropriate and sensitive techniques to adequately control them and related health risks for handlers of non-human primates in biomedical research centers and in breeding facilities. PMID:26374536

  13. Utility of cerebrospinal fluid drug concentration as a surrogate for unbound brain concentration in nonhuman primates.

    PubMed

    Nagaya, Yoko; Nozaki, Yoshitane; Kobayashi, Kazumasa; Takenaka, Osamu; Nakatani, Yosuke; Kusano, Kazutomi; Yoshimura, Tsutomu; Kusuhara, Hiroyuki

    2014-01-01

    In central nervous system drug discovery, cerebrospinal fluid (CSF) drug concentration (C(CSF)) has been widely used as a surrogate for unbound brain concentrations (C(u,brain)). However, previous rodent studies demonstrated that when drugs undergo active efflux by transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier, the C(CSF) overestimates the corresponding C(u,brain). To investigate the utility of C(CSF) as a surrogate for interstitial fluid (ISF) concentration (C(ISF)) in nonhuman primates, this study simultaneously determined the C(CSF) and C(ISF) of 12 compounds, including P-gp substrates, under steady-state conditions in cynomolgus monkeys using intracerebral microdialysis coupled with cisternal CSF sampling. Unbound plasma concentrations of non- or weak P-gp substrates were within 2.2-fold of the C(ISF) or C(CSF), whereas typical P-gp substrates (risperidone, verapamil, desloratadine, and quinidine) showed ISF-to-plasma unbound (K(p,uu,ISF)) and CSF-to-plasma unbound concentration ratios (K(p,uu,CSF)) that were appreciably lower than unity. Although the K(p,uu,CSF) of quinidine, verapamil, and desloratadine showed a trend of overestimating the K(p,uu,ISF), K(p,uu,CSF) showed a good agreement with K(p,uu,ISF) within 3-fold variations for all compounds examined. C(u,brain) of some basic compounds, as determined using brain homogenates, overestimated the C(ISF) and C(CSF). Therefore, C(CSF) could be used as a surrogate for C(ISF) in nonhuman primates.

  14. Oral administration of 3,4-methylenedioxymethamphetamine (MDMA) produces selective serotonergic depletion in the nonhuman primate.

    PubMed

    Ali, S F; Newport, G D; Scallet, A C; Binienda, Z; Ferguson, S A; Bailey, J R; Paule, M G; Slikker, W

    1993-01-01

    MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and home cage behavior as endpoints. Adult female rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors were measured in the home cage prior to, during, and after MDMA treatment. One month after the last dose, the animals were sacrificed and brains dissected into several regions for neurochemical analyses. 5-HT and 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations in any brain region except hippocampus in which 5-HT concentrations were decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decreased 5-HT and 5-HIAA concentrations in several cortical and midbrain structures. However, 5-HT and 5-HIAA concentrations in brain stem and hypothalamus were not significantly altered after any dose of MDMA. Combined with previous data from this laboratory, these results indicate that the decreased concentrations of 5-HT and 5-HIAA in selected brain regions show a selective dose-response relationship for MDMA-induced neurotoxicity as measured by serotonergic depletion in the nonhuman primate. PMID:7685472

  15. A novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.

    PubMed

    Kramski, Marit; Mätz-Rensing, Kerstin; Stahl-Hennig, Christiane; Kaup, Franz-Josef; Nitsche, Andreas; Pauli, Georg; Ellerbrok, Heinz

    2010-01-01

    The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus).A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1-3 days after onset of symptoms, even when very low infectious viral doses of 5x10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed.We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3x10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.

  16. Hydrogen and Oxygen Isotope Ratios in Body Water and Hair: Modeling Isotope Dynamics in Nonhuman Primates

    PubMed Central

    O’Grady, Shannon P.; Valenzuela, Luciano O.; Remien, Christopher H.; Enright, Lindsey E.; Jorgensen, Matthew J.; Kaplan, Jay R.; Wagner, Janice D.; Cerling, Thure E.; Ehleringer, James R.

    2012-01-01

    The stable isotopic composition of drinking water, diet, and atmospheric oxygen influence the isotopic composition of body water (2H/1H, 18O/16O expressed as δ2H and δ18O). In turn, body water influences the isotopic composition of organic matter in tissues, such as hair and teeth, which are often used to reconstruct historical dietary and movement patterns of animals and humans. Here, we used a nonhuman primate system (Macaca fascicularis) to test the robustness of two different mechanistic stable isotope models: a model to predict the δ2H and δ18O values of body water and a second model to predict the δ2H and δ18O values of hair. In contrast to previous human-based studies, use of nonhuman primates fed controlled diets allowed us to further constrain model parameter values and evaluate model predictions. Both models reliably predicted the δ2H and δ18O values of body water and of hair. Moreover, the isotope data allowed us to better quantify values for two critical variables in the models: the δ2H and δ18O values of gut water and the 18O isotope fractionation associated with a carbonyl oxygen-water interaction in the gut (αow). Our modeling efforts indicated that better predictions for body water and hair isotope values were achieved by making the isotopic composition of gut water approached that of body water. Additionally, the value of αow was 1.0164, in close agreement with the only other previously measured observation (microbial spore cell walls), suggesting robustness of this fractionation factor across different biological systems. PMID:22553163

  17. Attenuation correction for the large non-human primate brain imaging using microPET.

    PubMed

    Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R

    2010-04-21

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a (57)Co transmission point source with a 4% energy window. The optimal energy window for a (68)Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for (57)Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [(18)F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass (57)Co (4% energy window) or (68)Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  18. Attenuation correction for the large non-human primate brain imaging using microPET

    NASA Astrophysics Data System (ADS)

    Naidoo-Variawa, S.; Lehnert, W.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2010-04-01

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57Co transmission point source with a 4% energy window. The optimal energy window for a 68Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [18F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57Co (4% energy window) or 68Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  19. Study of the gastrointestinal parasitic fauna of captive non-human primates (Macaca fascicularis).

    PubMed

    Zanzani, Sergio Aurelio; Gazzonis, Alessia Libera; Epis, Sara; Manfredi, Maria Teresa

    2016-01-01

    The aim of this study was to examine helminths and protozoans in cynomolgus macaques (Macaca fascicularis) imported from registered breeding facilities in China and their relation to health risks for non-human primate handlers in biomedical research centers and in breeding facilities. Fresh fecal samples were collected from a total of 443 M. fascicularis and analyzed by copromicroscopical analysis, immunoenzymatic, or molecular assays. As to helminths, whose eggs were shed in 2.03% of the samples, Trichuris and Oesophagostomum were the only two taxa found, with low prevalence and low eggs per gram (EPG) values. Protozoans were more frequently detected (87.40%), with Entamoeba coli (85.19%) and Endolimax nana (79.26%) as the most prevalent species shed. Other parasites found by fecal smear examination were uninucleated-cyst-producing Entamoebas (78.52%), Iodamoeba bütschlii (42.96%), and Chilomastix mesnili (24.44%), while cysts of Balantidium coli (22.2%) were only observed by sedimentation. No coproantigens of Giardia duodenalis, Cryptosporidium spp., and Entamoeba histolytica complex were detected. Blastocystis sp. infection was noticed in 87.63% of macaques by PCR. These cynomolgus monkeys were infected with many subtypes (ST1, ST2, ST3, ST5, and ST7), where the predominant Blastocystis sp. subtypes were ST2 (77.5%), followed by ST1 (63.5%). Data collected confirmed the presence of potentially zoonotic parasites and a high parasite diversity, suggesting the need for appropriate and sensitive techniques to adequately control them and related health risks for handlers of non-human primates in biomedical research centers and in breeding facilities.

  20. Refractive Power and Biometric Properties of the Nonhuman Primate Isolated Crystalline Lens

    PubMed Central

    Borja, David; Ho, Arthur; Ziebarth, Noel M.; Acosta, Ana Carolina; Arrieta-Quintera, Esdras; Augusteyn, Robert C.; Parel, Jean-Marie

    2010-01-01

    Purpose. To characterize the age dependence of shape, refractive power, and refractive index of isolated lenses from nonhuman primates. Methods. Measurements were performed on ex vivo lenses from cynomolgus monkeys (cyno: n = 120; age, 2.7–14.3 years), rhesus monkeys (n = 61; age, 0.7–13.3 years), and hamadryas baboons (baboon: n = 16; age, 1.7–27.3 years). Lens thickness, diameter, and surface curvatures were measured with an optical comparator. Lens refractive power was measured with a custom optical system based on the Scheiner principle. The refractive contributions of the gradient, the surfaces, and the equivalent refractive index were calculated with optical ray-tracing software. The age dependence of the optical and biometric parameters was assessed. Results. Over the measured age range isolated lens thickness decreased (baboon: −0.04, cyno: −0.05, and rhesus: −0.06 mm/y) and equatorial diameter increased (logarithmically for the baboon and rhesus, and linearly for cyno: 0.07 mm/y). The isolated lens surfaces flattened and the corresponding refractive power from the surfaces decreased with age (−0.33, −0.48, and −0.68 D/y). The isolated lens equivalent refractive index decreased (only significant for the baboon, −0.001 D/y), and as a result the total isolated lens refractive power decreased with age (baboon: −1.26, cyno: −0.97, and rhesus: −1.76 D/y). Conclusions. The age-dependent trends in the optical and biometric properties, growth, and aging, of nonhuman primate lenses are similar to those of the pre-presbyopic human lens. As the lens ages, the decrease in refractive contributions from the gradient refractive index causes a rapid age-dependent decrease in maximally accommodated lens refractive power. PMID:20107174

  1. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts

    PubMed Central

    Chong, James J.H.; Yang, Xiulan; Don, Creighton W.; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M.; Van Biber, Benjamin; Cook, Savannah M.; Palpant, Nathan J; Gantz, Jay; Fugate, James A.; Muskheli, Veronica; Gough, G. Michael; Vogel, Keith W.; Astley, Cliff A.; Hotchkiss, Charlotte E.; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A.; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A.; Murry, Charles E.

    2014-01-01

    Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure 1 by providing human cardiomyocytes to support heart regeneration 2. Studies of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in small animal models have shown favorable effects of this treatment 3–7. It remains unknown, however, whether clinical scale hESC-CMs transplantation is feasible, safe or can provide large-scale myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (>1 billion cells/batch) and cryopreserved with good viability. Using a non-human primate (NHP) model of myocardial ischemia-reperfusion, we show that that cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs generates significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a three-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small animal models 7, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome. PMID:24776797

  2. Perceptual considerations in the use of colored photographic and video stimuli to study nonhuman primate behavior.

    PubMed

    Waitt, Corri; Buchanan-Smith, Hannah M

    2006-11-01

    The use of photographs, slides, computerized images, and video to study behavior is increasingly being employed in nonhuman primates. However, since these mediums have been designed to simulate natural coloration for normal trichromatic human vision, they can fail to reproduce color in meaningful and accurate ways for viewers with different visual systems. Given the range of color perception that exists both across and within different species, it is necessary to consider this variation in order to discern the suitability of these mediums for experimental use. Because of the high degree of visual similarity among humans, Old World monkeys, and apes, the use of photographic and video stimuli should be acceptable in terms of replicating naturalistic coloration and making noticeable color manipulations. However, among New World primates and prosimians, there exists a considerable degree of variation in color perceptual abilities depending on the species, sex, and allelic combination of the animals involved. Therefore, the use of these mediums to study behavior is problematic for these species, and should be done with caution. PMID:17044007

  3. Alternative methods for the use of non-human primates in biomedical research.

    PubMed

    Burm, Saskia M; Prins, Jan-Bas; Langermans, Jan; Bajramovic, Jeffrey J

    2014-01-01

    The experimental use of non-human primates (NHP) in Europe is tightly regulated and is only permitted when there are no alternatives available. As a result, NHP are most often used in late, pre-clinical phases of biomedical research. Although the impetus for scientists, politicians and the general public to replace, reduce and refine NHP in biomedical research is strong, the development of 3Rs technology for NHP poses specific challenges. In February 2014 a workshop on "Alternative methods for the use of NHP in biomedical research" was organized within the international exchange program of EUPRIM-Net II, a European infrastructure initiative that links biomedical primate research centers. The workshop included lectures by key scientists in the field of alternatives as well as by experts from governmental and non-governmental organizations. Furthermore, parallel sessions were organized to stimulate discussion on the challenges of advancing the use of alternative methods for NHP. Subgroups voted on four statements and together composed a list with opportunities and priorities. This report summarizes the presentations that were held, the content of the discussion sessions and concludes with recommendations on 3Rs development for NHP specifically. These include technical, conceptual as well as political topics.

  4. Positive reinforcement training as a technique to alter nonhuman primate behavior: quantitative assessments of effectiveness.

    PubMed

    Schapiro, Steven J; Bloomsmith, Mollie A; Laule, Gail E

    2003-01-01

    Many suggest that operant conditioning techniques can be applied successfully to improve the behavioral management of nonhuman primates in research settings. However, relatively little empirical data exist to support this claim. This article is a review of several studies that discussed applied positive reinforcement training techniques (PRT) on breeding/research colonies of rhesus macaques (Macaca mulatta) and chimpanzees (Pan troglodytes) at The University of Texas M. D. Anderson Cancer Center and measured their effectiveness. Empirical analyses quantified the amount of time required to train rhesus monkeys to come up, station, target, and stay. Additionally, a study found that time spent affiliating by female rhesus was changed as a function of training low affiliators to affiliate more and high affiliators to affiliate less. Another study successfully trained chimpanzees to feed without fighting and to come inside on command. PRT is an important behavioral management tool that can improve the care and welfare of primates in captivity. Published empirical findings are essential for managers to assess objectively the utility of positive reinforcement training techniques in enhancing captive management and research procedures.

  5. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    PubMed

    Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

  6. A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta)

    PubMed Central

    Salegio, Ernesto A.; Sparrey, Carolyn J.; Camisa, William; Fischer, Jason; Leasure, Jeremi; Buckley, Jennifer; Nout-Lomas, Yvette S.; Rosenzweig, Ephron S.; Moseanko, Rod; Strand, Sarah; Hawbecker, Stephanie; Lemoy, Marie-Josee; Haefeli, Jenny; Ma, Xiaokui; Nielson, Jessica L.; Edgerton, V.R.; Ferguson, Adam R.; Tuszynski, Mark H.

    2016-01-01

    Abstract The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies. PMID:26788611

  7. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    PubMed

    Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF. PMID:22558378

  8. Longitudinal Characterization of Escherichia coli in Healthy Captive Non-Human Primates

    PubMed Central

    Clayton, Jonathan B.; Danzeisen, Jessica L.; Trent, Ava M.; Murphy, Tami; Johnson, Timothy J.

    2014-01-01

    The gastrointestinal (GI) tracts of non-human primates (NHPs) are well known to harbor Escherichia coli, a known commensal of human beings and animals. While E. coli is a normal inhabitant of the mammalian gut, it also exists in a number of pathogenic forms or pathotypes, including those with predisposition for the GI tract as well as the urogenital tract. Diarrhea in captive NHPs has long been a problem in both zoo settings and research colonies, including the Como Zoo. It is an animal welfare concern, as well as a public health concern. E. coli has not been extensively studied; therefore, a study was performed during the summer of 2009 in collaboration with a zoo in Saint Paul, MN, which was previously experiencing an increased incidence and severity of diarrhea among their NHP collection. Fresh fecal samples were collected weekly from each member of the primate collection, between June and August of 2009, and E. coli were isolated. A total of 33 individuals were included in the study, representing eight species. E. coli isolates were examined for their genetic relatedness, phylogenetic relationships, plasmid replicon types, virulence gene profiles, and antimicrobial susceptibility profiles. A number of isolates were identified containing virulence genes commonly found in several different E. coli pathotypes, and there was evidence of clonal transmission of isolates between animals and over time. Overall, the manifestation of chronic diarrhea in the Como Zoo primate collection is a complex problem whose solution will require regular screening for microbial agents and consideration of environmental causes. This study provides some insight toward the sharing of enteric bacteria between such animals. PMID:26664923

  9. Old World Monkeys and New Age Science: The Evolution of Nonhuman Primate Systems Virology

    PubMed Central

    Palermo, Robert E.; Tisoncik-Go, Jennifer; Korth, Marcus J.; Katze, Michael G.

    2013-01-01

    Nonhuman primate (NHP) biomedical models are critical to our understanding of human health and disease, yet we are still in the early stages of developing sufficient tools to support primate genomic research that allow us to better understand the basis of phenotypic traits in NHP models of disease. A mere 7 years ago, the limited NHP transcriptome profiling that was being performed was done using complementary DNA arrays based on human genome sequences, and the lack of NHP genomic information and immunologic reagents precluded the use of NHPs in functional genomic studies. Since then, significant strides have been made in developing genomics capabilities for NHP research, from the rhesus macaque genome sequencing project to the construction of the first macaque-specific high-density oligonucleotide microarray, paving the way for further resource development and additional primate sequencing projects. Complete published draft genome sequences are now available for the chimpanzee ( Chimpanzee Sequencing Analysis Consortium 2005), bonobo ( Prufer et al. 2012), gorilla ( Scally et al. 2012), and baboon ( Ensembl.org 2013), along with the recently completed draft genomes for the cynomolgus macaque and Chinese rhesus macaque. Against this backdrop of both expanding sequence data and the early application of sequence-derived DNA microarrays tools, we will contextualize the development of these community resources and their application to infectious disease research through a literature review of NHP models of acquired immune deficiency syndrome and models of respiratory virus infection. In particular, we will review the use of -omics approaches in studies of simian immunodeficiency virus and respiratory virus pathogenesis and vaccine development, emphasizing the acute and innate responses and the relationship of these to the course of disease and to the evolution of adaptive immunity. PMID:24174440

  10. A word in the hand: action, gesture and mental representation in humans and non-human primates

    PubMed Central

    Cartmill, Erica A.; Beilock, Sian; Goldin-Meadow, Susan

    2012-01-01

    The movements we make with our hands both reflect our mental processes and help to shape them. Our actions and gestures can affect our mental representations of actions and objects. In this paper, we explore the relationship between action, gesture and thought in both humans and non-human primates and discuss its role in the evolution of language. Human gesture (specifically representational gesture) may provide a unique link between action and mental representation. It is kinaesthetically close to action and is, at the same time, symbolic. Non-human primates use gesture frequently to communicate, and do so flexibly. However, their gestures mainly resemble incomplete actions and lack the representational elements that characterize much of human gesture. Differences in the mirror neuron system provide a potential explanation for non-human primates' lack of representational gestures; the monkey mirror system does not respond to representational gestures, while the human system does. In humans, gesture grounds mental representation in action, but there is no evidence for this link in other primates. We argue that gesture played an important role in the transition to symbolic thought and language in human evolution, following a cognitive leap that allowed gesture to incorporate representational elements. PMID:22106432

  11. Genetic heterogeneity and phylogeny of Trichuris spp. from captive non-human primates based on ribosomal DNA sequence data.

    PubMed

    Cavallero, Serena; De Liberato, Claudio; Friedrich, Klaus G; Di Cave, David; Masella, Valentina; D'Amelio, Stefano; Berrilli, Federica

    2015-08-01

    Nematodes of the genus Trichuris, known as whipworms, are recognized to infect numerous mammalian species including humans and non-human primates. Several Trichuris spp. have been described and species designation/identification is traditionally based on host-affiliation, although cross-infection and hybridization events may complicate species boundaries. The main aims of the present study were to genetically characterize adult Trichuris specimens from captive Japanese macaques (Macaca fuscata) and grivets (Chlorocebus aethiops), using the ribosomal DNA (ITS) as molecular marker and to investigate the phylogeny and the extent of genetic variation also by comparison with data on isolates from other humans, non-human primates and other hosts. The phylogenetic analysis of Trichuris sequences from M. fuscata and C. aethiops provided evidences of distinct clades and subclades thus advocating the existence of additional separated taxa. Neighbor Joining and Bayesian trees suggest that specimens from M. fuscata may be distinct from, but related to Trichuris trichiura, while a close relationship is suggested between the subclade formed by the specimens from C. aethiops and the subclade formed by T. suis. The tendency to associate Trichuris sp. to host species can lead to misleading taxonomic interpretations (i.e. whipworms found in primates are identified as T. trichiura). The results here obtained confirm previous evidences suggesting the existence of Trichuris spp. other than T. trichiura infecting non-human living primates.

  12. Can grey parrots (Psittacus erithacus) succeed on a "complex" foraging task failed by nonhuman primates (Pan troglodytes, Pongo abelii, Sapajus apella) but solved by wrasse fish (Labroides dimidiatus)?

    PubMed

    Pepperberg, Irene M; Hartsfield, Leigh Ann

    2014-08-01

    Linking specific cognitive abilities of nonhuman species on a laboratory task to their evolutionary history-ecological niche can be a fruitful exercise in comparative psychology. Crucial issues, however, are the choice of task, the specific conditions of the task, and possibly the subjects' understanding or interpretation of the task. Salwiczek et al. (2012) compared cleaner wrasse fish (Labroides dimidaitus) to several nonhuman primate species (capuchins, Sapajus paella; chimpanzees, Pan troglodytes; orangutans, Pongo abelii) on a task purportedly related to the ecological demands of the fish, but not necessarily of the nonhuman primates; fish succeeded whereas almost all of the nonhuman primates that were tested failed. We replicated the two-choice paradigm of the task with three Grey parrots (Psittacus erithacus), whose ecology, evolutionary history, and cortical capacity are arguably more like those of nonhuman primates than fish. Greys succeeded at levels more like fish than all the nonhuman primates, suggesting possible alternative explanations for their success. Fish and nonhuman primate subjects also experienced a reversal of the initial conditions to test for generalization: Greys were similarly tested; they performed more like fish and capuchins (who now succeeded) than the apes (who continued to fail).

  13. Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters.

    PubMed

    Wolfe, Nathan D; Heneine, Walid; Carr, Jean K; Garcia, Albert D; Shanmugam, Vedapuri; Tamoufe, Ubald; Torimiro, Judith N; Prosser, A Tassy; Lebreton, Matthew; Mpoudi-Ngole, Eitel; McCutchan, Francine E; Birx, Deborah L; Folks, Thomas M; Burke, Donald S; Switzer, William M

    2005-05-31

    The human T-lymphotropic viruses (HTLVs) types 1 and 2 originated independently and are related to distinct lineages of simian T-lymphotropic viruses (STLV-1 and STLV-2, respectively). These facts, along with the finding that HTLV-1 diversity appears to have resulted from multiple cross-species transmissions of STLV-1, suggest that contact between humans and infected nonhuman primates (NHPs) may result in HTLV emergence. We investigated the diversity of HTLV among central Africans reporting contact with NHP blood and body fluids through hunting, butchering, and keeping primate pets. We show that this population is infected with a wide variety of HTLVs, including two previously unknown retroviruses: HTLV-4 is a member of a phylogenetic lineage that is distinct from all known HTLVs and STLVs; HTLV-3 falls within the phylogenetic diversity of STLV-3, a group not previously seen in humans. We also document human infection with multiple STLV-1-like viruses. These results demonstrate greater HTLV diversity than previously recognized and suggest that NHP exposure contributes to HTLV emergence. Our discovery of unique and divergent HTLVs has implications for HTLV diagnosis, blood screening, and potential disease development in infected persons. The findings also indicate that cross-species transmission is not the rate-limiting step in pandemic retrovirus emergence and suggest that it may be possible to predict and prevent disease emergence by surveillance of populations exposed to animal reservoirs and interventions to decrease risk factors, such as primate hunting.

  14. Hunting, law enforcement, and African primate conservation.

    PubMed

    N'Goran, Paul K; Boesch, Christophe; Mundry, Roger; N'Goran, Eliezer K; Herbinger, Ilka; Yapi, Fabrice A; Kühl, Hjalmar S

    2012-06-01

    Primates are regularly hunted for bushmeat in tropical forests, and systematic ecological monitoring can help determine the effect hunting has on these and other hunted species. Monitoring can also be used to inform law enforcement and managers of where hunting is concentrated. We evaluated the effects of law enforcement informed by monitoring data on density and spatial distribution of 8 monkey species in Taï National Park, Côte d'Ivoire. We conducted intensive surveys of monkeys and looked for signs of human activity throughout the park. We also gathered information on the activities of law-enforcement personnel related to hunting and evaluated the relative effects of hunting, forest cover and proximity to rivers, and conservation effort on primate distribution and density. The effects of hunting on monkeys varied among species. Red colobus monkeys (Procolobus badius) were most affected and Campbell's monkeys (Cercopithecus campbelli) were least affected by hunting. Density of monkeys irrespective of species was up to 100 times higher near a research station and tourism site in the southwestern section of the park, where there is little hunting, than in the southeastern part of the park. The results of our monitoring guided law-enforcement patrols toward zones with the most hunting activity. Such systematic coordination of ecological monitoring and law enforcement may be applicable at other sites.

  15. Effects of 60-Hz electric and magnetic fields on operant and social behavior and on neuroendocrine system of nonhuman primates

    SciTech Connect

    Rogers, W.R.; Coelho, A.M.; Easley, S.P.; Orr, J.L.; Reiter, R.J.; Rhodes, J.W.

    1992-09-24

    A series of pioneering electric and magnetic field experiments were completed using nonhuman primates and a unique, well-engineered, and reliable exposure facility. Effects of operant behavior, social behavior, and serum melatonin concentration were examined using 60 Hz field combinations of other 6 W/m and 0.6 G or 30 W/m and 1.0 G. Observations noted in the course of this study include: Combines electric and magnetic field exposure does not have any important effect on short-term memory; the transitory increases in social behavior observed in previous electric fields did not occur; combined electric and magnetic field exposure might lead to reduced behavioral frequency in baboon social groups; three experiments clearly establish that one set of exposure conditions does not produce molatonin suppression in nonhuman primates; and a small pilot experiment suggests that a different exposure protocol might result in melatonin suppression.

  16. Image-guided intracranial cannula placement for awake in vivo microdialysis in nonhuman primates

    NASA Astrophysics Data System (ADS)

    Chen, Antong; Bone, Ashleigh; Hines, Catherine D. G.; Dogdas, Belma; Montgomery, Tamara O.; Michener, Maria; Winkelmann, Christopher T.; Ghafurian, Soheil; Lubbers, Laura S.; Renger, John; Bagchi, Ansuman; Uslaner, Jason M.; Johnson, Colena; Zariwala, Hatim A.

    2016-03-01

    Intracranial microdialysis is used for sampling neurochemicals and large peptides along with their metabolites from the interstitial fluid (ISF) of the brain. The ability to perform this in nonhuman primates (NHP) e.g., rhesus could improve the prediction of pharmacokinetic (PK) and pharmacodynamics (PD) action of drugs in human. However, microdialysis in rhesus brains is not as routinely performed as in rodents. One challenge is that the precise intracranial probe placement in NHP brains is difficult due to the richness of the anatomical structure and the variability of the size and shape of brains across animals. Also, a repeatable and reproducible ISF sampling from the same animal is highly desirable when combined with cognitive behaviors or other longitudinal study end points. Toward that end, we have developed a semi-automatic flexible neurosurgical method employing MR and CT imaging to (a) derive coordinates for permanent guide cannula placement in mid-brain structures and (b) fabricate a customized recording chamber to implant above the skull for enclosing and safeguarding access to the cannula for repeated experiments. In order to place the intracranial guide cannula in each subject, the entry points in the skull and the depth in the brain were derived using co-registered images acquired from MR and CT scans. The anterior/posterior (A/P) and medial-lateral (M/L) rotation in the pose of the animal was corrected in the 3D image to appropriately represent the pose used in the stereotactic frame. An array of implanted fiducial markers was used to transform stereotactic coordinates to the images. The recording chamber was custom fabricated using computer-aided design (CAD), such that it would fit the contours of the individual skull with minimum error. The chamber also helped in guiding the cannula through the entry points down a trajectory into the depth of the brain. We have validated our method in four animals and our results indicate average placement error

  17. Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox).

    PubMed

    Mucker, Eric M; Goff, Arthur J; Shamblin, Joshua D; Grosenbach, Douglas W; Damon, Inger K; Mehal, Jason M; Holman, Robert C; Carroll, Darin; Gallardo, Nadia; Olson, Victoria A; Clemmons, Cody J; Hudson, Paul; Hruby, Dennis E

    2013-12-01

    Naturally occurring smallpox has been eradicated but remains a considerable threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ. 81:917-918, 2003). While effective, the smallpox vaccine is currently not recommended for routine use in the general public due to safety concerns (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective countermeasures, particularly those effective after exposure to smallpox, are needed. Currently, SIGA Technologies is developing the small-molecule oral drug, tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be efficacious in preventing lethal orthopoxviral disease in numerous animal models (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol. 79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E. Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R. Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg. 76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to be safe, with a good pharmacokinetic profile. In this study, the efficacy of tecovirimat was evaluated in both a prelesional and postlesional setting in nonhuman primates challenged intravenously with 1 × 10(8) PFU of Variola virus (VARV; the causative agent of smallpox), a model for smallpox disease in humans. Following challenge, 50% of placebo-treated controls succumbed to infection, while all tecovirimat-treated animals survived regardless of whether treatment was started at 2 or 4 days postinfection. In addition, tecovirimat treatment resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus shedding, and viral DNA circulating in the blood. Although clinical disease was evident in tecovirimat-treated animals, it was generally very mild and appeared to resolve earlier than in placebo

  18. Protective Potential of Antioxidant Enzymes as Vaccines for Schistosomiasis in a Non-Human Primate Model

    PubMed Central

    Carvalho-Queiroz, Claudia; Nyakundi, Ruth; Ogongo, Paul; Rikoi, Hitler; Egilmez, Nejat K.; Farah, Idle O.; Kariuki, Thomas M.; LoVerde, Philip T.

    2015-01-01

    Schistosomiasis remains a major cause of morbidity in the world. The challenge today is not so much in the clinical management of individual patients, but rather in population-based control of transmission in endemic areas. Despite recent large-scale efforts, such as integrated control programs aimed at limiting schistosomiasis by improving education and sanitation, molluscicide treatment programs and chemotherapy with praziquantel, there has only been limited success. There is an urgent need for complementary approaches, such as vaccines. We demonstrated previously that anti-oxidant enzymes, such as Cu–Zn superoxide dismutase (SOD) and glutathione S peroxidase (GPX), when administered as DNA-based vaccines induced significant levels of protection in inbred mice, greater than the target 40% reduction in worm burden compared to controls set as a minimum by the WHO. These results led us to investigate if immunization of non-human primates with antioxidants would stimulate an immune response that could confer protection as a prelude study for human trials. Issues of vaccine toxicity and safety that were difficult to address in mice were also investigated. All baboons in the study were examined clinically throughout the study and no adverse reactions occurred to the immunization. When our outbred baboons were vaccinated with two different formulations of SOD (SmCT-SOD and SmEC-SOD) or one of GPX (SmGPX), they showed a reduction in worm number to varying degrees, when compared with the control group. More pronounced, vaccinated animals showed decreased bloody diarrhea, days of diarrhea, and egg excretion (transmission), as well as reduction of eggs in the liver tissue and in the large intestine (pathology) compared to controls. Specific IgG antibodies were present in sera after immunizations and 10 weeks after challenge infection compared to controls. Peripheral blood mononuclear cells, mesenteric, and inguinal node cells from vaccinated animals proliferated and

  19. Nodular Worm Infections in Wild Non-human Primates and Humans Living in the Sebitoli Area (Kibale National Park, Uganda): Do High Spatial Proximity Favor Zoonotic Transmission?

    PubMed Central

    Cibot, Marie; Guillot, Jacques; Lafosse, Sophie; Bon, Céline; Seguya, Andrew; Krief, Sabrina

    2015-01-01

    Background Nodular Oesophagostomum genus nematodes are a major public health concern in some African regions because they can be lethal to humans. Their relatively high prevalence in people has been described in Uganda recently. While non-human primates also harbor Oesophagostomum spp., the epidemiology of this oesophagostomosis and the role of these animals as reservoirs of the infection in Eastern Africa are not yet well documented. Methodology/Principal Findings The present study aimed to investigate Oesophagostomum infection in terms of parasite species diversity, prevalence and load in three non-human primates (Pan troglodytes, Papio anubis, Colobus guereza) and humans living in close proximity in a forested area of Sebitoli, Kibale National Park (KNP), Uganda. The molecular phylogenetic analyses provided the first evidence that humans living in the Sebitoli area harbored O. stephanostomum, a common species in free-ranging chimpanzees. Chimpanzees were also infected by O. bifurcum, a common species described in human populations throughout Africa. The recently described Oesophagostomum sp. found in colobine monkeys and humans and which was absent from baboons in the neighboring site of Kanyawara in KNP (10 km from Sebitoli), was only found in baboons. Microscopic analyses revealed that the infection prevalence and parasite load in chimpanzees were significantly lower in Kanyawara than in Sebitoli, an area more impacted by human activities at its borders. Conclusions/Significance Three different Oesophagostomum species circulate in humans and non-human primates in the Sebitoli area and our results confirm the presence of a new genotype of Oesophagostomum recently described in Uganda. The high spatiotemporal overlap between humans and chimpanzees in the studied area coupled with the high infection prevalence among chimpanzees represent factors that could increase the risk of transmission for O. stephanostomum between the two primate species. Finally, the

  20. Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei.

    PubMed

    Alam, Shahabuddin; Amemiya, Kei; Bernhards, Robert C; Ulrich, Robert G; Waag, David M; Saikh, Kamal U

    2015-01-01

    Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy.

  1. The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893-2014.

    PubMed

    Davis, A Sally; Taubenberger, Jeffery K; Bray, Mike

    2015-05-01

    Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer's study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research. PMID:25746173

  2. Assessment of Foraging Devices as a Model for Decision-Making in Nonhuman Primate Environmental Enrichment

    PubMed Central

    Bennett, Allyson J; Perkins, Chaney M; Harty, Nicole M; Niu, Mengyao; Buelo, Audrey K; Luck, Melissa L; Pierre, Peter J

    2014-01-01

    Continued progress to move evidence-based best practices into community and regulatory animal welfare standards depends in part on developing common metrics to assess cost, benefit, and relative value. Here we describe a model approach to evidence-based evaluation and an example of comprehensive cost–benefit assessment for a common element of environmental enrichment plans for laboratory-housed nonhuman primates. Foraging devices encourage a species-typical activity that dominates the time budget of primates outside captivity and provide inherent cognitive challenges, physical activity demands, and multi-sensory stimulation. However, their implementation is not standard, and is challenged by perception of high costs and labor; nutritional and health concerns; and identification of best practices in implementation (that is, device types, food type, frequency of delivery and rotation). To address these issues, we directly compared monkeys’ engagement with different foraging devices and the comprehensive cost of implementing foraging opportunities. We recorded 14 adult male cynomolgus monkeys’ interactions with 7 types of devices filled with a range of enrichment foods. All devices elicited foraging behavior, but there were significant differences among them both initially and over subsequent observations. Devices that afforded opportunity for extraction of small food items and that posed manipulative challenge elicited greater manipulation. The cost of providing a foraging opportunity to a single monkey is roughly US$1, with approximately 80% attributable to labor. This study is the first to perform a rigorous cost–benefit analysis and comparison of common foraging devices included in environmental enrichment. Its broader significance lies in its contribution to the development of methods to facilitate improvement in evidence-based practices and common standards to enhance laboratory animal welfare. PMID:25255067

  3. Human/Nonhuman Primate AC-PC Ratio - Considerations for Translational Brain Measurements

    PubMed Central

    Fiandaca, Massimo S.; Salegio, Ernesto Aguilar; Yin, Dali; Richardson, R. Mark; Valles, Francisco E.; Larson, Paul S.; Starr, Philip A.; Lonser, Russell R.; Bankiewicz, Krystof S.

    2011-01-01

    This comparative magnetic resonance imaging (MRI) analysis evaluated the ratio of AC-PC (anterior commissure to posterior commissure) distance measures in selected groups of humans and nonhuman primates (NHPs). An understanding of the basis of this ratio between primate species may allow more accurate translation of NHP stereotactic targeting measurements to upcoming human trials. MRI datasets of adult humans [n=21], and juvenile and adult NHPs (Macaca fascicularis [n=40], and Macaca mulatta [n=32]), were evaluated in a mid-sagittal plane to obtain the AC-PC distance measure for each examined subject. Two trained evaluators, blinded to each other’s results, carried out three separate measurements of the AC-PC length for each subject. Each observer carried out measurements of the entire dataset [n=93] before repeating the measurements two additional times. Previous dataset measures were not available for review at the time of subsequent measures. Inter- and intra-observer variabilities were not statistically significant. Minimal intraspecies variation was found in the AC-PC measurement of our human and NHP groups. We found significant interspecies differences, however, more between humans and NHPs, and less between the NHP groups. Regression analysis confirms the strong linear relationship of AC-PC distance based primarily on species in our study groups. Human/NHP AC-PC ratios varied between 2.1 to 2.3 based on the compared NHP species groups. We conclude that the scale differences in brain measurements between NHPs and humans described in this study allows improved translation of stereotactic targeting coordinates in future human clinical trials, which may lead to improved efficacy and safety. PMID:21185868

  4. Concealed Fertility and Extended Female Sexuality in a Non-Human Primate (Macaca assamensis)

    PubMed Central

    Fürtbauer, Ines; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

    2011-01-01

    In numerous primates living in mixed-sex groups, females display probabilistic cues of fertility to simultaneously concentrate paternity to dominant males while diluting it amongst others as a means to reduce the risk of infanticide and to increase male care for offspring. A few species, however, lack these cues and potentially conceal fertility from males; yet, to date, little is known about mating patterns and their underlying proximate mechanisms in such species. Here, we investigated mating activity and sexual consortships relative to female reproductive state in wild Assamese macaques (Macaca assamensis), a species where females lack prominent anogenital swellings and copulation calls. During two mating seasons (2837 contact hours) we recorded sexual and social behaviors, sexual consortships, and collected 1178 fecal samples (n = 15 females) which were analyzed for progestogen concentrations to assess female reproductive state and to determine the timing of ovulation and conception. Although mostly conceiving in their first ovarian cycle, females were sexually receptive throughout the entire 4-month mating season, and within-cycle mating frequencies were not increased during fertile phases. Dominant males did not monopolize fertile matings, and consortships by high-ranking males lasted for long periods, which were not exclusively linked to female fertile phases. Furthermore, females copulated promiscuously but not randomly, i.e. for almost every female, matings were concentrated to a certain male, irrespective of male rank. Collectively, we demonstrate that fertility is undisclosed to males. The extreme extended female sexuality facilitated by concealed fertility may allow females to create differentiated mating relationships within a promiscuous mating system. Our study provides important new insight into the plasticity of female sexuality in non-human primates. PMID:21853074

  5. The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

    PubMed Central

    Davis, A. Sally; Taubenberger, Jeffery K.; Bray, Mike

    2015-01-01

    Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer’s study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research. PMID:25746173

  6. A new mark test for mirror self-recognition in non-human primates.

    PubMed

    Heschl, Adolf; Burkart, Judith

    2006-07-01

    For 30 years Gallup's (Science 167:86-87, 1970) mark test, which consists of confronting a mirror-experienced test animal with its own previously altered mirror image, usually a color mark on forehead, eyebrow or ear, has delivered valuable results about the distribution of visual self-recognition in non-human primates. Chimpanzees, bonobos, orangutans and, less frequently, gorillas can learn to correctly understand the reflection of their body in a mirror. However, the standard version of the mark test is good only for positively proving the existence of self-recognition. Conclusive statements about the lack of self-recognition are more difficult because of the methodological constraints of the test. This situation has led to a persistent controversy about the power of Gallup's original technique. We devised a new variant of the test which permits more unequivocal decisions about both the presence and absence of self-recognition. This new procedure was tested with marmoset monkeys (Callithrix jacchus), following extensive training with mirror-related tasks to facilitate performance in the standard mark test. The results show that a slightly altered mark test with a new marking substance (chocolate cream) can help to reliably discriminate between true negative results, indicating a real lack of ability to recognize oneself in a mirror, from false negative results that are due to methodological particularities of the standard test. Finally, an evolutionary hypothesis is put forward as to why many primates can use a mirror instrumentally - i.e. know how to use it for grasping at hidden objects - while failing in the decisive mark test.

  7. Utility, Limitations, and Future of Non-Human Primates for Dengue Research and Vaccine Development

    PubMed Central

    Sariol, Carlos A.; White, Laura J.

    2014-01-01

    Dengue is considered the most important emerging, human arboviruses, with worldwide distribution in the tropics. Unfortunately, there are no licensed dengue vaccines available or specific anti-viral drugs. The development of a dengue vaccine faces unique challenges. The four serotypes co-circulate in endemic areas, and pre-existing immunity to one serotype does not protect against infection with other serotypes, and actually may enhance severity of disease. One foremost constraint to test the efficacy of a dengue vaccine is the lack of an animal model that adequately recapitulates the clinical manifestations of a dengue infection in humans. In spite of this limitation, non-human primates (NHP) are considered the best available animal model to evaluate dengue vaccine candidates due to their genetic relatedness to humans and their ability to develop a viremia upon infection and a robust immune response similar to that in humans. Therefore, most dengue vaccines candidates are tested in primates before going into clinical trials. In this article, we present a comprehensive review of published studies on dengue vaccine evaluations using the NHP model, and discuss critical parameters affecting the usefulness of the model. In the light of recent clinical data, we assess the ability of the NHP model to predict immunological parameters of vaccine performances in humans and discuss parameters that should be further examined as potential correlates of protection. Finally, we propose some guidelines toward a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups. PMID:25309540

  8. Adrenarche in nonhuman primates: the evidence for it and the need to redefine it.

    PubMed

    Conley, A J; Bernstein, R M; Nguyen, A D

    2012-08-01

    Adrenarche is most commonly defined as a prepubertal increase in circulating adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfo-conjugate (DHEAS). This event is thought to have evolved in humans and some great apes but not in Old World monkeys, perhaps to promote brain development. Whether adrenarche represents a shared, derived developmental event in humans and our closest relatives, adrenal androgen secretion (and its regulation) is of considerable clinical interest. Specifically, adrenal androgens play a significant role in the pathophysiology of polycystic ovarian disease and breast and prostate cancers. Understanding the development of androgen secretion by the human adrenal cortex and identifying a suitable model for its study are therefore of central importance for clinical and evolutionary concerns. This review will examine the evidence for adrenarche in nonhuman primates (NHP) and suggest that a broader definition of this developmental event is needed, including morphological, biochemical, and endocrine criteria. Using such a definition, evidence from recent studies suggests that adrenarche evolved in Old World primates but spans a relatively brief period early in development compared with humans and some great apes. This emphasizes the need for frequent longitudinal sampling in evaluating developmental changes in adrenal androgen secretion as well as the tenuous nature of existing evidence of adrenarche in some species among the great apes. Central to an understanding of the regulation of adrenal androgen production in humans is the recognition of the complex nature of adrenarche and the need for more carefully conducted comparative studies and a broader definition in order to promote investigation among NHP in particular.

  9. Assessment of foraging devices as a model for decision-making in nonhuman primate environmental enrichment.

    PubMed

    Bennett, Allyson J; Perkins, Chaney M; Harty, Nicole M; Niu, Mengyao; Buelo, Audrey K; Luck, Melissa L; Pierre, Peter J

    2014-09-01

    Continued progress to move evidence-based best practices into community and regulatory animal welfare standards depends in part on developing common metrics to assess cost, benefit, and relative value. Here we describe a model approach to evidence-based evaluation and an example of comprehensive cost-benefit assessment for a common element of environmental enrichment plans for laboratory-housed nonhuman primates. Foraging devices encourage a species-typical activity that dominates the time budget of primates outside captivity and provide inherent cognitive challenges, physical activity demands, and multi-sensory stimulation. However, their implementation is not standard, and is challenged by perception of high costs and labor; nutritional and health concerns; and identification of best practices in implementation (that is, device types, food type, frequency of delivery and rotation). To address these issues, we directly compared monkeys' engagement with different foraging devices and the comprehensive cost of implementing foraging opportunities. We recorded 14 adult male cynomolgus monkeys' interactions with 7 types of devices filled with a range of enrichment foods. All devices elicited foraging behavior, but there were significant differences among them both initially and over subsequent observations. Devices that afforded opportunity for extraction of small food items and that posed manipulative challenge elicited greater manipulation. The cost of providing a foraging opportunity to a single monkey is roughly US$1, with approximately 80% attributable to labor. This study is the first to perform a rigorous cost-benefit analysis and comparison of common foraging devices included in environmental enrichment. Its broader significance lies in its contribution to the development of methods to facilitate improvement in evidence-based practices and common standards to enhance laboratory animal welfare. PMID:25255067

  10. Prefrontal inositol triphosphate is molecular correlate of working memory in nonhuman primates.

    PubMed

    López-Téllez, Juan F; López-Aranda, Manuel F; Navarro-Lobato, Irene; Masmudi-Martín, Mariam; Montañez, Elisa Martín; Calvo, Eduardo Blanco; Khan, Zafar U

    2010-02-24

    Working memory (WM) is a process of actively maintaining information in the mind for a relatively short period of time, and prefrontal cortex (PFC) has been thought to play a central role in its function. However, our understanding of underlying molecular events that translate into WM behavior remains elusive. To shed light on this issue, we have used three distinct nonhuman primate models of WM where each model represents three WM conditions: normal control, WM-deficient, and recuperated to normal from WM deficiency. Based on the hypothesis that there is a common molecular substrate for the coding of WM behavior, we have studied the relationship of these animals' performance on a WM task with their PFC levels of molecular components associated with Gq-phospholipase C and cAMP pathways, with the idea of identifying the footprints of such biomolecules. We observed that in all of the primate models WM deficiency was strongly related to the reduced concentration of IP(3) in PFC, whereas recuperation of WM-deficient animals to normal condition was associated with the normalization in IP(3) level. However, this correlation was absent or weak for cAMP, active protein kinase A, dopamine D(1) receptor, and Gq protein. In addition, WM deficiency related not only to pharmacological conditions but also to aging. Thus, it is suggested that optimal IP(3) activity is essential for normal WM function and the maintenance of intracellular IP(3)-mediated Ca(2+) level in PFC may serve as biochemical substrate for the expression of WM behavior.

  11. The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893-2014.

    PubMed

    Davis, A Sally; Taubenberger, Jeffery K; Bray, Mike

    2015-05-01

    Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer's study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research.

  12. Multi-Atlas Library for Eliminating Normalization Failures in Non-Human Primates.

    PubMed

    Maldjian, Joseph A; Shively, Carol A; Nader, Michael A; Friedman, David P; Whitlow, Christopher T

    2016-04-01

    Current tools for automated skull stripping, normalization, and segmentation of non-human primate (NHP) brain MRI studies typically demonstrate high failure rates. Many of these failures are due to a poor initial estimate for the affine component of the transformation. The purpose of this study is to introduce a multi-atlas approach to overcome these limitations and drive the failure rate to near zero. A library of study-specific templates (SST) spanning three Old World primate species (Macaca fascicularis, M. mulatta, Chlorocebus aethiops) was created using a previously described unbiased automated approach. Several modifications were introduced to the methodology to improve initial affine estimation at the study-specific template level, and at the individual subject level. These involve performing multiple separate normalizations to a multi-atlas library of templates and selecting the best performing template on the basis of a covariance similarity metric. This template was then used as an initialization for the affine component of subsequent skull stripping and normalization procedures. Normalization failure rate for SST generation and individual-subject segmentation on a set of 150 NHP was evaluated on the basis of visual inspection. The previous automated template creation procedure results in excellent skull stripping, segmentation, and atlas labeling across species. Failure rate at the individual-subject level was approximately 1%, however at the SST generation level it was 17%. Using the new multi-atlas approach, failure rate was further reduced to zero for both SST generation and individual subject processing. We describe a multi-atlas library registration approach for driving normalization failures in NHP to zero. It is straightforward to implement, and can have application to a wide variety of existing tools, as well as in difficult populations including neonates and the elderly. This approach is also an important step towards developing fully automated

  13. Detection of optogenetic stimulation in somatosensory cortex by non-human primates--towards artificial tactile sensation.

    PubMed

    May, Travis; Ozden, Ilker; Brush, Benjamin; Borton, David; Wagner, Fabien; Agha, Naubahar; Sheinberg, David L; Nurmikko, Arto V

    2014-01-01

    Neuroprosthesis research aims to enable communication between the brain and external assistive devices while restoring lost functionality such as occurs from stroke, spinal cord injury or neurodegenerative diseases. In future closed-loop sensorimotor prostheses, one approach is to use neuromodulation as direct stimulus to the brain to compensate for a lost sensory function and help the brain to integrate relevant information for commanding external devices via, e.g. movement intention. Current neuromodulation techniques rely mainly of electrical stimulation. Here we focus specifically on the question of eliciting a biomimetically relevant sense of touch by direct stimulus of the somatosensory cortex by introducing optogenetic techniques as an alternative to electrical stimulation. We demonstrate that light activated opsins can be introduced to target neurons in the somatosensory cortex of non-human primates and be optically activated to create a reliably detected sensation which the animal learns to interpret as a tactile sensation localized within the hand. The accomplishment highlighted here shows how optical stimulation of a relatively small group of mostly excitatory somatosensory neurons in the nonhuman primate brain is sufficient for eliciting a useful sensation from data acquired by simultaneous electrophysiology and from behavioral metrics. In this first report to date on optically neuromodulated behavior in the somatosensory cortex of nonhuman primates we do not yet dissect the details of the sensation the animals exerience or contrast it to those evoked by electrical stimulation, issues of considerable future interest.

  14. Mean Organ Doses Resulting From Non-Human Primate Whole Thorax Lung Irradiation Prescribed to Mid-Line Tissue.

    PubMed

    Prado, Charlotte; Kazi, Abdul; Bennett, Alexander; MacVittie, Thomas; Prado, Karl

    2015-11-01

    Multi-organ dose evaluations and the effects of heterogeneous tissue dose calculations have been retrospectively evaluated following irradiation to the whole thorax and lung in non-human primates (NHP). A clinical-based approach was established to evaluate actual doses received in the heart and lungs during whole thorax lung irradiation. Anatomical structure and organ densities have been introduced in the calculations to show the effects of dose distribution through heterogeneous tissue. Mean organ doses received by non-human primates undergoing whole thorax lung irradiations were calculated using a treatment planning system that is routinely used in clinical radiation oncology. The doses received by non-human primates irradiated following conventional dose calculations have been retrospectively reconstructed using computerized tomography-based, heterogeneity-corrected dose calculations. The use of dose volume descriptors for irradiation to organs at risk and tissue exposed to radiation is introduced. Mean and partial-volume doses to lung and heart are presented and contrasted. The importance of exact dose definitions is highlighted, and the relevance of precise dosimetry to establish organ-specific dose response relationships in NHP models of acute and delayed effects of acute radiation exposure is emphasized.

  15. Early Origins of Adult Disease: Approaches for Investigating the Programmable Epigenome in Humans, Nonhuman Primates, and Rodents

    PubMed Central

    Ganu, Radhika S.; Harris, R. Alan; Collins, Kiara; Aagaard, Kjersti M.

    2012-01-01

    According to the developmental origins of health and disease hypothesis, in utero experiences reprogram an individual for immediate adaptation to gestational perturbations, with the sequelae of later-in-life risk of metabolic disease. An altered gestational milieu with resultant adult metabolic disease has been observed in instances of both in utero constraint (e.g., from famine or uteroplacental insufficiency) and overt caloric abundance (e.g., from a maternal high-fat, caloric-dense diet). The commonality of the adult metabolic phenotype begs the question of how diverse in utero experiences (i.e., reprogramming events) converge on common metabolic pathways and how the memory of these events is maintained across the lifespan. We and others have investigated the molecular mechanisms underlying fetal programming and observed that epigenetic modifications to the fetal and placental epigenome accompany these reprogramming events. Based on several lines of emerging data in human and nonhuman primates, it is now felt that modified epigenetic signature—and the histone code in particular—underlies alterations in postnatal gene expression and metabolic pathways central to accurate functioning and maintenance of health. Because of the tissue lineage specificity of many of these modifications, nonhuman primates serve as an apt model system for the capacity to recapitulate human gene expression and regulation during development. This review summarizes recent epigenetic advances using rodent and primate (both human and nonhuman) models during in utero development and contributing to adult diseases later in life. PMID:23744969

  16. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates.

    PubMed

    Wang, Qidi; Zhang, Lianfeng; Kuwahara, Kazuhiko; Li, Li; Liu, Zijie; Li, Taisheng; Zhu, Hua; Liu, Jiangning; Xu, Yanfeng; Xie, Jing; Morioka, Hiroshi; Sakaguchi, Nobuo; Qin, Chuan; Liu, Gang

    2016-05-13

    Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471-503, S604-625, and S1164-1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597-603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597-603 and S604-625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597-603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection. PMID:27627203

  17. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates.

    PubMed

    Wang, Qidi; Zhang, Lianfeng; Kuwahara, Kazuhiko; Li, Li; Liu, Zijie; Li, Taisheng; Zhu, Hua; Liu, Jiangning; Xu, Yanfeng; Xie, Jing; Morioka, Hiroshi; Sakaguchi, Nobuo; Qin, Chuan; Liu, Gang

    2016-05-13

    Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471-503, S604-625, and S1164-1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597-603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597-603 and S604-625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597-603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection.

  18. Species-Specific Differences in the Expression and Regulation of α4β7 Integrin in Various Nonhuman Primates

    PubMed Central

    Byrareddy, Siddappa N.; Sidell, Neil; Arthos, James; Cicala, Claudia; Zhao, Chunxia; Little, Dawn M.; Dunbar, Paul; Yang, Gui X.; Pierzchalski, Keely; Kane, Maureen A.; Mayne, Ann E.; Song, Byeongwoon; Soares, Marcelo A.; Villinger, Francois; Fauci, Anthony S.; Ansari, Aftab A.

    2016-01-01

    Among nonhuman primates, SIV-infected Asian pigtailed macaques (PM) are relatively more susceptible to infection and disease progression than SIV-infected rhesus macaques (RM). In addition, SIV-infected African natural hosts such as the sooty mangabeys (SM) are resistant to disease. The mechanisms associated with such species-related variable clinical outcomes remain ill-defined but hold the potential to provide insights into the underlying mechanisms surrounding HIV pathogenesis. Recent findings indicate that the expression of the heterodimeric gut homing integrin α4β7 can influence both susceptibility and disease progression in RM. It was reasoned that differences in the frequencies/surface densities of α4β7-expressing lymphocytes might contribute to the differences in the clinical outcome of SIV infection among NHPs. In this article, we report that CD4+ T cells from PM constitutively express significantly higher levels of α4β7 than RM or SM. Retinoic acid, a key regulator of α4β7 expression, was paradoxically found at higher levels in the plasma of SM versus RM or PM. We also observed pairing of β7 with αE (αEβ7) on CD4+ T cells in the peripheral blood of SM, but not PM or RM. Finally, the differential mean density of expression of α4β7 in RM versus SM versus PM was predominantly dictated by species-specific sequence differences at the level of the β7 promoters, as determined by in vitro reporter/promoter construct transfection studies. We propose that differences in the regulation and expression of α4β7 may explain, in part, the differences in susceptibility and SIV disease progression in these NHP models. PMID:25948815

  19. Introduction to the special section: "the effects of bonds between human and nonhuman primates on primatological research and practice".

    PubMed

    Vitale, Augusto; Pollo, Simone

    2011-03-01

    This commentary introduces this special section on ‘‘the Effects of Bonds Between Human and Nonhuman Primates on Primatological Research and Practice.’’ The aim is to explore the different causes and consequences of bonding experiences between observers and observed in different primatological contexts. In the first contribution, Vitale asks what are the possible consequences of such bonding in behavioral primatology. Examples of beneficial consequences of this kind of relationship come fromstudies on cognitive abilities of great apes. Furthermore, an empathic attitude with the experimental animals leads to better care and attention toward individual welfare needs. Coleman discusses the particular case of nonhuman primates housed in research laboratories. Care-giving practices arediscussed in relation to scientific, ethical and emotional issues. Morimura et al. present the case of the first Japanese sanctuary for retiring chimpanzees from research where, in order to facilitate the social living of re-located chimpanzees, face-to-face interactions between caregivers and chimpanzees areessential. Asquith discusses the role of an thropomorphism, and proposes that this attitude can help to better understand the lives of primates, in more contextualized scenarios. In relation to this view, sheemphasizes how the term ‘‘primate culture’’ accords with some definition of the term ‘‘human culture.’’Fuentes, in his article asks whether national, class and ethnic characteristics can influence bonding between human and nonhuman primates, and calls for focused quantitative studies. Finally, Rose calls for the application of the concept of biosynergy, explained as promoting the formation of healthy and sustainable bonding relationships among living creatures. One of the most important aspects emerging from these papers is the need to better understand whether the issue of bonding in primatological studiescan be generalized to other areas of research such

  20. Preference and consequences: A preliminary look at whether preference impacts oral processing in non-human primates.

    PubMed

    Vinyard, Christopher J; Thompson, Cynthia L; Doherty, Alison; Robl, Nicholas

    2016-09-01

    Non-human primates demonstrate food preferences much like humans. We have little insight, however, into how those preferences impact oral processing in primates. To begin describing this relationship, we conducted a preliminary analysis measuring food preference in two tufted capuchins (Cebus apella) and comparing ranked preference to physiological variables during chewing of these foods. Food preference was assessed for each monkey across 12 foods, including monkey biscuits and 11 foods consumed by humans (e.g., various fruits and nuts). Animals chose from randomized pairs of foods to generate a ranked scale across the 12 foods. Contemporaneous with preference testing, electromyographic (EMG) activity was measured for the jaw-closing muscles to assess oral physiology during chewing of these foods. As expected, these capuchins exhibited clear preferences among these 12 foods. Based on their preferences, we identified sets of preferred and non-preferred brittle (i.e., almond versus monkey chow) and ductile (i.e., dates and prunes versus apricots) foods for physiological comparisons that broadly control variation in food mechanical properties (FMPs). As expected, oral physiology varied with FMPs in each animal. Within brittle and ductile groupings, we observed several significant differences in chewing cycle length and relative muscle activation levels that are likely related to food preference. These differences tended to be complex and individual specific. The two capuchins chewed non-preferred apricots significantly faster than preferred dates and prunes. Effect sizes for preference were smaller than those for FMPs, supporting the previous focus on FMPs in primate dietary research. Although preliminary, these results suggest that food preference may influence oral physiology in non-human primates. The prospect that this relationship exists in monkeys raises the possibility that a link between food preference and oral processing in humans may be based on shared

  1. Preference and consequences: A preliminary look at whether preference impacts oral processing in non-human primates.

    PubMed

    Vinyard, Christopher J; Thompson, Cynthia L; Doherty, Alison; Robl, Nicholas

    2016-09-01

    Non-human primates demonstrate food preferences much like humans. We have little insight, however, into how those preferences impact oral processing in primates. To begin describing this relationship, we conducted a preliminary analysis measuring food preference in two tufted capuchins (Cebus apella) and comparing ranked preference to physiological variables during chewing of these foods. Food preference was assessed for each monkey across 12 foods, including monkey biscuits and 11 foods consumed by humans (e.g., various fruits and nuts). Animals chose from randomized pairs of foods to generate a ranked scale across the 12 foods. Contemporaneous with preference testing, electromyographic (EMG) activity was measured for the jaw-closing muscles to assess oral physiology during chewing of these foods. As expected, these capuchins exhibited clear preferences among these 12 foods. Based on their preferences, we identified sets of preferred and non-preferred brittle (i.e., almond versus monkey chow) and ductile (i.e., dates and prunes versus apricots) foods for physiological comparisons that broadly control variation in food mechanical properties (FMPs). As expected, oral physiology varied with FMPs in each animal. Within brittle and ductile groupings, we observed several significant differences in chewing cycle length and relative muscle activation levels that are likely related to food preference. These differences tended to be complex and individual specific. The two capuchins chewed non-preferred apricots significantly faster than preferred dates and prunes. Effect sizes for preference were smaller than those for FMPs, supporting the previous focus on FMPs in primate dietary research. Although preliminary, these results suggest that food preference may influence oral physiology in non-human primates. The prospect that this relationship exists in monkeys raises the possibility that a link between food preference and oral processing in humans may be based on shared

  2. [Ethical and legal aspects of animal experiments on non-human primates].

    PubMed

    Luy, J

    2007-03-01

    Animal experiments on non-human primates give cause for ethical concerns for three reasons (1) the inclusion of "ethical animal protection" in the German Constitution (Article 20a of the "Grundgesetz" GG, 2002) has led to real consequences for the application process with respect to the use of primates for fundamental research; (2) the legal requirements in Europe to ensure animal welfare are currently being tightened and (3) the global problem of the protection of species, especially with respect to the capturing and subsequent sale of primates is still unsolved. As a result of the way humans interpret the term justice (the principle of equality) it was to be expected that great apes, being the animals that most closely resemble humans, would play a key role in the establishment of animal protection laws. In 1997,Great Britain and Ireland made it illegal to conduct experiments on great apes. In 1999, New Zealand went even further and created a kind of basic rights for great apes. In 2003,The Netherlands forbade animal experiments using great apes as did Sweden, which also included gibbons in this ban (which is in line with current taxonomy, which considers gibbons to belong to the family Hominidae). In 2006 Austria forbade experiments carried out on chimpanzees, bonobos, gorillas, orang-utans, and gibbons. Only recently, a state commission on ethics in Switzerland demanded that the Swiss government do the same. And the summer of 2006 saw a debate in Spain on the inclusion of the protection of great apes in the primary goals of the state. Due to the principle of equality, a further extension (both geographically and systemically) of the exclusion of great apes from animal experiments is to be expected. Since Article 20a GG on "ethical animal protection" came into effect on August 1,2002, the regulatory authorities in Germany have the right to independently check and control animal experiments as to their ethical tenability (Administrative Court Giessen, confirmed

  3. Biology of E1-Deleted Adenovirus Vectors in Nonhuman Primate Muscle

    PubMed Central

    Zoltick, Philip W.; Chirmule, Narendra; Schnell, Michael A.; Gao, Guang-ping; Hughes, Joseph V.; Wilson, James M.

    2001-01-01

    Adenovirus vectors have been studied as vehicles for gene transfer to skeletal muscle, an attractive target for gene therapies for inherited and acquired diseases. In this setting, immune responses to viral proteins and/or transgene products cause inflammation and lead to loss of transgene expression. A few studies in murine models have suggested that the destructive cell-mediated immune response to virally encoded proteins of E1-deleted adenovirus may not contribute to the elimination of transgene-expressing cells. However, the impact of immune responses following intramuscular administration of adenovirus vectors on transgene stability has not been elucidated in larger animal models such as nonhuman primates. Here we demonstrate that intramuscular administration of E1-deleted adenovirus vector expressing rhesus monkey erythropoietin or growth hormone to rhesus monkeys results in generation of a Th1-dependent cytotoxic T-cell response to adenovirus proteins. Transgene expression dropped significantly over time but was still detectable in some animals after 6 months. Systemic levels of adenovirus-specific neutralizing antibodies were generated, which blocked vector readministration. These studies indicate that the cellular and humoral immune response generated to adenovirus proteins, in the context of transgenes encoding self-proteins, hinders long-term transgene expression and readministration with first-generation vectors. PMID:11333904

  4. Frontal Non-Invasive Neurostimulation Modulates Antisaccade Preparation in Non-Human Primates

    PubMed Central

    Valero-Cabre, Antoni; Wattiez, Nicolas; Monfort, Morgane; François, Chantal; Rivaud-Péchoux, Sophie; Gaymard, Bertrand; Pouget, Pierre

    2012-01-01

    A combination of oculometric measurements, invasive electrophysiological recordings and microstimulation have proven instrumental to study the role of the Frontal Eye Field (FEF) in saccadic activity. We hereby gauged the ability of a non-invasive neurostimulation technology, Transcranial Magnetic Stimulation (TMS), to causally interfere with frontal activity in two macaque rhesus monkeys trained to perform a saccadic antisaccade task. We show that online single pulse TMS significantly modulated antisaccade latencies. Such effects proved dependent on TMS site (effects on FEF but not on an actively stimulated control site), TMS modality (present under active but not sham TMS on the FEF area), TMS intensity (intensities of at least 40% of the TMS machine maximal output required), TMS timing (more robust for pulses delivered at 150 ms than at 100 post target onset) and visual hemifield (relative latency decreases mainly for ipsilateral AS). Our results demonstrate the feasibility of using TMS to causally modulate antisaccade-associated computations in the non-human primate brain and support the use of this approach in monkeys to study brain function and its non-invasive neuromodulation for exploratory and therapeutic purposes. PMID:22701691

  5. DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates.

    PubMed

    Shin, Jieun; Maekawa, Tomoki; Abe, Toshiharu; Hajishengallis, Evlambia; Hosur, Kavita; Pyaram, Kalyani; Mitroulis, Ioannis; Chavakis, Triantafyllos; Hajishengallis, George

    2015-09-30

    DEL-1 (developmental endothelial locus-1) is an endothelial cell-secreted protein that regulates LFA-1 (lymphocyte function-associated antigen-1) integrin-dependent leukocyte recruitment and inflammation in various tissues. We identified a novel regulatory mechanism of DEL-1 in osteoclast biology. Specifically, we showed that DEL-1 is expressed by human and mouse osteoclasts and regulates their differentiation and resorptive function. Mechanistically, DEL-1 inhibited the expression of NFATc1, a master regulator of osteoclastogenesis, in a Mac-1 integrin-dependent manner. In vivo mechanistic analysis has dissociated the anti-inflammatory from the anti-bone-resorptive action of DEL-1 and identified structural components thereof mediating these distinct functions. Locally administered human DEL-1 blocked inflammatory periodontal bone loss in nonhuman primates-a relevant model of human periodontitis. The ability of DEL-1 to regulate both upstream (inflammatory cell recruitment) and downstream (osteoclastogenesis) events that lead to inflammatory bone loss paves the way to a new class of endogenous therapeutics for treating periodontitis and perhaps other inflammatory disorders. PMID:26424570

  6. Effects of 60 Hz electric fields on operant and social stress behaviors of nonhuman primates

    SciTech Connect

    Rogers, W.R.; Coelho, A.M. Jr.; Easley, S.P.; Lucas, J.H.; Moore, G.T.; Orr, J.L.; Smith, H.D.; Taylor, L.L.; Tuttle, M.L.

    1987-10-24

    The objective of this program is to investigate, using the baboon as a nonhuman primate surrogate for the human, possible behavioral effects associated with exposure to high intensity 60 Hz electric fields. Results from this program, along with information from experiments conducted elsewhere, will be used by the Department of Energy (DOE) to estimate and evaluate the likelihood of deleterious consequences resulting from exposure of humans to the electric fields associated with power transmission over high voltage lines. This research program consists of four major research projects, all of which have been successfully completed. The first project evaluated the potentially aversive character of exposure to 60 Hz electric fields by determining the threshold intensity that produces escape or avoidance responses. The second project estimated the threshold intensity for detection threshold was 12 kV/m; the range of means was 6 to 16 kV/m. The third project assessed, in separate experiments conducted at 30 and 60 kV/m, effects of chronic exposure to electric fields on the performance of two operant conditioning tasks, fixed ratio (FR), and differential reinforcement of low rate (DRL). In the same two experiments, the fourth project investigated, using the systematic quantitative observational sampling methods of primatology, the possible stress-inducing effects of chronic exposure to 60 Hz electric fields on the behavior of baboons living in small social groups. 131 refs., 87 figs., 123 tabs.

  7. Protection of non-human primates against glanders with a gold nanoparticle glycoconjugate vaccine

    PubMed Central

    Torres, Alfredo G.; Gregory, Anthony E.; Hatcher, Christopher L.; Vinet-Oliphant, Heather; Morici, Lisa A.; Titball, Richard W.; Roy, Chad J.

    2014-01-01

    The Gram-negative Burkholderia mallei is a zoonotic pathogen and the causative agent of glanders disease. Because the bacteria maintain the potential to be used as a biothreat agent, vaccine strategies are required for human glanders prophylaxis. A rhesus macaque (Macaca mulatta) model of pneumonic (inhalational) glanders was established and the protective properties of a nanoparticle glycoconjugate vaccine composed of B. thailandensis LPS conjugated to FliC was evaluated. An aerosol challenge dose of ~1×104 CFU B. mallei produced mortality in 50% of naïve animals (n = 2/4), 2–3 days post-exposure. Although survival benefit was not observed by vaccination with a glycoconjugate glanders vaccine (p=0.42), serum LPS-specific IgG titres were significantly higher on day 80 in 3 vaccinated animals who survived compared with 3 vaccinated animals who died. Furthermore, B. mallei was isolated from multiple organs of both non-vaccinated survivors, but not from any organs of 3 vaccinated survivors at 30 days post-challenge. Taken together, this is the first time a candidate vaccine has been evaluated in a non-human primate aerosol model of glanders and represents the initial step for consideration in pre-clinical studies. PMID:25533326

  8. Protection of non-human primates against glanders with a gold nanoparticle glycoconjugate vaccine.

    PubMed

    Torres, Alfredo G; Gregory, Anthony E; Hatcher, Christopher L; Vinet-Oliphant, Heather; Morici, Lisa A; Titball, Richard W; Roy, Chad J

    2015-01-29

    The Gram-negative Burkholderia mallei is a zoonotic pathogen and the causative agent of glanders disease. Because the bacteria maintain the potential to be used as a biothreat agent, vaccine strategies are required for human glanders prophylaxis. A rhesus macaque (Macaca mulatta) model of pneumonic (inhalational) glanders was established and the protective properties of a nanoparticle glycoconjugate vaccine composed of Burkholderia thailandensis LPS conjugated to FliC was evaluated. An aerosol challenge dose of ∼1×10(4) CFU B. mallei produced mortality in 50% of naïve animals (n=2/4), 2-3 days post-exposure. Although survival benefit was not observed by vaccination with a glycoconjugate glanders vaccine (p=0.42), serum LPS-specific IgG titers were significantly higher on day 80 in 3 vaccinated animals who survived compared with 3 vaccinated animals who died. Furthermore, B. mallei was isolated from multiple organs of both non-vaccinated survivors, but not from any organs of 3 vaccinated survivors at 30 days post-challenge. Taken together, this is the first time a candidate vaccine has been evaluated in a non-human primate aerosol model of glanders and represents the initial step for consideration in pre-clinical studies.

  9. Non-human primates in neuroscience research: The case against its scientific necessity.

    PubMed

    Bailey, Jarrod; Taylor, Kathy

    2016-03-01

    Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP research generally, but here we specifically focus on the development and interpretation of functional magnetic resonance imaging (fMRI), deep brain stimulation (DBS), the understanding of neural oscillations and memory, and investigation of the neural control of movement and of vision/binocular rivalry. The increasing power of human-specific methods, including advances in fMRI and invasive techniques such as electrocorticography and single-unit recordings, is discussed. These methods serve to render NHP approaches redundant. We conclude that the defence of NHP use is groundless, and that neuroscience would be more relevant and successful for humans, if it were conducted with a direct human focus. We have confidence in opposing NHP neuroscience, both on scientific as well as on ethical grounds. PMID:27031602

  10. Genome editing in nonhuman primates: approach to generating human disease models.

    PubMed

    Chen, Y; Niu, Y; Ji, W

    2016-09-01

    Nonhuman primates (NHPs) are superior than rodents to be animal models for the study of human diseases, due to their similarities in terms of genetics, physiology, developmental biology, social behaviour and cognition. Transgenic animals have become a key tool in functional genomics to generate models for human diseases and validate new drugs. However, until now, progress in the field of transgenic NHPs has been slow because of technological limitations. Many human diseases, including neurodegenerative disorders, are caused by mutations in endogenous genes. Fortunately, recent developments in precision gene editing have led to the generation of NHP models for human diseases. Since 2014, there have been several reports of the generation of monkey models using transcription activator-like endonucleases (TALENs) or clustered regularly interspaced short palindromic repeats (CRISPR/Cas9); some of these NHP models showed symptoms that were much closer to those of human diseases than have been seen previously in mouse models. No off-targeting was observed in the NHP models, and multiple gene knockout and biallelic mutants were feasible with low efficiency. These findings suggest that there are many possibilities to establish NHP models for human diseases that can mimic human diseases more faithfully than rodent models. PMID:27114283

  11. Surface roughness enhances the osseointegration of titanium headposts in non-human primates.

    PubMed

    Hacking, S A; Boyraz, P; Powers, B M; Sen-Gupta, E; Kucharski, W; Brown, C A; Cook, E P

    2012-11-15

    It is well recognized that micrometer and nanometer sized surface features enhance the skeletal attachment of implants within bone. However, little is known regarding the integration of implants placed outside the bone but in contact with the surface. Loosening of chronic skull anchored headposts in non-human primate based experiments can be a factor. The purpose of this study was to evaluate the effect of a simple and easily applied surface texture on bone apposition to titanium implants fixed to the periosteal surface of the skull. Implants possessed either a polished surface or a textured surface created by grit-basting followed by acid etching. The percent of bone in contact with the implant surface (bone apposition) to three polished and three textured implants was evaluated in one adult female monkey after 14 weeks. Upon harvest, implants were processed for undecalcified histology and regions of bone apposition were quantified using backscatter electron microscopy and digital image analysis. The bone apposition to textured implants was 62±20% and to polished implants was 42±21%. The application of a peak-and-pit like texture to the surface of titanium implants significantly increased bone apposition to titanium implants placed on the periosteal surface of the skull. This study demonstrates that titanium headposts can easily be modified to improve osseointegration using equipment and supplies available to most neurophysiological laboratories. In addition, implant texturing may have utility in areas including skeletal trauma and reconstruction where devices are placed in contact with the bone surface. PMID:22975472

  12. Diabetes mellitus accelerates Aβ pathology in brain accompanied by enhanced GAβ generation in nonhuman primates.

    PubMed

    Okabayashi, Sachi; Shimozawa, Nobuhiro; Yasutomi, Yasuhiro; Yanagisawa, Katsuhiko; Kimura, Nobuyuki

    2015-01-01

    Growing evidence suggests that diabetes mellitus (DM) is one of the strongest risk factors for developing Alzheimer's disease (AD). However, it remains unclear why DM accelerates AD pathology. In cynomolgus monkeys older than 25 years, senile plaques (SPs) are spontaneously and consistently observed in their brains, and neurofibrillary tangles are present at 32 years of age and older. In laboratory-housed monkeys, obesity is occasionally observed and frequently leads to development of type 2 DM. In the present study, we performed histopathological and biochemical analyses of brain tissue in cynomolgus monkeys with type 2 DM to clarify the relationship between DM and AD pathology. Here, we provide the evidence that DM accelerates Aβ pathology in vivo in nonhuman primates who had not undergone any genetic manipulation. In DM-affected monkey brains, SPs were observed in frontal and temporal lobe cortices, even in monkeys younger than 20 years. Biochemical analyses of brain revealed that the amount of GM1-ganglioside-bound Aβ (GAβ)--the endogenous seed for Aβ fibril formation in the brain--was clearly elevated in DM-affected monkeys. Furthermore, the level of Rab GTPases was also significantly increased in the brains of adult monkeys with DM, almost to the same levels as in aged monkeys. Intraneuronal accumulation of enlarged endosomes was also observed in DM-affected monkeys, suggesting that exacerbated endocytic disturbance may underlie the acceleration of Aβ pathology due to DM.

  13. Vocal turn-taking in a non-human primate is learned during ontogeny.

    PubMed

    Chow, Cecilia P; Mitchell, Jude F; Miller, Cory T

    2015-05-22

    Conversational turn-taking is an integral part of language development, as it reflects a confluence of social factors that mitigate communication. Humans coordinate the timing of speech based on the behaviour of another speaker, a behaviour that is learned during infancy. While adults in several primate species engage in vocal turn-taking, the degree to which similar learning processes underlie its development in these non-human species or are unique to language is not clear. We recorded the natural vocal interactions of common marmosets (Callithrix jacchus) occurring with both their sibling twins and parents over the first year of life and observed at least two parallels with language development. First, marmoset turn-taking is a learned vocal behaviour. Second, marmoset parents potentially played a direct role in guiding the development of turn-taking by providing feedback to their offspring when errors occurred during vocal interactions similarly to what has been observed in humans. Though species-differences are also evident, these findings suggest that similar learning mechanisms may be implemented in the ontogeny of vocal turn-taking across our Order, a finding that has important implications for our understanding of language evolution. PMID:25904663

  14. A Large-Scale Interface for Optogenetic Stimulation and Recording in Nonhuman Primates.

    PubMed

    Yazdan-Shahmorad, Azadeh; Diaz-Botia, Camilo; Hanson, Timothy L; Kharazia, Viktor; Ledochowitsch, Peter; Maharbiz, Michel M; Sabes, Philip N

    2016-03-01

    While optogenetics offers great potential for linking brain function and behavior in nonhuman primates, taking full advantage of that potential will require stable access for optical stimulation and concurrent monitoring of neural activity. Here we present a practical, stable interface for stimulation and recording of large-scale cortical circuits. To obtain optogenetic expression across a broad region, here spanning primary somatosensory (S1) and motor (M1) cortices, we used convection-enhanced delivery of the viral vector, with online guidance from MRI. To record neural activity across this region, we used a custom micro-electrocorticographic (μECoG) array designed to minimally attenuate optical stimuli. Lastly, we demonstrated the use of this interface to measure spatiotemporal responses to optical stimulation across M1 and S1. This interface offers a powerful tool for studying circuit dynamics and connectivity across cortical areas, for long-term studies of neuromodulation and targeted cortical plasticity, and for linking these to behavior. PMID:26875625

  15. Endocrine-Immune Interactions in Pregnant Non-Human Primates With Intrauterine Infection

    PubMed Central

    Novy, Miles J.

    1997-01-01

    Preterm birth remains the most common cause of perinatal mortality. Although the causes of preterm labor are multifactorial and vary according to gestational age, preterm labor and term labor share common cellular and molecular mechanisms, including stimulation of the fetal hypothalamic-pituitary-adrenal (HPA) axis and endocrine/immune system interactions. We have developed a non-human primate experimental model for intrauterine infection and preterm labor using chronically instrumented rhesus monkeys (Macaca mulatta) with timed gestations. We have documented the temporal and quantitative relationships among intrauterine infection, the synthesis and release of proinflammatory cytokines, prostaglandins, and fetal-placental steroid biosynthesis in this model. Infection-induced preterm parturition is characterized by significant elevations in amniotic fluid proinflammatory cytokines and by increases in fetal adrenal steroid biosynthesis, but not by corresponding increases in placental estrogen biosynthesis characteristic of spontaneous parturition. This suggests that activation of the fetal HPA axis by the stress of infection is accompanied by placental dysfunction and also that infection-induced preterm parturition is not dependent upon the increased estrogen biosynthesis observed in spontaneous parturition. These different endocrine and immune responses have important diagnostic and therapeutic implications in the management of preterm labor. PMID:18476167

  16. Vocal turn-taking in a non-human primate is learned during ontogeny.

    PubMed

    Chow, Cecilia P; Mitchell, Jude F; Miller, Cory T

    2015-05-22

    Conversational turn-taking is an integral part of language development, as it reflects a confluence of social factors that mitigate communication. Humans coordinate the timing of speech based on the behaviour of another speaker, a behaviour that is learned during infancy. While adults in several primate species engage in vocal turn-taking, the degree to which similar learning processes underlie its development in these non-human species or are unique to language is not clear. We recorded the natural vocal interactions of common marmosets (Callithrix jacchus) occurring with both their sibling twins and parents over the first year of life and observed at least two parallels with language development. First, marmoset turn-taking is a learned vocal behaviour. Second, marmoset parents potentially played a direct role in guiding the development of turn-taking by providing feedback to their offspring when errors occurred during vocal interactions similarly to what has been observed in humans. Though species-differences are also evident, these findings suggest that similar learning mechanisms may be implemented in the ontogeny of vocal turn-taking across our Order, a finding that has important implications for our understanding of language evolution.

  17. SEASONAL MORTALITY PATTERNS IN NON-HUMAN PRIMATES: IMPLICATIONS FOR VARIATION IN SELECTION PRESSURES ACROSS ENVIRONMENTS

    PubMed Central

    Gogarten, Jan F.; Brown, Leone M.; Chapman, Colin A.; Cords, Marina; Doran-Sheehy, Diane; Fedigan, Linda M.; Grine, Frederick E.; Perry, Susan; Pusey, Anne E.; Sterck, Elisabeth H. M.; Wich, Serge A.; Wright, Patricia C.

    2014-01-01

    Examining seasonal mortality patterns can yield insights into the drivers of mortality and thus potential selection pressures acting on individuals in different environments. We compiled adult and juvenile mortality data from nine wild non-human primate taxa to investigate the role of seasonality in patterns of mortality and address the following questions: Is mortality highly seasonal across species? Does greater environmental seasonality lead to more seasonal mortality patterns? If mortality is seasonal, is it higher during wet seasons or during periods of food scarcity? and Do folivores show less seasonal mortality than frugivores? We found seasonal mortality patterns in five of nine taxa, and mortality was more often tied to wet seasons than food-scarce periods, a relationship that may be driven by disease. Controlling for phylogeny, we found a positive relationship between the degree of environmental seasonality and mortality, with folivores exhibiting more seasonal mortality than frugivores. These results suggest that mortality patterns are influenced both by diet and degree of environmental seasonality. Applied to a wider array of taxa, analyses of seasonal mortality patterns may aid understanding of life-history evolution and selection pressures acting across a broad spectrum of environments and spatial and temporal scales. PMID:23025613

  18. Environmental modulation of drug taking: Nonhuman primate models of cocaine abuse and PET neuroimaging.

    PubMed

    Nader, Michael A; Banks, Matthew L

    2014-01-01

    The current review highlights the importance of environmental variables on cocaine self-administration in nonhuman primate models of drug abuse. In addition to describing the behavioral consequences, potential mechanisms of action are discussed, based on imaging results using the non-invasive and translational technique of positron emission tomography (PET). In this review, the role of three environmental variables - both positive and negative - are described: alternative non-drug reinforcers; social rank (as an independent variable) and punishment of cocaine self-administration. These environmental stimuli can profoundly influence brain function and drug self-administration. We focus on environmental manipulations involving non-drug alternatives (e.g., food reinforcement) using choice paradigms. Manipulations such as response cost and social variables (e.g., social rank, social stress) also influence the behavioral effects of drugs. Importantly, these manipulations are amenable to brain imaging studies. Taken together, these studies emphasize the profound impact environmental variables can have on drug taking, which should provide important information related to individual-subject variability in treatment responsiveness, and the imaging work may highlight pharmacological targets for medications related to treating drug abuse. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  19. Persistent Expression of FLAG-tagged Micro dystrophin in Nonhuman Primates Following Intramuscular and Vascular Delivery

    PubMed Central

    Rodino-Klapac, Louise R; Montgomery, Chrystal L; Bremer, William G; Shontz, Kimberly M; Malik, Vinod; Davis, Nancy; Sprinkle, Spencer; Campbell, Katherine J; Sahenk, Zarife; Clark, K Reed; Walker, Christopher M; Mendell, Jerry R; Chicoine, Louis G

    2009-01-01

    Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-terminus of micro-dystrophin to facilitate translational studies targeting DMD. Intramuscular (IM) injection of AAV8.MCK.micro-dys.FLAG in the tibialis anterior (TA) of macaques demonstrated robust gene expression, with muscle transduction (50–79%) persisting for up to 5 months. Success by IM injection was followed by targeted vascular delivery studies using a fluoroscopy-guided catheter threaded through the femoral artery. Three months after gene transfer, >80% of muscle fibers showed gene expression in the targeted muscle. No cellular immune response to AAV8 capsid, micro-dystrophin, or the FLAG tag was detected by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) at any time point with either route. In summary, an epitope-tagged micro-dystrophin cassette enhances the ability to evaluate site-specific localization and distribution of gene expression in the NHP in preparation for vascular delivery clinical trials. PMID:19904237

  20. A Microneedle Patch Containing Measles Vaccine is Immunogenic in Non-human Primates

    PubMed Central

    Edens, Chris; Collins, Marcus L.; Goodson, James L.; Rota, Paul A.; Prausnitz, Mark R.

    2015-01-01

    Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID50) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10 minutes, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. PMID:25770786

  1. Surface roughness enhances the osseointegration of titanium headposts in non-human primates.

    PubMed

    Hacking, S A; Boyraz, P; Powers, B M; Sen-Gupta, E; Kucharski, W; Brown, C A; Cook, E P

    2012-11-15

    It is well recognized that micrometer and nanometer sized surface features enhance the skeletal attachment of implants within bone. However, little is known regarding the integration of implants placed outside the bone but in contact with the surface. Loosening of chronic skull anchored headposts in non-human primate based experiments can be a factor. The purpose of this study was to evaluate the effect of a simple and easily applied surface texture on bone apposition to titanium implants fixed to the periosteal surface of the skull. Implants possessed either a polished surface or a textured surface created by grit-basting followed by acid etching. The percent of bone in contact with the implant surface (bone apposition) to three polished and three textured implants was evaluated in one adult female monkey after 14 weeks. Upon harvest, implants were processed for undecalcified histology and regions of bone apposition were quantified using backscatter electron microscopy and digital image analysis. The bone apposition to textured implants was 62±20% and to polished implants was 42±21%. The application of a peak-and-pit like texture to the surface of titanium implants significantly increased bone apposition to titanium implants placed on the periosteal surface of the skull. This study demonstrates that titanium headposts can easily be modified to improve osseointegration using equipment and supplies available to most neurophysiological laboratories. In addition, implant texturing may have utility in areas including skeletal trauma and reconstruction where devices are placed in contact with the bone surface.

  2. Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates

    SciTech Connect

    Green, Damian J.; Pagel, John M.; Nemecek, Eneida R.; Lin, Yukang; Kenoyer, Aimee L.; Pantelias, Anastasia; Hamlin, Donald K.; Wilbur, D. S.; Fisher, Darrell R.; Rajendran, Joseph G.; Gopal, Ajay K.; Park, Steven I.; Press, Oliver W.

    2009-08-06

    Pretargeted radioimmunotherapy (PRIT) is designed to enhance the directed delivery of radionuclides to malignant cells. Through a series of studies in nineteen nonhuman primates (M. fascicularis) the potential therapeutic advantage of anti-CD45 PRIT was evaluated. Anti-CD45 PRIT demonstrated a significant improvement in target-to-normal organ ratios of absorbed radiation when compared to directly radiolabeled bivalent antibody (conventional radioimmunotherapy [RIT]). Radio-DOTA-biotin administered 48 hours after anti-CD45 streptavidin fusion protein (FP) [BC8 (scFv)4SA] produced markedly lower concentrations of radiation in non-target tissues when compared to conventional RIT. PRIT generated superior target:normal organ ratios in the blood, lung and liver (10.3:1, 18.9:1 and 9.9:1 respectively) when compared to the conventional RIT controls (2.6:1, 6.4:1 and 2.9:1 respectively). The FP demonstrated superior retention in target tissues relative to comparable directly radiolabeled bivalent anti-CD45 RIT. The time-point of administration of the second step radiolabeled ligand (radio-DOTA-biotin) significantly impacted the biodistribution of radioactivity in target tissues. Rapid clearance of the FP from the circulation rendered unnecessary the addition of a synthetic clearing agent in this model. These results support proceeding to anti-CD45 PRIT clinical trials for patients with both leukemia and lymphoma.

  3. Effects of Chronic Manganese Exposure on Working Memory in Non-Human Primates

    PubMed Central

    Schneider, J.S.; Decamp, E.; Clark, K.; Bouquio, C.; Syversen, T.; Guilarte, T.R.

    2009-01-01

    Human exposure to manganese has been associated with a variety of cognitive deficits including learning and memory deficits. However, results from epidemiological studies have been inconsistent in describing the nature of such cognitive deficits. The present study was conducted to evaluate the effects of chronic Mn exposure on memory functioning in non-human primates and to correlate behavioral outcome with brain Mn levels in an attempt to explain outcome variability seen in prior studies. Cynomolgus macaque monkeys were trained to perform memory-related tasks (spatial working memory, non-spatial working memory, reference memory) and exposed to manganese sulfate (15–20 mg/kg/week) over an exposure period lasting 227.5 ± 17.3 days. Blood manganese levels were in the upper range of levels reported for human environmental, medical or occupational exposures. By the end of the manganese exposure period, animals developed mild deficits in spatial working memory, more significant deficits in non-spatial working memory and no deficits in reference memory. Linear regression analyses showed that for most brain regions sampled, there was a significant inverse relationship between working memory task performance and brain Mn concentration. These results suggest that chronic exposure to levels of manganese achieved in this study may have detrimental effects on working memory and that Mn levels achieved in several brain regions are inversely related to working memory performance. PMID:19133246

  4. Advantage of dichromats over trichromats in discrimination of color-camouflaged stimuli in nonhuman primates.

    PubMed

    Saito, Atsuko; Mikami, Akichika; Kawamura, Shoji; Ueno, Yoshikazu; Hiramatsu, Chihiro; Widayati, Kanthi A; Suryobroto, Bambang; Teramoto, Migaku; Mori, Yusuke; Nagano, Kunitoshi; Fujita, Kazuo; Kuroshima, Hika; Hasegawa, Toshikazu

    2005-12-01

    Due to a middle- to long-wavelength-sensitive (M/LWS) cone opsin polymorphism, there is considerable phenotypic variation in the color vision of New World monkeys. Many females have trichromatic vision, whereas some females and all males have dichromatic vision. The selective pressures that maintain this polymorphism are unclear. In the present study we compared the performance of dichromats and trichromats in a discrimination task. We examined tri- and dichromatic individuals of two species: brown capuchin monkeys (Cebus apella) and long-tailed macaques (Macaca fascicularis). We also examined one protanomalous chimpanzee (Pan troglodytes). The subjects' task was to discriminate a circular pattern from other patterns in which textural elements differed in orientation and thickness from the background. After they were trained with stimuli of a single color, the subjects were presented with color-camouflaged stimuli with a green/red mosaic overlaid onto the pattern. The dichromatic monkeys and the protanomalous chimpanzee selected the correct stimulus under camouflaged conditions at rates significantly above chance levels, while the trichromats did not. These findings demonstrate that dichromatic nonhuman primates possess a superior visual ability to discriminate color-camouflaged stimuli, and that such an ability may confer selective advantages with respect to the detection of cryptic foods and/or predators. PMID:16342068

  5. A thermostable bacterial cocaine esterase rapidly eliminates cocaine from brain in nonhuman primates

    PubMed Central

    Howell, L L; Nye, J A; Stehouwer, J S; Voll, R J; Mun, J; Narasimhan, D; Nichols, J; Sunahara, R; Goodman, M M; Carroll, F I; Woods, J H

    2014-01-01

    A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a KM of 1.33+0.085 μM. In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the first to evaluate the effects of CocE on cocaine brain levels. Positron emission tomogrpahy neuroimaging of [11C]cocaine was used to evaluate the time course of cocaine elimination from brain in the presence and absence of CocE in nonhuman primates. Systemic administration of CocE eliminated cocaine from the rhesus-monkey brain approximately three times faster than control conditions via peripheral actions through attenuating the input function from blood plasma. The efficiency of this process is sufficient to alleviate or prevent adverse central nervous system effects induced by cocaine. Although the present study used tracer doses of cocaine to access brain clearance, these findings further support the development of CocE for the treatment of acute cocaine toxicity. PMID:24984194

  6. Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels

    PubMed Central

    Killiany, Ronald J.

    2016-01-01

    Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on the posterior cingulate cortex, which is the “core hub” of the default mode network. In this study, 14 monkeys between 4 and 21 years were recruited, and MEGA-PRESS MRS was performed to measure GABA levels, in order to explore a potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r = −0.523, p = 0.081). There was also a near-significant trend between gray matter/white matter ratio and the GABA+/Creatine ratio (r = −0.518, p = 0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r = −0.028, p = 0.93). Therefore, age and gray matter/white matter ratio account for different part of R-squared (adjusted R-squared = 0.5187) as independent variables for predicting GABA levels. Adjusted R-squared is about 0.5 for two independent variables. These findings suggest that there is internal neurochemical variation of GABA levels in the nonhuman primates associated with normal aging and structural brain decline.

  7. Quantitative evaluation of MPTP-treated nonhuman parkinsonian primates in the HALLWAY task.

    PubMed

    Campos-Romo, Aurelio; Ojeda-Flores, Rafael; Moreno-Briseño, Pablo; Fernandez-Ruiz, Juan

    2009-03-15

    Parkinson's disease (PD) is a progressive neurodegenerative disorder. An experimental model of this disease is produced in nonhuman primates by the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this work, we put forward a new quantitative evaluation method that uses video recordings to measure the displacement, gate, gross and fine motor performance of freely moving subjects. Four Vervet monkeys (Cercopithecus aethiops) were trained in a behavioral observation hallway while being recorded with digital video cameras from four different angles. After MPTP intoxication the animals were tested without any drug and after 30 and 90 min of Levodopa/Carbidopa administration. Using a personal computer the following behaviors were measured and evaluated from the video recordings: displacement time across the hallway, reaching time towards rewards, ingestion time, number of attempts to obtain rewards, number of rewards obtained, and level of the highest shelf reached for rewards. Our results show that there was an overall behavioral deterioration after MPTP administration and an overall improvement after Levodopa/Carbidopa treatment. This demonstrates that the HALLWAY task is a sensitive and objective method that allows detailed behavioral evaluation of freely moving monkeys in the MPTP Parkinson's disease model.

  8. A non-human primate model of radiation-induced cachexia

    PubMed Central

    Cui, Wanchang; Bennett, Alexander W.; Zhang, Pei; Barrow, Kory R.; Kearney, Sean R.; Hankey, Kim G.; Taylor-Howell, Cheryl; Gibbs, Allison M.; Smith, Cassandra P.; MacVittie, Thomas J.

    2016-01-01

    Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20–25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease. PMID:27029502

  9. Automatic pose correction for image-guided nonhuman primate brain surgery planning

    NASA Astrophysics Data System (ADS)

    Ghafurian, Soheil; Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

    2016-03-01

    Intracranial delivery of recombinant DNA and neurochemical analysis in nonhuman primate (NHP) requires precise targeting of various brain structures via imaging derived coordinates in stereotactic surgeries. To attain targeting precision, the surgical planning needs to be done on preoperative three dimensional (3D) CT and/or MR images, in which the animals head is fixed in a pose identical to the pose during the stereotactic surgery. The matching of the image to the pose in the stereotactic frame can be done manually by detecting key anatomical landmarks on the 3D MR and CT images such as ear canal and ear bar zero position. This is not only time intensive but also prone to error due to the varying initial poses in the images which affects both the landmark detection and rotation estimation. We have introduced a fast, reproducible, and semi-automatic method to detect the stereotactic coordinate system in the image and correct the pose. The method begins with a rigid registration of the subject images to an atlas and proceeds to detect the anatomical landmarks through a sequence of optimization, deformable and multimodal registration algorithms. The results showed similar precision (maximum difference of 1.71 in average in-plane rotation) to a manual pose correction.

  10. Blood microsampling from the ear capillary in non-human primates.

    PubMed

    Lefevre, Arthur; Ballesta, Sébastien; Pozzobon, Mathieu; Charieau, Jean-Luc; Duperrier, Sandra; Sirigu, Angela; Duhamel, Jean-René

    2015-10-01

    Blood sampling from awake non-human primates (NHPs) is classically performed under constraint in the cephalic or saphenous vein. It is a challenging, potentially harmful and stressful procedure which may lead to biased results and raises ethical concerns. Laboratory NHPs undergo a head-restrained procedure allowing for a safer procedure of collecting blood from their ears. Using regular capillary blood collection devices 500 µL of blood can be easily withdrawn per puncture point, which is sufficient for performing most of the usual modern biological assays. This procedure has been validated by measuring total proteins, cortisol and vasopressin concentrations from concomitant blood samples taken from the saphenous vein and the ear capillary vessels of macaques (n = 16). We observed strong correlations between the blood concentrations of total proteins, cortisol and vasopressin (r = 0.72, r = 0.63, r = 0.83, respectively; all P values <0.01) taken from the saphenous vein and from the ear capillary. There were no significant differences between blood concentrations taken from the saphenous vein and the ear capillary. Our alternative to the classical blood collection procedure is harmless and can be routinely performed, which can therefore improve scientific results while increasing animal welfare in accordance with the 3R (replacement, reduction and refinement) principles.

  11. Lipid nanoparticle siRNA treatment of Ebola-virus-Makona-infected nonhuman primates.

    PubMed

    Thi, Emily P; Mire, Chad E; Lee, Amy C H; Geisbert, Joan B; Zhou, Joy Z; Agans, Krystle N; Snead, Nicholas M; Deer, Daniel J; Barnard, Trisha R; Fenton, Karla A; MacLachlan, Ian; Geisbert, Thomas W

    2015-05-21

    The current outbreak of Ebola virus in West Africa is unprecedented, causing more cases and fatalities than all previous outbreaks combined, and has yet to be controlled. Several post-exposure interventions have been employed under compassionate use to treat patients repatriated to Europe and the United States. However, the in vivo efficacy of these interventions against the new outbreak strain of Ebola virus is unknown. Here we show that lipid-nanoparticle-encapsulated short interfering RNAs (siRNAs) rapidly adapted to target the Makona outbreak strain of Ebola virus are able to protect 100% of rhesus monkeys against lethal challenge when treatment was initiated at 3 days after exposure while animals were viraemic and clinically ill. Although all infected animals showed evidence of advanced disease including abnormal haematology, blood chemistry and coagulopathy, siRNA-treated animals had milder clinical features and fully recovered, while the untreated control animals succumbed to the disease. These results represent the first, to our knowledge, successful demonstration of therapeutic anti-Ebola virus efficacy against the new outbreak strain in nonhuman primates and highlight the rapid development of lipid-nanoparticle-delivered siRNA as a countermeasure against this highly lethal human disease.

  12. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection.

    PubMed

    Geisbert, Thomas W; Strong, James E; Feldmann, Heinz

    2015-10-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions.

  13. Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates.

    PubMed

    Jackowski, Andrea; Perera, Tarique D; Abdallah, Chadi G; Garrido, Griselda; Tang, Cheuk Y; Martinez, Jose; Mathew, Sanjay J; Gorman, Jack M; Rosenblum, Leonard A; Smith, Eric L P; Dwork, Andrew J; Shungu, Dikoma C; Kaffman, Arie; Gelernter, Joel; Coplan, Jeremy D; Kaufman, Joan

    2011-04-30

    Male bonnet monkeys (Macaca radiata) were subjected to the variable foraging demand (VFD) early stress paradigm as infants, MRI scans were completed an average of 4 years later, and behavioral assessments of anxiety and ex-vivo corpus callosum (CC) measurements were made when animals were fully matured. VFD rearing was associated with smaller CC size, CC measurements were found to correlate with fearful behavior in adulthood, and ex-vivo CC assessments showed high consistency with earlier MRI measures. Region of interest (ROI) hippocampus and whole brain voxel-based morphometry assessments were also completed and VFD rearing was associated with reduced hippocampus and inferior and middle temporal gyri volumes. The animals were also characterized according to serotonin transporter genotype (5-HTTLPR), and the effect of genotype on imaging parameters was explored. The current findings highlight the importance of future research to better understand the effects of stress on brain development in multiple regions, including the corpus callosum, hippocampus, and other regions involved in emotion processing. Nonhuman primates provide a powerful model to unravel the mechanisms by which early stress and genetic makeup interact to produce long-term changes in brain development, stress reactivity, and risk for psychiatric disorders.

  14. Transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus.

    PubMed

    Garamszegi, Sara; Yen, Judy Y; Honko, Anna N; Geisbert, Joan B; Rubins, Kathleen H; Geisbert, Thomas W; Xia, Yu; Hensley, Lisa E; Connor, John H

    2014-01-01

    Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has been previously demonstrated that anticoagulant therapeutics increase the survival rate in EBOV-infected NHPs, and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated NHPs. In order to identify transcriptional signatures that correlate with survival following EBOV infection, we compared the mRNA expression profile in peripheral blood mononuclear cells from EBOV-infected NHPs that received anticoagulant treatment, to those that did not receive treatment. We identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. In addition, we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses, such as the inflammatory response, T cell death, and inhibition of viral replication. Notably, among survival-associated genes were subsets of genes that are transcriptionally regulated by (1) CCAAT/enhancer-binding protein alpha, (2) tumor protein 53, and (3) megakaryoblastic leukemia 1 and myocardin-like protein 2. These pathways merit further investigation as potential transcriptional signatures of host immune response to EBOV infection. PMID:25079789

  15. Behavioral and neurobiological characteristics of social stress versus depression in nonhuman primates.

    PubMed

    Shively, Carol A; Willard, Stephanie L

    2012-01-01

    The focus of the review is on the behavioral and physiological manifestations of stress versus depression. The purpose of the review is to evaluate the conceptual approach of using stress models as surrogates for depression. Social stress and depression have many characteristics in common and promote each other. Both have adverse effects on social relationships and the quality of life, and increase risk of other diseases. However, they are not the same constructs. In human and nonhuman primates, the behavior and neurobiology of stressed individuals differ from that of depressed individuals. Some similarities in stress physiology in socially stressed and depressed individuals have been used to support the use of stressed animals as models of depression, and much has been learned from stress models of depression. However, the studies reviewed here also suggest that the depressed state also has different characteristics than the stressed state, and studying the differences may be important to furthering our understanding of each of these constructs as well as their mutual relationship.

  16. Learning of spatial statistics in nonhuman primates: contextual cueing in baboons (Papio papio).

    PubMed

    Goujon, Annabelle; Fagot, Joel

    2013-06-15

    A growing number of theories of cognition suggest that many of our behaviors result from the ability to implicitly extract and use statistical redundancies present in complex environments. In an attempt to develop an animal model of statistical learning mechanisms in humans, the current study investigated spatial contextual cueing (CC) in nonhuman primates. Twenty-five baboons (Papio papio) were trained to search for a target (T) embedded within configurations of distrators (L) that were either predictive or non-predictive of the target location. Baboons exhibited an early CC effect, which remained intact after a 6-week delay and stable across extensive training of 20,000 trials. These results demonstrate the baboons' ability to learn spatial contingencies, as well as the robustness of CC as a cognitive phenomenon across species. Nevertheless, in both the youngest and oldest baboons, CC required many more trials to emerge than in baboons of intermediate age. As a whole, these results reveal strong similarities between CC in humans and baboons, suggesting similar statistical learning mechanisms in these two species. Therefore, baboons provide a valid model to investigate how statistical learning mechanisms develop and/or age during the life span, as well as how these mechanisms are implemented in neural networks, and how they have evolved throughout the phylogeny.

  17. Nonhuman primates will not respond to turn off strong 60 Hz electric fields

    SciTech Connect

    Rogers, W.R.; Orr, J.L.; Smith, H.D.

    1995-12-31

    Using a set of six baboons (Papio cynocephalus), the authors conducted a series of seven experiments designed to evaluate the potentially aversive character of a 60 Hz electric field (EF). Initially, the subjects were trained, using food rewards as the reinforcer, to respond only when a cue light was illuminated. Next, an EF was presented along with the cue light; responses produced delivery of a food pellet and turned off both the cue light and the EF. Then, stimulus and reward conditions were varied. The authors determined that (1) presence of a strong EF does not affect operant responding for food rewards, (2) subjects will not respond at normal rates when the only reinforcer is termination of a strong EF, (3) presence of a strong EF can serve as a discriminative stimulus, (4) presence of a strong EF does not affect extinction of an appetite-motivated task, and (5) presentation of an EF can become a secondary reinforcer. The pattern of results was consistent across all experiments, suggesting that an EF of as much as 65 kV/m is not aversive to nonhuman primates. Separately, the authors demonstrated that the average EF detection threshold for baboons is 12 kV/m. Thus, EF exposure at intensities well above the detection threshold and at species-scaled EF strengths greater than those found environmentally does not appear to be aversive.

  18. Neurovirulence Properties of Recombinant Vesicular Stomatitis Virus Vectors in Non-Human Primates

    PubMed Central

    Johnson, J. Erik; Nasar, Farooq; Coleman, John W.; Price, Roger E.; Javadian, Ali; Draper, Kenneth; Lee, Margaret; Reilly, Patricia A.; Clarke, David K.; Hendry, R. Michael; Udem, Stephen A.

    2007-01-01

    Although vesicular stomatitis virus (VSV) neurovirulence and pathogenicity in rodents have been well studied, little is known about VSV pathogenicity in non-human primates. To address this question, we measured VSV viremia, shedding, and neurovirulence in macaques. Following intranasal inoculation, macaques shed minimal recombinant VSV (rVSV) in nasal washes for one day post-inoculation; viremia was not detected. Following intranasal inoculation of macaques, wild type (wt) VSV, rVSV, and two rVSV-HIV vectors showed no evidence of spread to CNS tissues. However, macaques inoculated intrathalamically with wt VSV developed severe neurological disease. One of four macaques receiving rVSV developed clinical and histological signs similar to the wt group, while the remaining three macaques in this group and all of the macaques in the rVSV-HIV vector groups showed no clinical signs of disease and reduced severity of histopathology compared to the wt group. The implications of these findings for rVSV vaccine development are discussed. PMID:17098273

  19. Calretinin expression in hilar mossy cells of the hippocampal dentate gyrus of nonhuman primates and humans.

    PubMed

    Seress, László; Abrahám, Hajnalka; Czéh, Boldizsár; Fuchs, Eberhard; Léránth, Csaba

    2008-01-01

    Mossy cells, the major excitatory neurons of the hilus of the dentate gyrus constitutively express calretinin in several rodent species, including mouse and hamster, but not in rats. Several studies suggest that mossy cells of the monkey dentate gyrus are calretinin-positive, but others have reported mossy cells in monkeys to be devoid of detectable calretinin-like immunoreactivity. In the present study, the hilar region was investigated throughout the entire longitudinal extent of the hippocampal dentate gyrus in both Old World and New World monkeys, as well as in humans. In the examined four monkey species, mossy cells were found to be calretinin-positive at the uncal pole and at variable length within the main body of the dentate gyrus but not in the tail part. The associational pathway, formed by axons of mossy cells in the inner dentate molecular layer was calretinin-positive in more caudal sections, suggesting that mossy cell axon terminals may contain calretinin, whereas mossy cell somata may contain calretinin in a concentration too low to be detected by immunocytochemistry. In contrast, human mossy cells appear to be devoid of calretinin immunoreactivity in both their somata and their axon terminals. Taken together, mossy cells of nonhuman primates and humans exhibit different expression pattern for calretinin whereas they show similarities in neurochemical content, such as the cocaine and amphetamine-related transcript peptide. PMID:18189312

  20. Millimeter wave absorption in the nonhuman primate eye at 35 GHz and 94 GHz.

    PubMed

    Chalfin, Steven; D'Andrea, John A; Comeau, Paul D; Belt, Michael E; Hatcher, Donald J

    2002-07-01

    The purpose of this study was to evaluate anterior segment bioeffects of pulsed 35 GHz and 94 GHz microwave exposure in the nonhuman primate eye. Five juvenile rhesus monkeys (Macaca mulatta) underwent baseline anterior segment ocular assessment consisting of slit lamp examination, corneal topography, specular microscopy, and pachymetry. These studies were repeated after exposure of one eye to pulsed 35 GHz or 94 GHz microwaves at varied fluences, with the other eye serving as a control. The mean fluence required to produce a threshold corneal lesion (faint epithelial edema and fluorescein staining) was 7.5 J cm(-2) at 35 GHz and 5 J cm(-2) at 94 GHz. Transient changes in corneal topography and pachymetry were noted at these fluences. Endothelial cell counts remained unchanged. Threshold corneal injury from 35 GHz and 94 GHz microwave exposure is produced at fluences below those previously reported for CO2 laser radiation. These data may help elucidate the mechanism of thermal injury to the cornea, and resolve discrepancies between IEEE C95.1 (1999), NCRP (1986), and ICNIRP (1998) safety standards for exposure to non-ionizing radiation at millimeter wavelengths.

  1. Genome editing in nonhuman primates: approach to generating human disease models.

    PubMed

    Chen, Y; Niu, Y; Ji, W

    2016-09-01

    Nonhuman primates (NHPs) are superior than rodents to be animal models for the study of human diseases, due to their similarities in terms of genetics, physiology, developmental biology, social behaviour and cognition. Transgenic animals have become a key tool in functional genomics to generate models for human diseases and validate new drugs. However, until now, progress in the field of transgenic NHPs has been slow because of technological limitations. Many human diseases, including neurodegenerative disorders, are caused by mutations in endogenous genes. Fortunately, recent developments in precision gene editing have led to the generation of NHP models for human diseases. Since 2014, there have been several reports of the generation of monkey models using transcription activator-like endonucleases (TALENs) or clustered regularly interspaced short palindromic repeats (CRISPR/Cas9); some of these NHP models showed symptoms that were much closer to those of human diseases than have been seen previously in mouse models. No off-targeting was observed in the NHP models, and multiple gene knockout and biallelic mutants were feasible with low efficiency. These findings suggest that there are many possibilities to establish NHP models for human diseases that can mimic human diseases more faithfully than rodent models.

  2. A critical evaluation of developmental and reproductive toxicology in nonhuman primates.

    PubMed

    Faqi, Ali S

    2012-02-01

    The nonhuman primates (NHPs) are used in many areas of biomedical research where their similarities to humans make them exclusively valuable animal models. The use of NHPs in pre-clinical testing is expected to increase due to the increase in the development of biological compounds for therapeutic uses. The regulatory agencies around the world including Food and Drug Administration (FDA) generally requires developmental and reproductive toxicity (DART) testing of all new drugs to be used by women of childbearing age or men of reproductive potential. NHPs are most frequently used for DART testing when commonly used rodents and/or rabbits are not pharmacologically relevant species. Animal studies are unique in that assessment of reproduction and development as DART studies are not performed in controlled clinical trials; therefore, pre-clinical safety assessment forms the basis for risk assessment for marketed drug products. This paper provides a critical evaluation of developmental and reproductive toxicity studies in NHPs. The manuscript will focus on species selection, limitation of International Conference for Harmonization stages (A-F) using NHPs as a test system, study designs, logistical/technical challenges, and strength, and limitations. It will also pinpoint confounding factors inherent to the test system that may complicate the interpretation of the NHP DART data. PMID:22239078

  3. Symptomatic Models of Parkinson's Disease and L-DOPA-Induced Dyskinesia in Non-human Primates.

    PubMed

    Johnston, Tom M; Fox, Susan H

    2015-01-01

    Models of Parkinson's disease (PD) can be produced in several non-human primate (NHP) species by applying neurotoxic lesions to the nigrostriatal dopamine pathway. The most commonly used neurotoxin is MPTP, a compound accidentally discovered as a contaminant of street drugs. Compared to other neurotoxins, MPTP has the advantage of crossing the blood-brain barrier and can thus be administered systemically. MPTP-lesioned NHPs exhibit the main core clinical features of PD. When treated with L-DOPA, these NHP models develop involuntary movements resembling the phenomenology of human dyskinesias. In old-world NHP species (macaques, baboons), choreic and dystonic dyskinesias can be readily distinguished and quantified with specific rating scales. More recently, certain non-motor symptoms relevant to human PD have been described in L-DOPA-treated MPTP-NHPs, including a range of neuropsychiatric abnormalities and sleep disturbances. The main shortcomings of MPTP-NHP models consist in a lack of progression of the underlying neurodegenerative lesion, along with an inability to model the intracellular protein-inclusion pathology typical of PD. The strength of MPTP-NHP models lies in their face and predictive validity for symptomatic treatments of parkinsonian motor features. Indeed, these models have been instrumental to the development of several medical and surgical approaches that are currently applied to treat PD. PMID:25158623

  4. Non-human primates in neuroscience research: The case against its scientific necessity.

    PubMed

    Bailey, Jarrod; Taylor, Kathy

    2016-03-01

    Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP research generally, but here we specifically focus on the development and interpretation of functional magnetic resonance imaging (fMRI), deep brain stimulation (DBS), the understanding of neural oscillations and memory, and investigation of the neural control of movement and of vision/binocular rivalry. The increasing power of human-specific methods, including advances in fMRI and invasive techniques such as electrocorticography and single-unit recordings, is discussed. These methods serve to render NHP approaches redundant. We conclude that the defence of NHP use is groundless, and that neuroscience would be more relevant and successful for humans, if it were conducted with a direct human focus. We have confidence in opposing NHP neuroscience, both on scientific as well as on ethical grounds.

  5. Non-human primate FOG develops with advanced parkinsonism induced by MPTP Treatment.

    PubMed

    Revuelta, Gonzalo J; Uthayathas, Subramaniam; Wahlquist, Amy E; Factor, Stewart A; Papa, Stella M

    2012-10-01

    Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) and other forms of parkinsonism. The anatomical or pathophysiological correlates are poorly understood largely due to the lack of a well-established animal model. Here we studied whether FOG is reproduced in the non-human primate (NHP) model of PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (Genus Macaca, n=29) were examined for the development of FOG, and the leg movements were recorded with accelerometry. The relationships between developing FOG and the animals' characteristics, the MPTP treatments, and the modeled outcomes were determined. In parkinsonian monkeys FOG developed frequently (48%) manifesting similar characteristics to those seen in PD patients. In addition, FOG episodes in the monkey were accompanied by leg trembling with the typical duration (2-10s) and frequency (~7 Hz). The development of NHP FOG was significantly associated with the severity of parkinsonism, as shown by high motor disability scores (≥ 20) and levodopa-induced dyskinesia scores (p=0.01 and p=0.04, respectively). Differences in demographics and MPTP treatments (doses, treatment duration, etc.) had no influence on NHP FOG occurrence, with the exception of gender that showed FOG predominance in males (p=0.03). The unique features of FOG in PD can be replicated in severely parkinsonian macaques, and this represents the first description of a FOG animal model.

  6. Considerations in the Use of Nonhuman Primate Models of Ebola Virus and Marburg Virus Infection

    PubMed Central

    Geisbert, Thomas W.; Strong, James E.; Feldmann, Heinz

    2015-01-01

    The filoviruses, Ebola virus and Marburg virus, are zoonotic pathogens that cause severe hemorrhagic fever in humans and nonhuman primates (NHPs), with case-fatality rates ranging from 23% to 90%. The current outbreak of Ebola virus infection in West Africa, with >26 000 cases, demonstrates the long-underestimated public health danger that filoviruses pose as natural human pathogens. Currently, there are no vaccines or treatments licensed for human use. Licensure of any medical countermeasure may require demonstration of efficacy in the gold standard cynomolgus or rhesus macaque models of filovirus infection. Substantial progress has been made over the last decade in characterizing the filovirus NHP models. However, there is considerable debate over a variety of experimental conditions, including differences among filovirus isolates used, routes and doses of exposure, and euthanasia criteria, all of which may contribute to variability of results among different laboratories. As an example of the importance of understanding these differences, recent data with Ebola virus shows that an addition of a single uridine residue in the glycoprotein gene at the editing site attenuates the virus. Here, we draw on decades of experience working with filovirus-infected NHPs to provide a perspective on the importance of various experimental conditions. PMID:26063223

  7. Transcriptomal changes and functional annotation of the developing non-human primate choroid plexus

    PubMed Central

    Ek, C. Joakim; Nathanielsz, Peter; Li, Cun; Mallard, Carina

    2015-01-01

    The choroid plexuses are small organs that protrude into each brain ventricle producing cerebrospinal fluid that constantly bathes the brain. These organs differentiate early in development just after neural closure at a stage when the brain is little vascularized. In recent years the plexus has been shown to have a much more active role in brain development than previously appreciated thereby it can influence both neurogenesis and neural migration by secreting factors into the CSF. However, much of choroid plexus developmental function is still unclear. Most previous studies on this organ have been undertaken in rodents but translation into humans is not straightforward since they have a different timing of brain maturation processes. We have collected choroid plexus from three fetal gestational ages of a non-human primate, the baboon, which has much closer brain development to humans. The transcriptome of the plexuses was determined by next generation sequencing and Ingenuity Pathway Analysis software was used to annotate functions and enrichment of pathways of changes in the transcriptome. The number of unique transcripts decreased with development and the majority of differentially expressed transcripts were down-regulated through development suggesting a more complex and active plexus earlier in fetal development. The functional annotation indicated changes across widespread biological functions in plexus development. In particular we find age-dependent regulation of genes associated with annotation categories: Gene Expression, Development of Cardiovascular System, Nervous System Development and Molecular Transport. Our observations support the idea that the choroid plexus has roles in shaping brain development. PMID:25814924

  8. Benchmark dose analysis for Bacillus anthracis inhalation exposures in the nonhuman primate.

    PubMed

    Taft, Sarah C; Hines, Stephanie A

    2012-10-01

    There is considerable variability in the published lethality values for inhalation exposures of Bacillus anthracis. The lack of consensus on an acceptable dose-response relationship poses a significant challenge in the development of risk-based management approaches for use following a terrorist release of B. anthracis spores. This article reviewed available B. anthracis dose-response modeling and literature for the nonhuman primate, evaluated the use of the U.S. Environmental Protection Agency's Benchmark Dose Software (BMDS) to fit mathematical dose-response models to these data, and reported results of the benchmark dose analysis of suitable data sets. The BMDS was found to be a useful tool to evaluate dose-response relationships in microbial data, including that from B. anthracis exposure. An evaluation of the sources of variability identified in the published lethality data and the corresponding BMDS-derived lethality values found that varying levels of physical characterization of the spore product, differing receptor-specific exposure assumptions, choice of dose metrics, and the selected statistical methods all contributed to differences in lethality estimates. Recognition of these contributors to variability could ultimately facilitate agreement on a B. anthracis dose-response relationship through provision of a common description of necessary study considerations for acceptable dose-response data sets.

  9. Isolation of Anti-Ricin Protective Antibodies Exhibiting High Affinity from Immunized Non-Human Primates

    PubMed Central

    Noy-Porat, Tal; Rosenfeld, Ronit; Ariel, Naomi; Epstein, Eyal; Alcalay, Ron; Zvi, Anat; Kronman, Chanoch; Ordentlich, Arie; Mazor, Ohad

    2016-01-01

    Ricin, derived from the castor bean plant Ricinus communis, is one of the most potent and lethal toxins known, against which there is no available antidote. To date, the use of neutralizing antibodies is the most promising post-exposure treatment for ricin intoxication. The aim of this study was to isolate high affinity anti-ricin antibodies that possess potent toxin-neutralization capabilities. Two non-human primates were immunized with either a ricin-holotoxin- or subunit-based vaccine, to ensure the elicitation of diverse high affinity antibodies. By using a comprehensive set of primers, immune scFv phage-displayed libraries were constructed and panned. A panel of 10 antibodies (five directed against the A subunit of ricin and five against the B subunit) was isolated and reformatted into a full-length chimeric IgG. All of these antibodies were found to neutralize ricin in vitro, and several conferred full protection to ricin-intoxicated mice when given six hours after exposure. Six antibodies were found to possess exceptionally high affinity toward the toxin, with KD values below pM (koff < 1 × 10−7 s−1) that were well correlated with their ability to neutralize ricin. These antibodies, alone or in combination, could be used for the development of a highly-effective therapeutic preparation for post-exposure treatment of ricin intoxication. PMID:26950154

  10. Gastrointestinal protozoa in non-human primates of four zoological gardens in Belgium.

    PubMed

    Levecke, Bruno; Dorny, Pierre; Geurden, Thomas; Vercammen, Francis; Vercruysse, Jozef

    2007-09-30

    Gastrointestinal parasites are important infectious causes of diarrhoea in captive non-human primates (NHP). However, prevalence data of gastrointestinal parasites in zoological gardens are scarce. Therefore, a cross-sectional survey was conducted to estimate the occurrence of gastrointestinal parasites in NHP of four zoological gardens in Belgium. Between August 2004 and April 2006, 910 faecal samples were collected from 222 animals housed in 39 groups. The 31 species involved were representatives of prosimians, New World (NW) monkeys, Old World (OW) monkeys and apes. Because individual sampling was impossible, a statistical simulation was performed to estimate a sufficient sample size. All samples were microscopically examined after an acetic acid-ether concentration. Differences in host species susceptibility were examined by non-parametric tests. Entamoeba spp. (44%) and Giardia spp. (41%) were the most prevalent species. Other parasites detected were Endolimax nana (36%), Chilomastix mesnili (21%), Balantidium coli (13%), Trichuris spp. (10%), Iodamoeba bütschlii (5%) and Strongyloides spp. (5%). Parasites for which a significant difference in susceptibility at the level of host taxonomy was noted were Entamoeba spp. (p<0.001) and C. mesnili (p<0.05). Samples containing Entamoeba spp. were the most prevalent in OW monkeys (p<0.0083). Samples collected from OW monkeys contained the highest number of parasite species (p<0.0083). PMID:17656023

  11. Nonhuman Primate Models of Depression: Effects of Early Experience and Stress

    PubMed Central

    Worlein, Julie M.

    2014-01-01

    Depression causes significant morbidity in the human population. The Diathesis-Stress/Two-Hit model of depression hypothesizes that stress interacts with underlying (probably genetic) predispositions to produce a central nervous system that is primed to express psychopathology when confronted with stressful experiences later in life. Nonhuman primate (NHP) studies have been extensively utilized to test this model. NHPs are especially useful for studying effects of early experience, because many aspects of NHP infancy are similar to humans, whereas development occurs at an accelerated rate and therefore allows for more rapid assessment of experimental variables. In addition, the ability to manipulate putative risk factors, including introducing experimental stress during development, allows inference of causality not possible with human studies. This manuscript reviews experimental paradigms that have been utilized to model early adverse experience in NHPs, including peer-rearing, maternal separation, and variable foraging. It also provides examples of how this model has been used to investigate the effects of early experience on later neurobiology, physiology, and behavior associated with depression. We conclude that the NHP offers an excellent model to research mechanisms contributing to the Diathesis-Stress/Two-Hit model of depression. PMID:25225305

  12. Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections

    PubMed Central

    Freiden, Pamela; Feeroz, MM; Matsen, Frederick A; San, Sorn; Hasan, M Kamrul; Wang, David; Jones-Engel, Lisa; Schultz-Cherry, Stacey

    2015-01-01

    Astroviruses (AstVs) are positive sense, single-stranded RNA viruses transmitted to a wide range of hosts via the fecal-oral route. The number of AstV-infected animal hosts has rapidly expanded in recent years with many more likely to be discovered because of the advances in viral surveillance and next generation sequencing. Yet no study to date has identified human AstV genotypes in animals, although diverse AstV genotypes similar to animal-origin viruses have been found in children with diarrhea and in one instance of encephalitis. Here we provide important new evidence that non-human primates (NHP) can harbor a wide variety of mammalian and avian AstV genotypes, including those only associated with human infection. Serological analyses confirmed that >25% of the NHP tested had antibodies to human AstVs. Further, we identified a recombinant AstV with parental relationships to known human AstVs. Phylogenetic analysis suggests AstVs in NHP are on average evolutionarily much closer to AstVs from other animals than are AstVs from bats, a frequently proposed reservoir. Our studies not only demonstrate that human astroviruses can be detected in NHP but also suggest that NHP are unique in their ability to support diverse AstV genotypes, further challenging the paradigm that astrovirus infection is species-specific. PMID:26571270

  13. Cortical Innervation of the Hypoglossal Nucleus in the Non-Human Primate (Macaca mulatta)

    PubMed Central

    Morecraft, Robert J.; Stilwell-Morecraft, Kimberly S.; Solon-Cline, Kathryn M.; Ge, Jizhi; Darling, Warren G.

    2014-01-01

    The corticobulbar projection to the hypoglossal nucleus was studied from the frontal, parietal, cingulate and insular cortices in the rhesus monkey using high-resolution anterograde tracers and stereology. The hypoglossal nucleus received bilateral input from the face/head region of the primary (M1), ventrolateral pre- (LPMCv), supplementary (M2), rostral cingulate (M3), and caudal cingulate (M4) motor cortices. Additional bilateral corticohypoglossal projections were found from the dorsolateral premotor cortex (LPMCd), ventrolateral proisocortical motor area (ProM), ventrolateral primary somatosensory cortex (S1), rostral insula and pregenual region of the anterior cingulate gyrus (areas 24/32). Dense terminal projections arose from the ventral region of M1, moderate projections from LPMCv and rostral part of M2, with considerably less hypoglossal projections arising from the other cortical regions. These findings demonstrate that extensive regions of the non-human primate cerebral cortex innervate the hypoglossal nucleus. The widespread and bilateral nature of this corticobulbar connection suggests recovery of tongue movement after cortical injury that compromises a subset of these areas, may occur from spared corticohypoglossal projection areas located on the lateral, as well as medial surfaces of both hemispheres. Since functional imaging studies have shown that homologous cortical areas are activated in humans during tongue movement tasks, these corticobulbar projections may exist in the human brain. PMID:24752643

  14. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

    PubMed

    Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik F; Persson, Robert; Møller, Marianne R; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen M; Koch, Troels

    2012-02-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two locked nucleic acid (LNA) antisense oligonucleotides targeting PCSK9 produce sustained reduction of LDL-C in nonhuman primates after a loading dose (20 mg/kg) and four weekly maintenance doses (5 mg/kg). PCSK9 messenger RNA (mRNA) and serum PCSK9 protein were reduced by 85% which resulted in a 50% reduction in circulating LDL-C. Serum total cholesterol (TC) levels were reduced to the same extent as LDL-C with no reduction in high-density lipoprotein levels, demonstrating a specific pharmacological effect on LDL-C. The reduction in hepatic PCSK9 mRNA correlated with liver LNA oligonucleotide content. This verified that anti-PCSK9 LNA oligonucleotides regulated LDL-C through an antisense mechanism. The compounds were well tolerated with no observed effects on toxicological parameters (liver and kidney histology, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine). The pharmacologic evidence and initial safety profile of the compounds used in this study indicate that LNA antisense oligonucleotides targeting PCSK9 provide a viable therapeutic strategy and are potential complements to statins in managing high LDL-C.

  15. Laser-induced retinal nerve fiber layer injury in the nonhuman primate

    NASA Astrophysics Data System (ADS)

    Zwick, Harry; Belkin, Michael; Zuclich, Joseph A.; Lund, David J.; Schuschereba, Steven T.; Scales, David K.

    1996-04-01

    We have evaluated the acute effects of Argon laser injury to the retinal nerve fiber layer (NFL) in the non-human primate. Single Argon laser exposures of 150 millijoules were employed to induce retinal NFL injury. Retinal NFL injury is not acute; unlike its parallel in retinal disease it has two components that emanate from the acute retinal injury site. The ascending component is more visible, primarily because it is ascending toward the disk, representing ganglion cell axons cut off from their nutrient base, the ganglion cell body; the descending component may require up to 3 weeks to develop. Its characterization depends on the distribution of retinal NFL and the slower degeneration of the ganglion cell bodies. Fluorescein angiography suggest a retinal capillary loss that occurs in the capillary bed of the retinal NFL defect. It may reflect a reduced capillary vascular requirement of the NFL as well as a possible reduction of activity in the axonal transport mechanisms in the ascending NFL defect.

  16. Benchmark dose analysis for Bacillus anthracis inhalation exposures in the nonhuman primate.

    PubMed

    Taft, Sarah C; Hines, Stephanie A

    2012-10-01

    There is considerable variability in the published lethality values for inhalation exposures of Bacillus anthracis. The lack of consensus on an acceptable dose-response relationship poses a significant challenge in the development of risk-based management approaches for use following a terrorist release of B. anthracis spores. This article reviewed available B. anthracis dose-response modeling and literature for the nonhuman primate, evaluated the use of the U.S. Environmental Protection Agency's Benchmark Dose Software (BMDS) to fit mathematical dose-response models to these data, and reported results of the benchmark dose analysis of suitable data sets. The BMDS was found to be a useful tool to evaluate dose-response relationships in microbial data, including that from B. anthracis exposure. An evaluation of the sources of variability identified in the published lethality data and the corresponding BMDS-derived lethality values found that varying levels of physical characterization of the spore product, differing receptor-specific exposure assumptions, choice of dose metrics, and the selected statistical methods all contributed to differences in lethality estimates. Recognition of these contributors to variability could ultimately facilitate agreement on a B. anthracis dose-response relationship through provision of a common description of necessary study considerations for acceptable dose-response data sets. PMID:22469218

  17. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model)

    PubMed Central

    Broeckel, Rebecca; Haese, Nicole; Messaoudi, Ilhem; Streblow, Daniel N.

    2015-01-01

    Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs) serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis. PMID:26389957

  18. Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels

    PubMed Central

    Killiany, Ronald J.

    2016-01-01

    Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on the posterior cingulate cortex, which is the “core hub” of the default mode network. In this study, 14 monkeys between 4 and 21 years were recruited, and MEGA-PRESS MRS was performed to measure GABA levels, in order to explore a potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r = −0.523, p = 0.081). There was also a near-significant trend between gray matter/white matter ratio and the GABA+/Creatine ratio (r = −0.518, p = 0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r = −0.028, p = 0.93). Therefore, age and gray matter/white matter ratio account for different part of R-squared (adjusted R-squared = 0.5187) as independent variables for predicting GABA levels. Adjusted R-squared is about 0.5 for two independent variables. These findings suggest that there is internal neurochemical variation of GABA levels in the nonhuman primates associated with normal aging and structural brain decline. PMID:27660760

  19. Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells.

    PubMed

    Novobrantseva, Tatiana I; Borodovsky, Anna; Wong, Jamie; Klebanov, Boris; Zafari, Mohammad; Yucius, Kristina; Querbes, William; Ge, Pei; Ruda, Vera M; Milstein, Stuart; Speciner, Lauren; Duncan, Rick; Barros, Scott; Basha, Genc; Cullis, Pieter; Akinc, Akin; Donahoe, Jessica S; Narayanannair Jayaprakash, K; Jayaraman, Muthusamy; Bogorad, Roman L; Love, Kevin; Whitehead, Katie; Levins, Chris; Manoharan, Muthiah; Swirski, Filip K; Weissleder, Ralph; Langer, Robert; Anderson, Daniel G; de Fougerolles, Antonin; Nahrendorf, Matthias; Koteliansky, Victor

    2012-01-01

    Leukocytes are central regulators of inflammation and the target cells of therapies for key diseases, including autoimmune, cardiovascular, and malignant disorders. Efficient in vivo delivery of small interfering RNA (siRNA) to immune cells could thus enable novel treatment strategies with broad applicability. In this report, we develop systemic delivery methods of siRNA encapsulated in lipid nanoparticles (LNP) for durable and potent in vivo RNA interference (RNAi)-mediated silencing in myeloid cells. This work provides the first demonstration of siRNA-mediated silencing in myeloid cell types of nonhuman primates (NHPs) and establishes the feasibility of targeting multiple gene targets in rodent myeloid cells. The therapeutic potential of these formulations was demonstrated using siRNA targeting tumor necrosis factor-α (TNFα) which induced substantial attenuation of disease progression comparable to a potent antibody treatment in a mouse model of rheumatoid arthritis (RA). In summary, we demonstrate a broadly applicable and therapeutically relevant platform for silencing disease genes in immune cells. PMID:23344621

  20. A thermostable bacterial cocaine esterase rapidly eliminates cocaine from brain in nonhuman primates.

    PubMed

    Howell, L L; Nye, J A; Stehouwer, J S; Voll, R J; Mun, J; Narasimhan, D; Nichols, J; Sunahara, R; Goodman, M M; Carroll, F I; Woods, J H

    2014-01-01

    A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a K(M) of 1.33+0.085 μM. In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the first to evaluate the effects of CocE on cocaine brain levels. Positron emission tomogrpahy neuroimaging of [(11)C]cocaine was used to evaluate the time course of cocaine elimination from brain in the presence and absence of CocE in nonhuman primates. Systemic administration of CocE eliminated cocaine from the rhesus-monkey brain approximately three times faster than control conditions via peripheral actions through attenuating the input function from blood plasma. The efficiency of this process is sufficient to alleviate or prevent adverse central nervous system effects induced by cocaine. Although the present study used tracer doses of cocaine to access brain clearance, these findings further support the development of CocE for the treatment of acute cocaine toxicity. PMID:24984194

  1. Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration

    PubMed Central

    Freeman, Willard M.; VanGuilder, Heather D.; Guidone, Elizabeth; Krystal, John H.; Grant, Kathleen A.; Vrana, Kent E.

    2011-01-01

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. 2-dimensional in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within subject samples collected before exposure to ethanol and after three months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of SAA4, RBP, ITIH4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption. PMID:21303580

  2. Non-human primates exhibit disconjugate ocular counterroll to head roll tilts.

    PubMed

    Daddaoua, N; Dicke, P W; Thier, P

    2011-09-01

    To investigate the effect of head roll tilt on the binocular coordination of ocular counterroll in non-human primates, we measured binocular ocular counterroll in two rhesus monkeys fixating a straight ahead target, while adopting different head roll tilt positions. We used two infrared cameras to take snapshots of the left and the right eye in order to measure the resulting ocular counterroll responses. The horizontal and vertical components of the position of one of the two eyes where measured using an implanted 2D-search coil in one monkey and video-based eye tracking in the second one. We consistently observed disconjugate ocular counterroll responses to static head roll in both monkeys. Invariably, the eye positioned further away from ground level by roll tilting the head always exhibited larger ocular counterroll than the other eye. The pattern of disconjugacy of the ocular counterroll responses exhibited by rhesus monkey parallels the one described for humans. The correspondence between the two species suggests that monkeys may serve as useful models in studies of the neuronal underpinnings of tilt-induced ocular counterroll and the perceptual compensation of uncompensated retinal image tilt. PMID:21807017

  3. Interaction of non-human primate complement and antibodies with hypermucoviscous Klebsiella pneumoniae.

    PubMed

    Soto, Esteban; Marchi, Sylvia; Beierschmitt, Amy; Kearney, Michael; Francis, Stewart; VanNess, Kimberly; Vandenplas, Michel; Thrall, MaryAnna; Palmour, Roberta

    2016-01-01

    Emergent hypermucoviscosity (HMV) phenotypes of Klebsiella pneumoniae have been associated with increased invasiveness and pathogenicity in primates. In this study, we investigated the interaction of African green monkeys (AGM) (Chlorocebus aethiops sabaeus) complement and antibody with HMV and non-HMV isolates as in vitro models of primate infection. Significantly greater survival of HMV isolates was evident after incubation in normal serum or whole blood (p < 0.05) of AGM donors when compared to non-HMV strains. Greater survival of HMV strains (p < 0.05) was found after incubation in whole blood and serum from seropositive donors when compared to seronegative donor samples. Additionally, significantly greater amounts of K. pneumoniae were phagocytozed by AGM leukocytes when complement was active (p < 0.05), but no difference in uptake was observed when serum from seropositive or seronegative animals was used in challenged cells utilizing flow cytometry. Results demonstrate that interaction of cellular and humoral immune elements play a role in the in vitro killing of K. pneumoniae, particularly HMV isolates. Neither AGM serum, nor washed whole blood effectively killed HMV isolates; however, assays using heparinized whole blood of seronegative donors significantly reduced viability of HMV and non-HMV strains. The lack of bacterial killing observed in seropositive donors treatments could be at least partially associated with low IgG2 present in these animals. A better understanding of the pathogenesis of klebsiellosis in primates and host immune response is necessary to identify surface molecules that can induce both opsonizing and bactericidal antibody facilitating killing of Klebsiella, and the development of vaccines in human and animals. PMID:26951091

  4. Interaction of non-human primate complement and antibodies with hypermucoviscous Klebsiella pneumoniae.

    PubMed

    Soto, Esteban; Marchi, Sylvia; Beierschmitt, Amy; Kearney, Michael; Francis, Stewart; VanNess, Kimberly; Vandenplas, Michel; Thrall, MaryAnna; Palmour, Roberta

    2016-03-08

    Emergent hypermucoviscosity (HMV) phenotypes of Klebsiella pneumoniae have been associated with increased invasiveness and pathogenicity in primates. In this study, we investigated the interaction of African green monkeys (AGM) (Chlorocebus aethiops sabaeus) complement and antibody with HMV and non-HMV isolates as in vitro models of primate infection. Significantly greater survival of HMV isolates was evident after incubation in normal serum or whole blood (p < 0.05) of AGM donors when compared to non-HMV strains. Greater survival of HMV strains (p < 0.05) was found after incubation in whole blood and serum from seropositive donors when compared to seronegative donor samples. Additionally, significantly greater amounts of K. pneumoniae were phagocytozed by AGM leukocytes when complement was active (p < 0.05), but no difference in uptake was observed when serum from seropositive or seronegative animals was used in challenged cells utilizing flow cytometry. Results demonstrate that interaction of cellular and humoral immune elements play a role in the in vitro killing of K. pneumoniae, particularly HMV isolates. Neither AGM serum, nor washed whole blood effectively killed HMV isolates; however, assays using heparinized whole blood of seronegative donors significantly reduced viability of HMV and non-HMV strains. The lack of bacterial killing observed in seropositive donors treatments could be at least partially associated with low IgG2 present in these animals. A better understanding of the pathogenesis of klebsiellosis in primates and host immune response is necessary to identify surface molecules that can induce both opsonizing and bactericidal antibody facilitating killing of Klebsiella, and the development of vaccines in human and animals.

  5. Effects of 60-Hz electric and magnetic fields on operant and social behavior and on nueroendocrine system of nonhuman primates

    SciTech Connect

    Rogers, W.R.

    1993-01-22

    This series of experiments, using a well-characterized exposure facility and employing a variety of control procedures to study behavior and the neuroendocrine system of nonhuman primates, does not provide any evidence that exposure to power-frequency electric fields, or electric and magnetic fields in combination, for 12 hours per day for six weeks produces any deleterious effects in young-adult males. The primate experiments summarized here confirm the general conclusion indicated by experiments with rodents; although biological and behavioral changes can occur, there are no clear results establishing the occurrence of adverse effects in experiments involving relatively short-term exposure to environmentally-relevant electric or magnetic fields. Given the general agreement of the primate and rodent results, conclusions from the laboratory animal studies therefore presumably generalize well to humans.

  6. Differential Effects of Opioid-Related Ligands and NSAIDs in Nonhuman Primate Models of Acute and Inflammatory Pain

    PubMed Central

    Sukhtankar, Devki D.; Lee, Heeseung; Rice, Kenner C.; Ko, Mei-Chuan

    2013-01-01

    Rationale Carrageenan-induced hyperalgesia is a widely used pain model in rodents. However, characteristics of carrageenan-induced hyperalgesia and effects of analgesic drugs under these conditions are unknown in nonhuman primates. Objective The aims of this study were to develop carrageenan-induced hyperalgesia in rhesus monkeys and determine the efficacy and potency of agonists selective for the four opioid receptor subtypes in this model versus acute pain, as compared to NSAIDs. Results Tail-injection of carrageenan produced long-lasting thermal hyperalgesia in monkeys. Systemically administered agonists selective for opioid receptor subtypes i.e. fentanyl (mu/MOP), U-50488H (kappa/KOP), SNC80 (delta/DOP) and Ro 64-6198 (nociceptin/orphanin FQ/NOP) dose-dependently attenuated carrageenan-induced thermal hyperalgesia with different potencies. In absence of carrageenan, these agonists, except SNC80, blocked acute thermal nociception. Opioid-related ligands, especially Ro 64-6198, were much more potent for their antihyperalgesic than antinociceptive effects. Both effects were mediated by the corresponding receptor mechanisms. Only fentanyl produced scratching at antihyperalgesic and antinociceptive doses consistent with its pruritic effects in humans, illustrating a translational profile of MOP agonists in nonhuman primates. Similar to SNC80, systemically administered NSAIDs ketorolac and naproxen dose-dependently attenuated carrageenan-induced hyperalgesia but not acute nociception. Conclusion Using two different pain modalities in nonhuman primates, effectiveness of clinically available analgesics like fentanyl, ketorolac and naproxen was distinguished and their efficacies and potencies were compared with the selective KOP, DOP, and NOP agonists. The opioid-related ligands displayed differential pharmacological properties in regulating hyperalgesia and acute nociception in the same subjects. Such preclinical primate models can be used to investigate novel

  7. Comparison of nonhuman primate antibodies against Haemophilus influenzae type b polysaccharide with human antibodies in oligoclonality and in vivo protective potency.

    PubMed

    Kim, K H; Park, M K; Peeters, C C; Poolman, J T; Shearer, M H; Kennedy, R C; Nahm, M H

    1994-06-01

    Nonhuman primates are often used as a model for studying vaccines for humans. However, it is not always clear how closely the antibody responses in these species mimic human responses. Recent studies have characterized the human antibody response to Haemophilus influenzae type b (Hib) in great detail. In this study, we have compared the antibody response to Hib of humans with those of other primates. Studies of isoelectric points and V kappa subgroup usage show that, like humans, nonhuman primates produce oligoclonal antibodies. Also, monkey antibodies to the Hib polysaccharide are as protective as human antibodies in an in vivo model of Hib infection. Thus, we conclude that nonhuman primates produce antibodies to Hib polysaccharide that are structurally and functionally similar to human antibodies and are a good model for testing human vaccines.

  8. Placental Growth Factor Reduces Blood Pressure in a Uteroplacental Ischemia Model of Preeclampsia in Nonhuman Primates.

    PubMed

    Makris, Angela; Yeung, Kristen R; Lim, Shirlene M; Sunderland, Neroli; Heffernan, Scott; Thompson, John F; Iliopoulos, Jim; Killingsworth, Murray C; Yong, Jim; Xu, Bei; Ogle, Robert F; Thadhani, Ravi; Karumanchi, S Ananth; Hennessy, Annemarie

    2016-06-01

    An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia because of endothelial dysfunction. Circulating soluble fms-like tyrosine kinase 1 (sFLT-1) increases and placental growth factor (PlGF) reduces before and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a nonhuman primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of a 182-day pregnancy). Two weeks after uteroplacental ischemia, rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100 μg/kg per day) for 5 days. Blood pressure was monitored by intra-arterial radiotelemetry and sFLT-1 and PlGF by ELISA. Uteroplacental ischemia resulted in experimental preeclampsia evidenced by increased blood pressure, proteinuria, and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after uteroplacental ischemia. rhPlGF reduced systolic blood pressure in the treated group (-5.2±0.8 mm Hg; from 132.6±6.6 mm Hg to 124.1±7.6 mm Hg) compared with an increase in systolic blood pressure in controls (6.5±3 mm Hg; from 131.3±1.5 mm Hg to 138.6±1.5 mm Hg). Proteinuria reduced in the treated group (-72.7±55.7 mg/mmol) but increased in the control group. Circulating levels of total sFLT-1 were not affected by the administration of PlGF; however, a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference between the weights or lengths of the neonates in the rhPlGF or control group; however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia. PMID:27091894

  9. A non-human primate model of bipedal locomotion under restrained condition allowing gait studies and single unit brain recordings.

    PubMed

    Goetz, L; Piallat, B; Thibaudier, Y; Montigon, O; David, O; Chabardès, S

    2012-03-15

    For decades, several animal models of locomotion have allowed a better understanding of the basic physiological mechanisms of gait. However, unlike most of the mammals, the Order Primates is characterized by fundamental changes in locomotor behaviour. In particular, some primates use a specific pattern of locomotion and are able to naturally walk bipedally due possibly to a specific supra-spinal control of locomotion. These features must be taken into account when one considers to study the intrinsic properties of human gait. Thus, an experimental model of bipedal locomotion allowing precise and reproducible analysis of gait in non-human primate is still lacking. This study describes a non-human primate model of bipedal locomotion under restrained condition. We undertook a kinematic and biomechanic study in three Macaca fascicularis trained to walk bipedally on a treadmill. One of the primate was evaluated in complete head fixation. Gait visual analysis and electromyographic recordings provided pertinent description of the gait pattern. Step frequencies, step lengths, cycle and stance phase durations were correlated with Froude number (dimensionless velocity), whereas swing phase durations remained non-correlated. Gait patterns observed in our model were similar to those obtained in freely bipedal Macaca fuscata and to a lesser extend to Humans. Gait pattern was not modified by head fixation thereby allowing us to perform precise and repetitive micro electrode recordings of deep cerebral structures. Thus, the present model could provide a pertinent pre-clinical tool to study gait parameters and their neuronal control but also could be helpful to validate new therapeutics interventions. PMID:22155386

  10. Gadolinium Chelate Contrast Material in Pregnancy: Fetal Biodistribution in the Nonhuman Primate

    PubMed Central

    Roberts, Victoria H. J.; Schabel, Matthias C.; Grove, Kevin L.; Woods, Mark; Frias, Antonio E.

    2015-01-01

    Purpose To determine the extent to which gadolinium chelate is found in nonhuman primate fetal tissues and amniotic fluid at 19–45 hours after intravenous injection of a weight-appropriate maternal dose of the contrast agent gadoteridol. Materials and Methods Gravid Japanese macaques (n = 14) were maintained as approved by the institutional animal care and utilization committee. In the 3rd trimester of pregnancy, the macaques were injected with gadoteridol (0.1 mmol per kilogram of maternal weight). Fetuses were delivered by means of cesarean section within 24 hours of maternal injection (range, 19–21 hours; n = 11) or 45 hours after injection (n = 3). Gadolinium chelate levels in the placenta, fetal tissues, and amniotic fluid were obtained by using inductively coupled plasma mass spectrometry. The Wilcoxon rank sum test was used for quantitative comparisons. Results Gadoteridol was present in the fetoplacental circulation at much lower quantities than in the mother. At both time points, the distribution of gadolinium chelate in the fetus was comparable to that expected in an adult. The highest concentration of the injected dose (ID) was found in the fetal kidney (0.0161% ID per gram in the 19–21-hour group). The majority of the in utero gadolinium chelate was found in the amniotic fluid and the placenta (mean, 0.1361% ID per organ ± 0.076 [standard deviation] and 0.0939% ID per organ ± 0.0494, respectively). Data acquired 45 hours after injection showed a significant decrease in the gadolinium chelate concentration in amniotic fluid compared with that in the 19–21-hour group (from 0.0017% to 0.0007% ID per gram; P = .01). Conclusion Amounts of gadolinium chelate in the fetal tissues and amniotic fluid were minimal compared with the maternal ID. This may impact future clinical studies on the safety of gadolinium contrast agent use in pregnancy. © RSNA, 2015 PMID:25763829

  11. Age-related changes of auditory brainstem responses in nonhuman primates.

    PubMed

    Ng, Chi-Wing; Navarro, Xochi; Engle, James R; Recanzone, Gregg H

    2015-07-01

    Nonhuman primates, compared with humans and rodents, have historically been far less used for studies of age-related hearing loss, primarily because of their long life span and high cost of maintenance. Strong similarities in genetics, anatomy, and neurophysiology of the auditory nervous system between humans and monkeys, however, could provide fruitful opportunities to enhance our understanding of hearing loss. The present study used a common, noninvasive technique for testing hearing sensitivity in humans, the auditory brainstem response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys, particularly those above 21.5 yr of age, had missing ABR waveforms at high frequencies. Regression analyses revealed that ABR threshold increased as a function of age at peaks II and IV simultaneously. In the suprathreshold hearing condition (70 dB peak sound pressure level), ABR-based audiograms similarly varied as a function of age such that old monkeys had smaller peak amplitudes and delayed latencies at low, middle, and high frequencies. Peripheral hearing differences remained a major influence associated with age-related changes in audiometric functions of old monkeys at a comparable sensation level across animals. The present findings suggest that hearing loss occurs in old monkeys across a wide range of frequencies and that these deficits increase in severity with age. Parallel to prior studies in monkeys, we found weak effects of sex on hearing, and future investigations are necessary to clarify its role in age-related hearing loss. PMID:25972589

  12. Do robots have goals? How agent cues influence action understanding in non-human primates.

    PubMed

    Kupferberg, Aleksandra; Glasauer, Stefan; Burkart, Judith M

    2013-06-01

    The capacity to understand goals and intentions emerges early and universally in humans and is a basic precondition for the interpretation and prediction of others' actions, be it other humans, animals, or even robots. It is unclear, however, how this goal attribution system is acquired, in particular with regard to the role of prior experience with the actor and visual characteristics that are necessary. In four preferential looking time experiments we examined how familiarity, appearance, and movement of different agents influence the capability of marmosets to perceive the behavior of these agents as goal directed. To this end we compared the monkeys' reactions to the same goal-directed actions performed by four different agents: a human actor, a conspecific, a monkey-like small robot, and a black box. The results showed that monkeys attributed goals to the human actor, the conspecific, and the robot, but not the box. Thus, the monkeys extended their capacity for goal attribution not only to familiar agents, but also to agents not previously encountered, provided that they had some conspecific-like features. Our results suggest that in non-human primates, the system for goal attribution does not require previous experience with a specific agent or agent-category, as long as it exhibits certain visual characteristics like face, body or legs. Furthermore, the results suggest that the capacity to attribute goals emerged very early during evolution and, at least in marmoset monkeys, does not necessarily require pre-learned associations in order to fulfill its function when dealing with unfamiliar agents.

  13. Dietary soy effects on mammary gland development during the pubertal transition in nonhuman primates

    PubMed Central

    Dewi, Fitriya N.; Wood, Charles E.; Lees, Cynthia J.; Willson, Cynthia J.; Register, Thomas C.; Tooze, Janet A.; Franke, Adrian A.; Cline, J. Mark

    2013-01-01

    While epidemiologic studies suggest that soy intake early in life may reduce breast cancer risk, there are also concerns that exposure to soy isoflavones during childhood may alter pubertal development and hormonal profiles. Here, we assessed the effect of a high-soy diet on pubertal breast development, sex hormones, and growth in a nonhuman primate model. Pubertal female cynomolgus monkeys were randomized to receive a diet modeled on a typical North American diet with one of two protein sources for ~4.5 years: i) casein/lactalbumin (CL, n=12, as control) or ii) soy protein isolate with a human equivalent dose of 120 mg/day isoflavones (SOY, n=17), which is comparable to approximately four servings of soy foods. Pubertal exposure to the SOY diet did not alter onset of menarche, indicators of growth and pubertal progression, or circulating estradiol and progesterone concentrations. Greater endometrial area was seen in the SOY group on the first of 4 postmenarchal ultrasound measurements (P<0.05). There was a subtle effect of diet on breast differentiation whereby the SOY group showed higher numbers of differentiated large-sized lobular units and a lower proportion with immature ducts following menarche (P<0.05). Numbers of small lobules and terminal end buds and mammary epithelial cell proliferation did not differ by diet. Expression of progesterone receptor was lower in immature lobules of soy-fed animals (P<0.05). Our findings suggest that consumption of soy starting before menarche may result in modest effects consistent with a more differentiated breast phenotype in adulthood. PMID:23771522

  14. Immunogenicity of a prototype enterotoxigenic Escherichia coli adhesin vaccine in mice and nonhuman primates.

    PubMed

    Sincock, Stephanie A; Hall, Eric R; Woods, Colleen M; O'Dowd, Aisling; Poole, Steven T; McVeigh, Annette L; Nunez, Gladys; Espinoza, Nereyda; Miller, Milagros; Savarino, Stephen J

    2016-01-01

    Enterotoxigenic Escherichia coli (ETEC) are the most common cause of bacterial diarrhea in young children in developing countries and in travelers. Efforts to develop an ETEC vaccine have intensified in the past decade, and intestinal colonization factors (CFs) are somatic components of most investigational vaccines. CFA/I and related Class 5 fimbrial CFs feature a major stalk-forming subunit and a minor, antigenically conserved tip adhesin. We hypothesized that the tip adhesin is critical for stimulating antibodies that specifically inhibit ETEC attachment to the small intestine. To address this, we compared the capacity of donor strand complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, and CFA/I fimbriae to elicit anti-adhesive antibodies in mice, using hemagglutination inhibition (HAI) as proxy for neutralization of intestinal adhesion. When given with genetically attenuated heat-labile enterotoxin LTR192G as adjuvant by intranasal (IN) or orogastric (OG) vaccination, dscCfaE exceeded CFA/I fimbriae in eliciting serum HAI titers and anti-CfaE antibody titers. Based on these findings, we vaccinated Aotus nancymaae nonhuman primates (NHP) with dscCfaE alone or admixed with one of two adjuvants, LTR192G and cholera toxin B-subunit, by IN and OG administration. Only IN vaccination with dscCfaE with either adjuvant elicited substantial serum HAI titers and IgA and IgG anti-adhesin responses, with the latter detectable a year after vaccination. In conclusion, we have shown that dscCfaE elicits robust HAI and anti-adhesin antibody responses in both mice and NHPs when given with adjuvant by IN vaccination, encouraging further evaluation of an ETEC adhesin-based vaccine approach. PMID:26597148

  15. Chronic drug exposures during development in nonhuman primates: models of brain dysfunction in humans.

    PubMed

    Paule, Merle G

    2005-01-01

    This review of our work presents three specific examples of how nonhuman primates (rhesus monkeys, Macaca mulatta) have been used to study the effects of chronic drug exposures on brain function during different stages of development. In all cases, exposure levels similar to those experienced by humans were employed and the focus was on long-term--not acute--effects. In the case of the marijuana studies, exposures occurred during the adolescent period; for the cocaine studies, exposures occurred in binge-like fashion entirely before birth (in utero); and for the remacemide studies, exposures occurred daily in juveniles, prior to adolescence. An automated battery of behavioral tasks, the National Center for Toxicological Research Operant Test Battery (NCTR OTB), designed to assess aspects of motivation, visual discrimination, time perception, short-term memory, and learning, was used to monitor treatment effects. Chronic marijuana smoke exposure resulted in an 'amotivational' syndrome--even in weekend-only smokers--that resolved within three months of exposure cessation. In utero cocaine exposure was shown to cause behavioral rigidity or lack of plasticity as evidenced by the difficulty of subjects to adjust to rules changes for some OTB tasks. These effects were seen in adult subjects suggesting that the effects of gestational cocaine exposure are long-term or permanent. In addition, animals exposed to cocaine in utero were less sensitive to the behaviorally-disrupting effects of cocaine as adults. Remacemide caused profound and long-lasting, perhaps permanent, changes in learning task performance and because performance of this same task by children is significantly correlated with traditional measures of intelligence (IQ), these data suggest that such treatment may provide a valuable model of chemically-induced mental retardation. PMID:15970490

  16. Quantitation of complex brain function in children: preliminary evaluation using a nonhuman primate behavioral test battery.

    PubMed

    Paule, M G; Cranmer, J M; Wilkins, J D; Stern, H P; Hoffman, E L

    1988-01-01

    The performance of twenty children (3-11 years of age) in a complex operant test battery (OTB) was evaluated. The operant schedules, or tasks, used in the OTB were identical to those originally designed and currently used to assess complex brain function in nonhuman primate laboratory animals (monkeys). The OTB consisted of five operant tasks: 1) Progressive-Ratio [PR]; 2) Conditioned-Position Responding [CPR]; 3) Temporal Response Differentiation [TRD]; 4) Delayed Matching-to-Sample [DMTS] and 5) Incremental Repeated Acquisition [IRA]. These operant tasks are thought to engender responding indicative of processes associated with: 1) motivation; 2) color and position discrimination; 3) time-perception; 4) short-term memory and attention; and 5) learning, respectively. The parameters for each of the tasks in the OTB were optimized for use in the clinical setting to assess cognitive function in children. In the small population studied, performance in the IRA, DMB and TRD tasks was age related. Of the four 6-yr-olds studied, only those categorized as having either learning disabilities (LD, n = 1) or attention deficit disorders (ADD, n = 2) did not complete the "learning" task. By comparison of human and monkey performance in the OTB, we also hope to validate the use of laboratory animal models in research efforts designed to yield insight into complex human brain function. It is also hoped that assessment of children's performance in the tasks in the OTB will assist in the diagnosis and treatment of certain childhood disorders such as learning disabilities and/or attention deficit disorders. PMID:3143955

  17. Age-related changes of auditory brainstem responses in nonhuman primates

    PubMed Central

    Ng, Chi-Wing; Navarro, Xochi; Engle, James R.

    2015-01-01

    Nonhuman primates, compared with humans and rodents, have historically been far less used for studies of age-related hearing loss, primarily because of their long life span and high cost of maintenance. Strong similarities in genetics, anatomy, and neurophysiology of the auditory nervous system between humans and monkeys, however, could provide fruitful opportunities to enhance our understanding of hearing loss. The present study used a common, noninvasive technique for testing hearing sensitivity in humans, the auditory brainstem response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys, particularly those above 21.5 yr of age, had missing ABR waveforms at high frequencies. Regression analyses revealed that ABR threshold increased as a function of age at peaks II and IV simultaneously. In the suprathreshold hearing condition (70 dB peak sound pressure level), ABR-based audiograms similarly varied as a function of age such that old monkeys had smaller peak amplitudes and delayed latencies at low, middle, and high frequencies. Peripheral hearing differences remained a major influence associated with age-related changes in audiometric functions of old monkeys at a comparable sensation level across animals. The present findings suggest that hearing loss occurs in old monkeys across a wide range of frequencies and that these deficits increase in severity with age. Parallel to prior studies in monkeys, we found weak effects of sex on hearing, and future investigations are necessary to clarify its role in age-related hearing loss. PMID:25972589

  18. Characterization of a head-only aerosol exposure system for nonhuman primates.

    PubMed

    Dabisch, P A; Kline, J; Lewis, C; Yeager, J; Pitt, M L M

    2010-02-01

    A well-characterized exposure chamber is necessary to generate reproducible atmospheres for inhalation toxicology studies. The aim of the present study was to characterize a head-only exposure chamber for non-human primates. Aerosols containing bovine serum albumin (BSA) were used to characterize a 16-L dynamic airflow head-only exposure chamber. A 250-ml plastic bottle with a respirator attached located inside the chamber was used to simulate a breathing head. Chamber leak rate, mixing, and aerosol spatial distributions were quantified. The chamber concentration profile was measured at the chamber exhaust using an aerodynamic particle sizer. Aerosol spatial distribution was determined by collecting filter samples at several chamber locations. The particle size distribution was determined by collecting cascade impactor samples at several chamber locations. The estimated chamber leak rate was within standards suggested in the literature. The measured average aerosol residence time was similar to theoretical aerosol residence time, suggesting that the chamber was mixing well. Additionally, the average concentration measured at each of the sampling locations within the chamber was similar, and the within-run coefficients of variation (CV) across all sampling locations was similar to those reported in previously published studies, again suggesting that the aerosol concentration throughout the chamber was uniform. The particle size distribution was similar throughout the exposure chamber. Additionally, the BSA concentration and particle size distributions measured in the breathing zone of the simulated head were not significantly different from measurements made elsewhere in the chamber, suggesting that respiration does not affect the average aerosol concentration or particle size distribution at the mouth. PMID:20063997

  19. Frequent Simian Foamy Virus Infection in Persons Occupationally Exposed to Nonhuman Primates

    PubMed Central

    Switzer, William M.; Bhullar, Vinod; Shanmugam, Vedapuri; Cong, Mian-er; Parekh, Bharat; Lerche, Nicholas W.; Yee, JoAnn L.; Ely, John J.; Boneva, Roumiana; Chapman, Louisa E.; Folks, Thomas M.; Heneine, Walid

    2004-01-01

    The recognition that AIDS originated as a zoonosis heightens public health concerns associated with human infection by simian retroviruses endemic in nonhuman primates (NHPs). These retroviruses include simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus (STLV), simian type D retrovirus (SRV), and simian foamy virus (SFV). Although occasional infection with SIV, SRV, or SFV in persons occupationally exposed to NHPs has been reported, the characteristics and significance of these zoonotic infections are not fully defined. Surveillance for simian retroviruses at three research centers and two zoos identified no SIV, SRV, or STLV infection in 187 participants. However, 10 of 187 persons (5.3%) tested positive for SFV antibodies by Western blot (WB) analysis. Eight of the 10 were males, and 3 of the 10 worked at zoos. SFV integrase gene (int) and gag sequences were PCR amplified from the peripheral blood lymphocytes available from 9 of the 10 persons. Phylogenetic analysis showed SFV infection originating from chimpanzees (n = 8) and baboons (n = 1). SFV seropositivity for periods of 8 to 26 years (median, 22 years) was documented for six workers for whom archived serum samples were available, demonstrating long-standing SFV infection. All 10 persons reported general good health, and secondary transmission of SFV was not observed in three wives available for WB and PCR testing. Additional phylogenetic analysis of int and gag sequences provided the first direct evidence identifying the source chimpanzees of the SFV infection in two workers. This study documents more frequent infection with SFV than with other simian retroviruses in persons working with NHPs and provides important information on the natural history and species origin of these infections. Our data highlight the importance of studies to better define the public health implications of zoonotic SFV infections. PMID:14990698

  20. Immunogenicity of a prototype enterotoxigenic Escherichia coli adhesin vaccine in mice and nonhuman primates.

    PubMed

    Sincock, Stephanie A; Hall, Eric R; Woods, Colleen M; O'Dowd, Aisling; Poole, Steven T; McVeigh, Annette L; Nunez, Gladys; Espinoza, Nereyda; Miller, Milagros; Savarino, Stephen J

    2016-01-01

    Enterotoxigenic Escherichia coli (ETEC) are the most common cause of bacterial diarrhea in young children in developing countries and in travelers. Efforts to develop an ETEC vaccine have intensified in the past decade, and intestinal colonization factors (CFs) are somatic components of most investigational vaccines. CFA/I and related Class 5 fimbrial CFs feature a major stalk-forming subunit and a minor, antigenically conserved tip adhesin. We hypothesized that the tip adhesin is critical for stimulating antibodies that specifically inhibit ETEC attachment to the small intestine. To address this, we compared the capacity of donor strand complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, and CFA/I fimbriae to elicit anti-adhesive antibodies in mice, using hemagglutination inhibition (HAI) as proxy for neutralization of intestinal adhesion. When given with genetically attenuated heat-labile enterotoxin LTR192G as adjuvant by intranasal (IN) or orogastric (OG) vaccination, dscCfaE exceeded CFA/I fimbriae in eliciting serum HAI titers and anti-CfaE antibody titers. Based on these findings, we vaccinated Aotus nancymaae nonhuman primates (NHP) with dscCfaE alone or admixed with one of two adjuvants, LTR192G and cholera toxin B-subunit, by IN and OG administration. Only IN vaccination with dscCfaE with either adjuvant elicited substantial serum HAI titers and IgA and IgG anti-adhesin responses, with the latter detectable a year after vaccination. In conclusion, we have shown that dscCfaE elicits robust HAI and anti-adhesin antibody responses in both mice and NHPs when given with adjuvant by IN vaccination, encouraging further evaluation of an ETEC adhesin-based vaccine approach.

  1. Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors.

    PubMed

    Li, Shaoyong; Ling, Chen; Zhong, Li; Li, Mengxin; Su, Qin; He, Ran; Tang, Qiushi; Greiner, Dale L; Shultz, Leonard D; Brehm, Michael A; Flotte, Terence R; Mueller, Christian; Srivastava, Arun; Gao, Guangping

    2015-12-01

    Recombinant adeno-associated virus serotype 3B (rAAV3B) can transduce cultured human liver cancer cells and primary human hepatocytes efficiently. Serine (S)- and threonine (T)-directed capsid modifications further augment its transduction efficiency. Systemically delivered capsid-optimized rAAV3B vectors can specifically target cancer cells in a human liver cancer xenograft model, suggesting their potential use for human liver-directed gene therapy. Here, we compared transduction efficiencies of AAV3B and AAV8 vectors in cultured primary human hepatocytes and cancer cells as well as in human and mouse hepatocytes in a human liver xenograft NSG-PiZ mouse model. We also examined the safety and transduction efficacy of wild-type (WT) and capsid-optimized rAAV3B in the livers of nonhuman primates (NHPs). Intravenously delivered S663V+T492V (ST)-modified self-complementary (sc) AAV3B-EGFP vectors led to liver-targeted robust enhanced green fluorescence protein (EGFP) expression in NHPs without apparent hepatotoxicity. Intravenous injections of both WT and ST-modified rAAV3B.ST-rhCG vectors also generated stable super-physiological levels of rhesus chorionic gonadotropin (rhCG) in NHPs. The vector genome predominantly targeted the liver. Clinical chemistry and histopathology examinations showed no apparent vector-related toxicity. Our studies should be important and informative for clinical development of optimized AAV3B vectors for human liver-directed gene therapy.

  2. Flow Cytometry-Based Methods to Characterize Immune Senescence in Nonhuman Primates.

    PubMed

    Meyer, Christine; Haberthur, Kristen; Asquith, Mark; Messaoudi, Ilhem

    2015-01-01

    Flow cytometry is an invaluable technique that can be used to phenotypically and functionally characterize immune cell populations ex vivo. This technology has greatly advanced our ability to gain critical insight into age-related changes in immune function, commonly known as immune senescence. Rodents have been traditionally used to investigate the molecular mechanisms of immune senescence because they offer the distinct advantages of an extensive set of reagents, the presence of genetically modified strains, and a short lifespan that allows for longevity studies of short duration. More recently, nonhuman primates (NHPs), and specifically rhesus macaques, have emerged as a leading translational model to study various aspects of human aging. In contrast to rodents, they share significant genetic homology as well as physiological and behavioral characteristics with humans. Furthermore, rhesus macaques are a long-lived outbred species, which makes them an ideal translational model. Therefore, NHPs offer a unique opportunity to carry out mechanistic studies under controlled laboratory conditions (e.g., photoperiod, temperature, diet, and medications) in a species that closely mimics human biology. Moreover similar techniques (e.g., activity recording and MRI) can be used to measure physiological parameters in NHPs, making direct comparisons between NHP and human data sets possible. In addition, the outbred genetics of NHPs enables rigorous validation of research findings that goes beyond proof of principle. Finally, self-selection bias that is often unavoidable in human clinical trials can be completely eliminated with NHP studies. Here we describe flow cytometry-based methods to phenotypically and functionally characterize innate immune cells as well as T and B lymphocyte subsets from isolated peripheral blood mononuclear cells (PBMC) in rhesus macaques. PMID:26420709

  3. Progress and Prospects for Genetic Modification of Nonhuman Primate Models in Biomedical Research

    PubMed Central

    Chan, Anthony W. S.

    2013-01-01

    The growing interest of modeling human diseases using genetically modified (transgenic) nonhuman primates (NHPs) is a direct result of NHPs (rhesus macaque, etc.) close relation to humans. NHPs share similar developmental paths with humans in their anatomy, physiology, genetics, and neural functions; and in their cognition, emotion, and social behavior. The NHP model within biomedical research has played an important role in the development of vaccines, assisted reproductive technologies, and new therapies for many diseases. Biomedical research has not been the primary role of NHPs. They have mainly been used for safety evaluation and pharmacokinetics studies, rather than determining therapeutic efficacy. The development of the first transgenic rhesus macaque (2001) revolutionized the role of NHP models in biomedicine. Development of the transgenic NHP model of Huntington's disease (2008), with distinctive clinical features, further suggested the uniqueness of the model system; and the potential role of the NHP model for human genetic disorders. Modeling human genetic diseases using NHPs will continue to thrive because of the latest advances in molecular, genetic, and embryo technologies. NHPs rising role in biomedical research, specifically pre-clinical studies, is foreseeable. The path toward the development of transgenic NHPs and the prospect of transgenic NHPs in their new role in future biomedicine needs to be reviewed. This article will focus on the advancement of transgenic NHPs in the past decade, including transgenic technologies and disease modeling. It will outline new technologies that may have significant impact in future NHP modeling and will conclude with a discussion of the future prospects of the transgenic NHP model. PMID:24174443

  4. A wireless transmission neural interface system for unconstrained non-human primates

    NASA Astrophysics Data System (ADS)

    Fernandez-Leon, Jose A.; Parajuli, Arun; Franklin, Robert; Sorenson, Michael; Felleman, Daniel J.; Hansen, Bryan J.; Hu, Ming; Dragoi, Valentin

    2015-10-01

    Objective. Studying the brain in large animal models in a restrained laboratory rig severely limits our capacity to examine brain circuits in experimental and clinical applications. Approach. To overcome these limitations, we developed a high-fidelity 96-channel wireless system to record extracellular spikes and local field potentials from the neocortex. A removable, external case of the wireless device is attached to a titanium pedestal placed in the animal skull. Broadband neural signals are amplified, multiplexed, and continuously transmitted as TCP/IP data at a sustained rate of 24 Mbps. A Xilinx Spartan 6 FPGA assembles the digital signals into serial data frames for transmission at 20 kHz though an 802.11n wireless data link on a frequency-shift key-modulated signal at 5.7-5.8 GHz to a receiver up to 10 m away. The system is powered by two CR123A, 3 V batteries for 2 h of operation. Main results. We implanted a multi-electrode array in visual area V4 of one anesthetized monkey (Macaca fascicularis) and in the dorsolateral prefrontal cortex (dlPFC) of a freely moving monkey (Macaca mulatta). The implanted recording arrays were electrically stable and delivered broadband neural data over a year of testing. For the first time, we compared dlPFC neuronal responses to the same set of stimuli (food reward) in restrained and freely moving conditions. Although we did not find differences in neuronal responses as a function of reward type in the restrained and unrestrained conditions, there were significant differences in correlated activity. This demonstrates that measuring neural responses in freely moving animals can capture phenomena that are absent in the traditional head-fixed paradigm. Significance. We implemented a wireless neural interface for multi-electrode recordings in freely moving non-human primates, which can potentially move systems neuroscience to a new direction by allowing one to record neural signals while animals interact with their environment.

  5. Electric Field Model of Transcranial Electric Stimulation in Nonhuman Primates: Correspondence to Individual Motor Threshold

    PubMed Central

    Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.

    2015-01-01

    Objective To develop a pipeline for realistic head models of nonhuman primates (NHPs) for simulations of noninvasive brain stimulation, and use these models together with empirical threshold measurements to demonstrate that the models capture individual anatomical variability. Methods Based on structural MRI data, we created models of the electric field (E-field) induced by right unilateral (RUL) electroconvulsive therapy (ECT) in four rhesus macaques. Individual motor threshold (MT) was measured with transcranial electric stimulation (TES) administered through the RUL electrodes in the same subjects. Results The interindividual anatomical differences resulted in 57% variation in median E-field strength in the brain at fixed stimulus current amplitude. Individualization of the stimulus current by MT reduced the E-field variation in the target motor area by 27%. There was significant correlation between the measured MT and the ratio of simulated electrode current and E-field strength (r2 = 0.95, p = 0.026). Exploratory analysis revealed significant correlations of this ratio with anatomical parameters including of the superior electrode-to-cortex distance, vertex-to-cortex distance, and brain volume (r2 > 0.96, p < 0.02). The neural activation threshold was estimated to be 0.45 ± 0.07 V/cm for 0.2 ms stimulus pulse width. Conclusion These results suggest that our individual-specific NHP E-field models appropriately capture individual anatomical variability relevant to the dosing of TES/ECT. These findings are exploratory due to the small number of subjects. Significance This work can contribute insight in NHP studies of ECT and other brain stimulation interventions, help link the results to clinical studies, and ultimately lead to more rational brain stimulation dosing paradigms. PMID:25910001

  6. Social complexity parallels vocal complexity: a comparison of three non-human primate species

    PubMed Central

    Bouchet, Hélène; Blois-Heulin, Catherine; Lemasson, Alban

    2013-01-01

    Social factors play a key role in the structuring of vocal repertoires at the individual level, notably in non-human primates. Some authors suggested that, at the species level too, social life may have driven the evolution of communicative complexity, but this has rarely been empirically tested. Here, we use a comparative approach to address this issue. We investigated vocal variability, at both the call type and the repertoire levels, in three forest-dwelling species of Cercopithecinae presenting striking differences in their social systems, in terms of social organization as well as social structure. We collected female call recordings from twelve De Brazza's monkeys (Cercopithecus neglectus), six Campbell's monkeys (Cercopithecus campbelli) and seven red-capped mangabeys (Cercocebus torquatus) housed in similar conditions. First, we noted that the level of acoustic variability and individual distinctiveness found in several call types was related to their importance in social functioning. Contact calls, essential to intra-group cohesion, were the most individually distinctive regardless of the species, while threat calls were more structurally variable in mangabeys, the most “despotic” of our three species. Second, we found a parallel between the degree of complexity of the species' social structure and the size, diversity, and usage of its vocal repertoire. Mangabeys (most complex social structure) called twice as often as guenons and displayed the largest and most complex repertoire. De Brazza's monkeys (simplest social structure) displayed the smallest and simplest repertoire. Campbell's monkeys displayed an intermediate pattern. Providing evidence of higher levels of vocal variability in species presenting a more complex social system, our results are in line with the theory of a social-vocal coevolution of communicative abilities, opening new perspectives for comparative research on the evolution of communication systems in different animal taxa. PMID

  7. Chronic cortical and electromyographic recordings from a fully implantable device: preclinical experience in a nonhuman primate

    NASA Astrophysics Data System (ADS)

    Ryapolova-Webb, Elena; Afshar, Pedram; Stanslaski, Scott; Denison, Tim; de Hemptinne, Coralie; Bankiewicz, Krystof; Starr, Philip A.

    2014-02-01

    Objective. Analysis of intra- and perioperatively recorded cortical and basal ganglia local field potentials in human movement disorders has provided great insight into the pathophysiology of diseases such as Parkinson's, dystonia, and essential tremor. However, in order to better understand the network abnormalities and effects of chronic therapeutic stimulation in these disorders, long-term recording from a fully implantable data collection system is needed. Approach. A fully implantable investigational data collection system, the Activa® PC + S neurostimulator (Medtronic, Inc., Minneapolis, MN), has been developed for human use. Here, we tested its utility for extended intracranial recording in the motor system of a nonhuman primate. The system was attached to two quadripolar paddle arrays: one covering sensorimotor cortex, and one covering a proximal forelimb muscle, to study simultaneous cortical field potentials and electromyography during spontaneous transitions from rest to movement. Main results. Over 24 months of recording, movement-related changes in physiologically relevant frequency bands were readily detected, including beta and gamma signals at approximately 2.5 μV/\\sqrtHz and 0.7 μV/\\sqrt{Hz}, respectively. The system architecture allowed for flexible recording configurations and algorithm triggered data recording. In the course of physiological analyses, sensing artifacts were observed (˜1 μVrms stationary tones at fixed frequency), which were mitigated either with post-processing or algorithm design and did not impact the scientific conclusions. Histological examination revealed no underlying tissue damage; however, a fibrous capsule had developed around the paddles, demonstrating a potential mechanism for the observed signal amplitude reduction. Significance. This study establishes the usefulness of this system in measuring chronic brain and muscle signals. Use of this system may potentially be valuable in human trials of chronic brain

  8. Validating a Nonhuman Primate Model of Super-Selective Intraophthalmic Artery Chemotherapy: Comparing Ophthalmic Artery Diameters

    PubMed Central

    Ditta, Lauren C.; Choudhri, Asim F.; Tse, Brian C.; Landers, Mark M.; Haik, Barrett G.; Steinle, Jena J.; Williams, J. Scott; Wilson, Matthew W.

    2012-01-01

    Purpose. Superselective intraophthalmic artery chemotherapy (SSIOAC) is being used for treatment of retinoblastoma; however, the hemodynamic consequences and toxicities are not fully known. We developed a nonhuman primate (NHP) model of SSIOAC and reported our clinical observations. For validation, we compared ophthalmic artery (OA) diameters between NHPs and children (<6 years). Methods. Endovascular cannulation of the right OA was performed three times each in six adult male Rhesus macaques. Angiographic OA images were obtained and measured, and postmortem OAs were histologically sectioned and measured. Retrospectively, computed tomography (CT) and magnetic resonance (MR) angiography images of the head in children and adolescents (as an adult reference) were used to measure the OA luminal diameter at its origin. Results. The median angiographic diameter of treated NHP OA origins (n = 6) was 1.06 mm (range 0.94–1.56). Histologic measurements (8 of 12 NHP OAs) gave a median diameter of 1.09 mm (range 0.95–1.41). In 98 children (from 169 consecutive CT and MR angiography studies; median age 1.01 years, range 0.01–5.74), 186 OAs were measurable at the origin (median luminal diameter 1.28 mm, range 0.82–2.00; P = 0.16 for the angiographic NHP diameters versus pediatric cohort). Angiographic measurements of 34 OAs (of 20 consecutive studies of adolescents; median age 16.55 years, range 14.40–18.18) gave a median luminal diameter of 1.45 mm (origin, range 1.13–1.66; P < 0.0001, adolescent versus pediatric). Conclusions. Measurements of the OA luminal diameter at its origin were similar between our NHP and pediatric cohort, validating our NHP model for testing both the hemodynamic consequences and toxicities of SSIOAC. PMID:23111611

  9. Targeting of deep-brain structures in nonhuman primates using MR and CT Images

    NASA Astrophysics Data System (ADS)

    Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Connolly, Brett; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

    2015-03-01

    In vivo gene delivery in central nervous systems of nonhuman primates (NHP) is an important approach for gene therapy and animal model development of human disease. To achieve a more accurate delivery of genetic probes, precise stereotactic targeting of brain structures is required. However, even with assistance from multi-modality 3D imaging techniques (e.g. MR and CT), the precision of targeting is often challenging due to difficulties in identification of deep brain structures, e.g. the striatum which consists of multiple substructures, and the nucleus basalis of meynert (NBM), which often lack clear boundaries to supporting anatomical landmarks. Here we demonstrate a 3D-image-based intracranial stereotactic approach applied toward reproducible intracranial targeting of bilateral NBM and striatum of rhesus. For the targeting we discuss the feasibility of an atlas-based automatic approach. Delineated originally on a high resolution 3D histology-MR atlas set, the NBM and the striatum could be located on the MR image of a rhesus subject through affine and nonrigid registrations. The atlas-based targeting of NBM was compared with the targeting conducted manually by an experienced neuroscientist. Based on the targeting, the trajectories and entry points for delivering the genetic probes to the targets could be established on the CT images of the subject after rigid registration. The accuracy of the targeting was assessed quantitatively by comparison between NBM locations obtained automatically and manually, and finally demonstrated qualitatively via post mortem analysis of slices that had been labelled via Evan Blue infusion and immunohistochemistry.

  10. Hypersensitivity pneumonitis in nonhuman primates: studies on the relationship of immunoregulation and disease activity

    SciTech Connect

    Keller, R.H.; Calvanico, N.J.; Stevens, J.O.

    1982-01-01

    We investigated the relationship of immunoregulation to disease activity in a nonhuman primate model of pigeon breeder's disease. Two Macaca arctoides monkeys developed classical symptoms of hypersensitivity pneumonitis after sensitization and prolonged bronchial challenge, whereas 2 other monkeys remained asymptomatic after in vivo challenge. There were no differences in the percentages of T cells, B cells, monocytes, or FC..gamma..-bearing T cells between symptomatic and asymptomatic animals. Nonetheless, we found a population of concanavalin A-induced, pigeon serum- (PS) induced, and spontaneous T cells that functioned as suppressor cells in autologous in vitro co-cultures in asymptomatic animals that were missing or nonfunctional in symptomatic animals. Monocyte suppressors functioned in both groups. We used low-dose total body irradiation (TBI) to inactivate T suppressor cells. Fifteen radiation units of TBI caused no change in the physical activity, routine chemistries, or blood counts of the 4 animals. After TBI, however, the previously asymptomatic animals developed fever, tachypnea, and signs of pulmonary congestion after in vivo challenge with PS. There was no change in the response to challenge in the symptomatic group. This altered response to in vivo challenge in the previously asymptomatic group persisted for 2 wk after TBI. During this period the difference in in vitro immunoregulatory activity between Con A-induced, PS-induced, and spontaneous T cells in symptomatic and asymptomatic animals disappeared. Monocyte suppressors, however, continued to function in both groups after TBI. these data suggest that the monkey is an appropriate model for studies of human HP and that T cell immunoregulation may be an important element in the pathogenesis and disease activity of HP.

  11. Social Buffering of Stress Responses in Nonhuman Primates: Maternal Regulation of the Development of Emotional Regulatory Brain Circuits

    PubMed Central

    McCormack, Kai M.; Howell, Brittany R.

    2015-01-01

    Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses exists in different animal species, and has been examined in the context of the mother-infant relationship in addition to adults. Although it is a well-known effect, the biological mechanisms, which underlie it, as well as its developmental impact are not well understood. Here we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving we have shown that competent maternal care is critical for the development of healthy attachment, social behavior and emotional and stress regulation, as well as of neural circuits underlying these functions. PMID:26324227

  12. Social buffering of stress responses in nonhuman primates: Maternal regulation of the development of emotional regulatory brain circuits.

    PubMed

    Sanchez, Mar M; McCormack, Kai M; Howell, Brittany R

    2015-01-01

    Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses, exists in different animal species and has been examined in the context of the mother-infant relationship, in addition to adults. Although it is a well-known effect, the biological mechanisms that underlie it as well as its developmental impact are not well understood. Here, we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted, maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving, we have shown that competent maternal care is critical for the development of healthy attachment, social behavior, and emotional and stress regulation, as well as of the neural circuits underlying these functions.

  13. Social buffering of stress responses in nonhuman primates: Maternal regulation of the development of emotional regulatory brain circuits.

    PubMed

    Sanchez, Mar M; McCormack, Kai M; Howell, Brittany R

    2015-01-01

    Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses, exists in different animal species and has been examined in the context of the mother-infant relationship, in addition to adults. Although it is a well-known effect, the biological mechanisms that underlie it as well as its developmental impact are not well understood. Here, we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother-infant relationship is disrupted, maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent-infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving, we have shown that competent maternal care is critical for the development of healthy attachment, social behavior, and emotional and stress regulation, as well as of the neural circuits underlying these functions. PMID:26324227

  14. Distinct Expression Patterns Of Causative Genes Responsible For Hereditary Progressive Hearing Loss In Non-Human Primate Cochlea

    PubMed Central

    Hosoya, Makoto; Fujioka, Masato; Ogawa, Kaoru; Okano, Hideyuki

    2016-01-01

    Hearing impairment is the most frequent sensory deficit in humans. Deafness genes, which harbor pathogenic mutations that have been identified in families with hereditary hearing loss, are commonly expressed in the auditory end organ or the cochlea and may contribute to normal hearing function, yet some of the mouse models carrying these mutations fail to recapitulate the hearing loss phenotype. In this study, we find that distinct expression patterns of those deafness genes in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). We examined 20 genes whose expression in the cochlea has already been reported. The deafness genes GJB3, CRYM, GRHL2, DFNA5, and ATP6B1 were expressed in marmoset cochleae in patterns different from those in mouse cochleae. Of note, all those genes are causative for progressive hearing loss in humans, but not in mice. The other tested genes, including the deafness gene COCH, in which mutation recapitulates deafness in mice, were expressed in a similar manner in both species. The result suggests that the discrepancy in the expression between rodents and primates may account for the phenotypic difference. This limitation of the rodent models can be bypassed by using non-human primate models such as the marmoset. PMID:26915689

  15. Age-Related Degenerative Functional, Radiographic, and Histological Changes of the Shoulder in Non-Human Primates

    PubMed Central

    Plate, Johannes F.; Bates, Christopher M.; Mannava, Sandeep; Smith, Thomas L.; Jorgensen, Matthew J.; Register, Thomas C.; Stehle, John R.; High, Kevin P.; Shively, Carol A.; Kaplan, Jay R.; Saul, Katherine R.; Tuohy, Christopher J.

    2013-01-01

    Background Non-human primates have similar shoulder anatomy and physiology compared to humans and may represent a previously underutilized model for shoulder research. This study sought to identify naturally occurring bony and muscular degeneration in the shoulder of non-human primates and to assess relationships between structural and functional aspects of the shoulder and measures of physical function of the animals. We hypothesized that age-related degenerative changes in the shoulders of non-human primates would resemble those observed in aging humans. Methods Middle-aged (n=5, ages 9.4 to 11.8 years) and elderly (n=6, ages 19.8 to 26.4 years) female vervet monkeys were studied for changes in mobility and shoulder function, and radiographic and histologic signs of age-related degeneration. Results Four out of six (4/6) elderly animals had degenerative changes of the glenoid compared to 0/5 of the middle-aged animals (p=0.005). Elderly animals had glenoid retroversion, decreased joint space, walked slower and spent less time climbing and hanging than middle-aged vervets (p<0.05). Physical mobility and shoulder function correlated with glenoid version angle (p<0.05). Supraspinatus muscles of elderly animals were less dense (p=0.001), had decreased fiber cross-sectional area (p<0.001), but similar amounts of nuclear material (p=0.085). Degenerative rotator cuff tears were not observed in any of the eleven animals. Discussion and Conclusion The vervet monkey naturally undergoes age-related functional, radiographic and histological changes of the shoulder and may qualify as an animal model for selected translational research of shoulder osteoarthritis. Level of evidence Basic Science Study, in-vivo Animal Model PMID:23352182

  16. Laterality in Maternal Cradling and Infant Positional Biases: Implications for the Development and Evolution of Hand Preferences in Nonhuman Primates

    PubMed Central

    Hopkins, William D.

    2007-01-01

    Left-sided maternal cradling has been widely reported in human populations. In this paper, I review the evidence of laterality in maternal cradling and infant positional biases in non-human primates. The review revealed some evidence of population-left sided cradling in great apes but little consistency in bias was found among Old and New World monkeys. Very little data have been reported in prosimians. I further describe how asymmetries in either maternal cradling or infant positional biases may explain individual and species differences in hand preference. PMID:18049716

  17. Feasibility of noninvasive cavitation-guided blood-brain barrier opening using focused ultrasound and microbubbles in nonhuman primates

    NASA Astrophysics Data System (ADS)

    Tung, Yao-Sheng; Marquet, Fabrice; Teichert, Tobias; Ferrera, Vincent; Konofagou, Elisa E.

    2011-04-01

    In vivo transcranial and noninvasive cavitation detection with blood-brain barrier (BBB) opening in nonhuman primates is hereby reported. The BBB in monkeys was opened transcranically using focused ultrasound (FUS) in conjunction with microbubbles. A passive cavitation detector, confocal with the FUS transducer, was used to identify and monitor the bubble behavior. During sonication, the cavitation spectrum, which was found to be region-, pressure-, and bubble-dependent, provided real-time feedback regarding the opening occurrence and its properties. These findings demonstrate feasibility of transcranial, cavitation-guided BBB opening using FUS and microbubbles in noninvasive human applications.

  18. Protection of nonhuman primates against two species of Ebola virus infection with a single complex adenovirus vector.

    PubMed

    Pratt, William D; Wang, Danher; Nichols, Donald K; Luo, Min; Woraratanadharm, Jan; Dye, John M; Holman, David H; Dong, John Y

    2010-04-01

    Ebola viruses are highly pathogenic viruses that cause outbreaks of hemorrhagic fever in humans and other primates. To meet the need for a vaccine against the several types of Ebola viruses that cause human diseases, we developed a multivalent vaccine candidate (EBO7) that expresses the glycoproteins of Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SEBOV) in a single complex adenovirus-based vector (CAdVax). We evaluated our vaccine in nonhuman primates against the parenteral and aerosol routes of lethal challenge. EBO7 vaccine provided protection against both Ebola viruses by either route of infection. Significantly, protection against SEBOV given as an aerosol challenge, which has not previously been shown, could be achieved with a boosting vaccination. These results demonstrate the feasibility of creating a robust, multivalent Ebola virus vaccine that would be effective in the event of a natural virus outbreak or biological threat.

  19. Antiviral Activity of TMC353121, a Respiratory Syncytial Virus (RSV) Fusion Inhibitor, in a Non-Human Primate Model

    PubMed Central

    Ispas, Gabriela; Koul, Anil; Verbeeck, Johan; Sheehan, Jennifer; Sanders-Beer, Brigitte; Roymans, Dirk; Andries, Koen; Rouan, Marie-Claude; De Jonghe, Sandra; Bonfanti, Jean-François; Vanstockem, Marc; Simmen, Kenneth; Verloes, Rene

    2015-01-01

    Background The study assessed the antiviral activity of TMC353121, a respiratory syncytial virus (RSV) fusion inhibitor, in a preclinical non-human primate challenge model with a viral shedding pattern similar to that seen in humans, following continuous infusion (CI). Methods African green monkeys were administered TMC353121 through CI, in 2 studies. Study 1 evaluated the prophylactic and therapeutic efficacy of TMC353121 at a target plasma level of 50 ng/mL (n=15; Group 1: prophylactic arm [Px50], 0.033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 24 hours pre-infection to 10 days; Group 2: therapeutic arm [Tx50], 0.033mg/mL TMC353121 from 24 hours postinfection to 8 days; Group 3: control [Vh1] vehicle, 24 hours post-infection to 8 days). Study 2 evaluated the prophylactic efficacy of TMC353121 at target plasma levels of 5 and 500 ng/mL (n=12; Group 1: prophylactic 5 arm [Px5], 0.0033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 72 hours pre-infection to 14 days; Group 2: prophylactic 500 arm [Px500], 0.33 mg/mL TMC353121; Group 3:control [Vh2] vehicle, 14 days). Bronchoalveolar lavage fluid and plasma were collected every 2 days from day 1 postinfection for pharmacokinetics and safety analysis. Findings TMC353121 showed a dose-dependent antiviral activity, varying from 1log10 reduction of peak viral load to complete inhibition of the RSV replication. Complete inhibition of RSV shedding was observed for a relatively low plasma exposure (0.39 μg/mL) and was associated with a dose-dependent reduction in INFγ, IL6 and MIP1α. TMC353121 administered as CI for 16 days was generally well-tolerated. Conclusion TMC353121 exerted dose-dependent antiviral effect ranging from full inhibition to absence of antiviral activity, in a preclinical model highly permissive for RSV replication. No new safety findings emerged from the study. PMID:26010881

  20. A comparative study of the trabecular bony architecture of the talus in humans, non-human primates, and Australopithecus.

    PubMed

    DeSilva, Jeremy M; Devlin, Maureen J

    2012-09-01

    This study tested the hypothesis that talar trabecular microarchitecture reflects the loading patterns in the primate ankle joint, to determine whether talar trabecular morphology might be useful for inferring locomotor behavior in fossil hominins. Trabecular microarchitecture was quantified in the anteromedial, anterolateral, posteromedial, and posterolateral quadrants of the talar body in humans and non-human primates using micro-computed tomography. Trabecular bone parameters, including bone volume fraction, trabecular number and thickness, and degree of anisotropy differed between primates, but not in a manner entirely consistent with hypotheses derived from locomotor kinematics. Humans have highly organized trabecular struts across the entirety of the talus, consistent with the compressive loads incurred during bipedal walking. Chimpanzees possess a high bone volume fraction, consisting of plate-like trabecular struts. Orangutan tali are filled with a high number of thin, connected trabeculae, particularly in the anterior portion of the talus. Gorillas and baboons have strikingly similar internal architecture of the talus. Intraspecific analyses revealed no regional differences in trabecular architecture unique to bipedal humans. Of the 22 statistically significant regional differences in the human talus, all can also be found in other primates. Trabecular thickness, number, spacing, and connectivity density had the same regional relationship in the talus of humans, chimpanzees, gorillas, and baboons, suggesting a deeply conserved architecture in the primate talus. Australopithecus tali are human-like in most respects, differing most notably in having more oriented struts in the posteromedial quadrant of the body compared with the posterolateral quadrant. Though this result could mean that australopiths loaded their ankles in a unique manner during bipedal gait, the regional variation in degree of anisotropy was similar in humans, chimpanzees, and gorillas

  1. Low CA1 spine synapse density is further reduced by castration in male non-human primates.

    PubMed

    Leranth, Csaba; Prange-Kiel, Janine; Frick, Karyn M; Horvath, Tamas L

    2004-05-01

    The hippocampus plays a major role in learning and memory and its morphology and function are readily affected by gonadal hormones in female non-human primates. We sought to determine whether the gonads also affect pyramidal cell spine synapse density in the CA1 hippocampal area of male primates. Unbiased electron microscopic stereological calculations were performed to determine the volumetric density of pyramidal cell spine synapses and semiquantitative analyses on the surface density of glial fibrillary acidic protein-containing glia processes and the diameter of pyramidal cell apical dendrites in the CA1 area of intact and orchidectomized (1 month) St Kitts vervet monkeys (Chlorocebus aethiops sabaeus). The volumetric density (number of spine synapse/ micro m(3)) of spine synapses was significantly lower (40%) in the gonadectomized animals than in control monkeys; conversely, the density of glia processes was significantly higher (15%) and the diameter of dendritic shafts located in this area was also larger (30%) in the orchidectomized animals than in the controls. Strikingly, when compared to female values, intact male primates had lower spine synapse densities than either intact or ovariectomized females. Since the primate hippocampus is very similar to that of a human's, the present observations suggest that physiological levels of circulating androgen hormones are necessary to support normal spine synapse density in the CA1 stratum radiatum of human male hippocampus.

  2. Ethical review of projects involving non-human primates funded under the European Union's 7th Research Framework Programme.

    PubMed

    Sauer, Ursula; Phillips, Barry; Reid, Kirsty; Schmit, Véronique; Jennings, Maggy

    2013-09-01

    Internet searches were performed on projects involving non-human primates ('primates') funded under the European Union (EU) 7th Research Framework Programme (FP7), to determine how project proposals are assessed from an ethical point of view. Due to the incompleteness of the information publicly available, the types and severity of the experiments could not be determined with certainty, although in some projects the level of harm was considered to be 'severe'. Information was scarce regarding the numbers of primates, their sourcing, housing, care and fate, or the application of the Three Rs within projects. Project grant holders and the relevant Commission officer were consulted about their experiences with the FP7 ethics review process. Overall, it was seen as meaningful and beneficial, but some concerns were also noted. Ethical follow-up during project performance and upon completion was recognised as a valuable tool in ensuring that animal welfare requirements were adequately addressed. Based upon the outcome of the survey, recommendations are presented on how to strengthen the ethical review process under the upcoming Framework Programme 'Horizon 2020', while adequately taking into account the specific requirements of Directive 2010/63/EU, with the aim of limiting the harms inflicted on the animals and the numbers used, and ultimately, replacing the use of primates altogether. PMID:24168134

  3. Neurovirulence and Immunogenicity of Attenuated Recombinant Vesicular Stomatitis Viruses in Nonhuman Primates

    PubMed Central

    Nasar, Farooq; Chong, Siew; Johnson, J. Erik; Coleman, John W.; Lee, Margaret; Witko, Susan E.; Kotash, Cheryl S.; Abdullah, Rashed; Megati, Shakuntala; Luckay, Amara; Nowak, Becky; Lackner, Andrew; Price, Roger E.; Little, Peter; Kalyan, Narender; Randolf, Valerie; Javadian, Ali; Zamb, Timothy J.; Parks, Christopher L.; Egan, Michael A.; Eldridge, John; Hendry, Michael; Udem, Stephen A.

    2014-01-01

    ABSTRACT In previous work, a prototypic recombinant vesicular stomatitis virus Indiana serotype (rVSIV) vector expressing simian immunodeficiency virus (SIV) gag and human immunodeficiency virus type 1 (HIV-1) env antigens protected nonhuman primates (NHPs) from disease following challenge with an HIV-1/SIV recombinant (SHIV). However, when tested in a stringent NHP neurovirulence (NV) model, this vector was not adequately attenuated for clinical evaluation. For the work described here, the prototypic rVSIV vector was attenuated by combining specific G protein truncations with either N gene translocations or mutations (M33A and M51A) that ablate expression of subgenic M polypeptides, by incorporation of temperature-sensitive mutations in the N and L genes, and by deletion of the VSIV G gene to generate a replicon that is dependent on trans expression of G protein for in vitro propagation. When evaluated in a series of NHP NV studies, these attenuated rVSIV variants caused no clinical disease and demonstrated a very significant reduction in neuropathology compared to wild-type VSIV and the prototypic rVSIV vaccine vector. In spite of greatly increased in vivo attenuation, some of the rVSIV vectors elicited cell-mediated immune responses that were similar in magnitude to those induced by the much more virulent prototypic vector. These data demonstrate novel approaches to the rational attenuation of VSIV NV while retaining vector immunogenicity and have led to identification of an rVSIV N4CT1gag1 vaccine vector that has now successfully completed phase I clinical evaluation. IMPORTANCE The work described in this article demonstrates a rational approach to the attenuation of vesicular stomatitis virus neurovirulence. The major attenuation strategy described here will be most likely applicable to other members of the Rhabdoviridae and possibly other families of nonsegmented negative-strand RNA viruses. These studies have also enabled the identification of an attenuated

  4. Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43

    PubMed Central

    Uchida, Azusa; Sasaguri, Hiroki; Kimura, Nobuyuki; Tajiri, Mio; Ohkubo, Takuya; Ono, Fumiko; Sakaue, Fumika; Kanai, Kazuaki; Hirai, Takashi; Sano, Tatsuhiko; Shibuya, Kazumoto; Kobayashi, Masaki; Yamamoto, Mariko; Yokota, Shigefumi; Kubodera, Takayuki; Tomori, Masaki; Sakaki, Kyohei; Enomoto, Mitsuhiro; Hirai, Yukihiko; Kumagai, Jiro; Yasutomi, Yasuhiro; Mochizuki, Hideki; Kuwabara, Satoshi; Uchihara, Toshiki; Mizusawa, Hidehiro

    2012-01-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive motoneuron loss. Redistribution of transactive response deoxyribonucleic acid-binding protein 43 from the nucleus to the cytoplasm and the presence of cystatin C-positive Bunina bodies are considered pathological hallmarks of amyotrophic lateral sclerosis, but their significance has not been fully elucidated. Since all reported rodent transgenic models using wild-type transactive response deoxyribonucleic acid-binding protein 43 failed to recapitulate these features, we expected a species difference and aimed to make a non-human primate model of amyotrophic lateral sclerosis. We overexpressed wild-type human transactive response deoxyribonucleic acid-binding protein 43 in spinal cords of cynomolgus monkeys and rats by injecting adeno-associated virus vector into the cervical cord, and examined the phenotype using behavioural, electrophysiological, neuropathological and biochemical analyses. These monkeys developed progressive motor weakness and muscle atrophy with fasciculation in distal hand muscles first. They also showed regional cytoplasmic transactive response deoxyribonucleic acid-binding protein 43 mislocalization with loss of nuclear transactive response deoxyribonucleic acid-binding protein 43 staining in the lateral nuclear group of spinal cord innervating distal hand muscles and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with amyotrophic lateral sclerosis. Transactive response deoxyribonucleic acid-binding protein 43 mislocalization was an early or presymptomatic event and was later associated with neuron loss. These findings suggest that the transactive response deoxyribonucleic acid-binding protein 43 mislocalization leads to α-motoneuron degeneration. Furthermore, truncation of transactive response deoxyribonucleic acid-binding protein 43 was not a prerequisite for motoneuronal degeneration, and

  5. Live-Attenuated Measles Virus Vaccine Targets Dendritic Cells and Macrophages in Muscle of Nonhuman Primates

    PubMed Central

    Rennick, Linda J.; de Vries, Rory D.; Carsillo, Thomas J.; Lemon, Ken; van Amerongen, Geert; Ludlow, Martin; Nguyen, D. Tien; Yüksel, Selma; Verburgh, R. Joyce; Haddock, Paula; McQuaid, Stephen; de Swart, Rik L.

    2014-01-01

    virus was formulated according to protocols for production of commercial vaccine virus batches, and was subsequently used to assess viral tropism in nonhuman primates. The virus primarily replicated in professional antigen-presenting cells, which may explain why this LAV is so immunogenic and efficacious. PMID:25473055

  6. Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

    NASA Astrophysics Data System (ADS)

    Barrese, James C.; Aceros, Juan; Donoghue, John P.

    2016-04-01

    Objective. Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. Approach. We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. Main results. SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. Significance. These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does

  7. Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

    PubMed Central

    Barrese, James C; Aceros, Juan; Donoghue, John P

    2016-01-01

    Objective Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. Approach We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. Main results SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. Significance These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not

  8. Toxicity of culture material of Fusarium verticillioides strain MRC 826 to nonhuman primates.

    PubMed Central

    Gelderblom, W C; Seier, J V; Snijman, P W; Van Schalkwyk, D J; Shephard, G S; Marasas, W F

    2001-01-01

    to be used in long-term studies in nonhuman primates. PMID:11359695

  9. Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

    NASA Astrophysics Data System (ADS)

    Barrese, James C.; Rao, Naveen; Paroo, Kaivon; Triebwasser, Corey; Vargas-Irwin, Carlos; Franquemont, Lachlan; Donoghue, John P.

    2013-12-01

    systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicates that insulating material failure is the most significant factor. Significance. This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade.

  10. Evolution of the sweetness receptor in primates. II. Gustatory responses of non-human primates to nine compounds known to be sweet in man.

    PubMed

    Nofre, C; Tinti, J M; Glaser, D

    1996-12-01

    The gustatory responses of nine compounds, namely glycine, D-phenylalanine, D-tryptophan, cyanosuosan, magapame, sucrononate, campame, cyclamate and superaspartame, all known as sweet in man, were studied in 41 species or subspecies of non-human primates, selected among Prosimii (Lemuridae and Lorisidae), Platyrrhini (Callitrichidae and Cebidae) and Catarrhini (Cercopithecidae, Hylobatidae and Pongidae). The first six compounds are generally sweet to all primates, which implies that they interact with the primate sweetness receptors essentially through constant recognition sites. Campame is sweet only to Cebidae and Catarrhini, cyclamate only to Catarrhini, superaspartame principally to Callitrichidae and Catarrhini, which implies that all these compounds interact with the receptors partly through variable recognition sites. From the present work, from other previous results (where notably it was observed that alitame is sweet to all primates, ampame only to Prosimii and Catarrhini, and aspartame only to Catarrhini), and from the multipoint attachment (MPA) theory of sweetness reception (as elaborated by Nofre and Tinti from a detailed study of structure-activity relationships of various sweeteners in man), it is inferred that the primate sweetness receptors are very likely made up of eight recognition sites, of which the first, second, third, fourth, seventh and eighth are constant, and the fifth and sixth variable. From these results and from the MPA theory, it is also inferred that the recognition sites of the primate sweetness receptors could be: Asp-1 or Glu-1, Lys-2, Asp-3 or Glu-3, Thr-4, X-5, X-6, Thr-7, Ser-8, where the variable recognition sites X-5 and X-6 would be: Ala-5 and Ala-6 for Callitrichidae, Ser-5 and Ala-6 for Cebidae, Ala-5 and Thr-6 for Prosimii, and Thr-5 and Thr-6 for Catarrhini. By using Tupaiidae (tree shrews) as a reference outgroup and by means of other structural and functional molecular considerations, it appears that Callitrichidae

  11. Evolution of the sweetness receptor in primates. II. Gustatory responses of non-human primates to nine compounds known to be sweet in man.

    PubMed

    Nofre, C; Tinti, J M; Glaser, D

    1996-12-01

    The gustatory responses of nine compounds, namely glycine, D-phenylalanine, D-tryptophan, cyanosuosan, magapame, sucrononate, campame, cyclamate and superaspartame, all known as sweet in man, were studied in 41 species or subspecies of non-human primates, selected among Prosimii (Lemuridae and Lorisidae), Platyrrhini (Callitrichidae and Cebidae) and Catarrhini (Cercopithecidae, Hylobatidae and Pongidae). The first six compounds are generally sweet to all primates, which implies that they interact with the primate sweetness receptors essentially through constant recognition sites. Campame is sweet only to Cebidae and Catarrhini, cyclamate only to Catarrhini, superaspartame principally to Callitrichidae and Catarrhini, which implies that all these compounds interact with the receptors partly through variable recognition sites. From the present work, from other previous results (where notably it was observed that alitame is sweet to all primates, ampame only to Prosimii and Catarrhini, and aspartame only to Catarrhini), and from the multipoint attachment (MPA) theory of sweetness reception (as elaborated by Nofre and Tinti from a detailed study of structure-activity relationships of various sweeteners in man), it is inferred that the primate sweetness receptors are very likely made up of eight recognition sites, of which the first, second, third, fourth, seventh and eighth are constant, and the fifth and sixth variable. From these results and from the MPA theory, it is also inferred that the recognition sites of the primate sweetness receptors could be: Asp-1 or Glu-1, Lys-2, Asp-3 or Glu-3, Thr-4, X-5, X-6, Thr-7, Ser-8, where the variable recognition sites X-5 and X-6 would be: Ala-5 and Ala-6 for Callitrichidae, Ser-5 and Ala-6 for Cebidae, Ala-5 and Thr-6 for Prosimii, and Thr-5 and Thr-6 for Catarrhini. By using Tupaiidae (tree shrews) as a reference outgroup and by means of other structural and functional molecular considerations, it appears that Callitrichidae

  12. 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

  13. Encapsulating Non-Human Primate Multipotent Stromal Cells in Alginate via High Voltage for Cell-Based Therapies and Cryopreservation

    PubMed Central

    Gryshkov, Oleksandr; Pogozhykh, Denys; Hofmann, Nicola; Pogozhykh, Olena; Mueller, Thomas; Glasmacher, Birgit

    2014-01-01

    Alginate cell-based therapy requires further development focused on clinical application. To assess engraftment, risk of mutations and therapeutic benefit studies should be performed in an appropriate non-human primate model, such as the common marmoset (Callithrix jacchus). In this work we encapsulated amnion derived multipotent stromal cells (MSCs) from Callithrix jacchus in defined size alginate beads using a high voltage technique. Our results indicate that i) alginate-cell mixing procedure and cell concentration do not affect the diameter of alginate beads, ii) encapsulation of high cell numbers (up to 10×106 cells/ml) can be performed in alginate beads utilizing high voltage and iii) high voltage (15–30 kV) does not alter the viability, proliferation and differentiation capacity of MSCs post-encapsulation compared with alginate encapsulated cells produced by the traditional air-flow method. The consistent results were obtained over the period of 7 days of encapsulated MSCs culture and after cryopreservation utilizing a slow cooling procedure (1 K/min). The results of this work show that high voltage encapsulation can further be maximized to develop cell-based therapies with alginate beads in a non-human primate model towards human application. PMID:25259731

  14. Biocompatibility Assessment of Detonation Nanodiamond in Non-Human Primates and Rats Using Histological, Hematologic, and Urine Analysis.

    PubMed

    Moore, Laura; Yang, Junyu; Lan, Thanh T Ha; Osawa, Eiji; Lee, Dong-Keun; Johnson, William D; Xi, Jianzhong; Chow, Edward Kai-Hua; Ho, Dean

    2016-08-23

    Detonation nanodiamonds (DNDs) have been widely explored for biomedical applications ranging from cancer therapy to magnetic resonance imaging due to several promising properties. These include faceted surfaces that mediate potent drug binding and water coordination that have resulted in marked enhancements to the efficacy and safety of drug delivery and imaging. In addition, scalable processing of DNDs yields uniform particles. Furthermore, a broad spectrum of biocompatibility studies has shown that DNDs appear to be well-tolerated. Prior to the clinical translation of DNDs for indications that are addressed via intravenous administration, comprehensive assessment of DND safety in both small and large animal preclinical models is needed. This article reports the results of a DND biocompatibility study in both non-human primates and rats. The rat study was performed as a multiple dose subacute investigation in two cohorts that lasted for 2 weeks and included histological, serum, and urine analysis. The non-human primate study was performed as a dual gender, multiple dose, and long-term investigation in both standard/clinically relevant and elevated dosing cohorts that lasted for 6 months and included comprehensive serum, urine, histological, and body weight analysis. The results from these studies indicate that NDs are well-tolerated at clinically relevant doses. Examination of dose-dependent changes in biomarker levels provides important guidance for the downstream in-human validation of DNDs for clinical drug delivery and imaging. PMID:27439019

  15. Using naturalistic utterances to investigate vocal communication processing and development in human and non-human primates

    PubMed Central

    Talkington, William J.; Taglialatela, Jared P.; Lewis, James W.

    2013-01-01

    Humans and several non-human primates possess cortical regions that are most sensitive to vocalizations produced by their own kind (conspecifics). However, the use of speech and other broadly defined categories of behaviorally relevant natural sounds has led to many discrepancies regarding where voice-sensitivity occurs, and more generally the identification of cortical networks, “proto-networks” or protolanguage networks, and pathways that may be sensitive or selective for certain aspects of vocalization processing. In this prospective review we examine different approaches for exploring vocal communication processing, including pathways that may be, or become, specialized for conspecific utterances. In particular, we address the use of naturally produced non-stereotypical vocalizations (mimicry of other animal calls) as another category of vocalization for use with human and non-human primate auditory systems. We focus this review on two main themes, including progress and future ideas for studying vocalization processing in great apes (chimpanzees) and in very early stages of human development, including infants and fetuses. Advancing our understanding of the fundamental principles that govern the evolution and early development of cortical pathways for processing non-verbal communication utterances is expected to lead to better diagnoses and early intervention strategies in children with communication disorders, improve rehabilitation of communication disorders resulting from brain injury, and develop new strategies for intelligent hearing aid and implant design that can better enhance speech signals in noisy environments. PMID:23994296

  16. TT Virus Infection in Nonhuman Primates and Characterization of the Viral Genome: Identification of Simian TT Virus Isolates

    PubMed Central

    Abe, Kenji; Inami, Tomoko; Ishikawa, Koichi; Nakamura, Shin; Goto, Shunji

    2000-01-01

    Newly discovered TT virus (TTV) is widely distributed in human populations. To understand more about the relationship between TTV and its hosts, we tested 400 sera from various nonhuman primates for the presence of TTV DNA by PCR assay. We collected serum samples from 24 different species of nonhuman primates. TTV DNA was determined by PCR with primers designed from the 5′-end region of the TTV genome. Nucleotide sequencing and phylogenetic analysis of viral genomes were also performed. TTV DNA was detected in 87 of 98 (89%) chimpanzees and 3 of 21 (14%) crab-eating macaques. Nucleotide sequences of the PCR products obtained from both animals were 80 to 100% identical between two species. In contrast, the sequences differed from TTV isolates in humans by 24 to 33% at the nucleotide level and 36 to 50% at the amino acid level. Phylogenetic analysis demonstrated that all TTV isolates obtained from simians were distinct from the human TTV isolates. Furthermore, TTV in simians, but not in humans, was classified into three different genotypes. Our results indicate that TTV in simians represents a group different from, but closely related to, TTV in humans. From these results, we tentatively named this TTV simian TTV (s-TTV). The existence of the s-TTV will be important in determining the origin, nature, and transmission of human TTV and may provide useful animal models for studies of the infection and pathogenesis of this new DNA virus. PMID:10627568

  17. Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans.

    PubMed

    Blevins, James E; Baskin, Denis G

    2015-12-01

    The fact that more than 78 million adults in the US are considered overweight or obese highlights the need to develop new, effective strategies to treat obesity and its associated complications, including type 2 diabetes, kidney disease and cardiovascular disease. While the neurohypophyseal peptide oxytocin (OT) is well recognized for its peripheral effects to stimulate uterine contraction during parturition and milk ejection during lactation, release of OT within the brain is implicated in prosocial behaviors and in the regulation of energy balance. Previous findings indicate that chronic administration of OT decreases food intake and weight gain or elicits weight loss in diet-induced obese (DIO) mice and rats. Furthermore, chronic systemic treatment with OT largely reproduces the effects of central administration to reduce weight gain in DIO and genetically obese rodents at doses that do not appear to result in tolerance. These findings have now been recently extended to more translational models of obesity showing that chronic subcutaneous or intranasal OT treatment is sufficient to elicit body weight loss in DIO nonhuman primates and pre-diabetic obese humans. This review assesses the potential use of OT as a therapeutic strategy for treatment of obesity in rodents, nonhuman primates, and humans, and identifies potential mechanisms that mediate this effect.

  18. Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

    PubMed Central

    Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

    2014-01-01

    The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

  19. Good gibbons and evil macaques: a historical review on cognitive features of non-human primates in Chinese traditional culture.

    PubMed

    Zhang, Peng

    2015-07-01

    For several thousand years the ancient Chinese have accumulated rich knowledge, in the form of written literature and folklore, on the non-human primates widely distributed in China. I have used critical text analysis and discourse analysis to clarify when and how ancient Chinese distinguished gibbons from macaques. I divided the progress into four main stages, the Pre-Shang to Shang dynasty (before 1046 BC), the Zhou to Han dynasty (1046 BC-220 AD), the six dynasties to Song dynasty (220-1279 AD), and the Yuan to Qing dynasties (1279-1840 AD). I found that China's traditional cognition of gibbons and macaques emphasized the appearance of animals, organoleptic performance, or even whether or not their behavior was "moral". They described them as human-like animals by ethical standards but ignored the species itself. This kind of cognitive style actually embodies the "pursuit of goodness", which is the feature of Chinese traditional culture. This study presents some original views on Chinese traditional knowledge of non-human primates.

  20. Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates.

    PubMed

    Leranth, Csaba; Hajszan, Tibor; Szigeti-Buck, Klara; Bober, Jeremy; MacLusky, Neil J

    2008-09-16

    Exposure measurements from several countries indicate that humans are routinely exposed to low levels of bisphenol A (BPA), a synthetic xenoestrogen widely used in the production of polycarbonate plastics. There is considerable debate about whether this exposure represents an environmental risk, based on reports that BPA interferes with the development of many organs and that it may alter cognitive functions and mood. Consistent with these reports, we have previously demonstrated that BPA antagonizes spine synapse formation induced by estrogens and testosterone in limbic brain areas of gonadectomized female and male rats. An important limitation of these studies, however, is that they were based on rodent animal models, which may not be representative of the effects of human BPA exposure. To address this issue, we examined the influence of continuous BPA administration, at a daily dose equal to the current U.S. Environmental Protection Agency's reference safe daily limit, on estradiol-induced spine synapse formation in the hippocampus and prefrontal cortex of a nonhuman primate model. Our data indicate that even at this relatively low exposure level, BPA completely abolishes the synaptogenic response to estradiol. Because remodeling of spine synapses may play a critical role in cognition and mood, the ability of BPA to interfere with spine synapse formation has profound implications. This study is the first to demonstrate an adverse effect of BPA on the brain in a nonhuman primate model and further amplifies concerns about the widespread use of BPA in medical equipment, and in food preparation and storage. PMID:18768812

  1. High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

    NASA Astrophysics Data System (ADS)

    Naidoo-Variawa, S.; Hey-Cunningham, A. J.; Lehnert, W.; Kench, P. L.; Kassiou, M.; Banati, R.; Meikle, S. R.

    2007-11-01

    The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm3 FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm3) and 3D reprojection (3DRP) (5.9-9.1 mm3). A pilot 18F-2-fluoro-2-deoxy-d-glucose ([18F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

  2. Occurrence and genetic characterization of Giardia duodenalis from captive nonhuman primates by multi-locus sequence analysis.

    PubMed

    Martínez-Díaz, Rafael Alberto; Sansano-Maestre, José; Martínez-Herrero, María Del Carmen; Ponce-Gordo, Francisco; Gómez-Muñoz, María Teresa

    2011-09-01

    Giardia is the most common enteric protozoan that can be pathogenic to both humans and animals. Transmission can be direct through the faecal-oral route, or through ingestion of contaminated water or food. Genetic characterization of Giardia duodenalis isolates has demonstrated the existence of seven groups (assemblages A to G) which differ in their host distribution. Assemblages A and B are present in humans and other primates, dogs, cats, rodents, and other species of wild mammals, but the role of the different host animals in the epidemiology of human infection remains unclear. With this preliminary data, we can infer that nonhuman primates (NHP) might be a potential reservoir for zoonotic transmission. This research paper discusses the presence of Giardia in nonhuman primates housed in two Spanish zoological gardens (located in Valencia and Madrid). Twenty faecal samples obtained from 16 different species of NHP were studied; 70% were positives to Giardia, and genetic analyses were performed by sequencing of four genes (SSrRNA, glutamate dehydrogenase, triose phosphate isomerase, and beta-giardin). The assemblage A was the most frequent (63.4%) in the species studied. A sequence from a red ruffed lemur (corresponding to genotype AI) was obtained, and this is the first reported sequence of a gdh gene obtained from this species. The multi-locus sequence analysis was also performed on the samples positive to nested PCR belonging to assemblage B. After amplification using the GDHeF, GDHiF, and GDHiR gdh primers; AL3543, AL3546, AL3544, and AL3545 tpi primers; G7, G759, GBF, and GBR bg primers, amplicons of 432, 500, and 511 bp respectively were obtained. Amplification products were sequenced and the sequence and phylogenetic analyses showed that genotype IV like was the most frequent in the samples belonging to this assemblage. PMID:21327988

  3. Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

    PubMed Central

    Geisbert, Joan B; Shedlock, Devon J; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V; Popernack, Paul M; Yang, Zhi-Yong; Pau, Maria G; Roederer, Mario; Koup, Richard A; Goudsmit, Jaap; Jahrling, Peter B; Nabel, Gary J

    2006-01-01

    Background Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. Methods and Findings To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 1010 particles, two logs lower than that used previously. Conclusions Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 1010 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate. PMID:16683867

  4. Zoo Praxis and Theories: Teaching the Well-Being of Nonhuman Primates

    ERIC Educational Resources Information Center

    Burton, Frances

    2004-01-01

    Zoo projects that encourage reflective learning and are legitimate undertakings for untrained undergraduates are hard to develop. In this article, the author, as a professor in anthropology, discusses and teaches primate studies. His pedagogical goal in teaching primate studies is to enhance the process of learning, and to consider that students…

  5. "Vision for Action" in Young Children Aligning Multi-Featured Objects: Development and Comparison with Nonhuman Primates.

    PubMed

    Fragaszy, Dorothy Munkenbeck; Kuroshima, Hika; Stone, Brian W

    2015-01-01

    Effective vision for action and effective management of concurrent spatial relations underlie skillful manipulation of objects, including hand tools, in humans. Children's performance in object insertion tasks (fitting tasks) provides one index of the striking changes in the development of vision for action in early life. Fitting tasks also tap children's ability to work with more than one feature of an object concurrently. We examine young children's performance on fitting tasks in two and three dimensions and compare their performance with the previously reported performance of adult individuals of two species of nonhuman primates on similar tasks. Two, three, and four year-old children routinely aligned a bar-shaped stick and a cross-shaped stick but had difficulty aligning a tomahawk-shaped stick to a matching cut-out. Two year-olds were especially challenged by the tomahawk. Three and four year-olds occasionally held the stick several inches above the surface, comparing the stick to the surface visually, while trying to align it. The findings suggest asynchronous development in the ability to use vision to achieve alignment and to work with two and three spatial features concurrently. Using vision to align objects precisely to other objects and managing more than one spatial relation between an object and a surface are already more elaborated in two year-old humans than in other primates. The human advantage in using hand tools derives in part from this fundamental difference in the relation between vision and action between humans and other primates.

  6. Overlapping expression of anion exchangers in the cochlea of a non-human primate suggests functional compensation.

    PubMed

    Hosoya, Makoto; Fujioka, Masato; Kobayashi, Reona; Okano, Hideyuki; Ogawa, Kaoru

    2016-09-01

    Ion homeostasis in the inner ear is essential for proper hearing. Anion exchangers are one of the transporters responsible for the maintenance of homeostasis, but their expression profile in the primate cochlea has not been fully characterized. However, species-specific overlapping expression patterns and functional compensation in other organs, such as the kidney, pancreas and small intestine, have been reported. Here, we determined the expression patterns of the anion exchangers SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A11, SLC4A2 and SLC4A3 in the cochlea of a non-human primate, the common marmoset (Callithrix jacchus). Although the pattern of expression of SLC26A4 and SLC26A5 was similar to that in rodents, SLC26A7, SLC4A2, SLC4A3 exhibited different distributions. Notably, five transporters, SLC26A4, SLC26A6, SLC26A11 SLC4A2 and SLC4A3, were expressed in the cells of the outer sulcus. Our results reveal a species-specific distribution pattern of anion exchangers in the cochlea, particularly in the outer sulcus cells, suggesting functional compensation among these exchangers. This "primate-specific" pattern may be related to the human-specific hearing loss phenotypes of channelopathy disorders, including the SLC26A4-related diseases Pendred syndrome/DFNB4. PMID:27091614

  7. Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

    PubMed Central

    Barrese, James C; Rao, Naveen; Paroo, Kaivon; Triebwasser, Corey; Vargas-Irwin, Carlos; Franquemont, Lachlan; Donoghue, John P

    2016-01-01

    systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicate that insulating material failure is the most significant factor. Significance This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade. PMID:24216311

  8. Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.

    PubMed

    Wang, Junru; Shao, Lijian; Hendrickson, Howard P; Liu, Liya; Chang, Jianhui; Luo, Yi; Seng, John; Pouliot, Mylene; Authier, Simon; Zhou, Daohong; Allaben, William; Hauer-Jensen, Martin

    2015-11-01

    The non-human primate has been a useful model for studies of human acute radiation syndrome (ARS). However, to date structural changes in various parts of the intestine after total body irradiation (TBI) have not been systematically studied in this model. Here we report on our current study of TBI-induced intestinal structural injury in the non-human primate after doses typically associated with hematopoietic ARS. Twenty-four non-human primates were divided into three groups: sham-irradiated control group; and total body cobalt-60 (60Co) 6.7 Gy gamma-irradiated group; and total body 60Co 7.4 Gy gamma-irradiated group. After animals were euthanized at day 4, 7 and 12 postirradiation, sections of small intestine (duodenum, proximal jejunum, distal jejunum and ileum) were collected and fixed in 10% formalin. The intestinal mucosal surface length, villus height and crypt depths were assessed by computer-assisted image analysis. Plasma citrulline levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total bone marrow cells were counted and hematopoietic stem/progenitor cells in bone marrow were analyzed by flow cytometer. Histopathologically, all segments exhibited conspicuous disappearance of plicae circulares and prominent atrophy of crypts and villi. Intestinal mucosal surface length was significantly decreased in all intestinal segments on day 4, 7 and 12 after irradiation (P < 0.02-P < 0.001). Villus height was significantly reduced in all segments on day 4 and 7 (P = 0.02-0.005), whereas it had recovered by day 12 (P > 0.05). Crypt depth was also significantly reduced in all segments on day 4, 7 and 12 after irradiation (P < 0.04-P < 0.001). Plasma citrulline levels were dramatically reduced after irradiation, consistent with intestinal mucosal injury. Both 6.7 and 7.4 Gy TBI reduced total number of bone marrow cells. And further analysis showed that the number and function of CD45(+)CD34(+) hematopoietic stem/progenitors in bone

  9. Species specificity of the NS1 protein of influenza B virus: NS1 binds only human and non-human primate ubiquitin-like ISG15 proteins.

    PubMed

    Sridharan, Haripriya; Zhao, Chen; Krug, Robert M

    2010-03-12

    Influenza B viruses, which cause a highly contagious respiratory disease every year, are restricted to humans, but the basis for this restriction had not been determined. Here we provide one explanation for this restriction: the species specificity exhibited by the NS1 protein of influenza B virus (NS1B protein). This viral protein combats a major host antiviral response by binding the interferon-alpha/beta-induced, ubiquitin-like ISG15 protein and inhibiting its conjugation to an array of proteins. We demonstrate that the NS1B protein exhibits species-specific binding; it binds human and non-human primate ISG15 but not mouse or canine ISG15. In both transfection assays and virus-infected cells, the NS1B protein binds and relocalizes only human and non-human primate ISG15 from the cytoplasm to nuclear speckles. Human and non-human primate ISG15 proteins consist of two ubiquitin-like domains separated by a short hinge linker of five amino acids. Remarkably, this short hinge plays a large role in the species-specific binding by the NS1B protein. The hinge of human and non-human primate ISG15, which has a sequence that differs from that of other mammalian ISG15 proteins, including mouse and canine ISG15, is absolutely required for binding the NS1B protein. Consequently, the ISG15 proteins of humans and non-human primates are the only mammalian ISG15 proteins that would bind NS1B.

  10. Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail.

    PubMed

    Kugelman, Jeffrey R; Kugelman-Tonos, Johanny; Ladner, Jason T; Pettit, James; Keeton, Carolyn M; Nagle, Elyse R; Garcia, Karla Y; Froude, Jeffrey W; Kuehne, Ana I; Kuhn, Jens H; Bavari, Sina; Zeitlin, Larry; Dye, John M; Olinger, Gene G; Sanchez-Lockhart, Mariano; Palacios, Gustavo F

    2015-09-29

    MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape. PMID:26365189

  11. Route and method of delivery of DNA vaccine influence immune responses in mice and non-human primates.

    PubMed Central

    McCluskie, M. J.; Brazolot Millan, C. L.; Gramzinski, R. A.; Robinson, H. L.; Santoro, J. C.; Fuller, J. T.; Widera, G.; Haynes, J. R.; Purcell, R. H.; Davis, H. L.

    1999-01-01

    BACKGROUND: In spite of the large number of studies that have evaluated DNA-based immunization, few have directly compared the immune responses generated by different routes of immunization, particularly in non-human primates. Here we examine the ability of a hepatitis B surface antigen (HBsAg)-encoding plasmid to induce immune responses in mice and non-human primates (rhesus monkeys: Macaca mulatta) after delivery by a number of routes. MATERIALS AND METHODS: Eight different injected [intraperitoneal (IP), intradermal (ID), intravenous (IV), intramuscular (IM), intraperineal (IPER), subcutaneous (SC), sublingual (SL), vaginal wall (VW)] and six noninjected [intranasal inhalation (INH), intranasal instillation (INS), intrarectal (IR), intravaginal (IVAG), ocular (Oc), oral feeding (oral)] routes and the gene gun (GG) were used to deliver HBsAg-expressing plasmid DNA to BALB/c mice. Sera were assessed for HBsAg-specific antibodies (anti-HBs, IgG, IgG1, IgG2a) and cytotoxic T lymphocyte (CTL) activity measured. Three of the most commonly used routes (IM, ID, GG) were compared in rhesus monkeys, also using HBsAg-expressing vectors. Monkeys were immunized with short (0-, 4- and 8-week) or long (0-, 12- and 24-week) intervals between boosts, and in the case of GG, also with different doses, and their sera were assessed for anti-HBs. RESULTS: In one study, anti-HBs were detected in plasma of mice treated by five of eight of the injected and none of the six noninjected routes. The highest levels of anti-HBs were induced by IM and IV injections, although significant titers were also obtained with SL and ID. Each of these routes also induced CTL, as did IPER and VW and one noninjected route (INH) that failed to induce antibodies. In a second study, GG (1.6 microg) was compared to ID and IM (100 microg) delivery. Significant titers were obtained by all routes after only one boost, with the highest levels detected by IM. Delivery to the skin by GG induced exclusively IgG1

  12. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

    NASA Astrophysics Data System (ADS)

    Veiseh, Omid; Doloff, Joshua C.; Ma, Minglin; Vegas, Arturo J.; Tam, Hok Hei; Bader, Andrew R.; Li, Jie; Langan, Erin; Wyckoff, Jeffrey; Loo, Whitney S.; Jhunjhunwala, Siddharth; Chiu, Alan; Siebert, Sean; Tang, Katherine; Hollister-Lock, Jennifer; Aresta-Dasilva, Stephanie; Bochenek, Matthew; Mendoza-Elias, Joshua; Wang, Yong; Qi, Merigeng; Lavin, Danya M.; Chen, Michael; Dholakia, Nimit; Thakrar, Raj; Lacík, Igor; Weir, Gordon C.; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

    2015-06-01

    The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals and plastics, significantly abrogated foreign body reactions and fibrosis when compared with smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5-mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than five times longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved simply by tuning their spherical dimensions.

  13. Comparison of ICRP 67 and Other Plutonium Systemic Model Predictions with the Biokinetic Data from Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Krage, Eric Stephen; Brey, Richard Ray; Guilmette, Raymond A

    2016-04-01

    Despite the presence of a relatively large amount of human data available on the metabolism of plutonium, the experimental animal data is still important in constructing and parameterizing the biokinetic models. Recognizing this importance, the biokinetic data obtained from studies done by P.W. Durbin in nonhuman primates (NHP) were evaluated against the ICRP 67 systemic model and the two human models developed thereafter. The default transfer rates recommended for adult humans in these models predict the urinary excretion in NHP to a certain extent. However, they were unable to describe the fecal excretion rates several days post intake and the activities in skeleton and liver at the time of the death. These inconsistencies between the human reference models and the NHP biokinetic data are the result of metabolic and physiological differences between the species, as demonstrated by early biokinetic studies. PMID:26910028

  14. Successful implementation of cooperative handling eliminates the need for restraint in a complex nonhuman primate disease model

    PubMed Central

    Graham, Melanie L; Rieke, Eric F; Mutch, Lucas A; Zolondek, Elizabeth K; Faig, Aaron W; DuFour, Theresa A; Munson, James W; Kittredge, Jessica A; Schuurman, Henk-Jan

    2011-01-01

    Introduction Streptozotocin-induced diabetic nonhuman primates are used to study efficacy and safety of innovative immunosuppression after islet transplantation. We implemented a training program for medical management of a chronic disease state. Methods Cooperation with hand feeding and drinking; shifting; and limb presentation were trained utilizing predominately positive but also negative reinforcement in 52 animals compared with 28 macaques subjected to conventional physical and/or chemical restraint. The success of and timing of behavior acquisition was evaluated in a representative subset of 14 animals. Results Over 90% of animals were successful in behavior acquisition. Programmatically this resulted in complete elimination of chair restraint and negligible requirement for sedation. About half of trained animals had no to moderate thymic involution, indicative of a substantial reduction in stress. Conclusion Cooperative handling enhances animal well-being. This contributes to validity of scientific results and eliminates model-induced confounding that can obstruct interpretation of safety and efficacy data. PMID:22150842

  15. Emergence of Ebola Virus Escape Variants in Infected Nonhuman Primates Treated with the MB-003 Antibody Cocktail.

    PubMed

    Kugelman, Jeffrey R; Kugelman-Tonos, Johanny; Ladner, Jason T; Pettit, James; Keeton, Carolyn M; Nagle, Elyse R; Garcia, Karla Y; Froude, Jeffrey W; Kuehne, Ana I; Kuhn, Jens H; Bavari, Sina; Zeitlin, Larry; Dye, John M; Olinger, Gene G; Sanchez-Lockhart, Mariano; Palacios, Gustavo F

    2015-09-29

    MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape.

  16. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

    PubMed Central

    Veiseh, Omid; Doloff, Joshua C.; Ma, Minglin; Vegas, Arturo J.; Tam, Hok Hei; Bader, Andrew R.; Li, Jie; Langan, Erin; Wyckoff, Jeffrey; Loo, Whitney S.; Jhunjhunwala, Siddharth; Chiu, Alan; Siebert, Sean; Tang, Katherine; Hollister-Lock, Jennifer; Aresta-Dasilva, Stephanie; Bochenek, Matthew; Mendoza-Elias, Joshua; Wang, Yong; Qi, Merigeng; Lavin, Danya M.; Chen, Michael; Dholakia, Nimit; Thakrar, Raj; Lacík, Igor; Weir, Gordon C.; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

    2015-01-01

    The efficacy of implanted biomedical devices is often compromised by host recognition and subsequent foreign body responses. Here, we demonstrate the role of the geometry of implanted materials on their biocompatibility in vivo. In rodent and non-human primate animal models, implanted spheres 1.5 mm and above in diameter across a broad spectrum of materials, including hydrogels, ceramics, metals, and plastics, significantly abrogated foreign body reactions and fibrosis when compared to smaller spheres. We also show that for encapsulated rat pancreatic islet cells transplanted into streptozotocin-treated diabetic C57BL/6 mice, islets prepared in 1.5 mm alginate capsules were able to restore blood-glucose control for up to 180 days, a period more than 5-fold longer than for transplanted grafts encapsulated within conventionally sized 0.5-mm alginate capsules. Our findings suggest that the in vivo biocompatibility of biomedical devices can be significantly improved by simply tuning their spherical dimensions. PMID:25985456

  17. Comparison of ICRP 67 and Other Plutonium Systemic Model Predictions with the Biokinetic Data from Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Krage, Eric Stephen; Brey, Richard Ray; Guilmette, Raymond A

    2016-04-01

    Despite the presence of a relatively large amount of human data available on the metabolism of plutonium, the experimental animal data is still important in constructing and parameterizing the biokinetic models. Recognizing this importance, the biokinetic data obtained from studies done by P.W. Durbin in nonhuman primates (NHP) were evaluated against the ICRP 67 systemic model and the two human models developed thereafter. The default transfer rates recommended for adult humans in these models predict the urinary excretion in NHP to a certain extent. However, they were unable to describe the fecal excretion rates several days post intake and the activities in skeleton and liver at the time of the death. These inconsistencies between the human reference models and the NHP biokinetic data are the result of metabolic and physiological differences between the species, as demonstrated by early biokinetic studies.

  18. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease.

    PubMed

    Hadaczek, Piotr; Stanek, Lisa; Ciesielska, Agnieszka; Sudhakar, Vivek; Samaranch, Lluis; Pivirotto, Philip; Bringas, John; O'Riordan, Catherine; Mastis, Bryan; San Sebastian, Waldy; Forsayeth, John; Cheng, Seng H; Bankiewicz, Krystof S; Shihabuddin, Lamya S

    2016-01-01

    Huntington's disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease. PMID:27408903

  19. Fully Human Monoclonal Antibody Inhibitors of the Neonatal Fc Receptor Reduce Circulating IgG in Non-Human Primates

    PubMed Central

    Nixon, Andrew E.; Chen, Jie; Sexton, Daniel J.; Muruganandam, Arumugam; Bitonti, Alan J.; Dumont, Jennifer; Viswanathan, Malini; Martik, Diana; Wassaf, Dina; Mezo, Adam; Wood, Clive R.; Biedenkapp, Joseph C.; TenHoor, Chris

    2015-01-01

    The therapeutic management of antibody-mediated autoimmune disease typically involves immunosuppressant and immunomodulatory strategies. However, perturbing the fundamental role of the neonatal Fc receptor (FcRn) in salvaging IgG from lysosomal degradation provides a novel approach – depleting the body of pathogenic immunoglobulin by preventing IgG binding to FcRn and thereby increasing the rate of IgG catabolism. Herein, we describe the discovery and preclinical evaluation of fully human monoclonal IgG antibody inhibitors of FcRn. Using phage display, we identified several potent inhibitors of human-FcRn in which binding to FcRn is pH-independent, with over 1000-fold higher affinity for human-FcRn than human IgG-Fc at pH 7.4. FcRn antagonism in vivo using a human-FcRn knock-in transgenic mouse model caused enhanced catabolism of exogenously administered human IgG. In non-human primates, we observed reductions in endogenous circulating IgG of >60% with no changes in albumin, IgM, or IgA. FcRn antagonism did not disrupt the ability of non-human primates to mount IgM/IgG primary and secondary immune responses. Interestingly, the therapeutic anti-FcRn antibodies had a short serum half-life but caused a prolonged reduction in IgG levels. This may be explained by the high affinity of the antibodies to FcRn at both acidic and neutral pH. These results provide important preclinical proof of concept data in support of FcRn antagonism as a novel approach to the treatment of antibody-mediated autoimmune diseases. PMID:25954273

  20. Fully human monoclonal antibody inhibitors of the neonatal fc receptor reduce circulating IgG in non-human primates.

    PubMed

    Nixon, Andrew E; Chen, Jie; Sexton, Daniel J; Muruganandam, Arumugam; Bitonti, Alan J; Dumont, Jennifer; Viswanathan, Malini; Martik, Diana; Wassaf, Dina; Mezo, Adam; Wood, Clive R; Biedenkapp, Joseph C; TenHoor, Chris

    2015-01-01

    The therapeutic management of antibody-mediated autoimmune disease typically involves immunosuppressant and immunomodulatory strategies. However, perturbing the fundamental role of the neonatal Fc receptor (FcRn) in salvaging IgG from lysosomal degradation provides a novel approach - depleting the body of pathogenic immunoglobulin by preventing IgG binding to FcRn and thereby increasing the rate of IgG catabolism. Herein, we describe the discovery and preclinical evaluation of fully human monoclonal IgG antibody inhibitors of FcRn. Using phage display, we identified several potent inhibitors of human-FcRn in which binding to FcRn is pH-independent, with over 1000-fold higher affinity for human-FcRn than human IgG-Fc at pH 7.4. FcRn antagonism in vivo using a human-FcRn knock-in transgenic mouse model caused enhanced catabolism of exogenously administered human IgG. In non-human primates, we observed reductions in endogenous circulating IgG of >60% with no changes in albumin, IgM, or IgA. FcRn antagonism did not disrupt the ability of non-human primates to mount IgM/IgG primary and secondary immune responses. Interestingly, the therapeutic anti-FcRn antibodies had a short serum half-life but caused a prolonged reduction in IgG levels. This may be explained by the high affinity of the antibodies to FcRn at both acidic and neutral pH. These results provide important preclinical proof of concept data in support of FcRn antagonism as a novel approach to the treatment of antibody-mediated autoimmune diseases. PMID:25954273

  1. TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models

    PubMed Central

    Tougan, Takahiro; Aoshi, Taiki; Coban, Cevayir; Katakai, Yuko; Kai, Chieko; Yasutomi, Yasuhiro; Ishii, Ken J.; Horii, Toshihiro

    2013-01-01

    The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Ongoing clinical trials suggest the efficacy of the SE36 vaccine could be increased by the incorporation of more effective adjuvants into the vaccine formulation. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. Administration of a crude extract of P. falciparum parasite resulted in the induction of more SE36-specific IgG antibodies in monkeys vaccinated with a combination of SE36/AHG and adjuvant, as opposed to vaccination with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized with the combined SE36/AHG and K3 ODN formulation effectively suppressed parasitemia and symptoms of malaria following challenge infections. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG demonstrates safety, potent immunogenicity and efficacy in nonhuman primates, and this vaccine formulation may form the basis of a more effective malaria vaccine. PMID:23291928

  2. TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models.

    PubMed

    Tougan, Takahiro; Aoshi, Taiki; Coban, Cevayir; Katakai, Yuko; Kai, Chieko; Yasutomi, Yasuhiro; Ishii, Ken J; Horii, Toshihiro

    2013-02-01

    The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Ongoing clinical trials suggest the efficacy of the SE36 vaccine could be increased by the incorporation of more effective adjuvants into the vaccine formulation. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. Administration of a crude extract of P. falciparum parasite resulted in the induction of more SE36-specific IgG antibodies in monkeys vaccinated with a combination of SE36/AHG and adjuvant, as opposed to vaccination with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized with the combined SE36/AHG and K3 ODN formulation effectively suppressed parasitemia and symptoms of malaria following challenge infections. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG demonstrates safety, potent immunogenicity and efficacy in nonhuman primates, and this vaccine formulation may form the basis of a more effective malaria vaccine. PMID:23291928

  3. Multiple factors may influence the performance of a visual prosthesis based on intracortical microstimulation: nonhuman primate behavioural experimentation

    NASA Astrophysics Data System (ADS)

    Torab, K.; Davis, T. S.; Warren, D. J.; House, P. A.; Normann, R. A.; Greger, B.

    2011-06-01

    We hypothesize that a visual prosthesis capable of evoking high-resolution visual perceptions can be produced using high-electrode-count arrays of penetrating microelectrodes implanted into the primary visual cortex of a blind human subject. To explore this hypothesis, and as a prelude to human psychophysical experiments, we have conducted a set of experiments in primary visual cortex (V1) of non-human primates using chronically implanted Utah Electrode Arrays (UEAs). The electrical and recording properties of implanted electrodes, the high-resolution visuotopic organization of V1, and the stimulation levels required to evoke behavioural responses were measured. The impedances of stimulated electrodes were found to drop significantly immediately following stimulation sessions, but these post-stimulation impedances returned to pre-stimulation values by the next experimental session. Two months of periodic microstimulation at currents of up to 96 µA did not impair the mapping of receptive fields from local field potentials or multi-unit activity, or impact behavioural visual thresholds of light stimuli that excited regions of V1 that were implanted with UEAs. These results demonstrate that microstimulation at the levels used did not cause functional impairment of the electrode array or the neural tissue. However, microstimulation with current levels ranging from 18 to 76 µA (46 ± 19 µA, mean ± std) was able to elicit behavioural responses on eight out of 82 systematically stimulated electrodes. We suggest that the ability of microstimulation to evoke phosphenes and elicit a subsequent behavioural response may depend on several factors: the location of the electrode tips within the cortical layers of V1, distance of the electrode tips to neuronal somata, and the inability of nonhuman primates to recognize and respond to a generalized set of evoked percepts.

  4. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates

    PubMed Central

    Krivokrysenko, Vadim I.; Toshkov, Ilia A.; Gleiberman, Anatoli S.; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K.; Narizhneva, Natalya V.; Singh, Vijay K.; Whitnall, Mark H.; Purmal, Andrei A.; Shakhov, Alexander N.; Gudkov, Andrei V.; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1–48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40–60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  5. Receptor interactions involved in adenoviral-mediated gene delivery after systemic administration in non-human primates.

    PubMed

    Smith, Theodore A G; Idamakanti, Neeraja; Marshall-Neff, Jennifer; Rollence, Michele L; Wright, Patrick; Kaloss, Michele; King, Laura; Mech, Christine; Dinges, Lisa; Iverson, William O; Sherer, Alfred D; Markovits, Judit E; Lyons, Russette M; Kaleko, Michael; Stevenson, Susan C

    2003-11-20

    Adenovirus serotype 5 (Ad5)-based vectors can bind at least three separate cell surface receptors for efficient cell entry: the coxsackie-adenovirus receptor (CAR), alpha nu integrins, and heparan sulfate glycosaminoglycans (HSG). To address the role of each receptor involved in adenoviral cell entry, we mutated critical amino acids in fiber or penton to inhibit receptor interaction. A series of five adenoviral vectors was prepared and the biodistribution of each was previously characterized in mice. To evaluate possible species differences in Ad vector tropism, we characterized the effects of each detargeting mutation in non-human primates after systemic delivery to confirm our conclusions made in mice. In non-human primates, CAR was found to have minimal effects on vector delivery to all organs examined including liver and spleen. Cell-surface alpha nu integrins played a significant role in delivery of vector to the spleen, lung and kidney. The fiber shaft mutation S*, which presumably inhibits HSG binding, was found to significantly decrease delivery to all organs examined. The ability to detarget the liver corresponded with decreased elevations in liver serum enzymes (aspartate transferase [AST] and alanine transferase [ALT]) 24 hr after vector administration and also in serum interleukin (IL)-6 levels 6 hr after vector administration. The biodistribution data generated in cynomolgus monkeys correspond with those data derived from mice, demonstrating that CAR binding is not the major determinant of viral tropism in vivo. Vectors containing the fiber shaft modification may provide for a detargeted adenoviral vector on which to introduce new tropisms for the development of targeted, systemically deliverable adenoviral vectors for human clinical application.

  6. A Large-Scale Investigation of Hypoxia-Preconditioned Allogeneic Mesenchymal Stem Cells for Myocardial Repair in Nonhuman Primates

    PubMed Central

    Hu, Xinyang; Xu, Yinchuan; Zhong, Zhiwei; Wu, Yan; Zhao, Jing; Wang, Yingchao; Cheng, Haifeng; Kong, Minjian; Zhang, Fengjiang; Chen, Qi; Sun, Jianzhong; Li, Qian; Jin, Jing; Li, Qingju; Chen, Lihong; Wang, Chen; Zhan, Hongwei; Fan, Youqi; Yang, Qian; Yu, Lei; Wu, Rongrong; Liang, Jie; Zhu, Jinyun; Wang, Ya; Jin, Yiping; Lin, Yifan; Yang, Fan; Jia, Liangliang; Zhu, Wei; Chen, Jinghai; Yu, Hong

    2016-01-01

    Rationale: The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem-cell–based myocardial therapy are needed. Objective: The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP-MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation. Methods and Results: MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1×107 cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells–treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications. Conclusions: Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted. PMID:26838793

  7. A maternal high-fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates

    PubMed Central

    Suter, Melissa A.; Chen, Aishe; Burdine, Marie S.; Choudhury, Mahua; Harris, R. Alan; Lane, Robert H.; Friedman, Jacob E.; Grove, Kevin L.; Tackett, Alan J.; Aagaard, Kjersti M.

    2012-01-01

    In nonhuman primates, we previously demonstrated that a maternal high-fat diet (MHFD) induces fetal nonalcoholic fatty liver disease (NAFLD) and alters the fetal metabolome. These changes are accompanied by altered acetylation of histone H3 (H3K14ac). However, the mechanism behind this alteration in acetylation remains unknown. As SIRT1 is both a lysine deacetylase and a crucial sensor of cellular metabolism, we hypothesized that SIRT1 may be involved in fetal epigenomic alterations. Here we show that in utero exposure to a MHFD, but not maternal obesity per se, increases fetal H3K14ac with concomitant decreased SIRT1 expression and diminished in vitro protein and histone deacetylase activity. MHFD increased H3K14ac and DBC1-SIRT1 complex formation in fetal livers, both of which were abrogated with diet reversal despite persistent maternal obesity. Moreover, MHFD was associated with altered expression of known downstream effectors deregulated in NAFLD and modulated by SIRT1 (e.g., PPARΑ, PPARG, SREBF1, CYP7A1, FASN, and SCD). Finally, ex vivo purified SIRT1 retains deacetylase activity on an H3K14ac peptide substrate with preferential activity toward acetylated histone H3; mutagenesis of the catalytic domain of SIRT1 (H363Y) abrogates H3K14ac deacetylation. Our data implicate SIRT1 as a likely molecular mediator of the fetal epigenome and metabolome under MHFD conditions.—Suter, M. A., Chen, A., Burdine, M. S., Choudhury, M., Harris, R. A., Lane, R. H., Friedman, J. E., Grove, K. L., Tackett, A. J., Aagaard, K. M. A maternal high-fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates. PMID:22982377

  8. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

    PubMed

    Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  9. 77 FR 6971 - Establishment of User Fees for Filovirus Testing of Nonhuman Primate Liver Samples

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ...), have been used to support implementation of these regulations. On January 5, 2011 (76 FR 678), HHS/CDC...) Pursuant to 48 FR 9374 (list of HHS/CDC program actions that are categorically excluded from the NEPA.... Available upon request: (404) 639-1600. 3. 55 FR 10288, March 20, 1990, ``Importation of Nonhuman...

  10. Eocene primates of South America and the African origins of New World monkeys.

    PubMed

    Bond, Mariano; Tejedor, Marcelo F; Campbell, Kenneth E; Chornogubsky, Laura; Novo, Nelson; Goin, Francisco

    2015-04-23

    The platyrrhine primates, or New World monkeys, are immigrant mammals whose fossil record comes from Tertiary and Quaternary sediments of South America and the Caribbean Greater Antilles. The time and place of platyrrhine origins are some of the most controversial issues in primate palaeontology, although an African Palaeogene ancestry has been presumed by most primatologists. Until now, the oldest fossil records of New World monkeys have come from Salla, Bolivia, and date to approximately 26 million years ago, or the Late Oligocene epoch. Here we report the discovery of new primates from the ?Late Eocene epoch of Amazonian Peru, which extends the fossil record of primates in South America back approximately 10 million years. The new specimens are important for understanding the origin and early evolution of modern platyrrhine primates because they bear little resemblance to any extinct or living South American primate, but they do bear striking resemblances to Eocene African anthropoids, and our phylogenetic analysis suggests a relationship with African taxa. The discovery of these new primates brings the first appearance datum of caviomorph rodents and primates in South America back into close correspondence, but raises new questions about the timing and means of arrival of these two mammalian groups. PMID:25652825

  11. Eocene primates of South America and the African origins of New World monkeys

    NASA Astrophysics Data System (ADS)

    Bond, Mariano; Tejedor, Marcelo F.; Campbell, Kenneth E.; Chornogubsky, Laura; Novo, Nelson; Goin, Francisco

    2015-04-01

    The platyrrhine primates, or New World monkeys, are immigrant mammals whose fossil record comes from Tertiary and Quaternary sediments of South America and the Caribbean Greater Antilles. The time and place of platyrrhine origins are some of the most controversial issues in primate palaeontology, although an African Palaeogene ancestry has been presumed by most primatologists. Until now, the oldest fossil records of New World monkeys have come from Salla, Bolivia, and date to approximately 26 million years ago, or the Late Oligocene epoch. Here we report the discovery of new primates from the ?Late Eocene epoch of Amazonian Peru, which extends the fossil record of primates in South America back approximately 10 million years. The new specimens are important for understanding the origin and early evolution of modern platyrrhine primates because they bear little resemblance to any extinct or living South American primate, but they do bear striking resemblances to Eocene African anthropoids, and our phylogenetic analysis suggests a relationship with African taxa. The discovery of these new primates brings the first appearance datum of caviomorph rodents and primates in South America back into close correspondence, but raises new questions about the timing and means of arrival of these two mammalian groups.

  12. Eocene primates of South America and the African origins of New World monkeys.

    PubMed

    Bond, Mariano; Tejedor, Marcelo F; Campbell, Kenneth E; Chornogubsky, Laura; Novo, Nelson; Goin, Francisco

    2015-04-23

    The platyrrhine primates, or New World monkeys, are immigrant mammals whose fossil record comes from Tertiary and Quaternary sediments of South America and the Caribbean Greater Antilles. The time and place of platyrrhine origins are some of the most controversial issues in primate palaeontology, although an African Palaeogene ancestry has been presumed by most primatologists. Until now, the oldest fossil records of New World monkeys have come from Salla, Bolivia, and date to approximately 26 million years ago, or the Late Oligocene epoch. Here we report the discovery of new primates from the ?Late Eocene epoch of Amazonian Peru, which extends the fossil record of primates in South America back approximately 10 million years. The new specimens are important for understanding the origin and early evolution of modern platyrrhine primates because they bear little resemblance to any extinct or living South American primate, but they do bear striking resemblances to Eocene African anthropoids, and our phylogenetic analysis suggests a relationship with African taxa. The discovery of these new primates brings the first appearance datum of caviomorph rodents and primates in South America back into close correspondence, but raises new questions about the timing and means of arrival of these two mammalian groups.

  13. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

    PubMed Central

    Pierantoni, Angiolo; Esposito, Maria Luisa; Ammendola, Virginia; Napolitano, Federico; Grazioli, Fabiana; Abbate, Adele; del Sorbo, Mariarosaria; Siani, Loredana; D’Alise, Anna Morena; Taglioni, Alessandra; Perretta, Gemma; Siccardi, Antonio; Soprana, Elisa; Panigada, Maddalena; Thom, Michelle; Scarselli, Elisa; Folgori, Antonella; Colloca, Stefano; Taylor, Geraldine; Cortese, Riccardo; Nicosia, Alfredo; Capone, Stefania; Vitelli, Alessandra

    2015-01-01

    Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing. PMID:26015988

  14. Moving beyond the welfare standard of psychological well-being for nonhuman primates: the case of chimpanzees.

    PubMed

    Gluck, John P

    2014-04-01

    Since 1985, the US Animal Welfare Act and Public Health Service policy have required that researchers using nonhuman primates in biomedical and behavioral research develop a plan "for a physical environment adequate to promote the psychological well-being of primates." In pursuing this charge, housing attributes such as social companionship, opportunities to express species-typical behavior, suitable space for expanded locomotor activity, and nonstressful relationships with laboratory personnel are dimensions that have dominated the discussion. Regulators were careful not to direct a specific set of prescriptions (i.e., engineering standards) for the attainment of these goals, but to leave the design of the programs substantially up to "professional judgment" at the local level. Recently, however, the Institute of Medicine, in its path-finding 2011 report on the necessity of chimpanzee use in research, bypassed this flexible and contingent concept, and instead, required as a central precondition that chimpanzees be housed in "ethologically appropriate" environments. In so doing, obligations of ethical treatment of one great ape species were elevated above the needs of some research. The evolution and significance of this change are discussed. PMID:24627265

  15. Moving beyond the welfare standard of psychological well-being for nonhuman primates: the case of chimpanzees.

    PubMed

    Gluck, John P

    2014-04-01

    Since 1985, the US Animal Welfare Act and Public Health Service policy have required that researchers using nonhuman primates in biomedical and behavioral research develop a plan "for a physical environment adequate to promote the psychological well-being of primates." In pursuing this charge, housing attributes such as social companionship, opportunities to express species-typical behavior, suitable space for expanded locomotor activity, and nonstressful relationships with laboratory personnel are dimensions that have dominated the discussion. Regulators were careful not to direct a specific set of prescriptions (i.e., engineering standards) for the attainment of these goals, but to leave the design of the programs substantially up to "professional judgment" at the local level. Recently, however, the Institute of Medicine, in its path-finding 2011 report on the necessity of chimpanzee use in research, bypassed this flexible and contingent concept, and instead, required as a central precondition that chimpanzees be housed in "ethologically appropriate" environments. In so doing, obligations of ethical treatment of one great ape species were elevated above the needs of some research. The evolution and significance of this change are discussed.

  16. "Vision for Action" in Young Children Aligning Multi-Featured Objects: Development and Comparison with Nonhuman Primates.

    PubMed

    Fragaszy, Dorothy Munkenbeck; Kuroshima, Hika; Stone, Brian W

    2015-01-01

    Effective vision for action and effective management of concurrent spatial relations underlie skillful manipulation of objects, including hand tools, in humans. Children's performance in object insertion tasks (fitting tasks) provides one index of the striking changes in the development of vision for action in early life. Fitting tasks also tap children's ability to work with more than one feature of an object concurrently. We examine young children's performance on fitting tasks in two and three dimensions and compare their performance with the previously reported performance of adult individuals of two species of nonhuman primates on similar tasks. Two, three, and four year-old children routinely aligned a bar-shaped stick and a cross-shaped stick but had difficulty aligning a tomahawk-shaped stick to a matching cut-out. Two year-olds were especially challenged by the tomahawk. Three and four year-olds occasionally held the stick several inches above the surface, comparing the stick to the surface visually, while trying to align it. The findings suggest asynchronous development in the ability to use vision to achieve alignment and to work with two and three spatial features concurrently. Using vision to align objects precisely to other objects and managing more than one spatial relation between an object and a surface are already more elaborated in two year-old humans than in other primates. The human advantage in using hand tools derives in part from this fundamental difference in the relation between vision and action between humans and other primates. PMID:26440979

  17. “Vision for Action” in Young Children Aligning Multi-Featured Objects: Development and Comparison with Nonhuman Primates

    PubMed Central

    2015-01-01

    Effective vision for action and effective management of concurrent spatial relations underlie skillful manipulation of objects, including hand tools, in humans. Children’s performance in object insertion tasks (fitting tasks) provides one index of the striking changes in the development of vision for action in early life. Fitting tasks also tap children’s ability to work with more than one feature of an object concurrently. We examine young children’s performance on fitting tasks in two and three dimensions and compare their performance with the previously reported performance of adult individuals of two species of nonhuman primates on similar tasks. Two, three, and four year-old children routinely aligned a bar-shaped stick and a cross-shaped stick but had difficulty aligning a tomahawk-shaped stick to a matching cut-out. Two year-olds were especially challenged by the tomahawk. Three and four year-olds occasionally held the stick several inches above the surface, comparing the stick to the surface visually, while trying to align it. The findings suggest asynchronous development in the ability to use vision to achieve alignment and to work with two and three spatial features concurrently. Using vision to align objects precisely to other objects and managing more than one spatial relation between an object and a surface are already more elaborated in two year-old humans than in other primates. The human advantage in using hand tools derives in part from this fundamental difference in the relation between vision and action between humans and other primates. PMID:26440979

  18. Differences in mineral metabolism among nonhuman primates receiving diets with only vitamin D3 or only vitamin D2.

    PubMed

    Marx, S J; Jones, G; Weinstein, R S; Chrousos, G P; Renquist, D M

    1989-12-01

    We tested for differences in aspects of mineral metabolism during the administration of diets with only vitamin D3 or only vitamin D2 in four nonhuman anthropoid primate species [two catarrhini, Macaca fascicularis (crab-eating macaque) and Macaca mulatta (rhesus macaque), and two platyrrhini, Saimiri sciureus (squirrel monkey) and Aotus vociferans (night monkey)]. All four species maintained approximately 2- to 3-fold higher serum 25-hydroxyvitamin D (25OHD) level while receiving vitamin D3 than while receiving similar amounts of vitamin D2. Serum 25OHD in M. mulatta receiving the standard primate dietary supplement of vitamin D3 was high enough (360 +/- 60 vs. 70 +/- 25 nM in vitamin D-supplemented humans; P less than 0.0001) to suggest that this widely used level of vitamin D3 supplementation is excessive for some M. mulatta. Serum 24,25-dihydroxyvitamin D [24,25-(OH)2D] in A. vociferans was uniquely high [P less than 0.01; species mean, 19 +/- 5, 95 +/- 12, and 27 +/- 5 nM in groups receiving diets with 1.5 IU vitamin D3/g, 6.6 IU vitamin D3/g, and 15 IU vitamin D2/g, respectively; mean 24,25-(OH)2D from the other three species pooled across three diets was 7 +/- 5 nM]. We confirmed relative resistance to 1,25-(OH)2D in S. sciureus, manifested by osteomalacia and moderately high serum 1,25-(OH)2D. Serum 1,25-(OH)2D in S. sciureus increased 4-fold (P less than 0.05) when the precursor in serum was changed from 250HD3 to 250HD2, suggesting that this species shows more severe resistance to 1,25-(OH)2D2 than to 1,25-(OH)2D3. In conclusion, we found many differences in vitamin D metabolism among four nonhuman anthropoid primate species. The striking feature in A. vociferans (high, 24,25-(OH)2D without high 25OHD in serum independent of whether diet contained only vitamin D3 or only vitamin D2) should allow determination of whether 24,25-(OH)2D functions as a unique agonist or an inactive metabolite in this species.

  19. Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

    PubMed Central

    Aversi-Ferreira, Roqueline A. G. M. F.; Bretas, Rafael Vieira; Maior, Rafael Souto; Davaasuren, Munkhzul; Paraguassú-Chaves, Carlos Alberto; Nishijo, Hisao; Aversi-Ferreira, Tales Alexandre

    2014-01-01

    The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing. PMID:24860810

  20. Sources of variation in hair cortisol in wild and captive non-human primates.

    PubMed

    Fourie, Nicolaas H; Brown, Janine L; Jolly, Clifford J; Phillips-Conroy, Jane E; Rogers, Jeffrey; Bernstein, Robin M

    2016-04-01

    Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results. PMID:26884274

  1. Comparative study of lectin reactivity in the vomeronasal organ of human and nonhuman primates.

    PubMed

    Kinzinger, Jonathan H; Johnson, Edward W; Bhatnagar, Kunwar P; Bonar, Christopher J; Burrows, Anne M; Mooney, Mark P; Siegel, Michael I; Smith, Timothy D

    2005-06-01

    The main and accessory olfactory systems of certain mammals (e.g., rodents, ungulates, and carnivores) have been investigated using lectin histochemistry to probe for sugar residues that may reflect physiological aspects of signal transduction or development. Morphologically, the vomeronasal organs (VNOs) of strepsirrhine primates (lemurs and lorises) are typical of functional VNOs in other mammals, whereas in humans and chimpanzees the VNOs appear vestigial. However, the human VNO is considered functional by some authors. To elucidate the cellular nature of the VNO in human and chimpanzees, a panel of six lectins (Con-A, ECL, PNA, RCA, s-WGA, and UEA-1) was applied to the VNO in eight species of primates, including humans and chimpanzees. The results indicated that there were few, if any, lectin-reactive cells in the human or chimpanzee VNO that resembled those seen in the vomeronasal neuroepithelium in other primates. The overall pattern of lectin reactivity in the human and chimpanzee VNO is unlike that seen in mammals with chemosensory VNOs, suggesting that the VNO of these hominoids does not function similarly to that of other primates.

  2. Sources of variation in hair cortisol in wild and captive non-human primates.

    PubMed

    Fourie, Nicolaas H; Brown, Janine L; Jolly, Clifford J; Phillips-Conroy, Jane E; Rogers, Jeffrey; Bernstein, Robin M

    2016-04-01

    Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results.

  3. Molecular identification and characterization of Mycobacterium avium subspecies paratuberculosis in free living non-human primate (Rhesus macaques) from North India.

    PubMed

    Singh, S V; Singh, A V; Singh, P K; Kumar, A; Singh, B

    2011-05-01

    In recent years, Mycobacterium avium subspecies paratuberculosis (MAP) has emerged as major animal pathogen with significant zoonotic concerns, worldwide. MAP infection is endemic in domestic and wild ruminant population in India. However, information on MAP infection in free ranging animal species and non human primates is limited. Present study aimed to estimate the status of MAP infection in free living Rhesus macaques suffering with multiple clinical conditions (coughing and loose stool). A total of 25 stool samples were collected from six colonies of Rhesus macaques from Mathura region (North India) and screened for the presence of MAP, using microscopic examination and IS900 PCR, directly from stool samples. PCR positive DNA samples were further genotyped using IS1311 PCR-restriction enzyme analysis. Of the 25 stool samples, 10 (40.0%) and 2 (8.0%) were positive for MAP using microscopic examination and direct IS900 PCR, respectively. IS900 PCR positive DNA samples were genotyped as 'Indian Bison type', which is a major MAP genotype infecting domestic and wild ruminant species and human beings in India. Prevalence of MAP in Rhesus macaques (Indian monkeys) was moderately high and confirmed interspecies sharing of MAP between domestic livestock and non-human primates. Presence of MAP in non-human primates, support the etiological role of MAP in inflammatory bowel disease patients. Indian monkeys may serve as model for understanding the role of non-human primates in sustenance, transmission and pathogenesis of MAP infection.

  4. Oligocene primates from China reveal divergence between African and Asian primate evolution.

    PubMed

    Ni, Xijun; Li, Qiang; Li, Lüzhou; Beard, K Christopher

    2016-05-01

    Profound environmental and faunal changes are associated with climatic deterioration during the Eocene-Oligocene transition (EOT) roughly 34 million years ago. Reconstructing how Asian primates responded to the EOT has been hindered by a sparse record of Oligocene primates on that continent. Here, we report the discovery of a diverse primate fauna from the early Oligocene of southern China. In marked contrast to Afro-Arabian Oligocene primate faunas, this Asian fauna is dominated by strepsirhines. There appears to be a strong break between Paleogene and Neogene Asian anthropoid assemblages. Asian and Afro-Arabian primate faunas responded differently to EOT climatic deterioration, indicating that the EOT functioned as a critical evolutionary filter constraining the subsequent course of primate evolution across the Old World. PMID:27151861

  5. Reference in human and non-human primate communication: What does it take to refer?

    PubMed

    Sievers, Christine; Gruber, Thibaud

    2016-07-01

    The concept of functional reference has been used to isolate potentially referential vocal signals in animal communication. However, its relatedness to the phenomenon of reference in human language has recently been brought into question. While some researchers have suggested abandoning the concept of functional reference altogether, others advocate a revision of its definition to include contextual cues that play a role in signal production and perception. Empirical and theoretical work on functional reference has also put much emphasis on how the receiver understands the referential signal. However, reference, as defined in the linguistic literature, is an action of the producer, and therefore, any definition describing reference in non-human animals must also focus on the producer. To successfully determine whether a signal is used to refer, we suggest an approach from the field of pragmatics, taking a closer look at specific situations of signal production, specifically at the factors that influence the production of a signal by an individual. We define the concept of signaller's reference to identify intentional acts of reference produced by a signaller independently of the communicative modality, and illustrate it with a case study of the hoo vocalizations produced by wild chimpanzees during travel. This novel framework introduces an intentional approach to referentiality. It may therefore permit a closer comparison of human and non-human animal referential behaviour and underlying cognitive processes, allowing us to identify what may have emerged solely in the human lineage. PMID:26971953

  6. Application of NCRP 156 Wound Model and ICRP 67 Systemic Plutonium Model for Analysis of Urine Data from Simulated Wounds in Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Guilmette, Raymond A; Konzen, Kevin; Krage, Eric S; Brey, Richard R

    2016-07-01

    The predictions of the wound model described in NCRP Report No. 156, coupled with the systemic model described in ICRP 67, were compared with the actual urinary excretion data and wound retention data from nonhuman primates injected intramuscularly or subcutaneously with Pu(IV) citrate. The results indicated that the early behavior of Pu(IV) citrate in wounds can be adequately described by the default retention parameters for moderately retained radionuclides suggested by the report. The urinary excretion rates after 200 d post intake could not be described well by the parameters of any of the default wound models because of the differences in the systemic handling of plutonium by humans compared to nonhuman primates. PMID:27218296

  7. Application of NCRP 156 Wound Model and ICRP 67 Systemic Plutonium Model for Analysis of Urine Data from Simulated Wounds in Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Guilmette, Raymond A; Konzen, Kevin; Krage, Eric S; Brey, Richard R

    2016-07-01

    The predictions of the wound model described in NCRP Report No. 156, coupled with the systemic model described in ICRP 67, were compared with the actual urinary excretion data and wound retention data from nonhuman primates injected intramuscularly or subcutaneously with Pu(IV) citrate. The results indicated that the early behavior of Pu(IV) citrate in wounds can be adequately described by the default retention parameters for moderately retained radionuclides suggested by the report. The urinary excretion rates after 200 d post intake could not be described well by the parameters of any of the default wound models because of the differences in the systemic handling of plutonium by humans compared to nonhuman primates.

  8. Human-nonhuman primate interactions amongst Tikuna people: perceptions and local initiatives for resource management in Amacayacu in the Colombian Amazon.

    PubMed

    Parathian, Hannah E; Maldonado, Angela M

    2010-09-01

    This study assesses the impact of hunting on the densities of nonhuman primates in two indigenous Tikuna territories (Mocagua and San Martín), overlapping Amacayacu National Park in the Colombian Amazon. Large-bodied primates were once favored prey by Tikunas, but are now rarely hunted owing to the diminishing primate populations. We evaluate the effect of a hunting ban on woolly monkeys (Lagothrix lagothricha) by the residents of Mocagua, using qualitative and quantitative methods. Hunting records showed that from February 2005 to February 2009, a total of 25,142 kg of mammal bushmeat were harvested in Mocagua and San Martín. Primates constituted 345 kg of the total harvest. From 223 kg of large-bodied primates extracted for subsistence purposes, 160 kg were hunted in San Martín and 64 kg in Mocagua. Large-bodied primates made up 70% of the total primate biomass in Mocagua (398 kg/km(2)) and 22% in San Martín (199 kg/km(2)). From dietary records, we found bushmeat constituted 30% of protein consumption in Mocagua and 37% in San Martín. Primates were absent in records from Mocagua, and appeared only three times in those from San Martín suggesting inconsistencies with hunting data. Despite its moderate consumption, bushmeat was identified as a highly valued food source during focus group activities. Primate pet-keeping and part utilization were observed in San Martín but not in Mocagua, possibly as a consequence of fewer primates being hunted. We suggest that Mocagua provides an example of how community-based conservation strategies can be achieved, where opportunities for employment in tourism and alternative food sources are available.

  9. Endotoxin-Induced Systemic Inflammation Activates Microglia: [11C]PBR28 Positron Emission Tomography in Nonhuman Primates

    PubMed Central

    Hannestad, Jonas; Gallezot, Jean-Dominique; Schafbauer, Thomas; Lim, Keunpoong; Kloczynski, Tracy; Morris, Evan D.; Carson, Richard E; Ding, Yu-Shin; Cosgrove, Kelly

    2013-01-01

    Microglia play an essential role in many brain diseases. Microglia are activated by local tissue damage or inflammation, but systemic inflammation can also activate microglia. An important clinical question is whether the effects of systemic inflammation on microglia mediates the deleterious effects of systemic inflammation in diseases such as Alzheimer's dementia, multiple sclerosis, and stroke. Positron Emission Tomography (PET) imaging with ligands that bind to Translocator Protein (TSPO) can be used to detect activated microglia. The aim of this study was to evaluate whether the effect of systemic inflammation on microglia could be measured with PET imaging in nonhuman primates, using the TSPO ligand [11C]PBR28. Methods Six female baboons (Papio anubis) were scanned before and at 1 h and/or 4h and/or 22h after intravenous administration of E. coli lipopolysaccharide (LPS; 0.1 mg/kg), which induces systemic inflammation. Regional time-activity data from regions of interest (ROIs) were fitted to the two-tissue compartmental model, using the metabolite-corrected arterial plasma curve as input function. Total volume of distribution (VT) of [11C]PBR28 was used as a measure of total ligand binding. The primary outcome was change in VT from baseline. Serum levels of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) were used to assess correlations between systemic inflammation and microglial activation. In one baboon, immunohistochemistry was used to identify cells expressing TSPO. Results LPS administration increased [11C]PBR28 binding (F(3,6)=5.1, p=.043) with a 29±16 % increase at 1h (n = 4) and a 62±34% increase at 4h (n = 3) post-LPS. There was a positive correlation between serum IL-1β and IL-6 levels and the increase in [11C]PBR28 binding. TSPO immunoreactivity occurred almost exclusively in microglia and rarely in astrocytes. Conclusion In the nonhuman-primate brain, LPS-induced systemic

  10. Ephrin/Eph receptor expression in brain of adult nonhuman primates: implications for neuroadaptation.

    PubMed

    Xiao, Danqing; Miller, Gregory M; Jassen, Amy; Westmoreland, Susan V; Pauley, Douglas; Madras, Bertha K

    2006-01-01

    In developing brain, Eph receptors and their ephrin ligands (Ephs/ephrins) are implicated in facilitating topographic guidance of a number of pathways, including the nigrostriatal and mesolimbic dopamine (DA) pathways. In adult rodent brain, these molecules are implicated in neuronal plasticity associated with learning and memory. Cocaine significantly alters the expression of select members of this family of axonal guidance molecules, implicating Ephs, ephrins in drug-induced neuroadaptation. The potential contribution of Ephs, ephrins to cocaine-induced reorganization of striatal circuitry brain in primates [Saka, E., Goodrich, C., Harlan, P., Madras, B.K., Graybiel, A.M., 2004. Repetitive behaviors in monkeys are linked to specific striatal activation patterns. J. Neurosci. 24, 7557-7565] is unknown because there are no documented reports of Eph/ephrin expression or function in adult primate brain. We now report that brains of adult old and new world monkeys express mRNA encoding EphA4 receptor and ephrin-B2 ligand, implicated in topographic guidance of dopamine and striatal neurons during development. Their encoded proteins distributed highly selectively in regions of adult monkey brain. EphA4 mRNA levels were prominent in the DA-rich caudate/putamen, nucleus accumbens and globus pallidus, as well as the medial and orbitofrontal cortices, hippocampus, amygdala, thalamus and cerebellum. Immunocytochemical localization of EphA4 protein revealed discrete expression in caudate/putamen, globus pallidus, substantia nigra, cerebellar Purkinje cells, pyramidal cells of frontal cortices (layers II, III and V) and the subgranular zone of the hippocampus. Evidence for EphA4 expression in dopamine neurons emerged from colocalization with tyrosine-hydroxylase-positive terminals in striatum and substantia nigra and ventral tegmental area cell bodies. The association of axonal guidance molecules with drug-induced reorganization of adult primate brain circuitry warrants

  11. A study of placental transfer mechanisms in nonhuman primates using (/sup 14/C)phenylalanine

    SciTech Connect

    Pueschel, S.M.; Boylan, J.M.; Jackson, B.T.; Piasecki, G.J.

    1982-02-01

    Placental transfer mechanisms were investigated in pregnant Macaca Fascicularis and Macaca mulatta during the gestational age of 120 to 130 days. These primates underwent an operative procedure that allowed continuous fetal blood sampling. The administration of (/sup 14/C)phenylalanine into the maternal circulation revealed a significant increase of radioactive material in the fetal circulation, indicating an active placental transport mechanism unidirectional to the fetus. When (/sup 14/C)phenylalanine was injected into the fetus, radioactive aromatic amino acids in the maternal circulation increased only slightly over time, resembling a simple diffusion process.

  12. Teratogenicity studies on late blighted potatoes in nonhuman primates (Macaca mulatta and Saguinus labiatus).

    PubMed

    Allen, J R; Marlar, R J; Chesney, C F; Helgeson, J P; Kelman, A; Weckel, G; Traisman, E; White, J W

    1977-02-01

    Female rhesus monkeys and marmosets were fed a diet containing blighted potatoes (Phytophthora infestans) at a level of 10g/kg per day for at least two weeks prior to breeding and six weeks following conception in order to gain additional information on the association of blighted potatoes and the development of anencephaly and spina bifida in primate species. There was an absence of either of these neural-tube defects in 32 rhesus and 14 marmoset infants whose mothers had received a blighted potato diet. In addition there were no cranial osseous defects. There were, however, two rhesus monkey infants with internal hydrocephalus whose mothers had consumed blighted potatoes.

  13. Investigation of effects of 60-Hz electric and magnetic fields on operant and social behavior and on the neuroendocrine system of nonhuman primates

    SciTech Connect

    Smith, H.D.

    1993-01-22

    The objective of this program is to investigate behavioral and neuroendocrine effects associated with exposure to 60-Hz electric and magnetic fields (E/MF), using the baboon (Papio cynocephalus) as a nonhuman primate surrogate for the human. Results from this program, along with information from experiments conducted elsewhere, could be used to estimate and evaluate the likelihood of deleterious consequences of human exposure to the electric and magnetic fields associated with electric power transmission.

  14. Investigation of effects of 60-Hz electric and magnetic fields on operant and social behavior and on the neuroendocrine system of nonhuman primates. Annual report, FY1992

    SciTech Connect

    Smith, H.D

    1993-01-22

    The objective of this program is to investigate behavioral and neuroendocrine effects associated with exposure to 60-Hz electric and magnetic fields (E/MF), using the baboon (Papio cynocephalus) as a nonhuman primate surrogate for the human. Results from this program, along with information from experiments conducted elsewhere, could be used to estimate and evaluate the likelihood of deleterious consequences of human exposure to the electric and magnetic fields associated with electric power transmission.

  15. An implicit measure of olfactory performance for non-human primates reveals aversive and pleasant odor conditioning.

    PubMed

    Livneh, Uri; Paz, Rony

    2010-09-30

    We have little understanding of how odorants are processed in neural networks of the primate brain. Because chemo-stimuli are harder to control than physical stimuli (e.g. vision, audition), such research was limited by the temporal resolution, accuracy, and reliability of olfactometers (odor producing machines). Recent advances were able to create olfactometers that overcome these limitations, allowing their use together with neuroimaging techniques in humans. From the behavioral point of view, olfaction research requires a behavioral measure that can be used to quantify olfactory performance. This becomes a real problem when working with animals, where, unlike humans, explicit measures are harder to obtain. Furthermore, because odorants are powerful primitive reinforcers, such implicit measures can be beneficial to use in learning paradigms. Here we describe an olfactometer suitable for use in non-human primates, and an end-port design that allows the accurate measure of real-time respiratory modulations that are elicited in response to odor presentation. We demonstrate that this implicit measure is differentially modulated when experiencing pleasant or aversive odors. We then present an experimental paradigm in which monkeys learn to associate tones with odors, and show that the time delay from the conditioned stimuli to the next breath can be used to measure learning and memory expression in this paradigm. Using this construct, we reveal olfactory performance during acquisition and extinction of odor conditioning. These techniques can be used in electrophysiological recordings from relevant brain areas to shed light on neural networks involved in odor processing and reinforcement-learning.

  16. On the origins of human handedness and language: a comparative review of hand preferences for bimanual coordinated actions and gestural communication in nonhuman primates.

    PubMed

    Meguerditchian, Adrien; Vauclair, Jacques; Hopkins, William D

    2013-09-01

    Within the evolutionary framework about the origin of human handedness and hemispheric specialization for language, the question of expression of population-level manual biases in nonhuman primates and their potential continuities with humans remains controversial. Nevertheless, there is a growing body of evidence showing consistent population-level handedness particularly for complex manual behaviors in both monkeys and apes. In the present article, within a large comparative approach among primates, we will review our contribution to the field and the handedness literature related to two particular sophisticated manual behaviors regarding their potential and specific implications for the origins of hemispheric specialization in humans: bimanual coordinated actions and gestural communication. Whereas bimanual coordinated actions seem to elicit predominance of left-handedness in arboreal primates and of right-handedness in terrestrial primates, all handedness studies that have investigated gestural communication in several primate species have reported stronger degree of population-level right-handedness compared to noncommunicative actions. Communicative gestures and bimanual actions seem to affect differently manual asymmetries in both human and nonhuman primates and to be related to different lateralized brain substrates. We will discuss (1) how the data of hand preferences for bimanual coordinated actions highlight the role of ecological factors in the evolution of handedness and provide additional support the postural origin theory of handedness proposed by MacNeilage [MacNeilage [2007]. Present status of the postural origins theory. In W. D. Hopkins (Ed.), The evolution of hemispheric specialization in primates (pp. 59-91). London: Elsevier/Academic Press] and (2) the hypothesis that the emergence of gestural communication might have affected lateralization in our ancestor and may constitute the precursors of the hemispheric specialization for language.

  17. A silicon based implantable microelectrode array for electrophysiological and dopamine recording from cortex to striatum in the non-human primate brain.

    PubMed

    Zhang, Song; Song, Yilin; Wang, Mixia; Zhang, Zhiming; Fan, Xinyi; Song, Xianteng; Zhuang, Ping; Yue, Feng; Chan, Piu; Cai, Xinxia

    2016-11-15

    Dual-mode, multielectrode recordings have become routine in rodent neuroscience research and have recently been adapted to the non-human primate. However, robust and reliable application of acute, multielectrode recording methods in monkeys especially for deep brain nucleus research remains a challenge. In this paper, We described a low cost silicon based 16-site implantable microelectrode array (MEA) chip fabricated by standard lithography technology for in vivo test. The array was 25mm long and designed to use in non-human primate models, for electrophysiological and electrochemical recording. We presented a detailed protocol for array fabrication, then showed that the device can record Spikes, LFPs and dopamine (DA) variation continuously from cortex to striatum in an esthetized monkey. Though our experiment, high-quality electrophysiological signals were obtained from the animal. Across any given microelectrode, spike amplitudes ranged from 70 to 300μV peak to peak, with a mean signal-to-noise ratio of better than 5:1. Calibration results showed the MEA probe had high sensitivity and good selectivity for DA. The DA concentration changed from 42.8 to 481.6μM when the MEA probe inserted from cortex into deep brain nucleus of striatum, which reflected the inhomogeneous distribution of DA in brains. Compared with existing methods allowing single mode (electrophysiology or electrochemistry) recording. This system is designed explicitly for dual-mode recording to meet the challenges of recording in non-human primates. PMID:27155116

  18. On the pursuit of the brain network for proto-syntactic learning in non-human primates: conceptual issues and neurobiological hypotheses.

    PubMed

    Petkov, Christopher I; Wilson, Benjamin

    2012-07-19

    Songbirds have become impressive neurobiological models for aspects of human verbal communication because they learn to sequence their song elements, analogous, in some ways, to how humans learn to produce spoken sequences with syntactic structure. However, mammals such as non-human primates are considered to be at best limited-vocal learners and not able to sequence their vocalizations, although some of these animals can learn certain 'artificial grammar' sequences. Thus, conceptual issues have slowed the progress in exploring potential neurobiological homologues to language-related processes in species that are taxonomically closely related to humans. We consider some of the conceptual issues impeding a pursuit of, as we define them, 'proto-syntactic' capabilities and their neuronal substrates in non-human animals. We also discuss ways to better bridge comparative behavioural and neurobiological data between humans and other animals. Finally, we propose guiding neurobiological hypotheses with which we aim to facilitate the future testing of the level of correspondence between the human brain network for syntactic-learning and related neurobiological networks present in other primates. Insights from the study of non-human primates and other mammals are likely to complement those being obtained in birds to further our knowledge of the human language-related network at the cellular level.

  19. “Juggling” Behavior in Wild Hainan Gibbons, a New Finding in Nonhuman Primates

    PubMed Central

    Deng, Huaiqing; Zhou, Jiang

    2016-01-01

    Many species of primates use tools and manipulate objects. Environmental objects, such as sticks and branches, are used in locomotion, display, conflict, nesting, and foraging. This study presents observations regarding endangered male Hainan gibbons (Nomascus hainanus) selecting sticks and then throwing and catching them repeatedly. This act of Hainan gibbons was termed as “juggling” behavior. This study is the first record of branch use of this kind in free-living gibbons. While it is impossible to experiment on this only remaining population of Hainan gibbons, the deliberate acquisition and then throwing and catching of a stick raises myriad questions regarding their function. The study determined that the juggling behavior of Hainan gibbons, in the process of their brachiation, helps them accurately judge the distance and support strength of an object. It was also found that an adult individual’s proficiency in juggling behavior was much higher than that of a youth. Of all gibbon species, the juggling behavior of Hainan gibbon has a high degree of behavior refinement. Gibbons have the longest forearm than any other primates, which helps them in such performances—a unique mechanism that allows them to perform such unique activities, including juggling. PMID:27030317

  20. Individual differences in temperament and behavioral management practices for nonhuman primates

    PubMed Central

    Coleman, Kristine

    2011-01-01

    Effective behavioral management plans are tailored to unique behavioral patterns of each individual species. However, even within a species behavioral needs of individuals can vary. Factors such as age, sex, and temperament can affect behavioral needs of individuals. While some of these factors, such as age and sex, are taken into account, other factors, such as an individual’s temperament, are rarely specifically provided for in behavioral management plans. However, temperament may affect how animals respond to socialization, positive reinforcement training and other forms of enrichment. This review will examine how individual differences in temperament might affect, or be affected by, behavioral management practices for captive primates. Measuring temperament may help us predict outcome of social introductions. It can also predict which animals may be difficult to train using traditional methods. Further, knowledge of temperament may be able to help identify individuals at risk for development of behavioral problems. Taken together, understanding individual differences in temperament of captive primates can help guide behavioral management decisions. PMID:22518067

  1. Hip Anatomy and Ontogeny of Lower Limb Musculature in Three Species of Nonhuman Primates

    PubMed Central

    Baker, Jeremy J.; Searight, Katherine J.; Stump, Madeliene Atzeva; Kehrer, Matthew B.; Shanafelt, Colleen; Graham, Eric; Smith, Timothy D.

    2011-01-01

    The hip region is examined to determine what aspects of musculoskeletal anatomy are precociously developed in primate species with highly specialized modes of locomotion. Muscles of the hind limb were removed and weighed in each specimen, and the hip joint of selected specimens was studied in stained serial sections. No perinatal differences among species are evident, but in adults, the hip joint of Galago moholi (a leaping specialist) appears to have proportionally thick articular cartilage (relative to the subchondral plate) compared to two species of cheirogaleids. Muscle mass distribution in the hind limbs confirms previous observations that the quadriceps femoris muscle is especially large in Galago (in percent mass of the entire hind limb), while the hip region is smaller compared to the more quadrupedal cheirogaleids. Across age groups, the species with the least specialized locomotion as adults, Cheirogaleus medius, shows little or no change in proximal to distal percentage distribution of muscle mass. Galago has a larger percentage mass gain in the thigh. We suggest that muscle mass gain to specific limb segments may be a critical milestone for primates with extremely specialized modes of locomotion. PMID:22567295

  2. Detection of anti-Leptospira antibodies in captive nonhuman primates from Salvador, Brazil.

    PubMed

    Pinna, Melissa H; Martins, Gabriel; Pinheiro, Ana Carla O; Almeida, Daniela S; Oriá, Arianne P; Lilenbaum, Walter

    2012-01-01

    Leptospirosis is a widely distributed zoonosis that affects several species of domestic and wild animals. Under captive conditions, Leptospirosis is a potential problem because the physical conditions in most zoos and research centers cannot prevent the captive animals from being exposed to rodents, raccoons, opossums, and other local wildlife that are known carriers. Yet, despite the potential risk, animals that are destined for reintroduction into the wild are not routinely tested for anti-Leptospira antibodies before their release. The purpose of this study was to determine the occurrence of anti-Leptospira antibodies in captive New World monkeys that were housed in the Wild Animals Screening Center in Salvador, Brazil. Blood samples were collected from 44 monkeys (28 Callithrix jacchus, eight Callithrix pennicilata, and eight Cebus sp.). The animals were screened for antibodies with the microscopic agglutination test. Twenty-five (56.8%) primates were seroreactive, with Icterohaemorrhagiae being the most frequent serogroup. None of the monkeys, however, presented clinical signs of leptospirosis. Thus, seroreactivity with low titers in asymptomatic animals, as observed in this study, suggests exposure to the agent. The unexpected predominance of the serogroup Icterohaemorrhagiae further suggests that exposure to this serogroup occurred in captivity. Therefore, the dangerous possibility cannot be ignored that reintroduced monkeys will carry the leptospiral serovars into wild populations. In conclusion, primates exposed to urban serovars before their release from captivity represent a potentially significant health risk to wild populations.

  3. Germline and somatic imprinting in the nonhuman primate highlights species differences in oocyte methylation

    PubMed Central

    Cheong, Clara Y.; Chng, Keefe; Ng, Shilen; Chew, Siew Boom; Chan, Louiza; Ferguson-Smith, Anne C.

    2015-01-01

    Genomic imprinting is an epigenetic mechanism resulting in parental allele-specific gene expression. Defects in normal imprinting are found in cancer, assisted reproductive technologies, and several human syndromes. In mouse models, germline-derived DNA methylation is shown to regulate imprinting. Though imprinting is largely conserved between mammals, species- and tissue-specific domains of imprinted expression exist. Using the cynomolgus macaque (Macaca fascicularis) to assess primate-specific imprinting, we present a comprehensive view of tissue-specific imprinted expression and DNA methylation at established imprinted gene clusters. For example, like mouse and unlike human, macaque IGF2R is consistently imprinted, and the PLAGL1, INPP5F transcript variant 2, and PEG3 imprinting control regions are not methylated in the macaque germline but acquire this post-fertilization. Methylome data from human early embryos appear to support this finding. These suggest fundamental differences in imprinting control mechanisms between primate species and rodents at some imprinted domains, with implications for our understanding of the epigenetic programming process in humans and its influence on disease. PMID:25862382

  4. Cyclic remodeling of the nonhuman primate endometrium: a model for understanding endometrial receptivity.

    PubMed

    Slayden, Ov Daniel

    2014-09-01

    Old World monkeys display physiological responses to steroid hormones that are similar to those of women. In this review, we describe cyclic morphological changes that take place within the uterus of Old World primates during the menstrual cycle. In primates, estrogen stimulates endometrial growth in the follicular phase of the menstrual cycle. Progesterone secreted in the luteal phase acts to induce secretory differentiation, which is required for successful embryo implantation. During the differentiation process, endometrial estrogen receptor-1 (ESR-1) is suppressed, and reduced staining for ESR-1 is a definitive marker of the onset of uterine receptivity. Downregulation of ESR-1 is topographically limited to the functionalis (upper) zones of the endometrium, the zones in which embryo implantation occurs, indicating that zone-specific factors play a role in the differentiation process. Future genomic and proteomic studies are expected to reveal additional markers for diagnosing endometrial receptivity. Due to the distinct zonal response of the endometrium to ovarian steroids, accurate histological characterization will remain necessary to interpret novel targets in the assessment of fertility. PMID:24959820

  5. Home cage locomotor changes in non-human primates after prolonged welding-fume exposure.

    PubMed

    Kim, Choong Yong; Sung, Jae Hyuck; Chung, Yong Hyun; Park, Jung Duck; Han, Jeong Hee; Lee, Jong Seong; Heo, Jeong Doo; Yu, Il Je

    2013-12-01

    To define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31 mg/m(3) total suspended particulate (TSP), 0.9 mg/m(3) of Mn), and high concentration (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of TSP. The monkeys were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day over 8 months in an inhalation chamber system equipped with an automatic fume generator. The home cage locomotor activity and patterns were determined using a camera system over 2-4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor activity of the high-concentration primates was found to be 5-6 times higher than that of the unexposed primates, and this increased locomotor activity was maintained for 7 weeks after ceasing the welding-fume exposure, eventually subsiding to three times higher after 13 weeks of recovery. Therefore, the present results, along with our previous observations of a high magnetic resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn concentration, indicate that prolonged welding-fume exposure can cause neurobehavioral changes in cynomolgus monkeys. PMID:24304306

  6. The effect of head-down tilt and water immersion on intracranial pressure in nonhuman primates

    NASA Technical Reports Server (NTRS)

    Keil, Lanny C.; Mckeever, Kenneth H.; Skidmore, Michael G.; Hines, John; Severs, Walter B.

    1992-01-01

    Intracranial pressure (ICP) is investigated in primates during and after -6-deg head-down tilt (HDT) and immersion in water to examine the effects of the headward fluid shift related to spaceflight. Following the HDT the primates are subjected to head-out thermoneutral water immersion, and the ICP is subsequently measured. ICP is found to increase from 3.8 +/- 1.1 to 5.3 +/- 1.3 mm Hg during the horizontal control period. ICP stabilizes at -6.3 +/- 1.3 mm Hg and then increases to -2.2 +/- 1.9 mm Hg during partial immersion, and ICP subsequently returns to preimmersion levels after immersion. These data indicate that exposure to HDT or water immersion lead to an early sharp increase in ICP, and water immersion alone leads to higher ICP levels. A significant conclusion of the work is that the ICP did not approach pathological levels, and this finding is relevant to human spaceflight research.

  7. Home cage locomotor changes in non-human primates after prolonged welding-fume exposure.

    PubMed

    Kim, Choong Yong; Sung, Jae Hyuck; Chung, Yong Hyun; Park, Jung Duck; Han, Jeong Hee; Lee, Jong Seong; Heo, Jeong Doo; Yu, Il Je

    2013-12-01

    To define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31 mg/m(3) total suspended particulate (TSP), 0.9 mg/m(3) of Mn), and high concentration (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of TSP. The monkeys were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day over 8 months in an inhalation chamber system equipped with an automatic fume generator. The home cage locomotor activity and patterns were determined using a camera system over 2-4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor activity of the high-concentration primates was found to be 5-6 times higher than that of the unexposed primates, and this increased locomotor activity was maintained for 7 weeks after ceasing the welding-fume exposure, eventually subsiding to three times higher after 13 weeks of recovery. Therefore, the present results, along with our previous observations of a high magnetic resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn concentration, indicate that prolonged welding-fume exposure can cause neurobehavioral changes in cynomolgus monkeys.

  8. Individual differences in temperament and behavioral management practices for nonhuman primates.

    PubMed

    Coleman, Kristine

    2012-03-01

    Effective behavioral management plans are tailored to unique behavioral patterns of each individual species. However, even within a species behavioral needs of individuals can vary. Factors such as age, sex, and temperament can affect behavioral needs of individuals. While some of these factors, such as age and sex, are taken into account, other factors, such as an individual's temperament, are rarely specifically provided for in behavioral management plans. However, temperament may affect how animals respond to socialization, positive reinforcement training and other forms of enrichment. This review will examine how individual differences in temperament might affect, or be affected by, behavioral management practices for captive primates. Measuring temperament may help us predict outcome of social introductions. It can also predict which animals may be difficult to train using traditional methods. Further, knowledge of temperament may be able to help identify individuals at risk for development of behavioral problems. Taken together, understanding individual differences in temperament of captive primates can help guide behavioral management decisions.

  9. Generalization of category knowledge and dimensional categorization in humans (Homo sapiens) and nonhuman primates (Macaca mulatta).

    PubMed

    Smith, J David; Zakrzewski, Alexandria C; Johnston, Jennifer J R; Roeder, Jessica L; Boomer, Joseph; Ashby, F Gregory; Church, Barbara A

    2015-10-01

    A theoretical framework within neuroscience distinguishes humans' implicit and explicit systems for category learning. We used a perceptual-categorization paradigm to ask whether nonhumans share elements of these systems. Participants learned categories that foster implicit or explicit categorization in humans, because they had a multidimensional, information-integration (II) solution or a unidimensional, rule-based (RB) solution. Then humans and macaques generalized their category knowledge to new, untested regions of the stimulus space. II generalization was impaired, suggesting that II category learning is conditioned and constrained by stimulus generalization to its original, trained stimulus contexts. RB generalization was nearly seamless, suggesting that RB category knowledge in humans and monkeys has properties that grant it some independence from the original, trained stimulus contexts. These findings raise the questions of (a) how closely macaques' dimensional categorization verges on humans' explicit/declarative categorization, and (b) how far macaques' dimensional categorization has advanced beyond that in other vertebrate species. PMID:26167774

  10. Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington’s disease

    PubMed Central

    Hadaczek, Piotr; Stanek, Lisa; Ciesielska, Agnieszka; Sudhakar, Vivek; Samaranch, Lluis; Pivirotto, Philip; Bringas, John; O’Riordan, Catherine; Mastis, Bryan; San Sebastian, Waldy; Forsayeth, John; Cheng, Seng H; Bankiewicz, Krystof S; Shihabuddin, Lamya S

    2016-01-01

    Huntington’s disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease. PMID:27408903

  11. Manganese neurotoxicity: new perspectives from behavioral, neuroimaging, and neuropathological studies in humans and non-human primates

    PubMed Central

    Guilarte, Tomás R.

    2013-01-01

    Manganese (Mn) is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinsonism. Historically, studies on the effects of Mn in humans and experimental animals have been concerned with effects on the basal ganglia and the dopaminergic system as it relates to movement abnormalities. However, emerging studies are beginning to provide significant evidence of Mn effects on cortical structures and cognitive function at lower levels than previously recognized. This review advances new knowledge of putative mechanisms by which exposure to excess levels of Mn alters neurobiological systems and produces neurological deficits not only in the basal ganglia but also in the cerebral cortex. The emerging evidence suggests that working memory is significantly affected by chronic Mn exposure and this may be mediated by alterations in brain structures associated with the working memory network including the caudate nucleus in the striatum, frontal cortex and parietal cortex. Dysregulation of the dopaminergic system may play an important role in both the movement abnormalities as well as the neuropsychiatric and cognitive function deficits that have been described in humans and non-human primates exposed to Mn. PMID:23805100

  12. Resveratrol supplementation confers neuropr