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Sample records for brazilian non-human primates

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

    Science.gov (United States)

    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.

  2. Archiving and Databasing of Non-Human Primate Impact Data

    National Research Council Canada - National Science Library

    Dobie, Thomas

    2001-01-01

    The National Biodynamics Laboratory (NBDL) of the University of New Orleans has preserved recoverable indirect impact acceleration data from non-human primate subject tests performed by the former Naval Biodynamics Laboratory...

  3. Simian malaria at two sites in the Brazilian Amazon: I-The infection rates of Plasmodium brasilianum in non-human primates

    Directory of Open Access Journals (Sweden)

    Ricardo Lourenço-de-Oliveira

    1995-06-01

    Full Text Available The parasite that causes simian malaria in the Brazilian Amazon, Plasmodium brasilianum, is infective to man. In this region, where humans live within and in close proximity to the forest, it was suspected that this parasite could be the cause of a zoonosis. A study was performed in the areas surrounding two hydroelectric plants in the Amazon, Balbina and Samuel, aiming at determining the zoonotic potential of this parasite. P. brasilianum was detected in, respectively, 15.8% and 9.9% of 126 and 252 primates belonging to seven and eight species examined from Balbina and Samuel. The highest malaria infection rates were found among the red-howler monkey Alouatta seniculus straminea (32.3%, the bearded-saki Chiropotes satanas chiropotes (50% and the spider-monkey Ateles paniscus paniscus (2[1+] from Balbina and in the squirrel-monkey Saimiri ustus (21% and the black-faced-spider-monkey Ateles paniscus chamek (28.6% from Samuel.

  4. [Advance of gene-modified non-human primate models].

    Science.gov (United States)

    Liu, Zhen; Cai, Yijun; Sun, Qiang

    2017-10-25

    Non-human primates would be particularly valuable in life sciences and biomedical research area. Gene-modified monkeys with gene overexpression or loss of function have been successfully generated with the rapid advance in gene manipulation technology such as lentivirus infection and programmable nucleases (ZFN, TALEN, CRISPR-Cas9). Here we review the recent development on gene-modified monkey generation by lentivirus and programmable nucleases. Then we discuss three concerns, the long time for sexual maturation, the off target and the mosaicism of founders, which limit the wide application of gene-modified non-human-primates. At last, hotspots and future trend for gene-modified non-human-primates generation are proposed.

  5. Male germline stem cells in non-human primates

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    S. Sharma

    2017-09-01

    Full Text Available Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs. These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28 during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of

  6. Non-human primates in outdoor enclosures: Risk for infection with rodent-borne hantaviruses

    OpenAIRE

    Mertens, M; Essbauer, S.S.; Rang, A.; Schröder, J.; Splettstoesser, W.D.; Kretzschmar, C.; Krüger, D.H.; Groschup, M. H.; Mätz-Rensing, K; Ulrich, R. G.

    2010-01-01

    ABSTRACT Different species of non-human primates have been exploited as animal disease models for human hantavirus infections. To study the potential risk of natural hantavirus infection of non-human primates, we investigated serum samples from non-human primates of three non-human primate species living in outdoor enclosures of the German Primate Center (GPC), Gottingen, located in a hantavirus endemic region of central Germany. For that purpose we used serological assays based on...

  7. Localization of b-defensin genes in non human primates

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    M Ventura

    2009-06-01

    Full Text Available Defensins are a family of host defence peptides that play an important role in the innate immunity of mammalian and avian species. In humans, four b-defensins have been isolated so far, corresponding to the products of the genes DEFB1 (h-BD1, GenBank accession number NM_005218; DEFB4 (h-Bd2, NM_004942.2, DEFB103 (h-BD3, NM_018661; and DEFB104 (hBD4, NM_080389 mapping on chromosome 8p23.22. We have localized b- defensin genes on metaphasic chromosomes of great apes and several non-human primate species to determine their physical mapping. Using fluorescent in situ hybridization and BAC probes containing the four b-defensin genes, we have mapped the homologous regions to the b-defensin genes on chromosome 8p23-p.22 in non-human primates, while no signals were detected on prosimians chromosomes.

  8. Non-Human Primate Models of Orthopoxvirus Infections

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    Anne Schmitt

    2014-06-01

    Full Text Available Smallpox, one of the most destructive diseases, has been successfully eradicated through a worldwide vaccination campaign. Since immunization programs have been stopped, the number of people with vaccinia virus induced immunity is declining. This leads to an increase in orthopoxvirus (OPXV infections in humans, as well as in animals. Additionally, potential abuse of Variola virus (VARV, the causative agent of smallpox, or monkeypox virus, as agents of bioterrorism, has renewed interest in development of antiviral therapeutics and of safer vaccines. Due to its high risk potential, research with VARV is restricted to two laboratories worldwide. Therefore, numerous animal models of other OPXV infections have been developed in the last decades. Non-human primates are especially suitable due to their close relationship to humans. This article provides a review about on non-human primate models of orthopoxvirus infections.

  9. Smallpox and monkeypox in non-human primates.

    Science.gov (United States)

    Arita, I; Henderson, D A

    1968-01-01

    In considering global eradication of smallpox the absence of an animal reservoir is important. Present knowledge of experimental infection of non-human primates with variola virus and of a related virus infection in monkeys, termed monkeypox, is examined.From the literature review and the results of a survey of captive monkeys in 26 major biological institutions it is concluded that outbreaks of supposed smallpox and monkeypox are not frequent and that man may be comparatively insusceptible to monkeypox. A natural reservoir of smallpox in non-human primates is thought to be unlikely although further studies are warranted since the survey reveals that certain species of monkeys can be infected with smallpox and that infected monkeys can transmit infection to others.

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

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, V.; Coto, E.; Gonzalez-Roces, S.; Lopez-Larrea, C. [Hospital Central de Asturias, Oviedo (Spain)] [and others

    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.

  11. Quality management for the international transportation of non-human primates

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    David B. Elmore

    2008-03-01

    Full Text Available Safe and humane transportation of live animals requires dedicated, informed personnel who carefully plan and attend to the details of appropriate animal care and handling throughout the shipping process. Specifically, although transportation of non-human primates shares goals common to all live animal transport, it also poses unique challenges stemming from the nature of these animals. Some of these unique challenges of transporting non-human primates, include the impact of public perception of non-human primates as cargo, maintaining biosecurity of non-human primate cargo, safety of both the non-human primate and public contacts, meeting the vital husbandry needs of varying species of non-human primates and compliance with numerous regulatory agencies, which may have overlapping responsibilities. This discussion will focus on these important considerations, as they relate to the legal international transportation of non-human primates for scientific use.

  12. A perceptual pitch boundary in a non-human primate

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    Olivier eJoly

    2014-09-01

    Full Text Available Pitch is an auditory percept critical to the perception of music and speech, and for these harmonic sounds, pitch is closely related to the repetition rate of the acoustic wave. This paper reports a test of the assumption that non-human primates and especially rhesus monkeys perceive the pitch of these harmonic sounds much as humans do. A new procedure was developed to train macaques to discriminate the pitch of harmonic sounds and thereby demonstrate that the lower limit for pitch perception in macaques is close to 30 Hz, as it is in humans. Moreover, when the phases of successive harmonics are alternated to cause a pseudo-doubling of the repetition rate, the lower pitch boundary in macaques decreases substantially, as it does in humans. The results suggest that both species use neural firing times to discriminate pitch, at least for sounds with relatively low repetition rates.

  13. Immunology studies in non-human primate models of tuberculosis.

    Science.gov (United States)

    Flynn, JoAnne L; Gideon, Hannah P; Mattila, Joshua T; Lin, Philana Ling

    2015-03-01

    Non-human primates, primarily macaques, have been used to study tuberculosis for decades. However, in the last 15 years, this model has been refined substantially to allow careful investigations of the immune response and host-pathogen interactions in Mycobacterium tuberculosis infection. Low-dose challenge with fully virulent strains in cynomolgus macaques result in the full clinical spectrum seen in humans, including latent and active infection. Reagents from humans are usually cross-reactive with macaques, further facilitating the use of this model system to study tuberculosis. Finally, macaques develop the spectrum of granuloma types seen in humans, providing a unique opportunity to investigate bacterial and host factors at the local (lung and lymph node) level. Here, we review the past decade of immunology and pathology studies in macaque models of tuberculosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. A Non-Human Primate Model of Severe Pneumococcal Pneumonia

    Science.gov (United States)

    Reyes, Luis F.; Restrepo, Marcos I.; Hinojosa, Cecilia A.; Soni, Nilam J.; Shenoy, Anukul T.; Gilley, Ryan P.; Gonzalez-Juarbe, Norberto; Noda, Julio R.; Winter, Vicki T.; de la Garza, Melissa A.; Shade, Robert E.; Coalson, Jacqueline J.; Giavedoni, Luis D.; Anzueto, Antonio; Orihuela, Carlos J.

    2016-01-01

    Rationale Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. Objective To develop a non-human primate model of pneumococcal pneumonia. Methods Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Results Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. Conclusions We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes. PMID:27855182

  15. Oscillatory correlates of memory in non-human primates.

    Science.gov (United States)

    Jutras, Michael J; Buffalo, Elizabeth A

    2014-01-15

    The ability to navigate through our environment, explore with our senses, track the passage of time, and integrate these various components to form the experiences which make up our lives is shared among humans and animals. The use of animal models to study memory, coupled with electrophysiological techniques that permit the direct measurement of neural activity as memories are formed and retrieved, has provided a wealth of knowledge about these mechanisms. Here, we discuss current knowledge regarding the specific role of neural oscillations in memory, with particular emphasis on findings derived from non-human primates. Some of these findings provide evidence for the existence in the primate brain of mechanisms previously identified only in rodents and other lower mammals, while other findings suggest parallels between memory-related activity and processes observed in other cognitive modalities, including attention and sensory perception. Taken together, these results provide insight into how network activity may be organized to promote memory formation, and suggest that key aspects of this activity are similar across species, providing important information about the organization of human memory. © 2013 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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…

  17. African Non-Human Primates Host Diverse Enteroviruses.

    Directory of Open Access Journals (Sweden)

    Illich Manfred Mombo

    Full Text Available Enteroviruses (EVs belong to the family Picornaviridae and are responsible for mild to severe diseases in mammals including humans and non-human primates (NHP. Simian EVs were first discovered in the 1950s in the Old World Monkeys and recently in wild chimpanzee, gorilla and mandrill in Cameroon. In the present study, we screened by PCR EVs in 600 fecal samples of wild apes and monkeys that were collected at four sites in Gabon. A total of 32 samples were positive for EVs (25 from mandrills, 7 from chimpanzees, none from gorillas. The phylogenetic analysis of VP1 and VP2 genes showed that EVs identified in chimpanzees were members of two human EV species, EV-A and EV-B, and those identified in mandrills were members of the human species EV-B and the simian species EV-J. The identification of two novel enterovirus types, EV-B112 in a chimpanzee and EV-B113 in a mandrill, suggests these NHPs could be potential sources of new EV types. The identification of EV-B107 and EV90 that were previously found in humans indicates cross-species transfers. Also the identification of chimpanzee-derived EV110 in a mandrill demonstrated a wide host range of this EV. Further research of EVs in NHPs would help understanding emergence of new types or variants, and evaluating the real risk of cross-species transmission for humans as well for NHPs populations.

  18. Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities.

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    Suleyman Yildirim

    Full Text Available BACKGROUND: Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]. Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny. CONCLUSION/SIGNIFICANCE: Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species

  19. Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

    Directory of Open Access Journals (Sweden)

    B.G. Nath

    2013-08-01

    Full Text Available The present study investigated 37 serum samples of non-human primates in Assam State Zoo and the Department of Forest and Environment, Govt. of Assam for seroprevalence of hepatitis A virus infection during the period from December, 2007 to November, 2009. Four serum samples were also collected from animal keepers of the zoo to investigate transmission of the disease to the attendants working with these primates. Competitive ELISA was performed using hepatitis A virus ELISA kit (Wanti Hep. AV to detect hepatitis A virus antibody in serum samples. Ten (27.21% of the non-human primate samples and three (75% human samples had detectable anti-hepatitis A virus antibodies. Living status of the non-human primates (Free living was a high potential risk for hepatitis A virus infection. Seroprevalence of hepatitis A virus infection had significant difference between free living non-human primates and captive non-human primates (P less than 0.05. No significant difference (p=0.86 was seen between male and female non-human primates

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

    OpenAIRE

    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...

  1. Using non-human primates to benefit humans: research and organ transplantation.

    Science.gov (United States)

    Shaw, David; Dondorp, Wybo; de Wert, Guido

    2014-11-01

    Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use.

  2. Marburg and Ebola virus infections in laboratory non-human primates: a literature review.

    Science.gov (United States)

    Schou, S; Hansen, A K

    2000-04-01

    Several non-human primate species are used as laboratory animals for various types of studies. Although importation of monkeys may introduce different diseases, special attention has recently been drawn to Marburg and Ebola viruses. This review presented here discusses the potential risk of these viruses for persons working with non-human primates as laboratory animals by focusing on epidemiology, virology, symptoms, pathogenesis, natural reservoir, transmission, quarantine of non-human primates, therapy, and prevention. A total of 23 Marburg and Ebola virus outbreaks causing viral hemorrhagic fever has been reported among humans and monkeys since the first outbreak in Marburg, Germany in 1967. Most of the 1,100 human cases, with nearly 800 deaths, developed in Africa due mainly to direct and intimate contact with infected patients. Few human cases have developed after contact with non-human primates used for various scientific purposes. However, adequate quarantine should be applied to prevent human infections not only due to Marburg and Ebola viruses, but also to other infective agents. By following proper guidelines, the filovirus infection risk for people working with non-human primates during quarantine exists, but is minimal. There seems to be little risk for filovirus infections after an adequate quarantine period. Therefore, non-human primates can be used as laboratory animals, with little risk of filovirus infections, provided adequate precautions are taken.

  3. Non-human primate regulatory T cells: Current biology and implications for transplantation

    NARCIS (Netherlands)

    E.M. Dons (Eefje); G. Raimondi (Giorgio); D.K.C. Cooper (David); A.W. Thomson (Angus)

    2010-01-01

    textabstractRegulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we discuss the properties of non-human

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

    Science.gov (United States)

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

    2012-01-01

    Many publications consider that Alzheimer's disease (AD) is exclusive to the human species, and that no other animal species suffers from the disease. However, various studies have shown that some species can present with some of the defining characteristics of the human disease, including both neuropathological changes and cognitive-behavioural symptoms. In this work, the results published (PubMed) on senile brain changes in non-human primates of different degrees of evolution, are reviewed. The neuropathological changes associated with the accumulation of amyloid or highly phosphorylated tau protein are rare outside the primate order, but in all the sub-orders, families, genera and species of non-human primates that have been studied, some senile individuals have shown amyloid accumulation in the brain. In fact, in some species the presence of these deposits in senility is constant. Changes related to the accumulation of tau protein are always of very little significance, and have been detected only in some non-human primate species, both little evolved and highly evolved. In different species of non-human primates, some types of cognitive-behavioural changes are more common in some senile individuals when compared with both normal adult individuals and other senile individuals of the species. The importance of determining the longevity of the species in different habitats (natural habitats, new habitats, semi-captivity, captivity) is stressed in these studies. Morphological, histochemical and cognitive-behavioural features similar to those observed in elderly humans are present in senile non-human primates. Moreover, other characteristics seen in non-human primates could be indicative of a pathological «Alzheimer type» ageing. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  5. Utility of non-human primates in drug development: Comparison of non-human primate and human drug-metabolizing cytochrome P450 enzymes.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

    2016-12-01

    Cynomolgus monkeys (Macaca fascicularis, an Old World Monkey) have been widely used as a non-human primate model in preclinical studies because of their genetic and physiological similarity to humans. This trend has been followed by common marmoset (Callithrix jacchus, a New World Monkey). However, drug-metabolism properties in these non-human primates have not been fully understood due to limited information on cytochrome P450 (P450) enzymes, major drug-metabolizing enzymes in humans. Multiple forms of cynomolgus monkey P450 enzymes have been identified and characterized in comparison to those of humans, including a cynomolgus monkey specific form, P450 2C76. Similarly, marmoset P450 1A/B, 2A, 2C, 2D, and 4F enzymes were recently identified and characterized to understand drug metabolism properties. In this research update, updates for marmoset, cynomolgus monkey, and human P450 cDNAs are provided. Marmoset and cynomolgus monkey P450 enzymes showed high sequence homology to their human counterparts and generally had similar substrate recognition functionality to human P450 enzymes; however, they also possibly contribute to limited specific differences in drug oxidative metabolism partly due to small differences in amino acid residues. These findings provide a foundation for successful use of non-human primates as preclinical models and will help to further understand molecular mechanisms of human P450 function. In addition to the P450 enzymes, flavin-containing monooxygenases, another monooxygenase family, in these non-human primates have been found to be involved in the oxidation of a variety of compounds associated with pharmacological and/or toxicological effects in humans and are also described. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The use of non-human primates as animal models for the study of hepatitis viruses

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    C.L. Vitral

    1998-08-01

    Full Text Available Hepatitis viruses belong to different families and have in common a striking hepatotropism and restrictions for propagation in cell culture. The transmissibility of hepatitis is in great part limited to non-human primates. Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus can induce hepatitis in a number of Old World and New World monkey species, while the host range of non-human primates susceptible to hepatitis viruses transmitted by the parenteral route (hepatitis B virus, hepatitis C virus and hepatitis delta virus is restricted to few species of Old World monkeys, especially the chimpanzee. Experimental studies on non-human primates have provided an invaluable source of information regarding the biology and pathogenesis of these viruses, and represent a still indispensable tool for vaccine and drug testing.

  7. Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

    OpenAIRE

    B.G. NATH; Chakraborty, A.; Sarma, D. K.; Rahman, T; P.K. Boro

    2013-01-01

    The present study investigated 37 serum samples of non-human primates in Assam State Zoo and the Department of Forest and Environment, Govt. of Assam for seroprevalence of hepatitis A virus infection during the period from December, 2007 to November, 2009. Four serum samples were also collected from animal keepers of the zoo to investigate transmission of the disease to the attendants working with these primates. Competitive ELISA was performed using hepatitis A virus ELISA kit (Wanti Hep. AV...

  8. Genome-wide comparative analysis of microRNAs in three non-human primates

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    Brameier Markus

    2010-03-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are negative regulators of gene expression in multicellular eukaryotes. With the recently completed sequencing of three primate genomes, the study of miRNA evolution within the primate lineage has only begun and may be expected to provide the genetic and molecular explanations for many phenotypic differences between human and non-human primates. Findings We scanned all three genomes of non-human primates, including chimpanzee (Pan troglodytes, orangutan (Pongo pygmaeus, and rhesus monkey (Macaca mulatta, for homologs of human miRNA genes. Besides sequence homology analysis, our comparative method relies on various postprocessing filters to verify other features of miRNAs, including, in particular, their precursor structure or their occurrence (prediction in other primate genomes. Our study allows direct comparisons between the different species in terms of their miRNA repertoire, their evolutionary distance to human, the effects of filters, as well as the identification of common and species-specific miRNAs in the primate lineage. More than 500 novel putative miRNA genes have been discovered in orangutan that show at least 85 percent identity in precursor sequence. Only about 40 percent are found to be 100 percent identical with their human ortholog. Conclusion Homologs of human precursor miRNAs with perfect or near-perfect sequence identity may be considered to be likely functional in other primates. The computational identification of homologs with less similar sequence, instead, requires further evidence to be provided.

  9. Immunogenicity of mAbs in non-human primates during nonclinical safety assessment

    NARCIS (Netherlands)

    van Meer, P.J.K.; Kooijman, M.; Brinks, V.; Gispen-de Wied, C.C.; Silva-Lima, B.; Moors, E.H.M.; Schellekens, H.

    2013-01-01

    The immunogenicity of biopharmaceuticals used in clinical practice remains an unsolved challenge in drug development. Non-human primates (NHPs) are often the only relevant animal model for the development of monoclonal antibodies (mAbs), but the immune response of NHPs to therapeutic mAbs is not

  10. Non-Human Primate Regulatory T Cells: Current Biology and Implications for Transplantation

    Science.gov (United States)

    Dons, Eefje M.; Raimondi, Giorgio; Cooper, David K.C.; Thomson, Angus W.

    2010-01-01

    Regulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate (NHP) model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein we discuss the properties of NHP Treg and prospects for their evaluation in allo- and xenotransplantation. PMID:20671597

  11. The value of non-human primates in the development of therapeutic monoclonal antibodies

    NARCIS (Netherlands)

    Van Meer, P.J.K.|info:eu-repo/dai/nl/34153790X; Kooijman, M.|info:eu-repo/dai/nl/322905788; Van Der Laan, J.W.|info:eu-repo/dai/nl/374879966; Moors, E.H.M.|info:eu-repo/dai/nl/20241664X; Schellekens, H.|info:eu-repo/dai/nl/068406762

    2011-01-01

    The pharmaceutical industry is increasingly focusing on the development of biological therapeutics. These molecules generally cause no off-target toxicity and are highly species specific. Therefore, non-human primates (NHPs) are often the only relevant species in which to conduct regulatory safety

  12. Opportunistic infections in non-human primates exposed to immunomodulatory biotherapeutics: considerations and case examples.

    Science.gov (United States)

    Hutto, David L

    2010-01-01

    Immunomodulatory biotherapeutics are most often evaluated for safety preclinically by way of repeat dose toxicity studies in non-human primates. Since immunomodulation is expected with this class of therapeutics, and since non-human primates share many opportunistic or latent infectious agents with humans, non-human primates in these toxicity studies may present with opportunistic or recrudescent infections that would be of concern if they occurred clinically in humans. In such instances, it is suggested that non-clinical safety assessment scientists consider a series of key questions that aim to clarify the relationship of the findings to the biotherapeutic under study and the expected predictivity of the findings to the human clinical setting. In this review, relevant case examples are considered comprising (i) gammaherpesviruses-mediated B-lymphocyte proliferation associated with a T-lymphocyte depleting fusion protein; (ii) increased plasmodial hemoparasite burdens associated with a monoclonal antibody inhibitory to T-lymphocyte trafficking and macrophage function, and (iii) the expected predictivity of non-human primate models for the occurrence of encephalic polyomavirus infections.

  13. Mosquitoes as potential bridge vectors of malaria parasites from non-human primates to humans

    NARCIS (Netherlands)

    Verhulst, N.O.; Smallegange, R.C.; Takken, W.

    2012-01-01

    Malaria is caused by Plasmodium parasites which are transmitted by mosquitoes. Until recently, human malaria was considered to be caused by human-specific Plasmodium species. Studies on Plasmodium parasites in non-human primates (NHPs), however, have identified parasite species in gorillas and

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

    Science.gov (United States)

    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. Non-human primates in outdoor enclosures: risk for infection with rodent-borne hantaviruses.

    Science.gov (United States)

    Mertens, M; Essbauer, S S; Rang, A; Schröder, J; Splettstoesser, W D; Kretzschmar, C; Krüger, D H; Groschup, M H; Mätz-Rensing, K; Ulrich, R G

    2011-01-27

    Different species of non-human primates have been exploited as animal disease models for human hantavirus infections. To study the potential risk of natural hantavirus infection of non-human primates, we investigated serum samples from non-human primates of three species living in outdoor enclosures of the German Primate Center (GPC), Göttingen, located in a hantavirus endemic region of central Germany. For that purpose we used serological assays based on recombinant antigens of the bank vole (Myodes glareolus) transmitted Puumala virus (PUUV) and the common and field vole (Microtus arvalis, Microtus agrestis) associated Tula virus (TULV) which are both broadly geographically distributed in Germany. In 24 out of 251 (9.6%) monkey sera collected in 2006 PUUV- and/or TULV-reactive immunoglobulin G (IgG) antibodies were detected. Investigation of follow-up sera from 13 animals confirmed for two animals a seroconversion due to hantavirus exposure at the GPC. To prove the origin of the infection, wild rodents from the surrounding regions were analyzed by hantavirus-specific reverse transcriptase-PCR analysis. In 6 of the 73 investigated bank voles and 3 of the 19 investigated Microtus spp. PUUV- and TULV-specific nucleic acid sequences, respectively, were detected. In conclusion, our investigations demonstrate for the first time natural infections of non-human primates in outdoor enclosures in Germany. These findings highlight the importance of hantavirus surveillance in those primate housings and corresponding preventive measures against wild rodents, particularly in hantavirus endemic regions. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates.

    Science.gov (United States)

    Deschamps, Jack-Yves; Gaulier, Jean-Michel; Podevin, Guillaume; Cherel, Yan; Ferry, Nicolas; Roux, Françoise A

    2012-11-01

    CASE HISTORY AND PRESENTATION: Two non-human primates (Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 μg hour(-1) transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. MANAGEMENT AND FOLLOW-UP: Attempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 μg L(-1) ) confirmed fentanyl overdose. This report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  17. Characterization of a 2016 Clinical Isolate of Zika Virus in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Li

    2016-10-01

    Full Text Available Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV. Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10 days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics.

  18. Characterization of a 2016 Clinical Isolate of Zika Virus in Non-human Primates.

    Science.gov (United States)

    Li, Xiao-Feng; Dong, Hao-Long; Huang, Xing-Yao; Qiu, Ye-Feng; Wang, Hong-Jiang; Deng, Yong-Qiang; Zhang, Na-Na; Ye, Qing; Zhao, Hui; Liu, Zhong-Yu; Fan, Hang; An, Xiao-Ping; Sun, Shi-Hui; Gao, Bo; Fa, Yun-Zhi; Tong, Yi-Gang; Zhang, Fu-Chun; Gao, George F; Cao, Wu-Chun; Shi, Pei-Yong; Qin, Cheng-Feng

    2016-10-01

    Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV). Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Neurovirulence properties of recombinant vesicular stomatitis virus vectors in non-human primates

    OpenAIRE

    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 ...

  20. Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates

    OpenAIRE

    Deschamps, Jack-Yves; Gaulier, Jean-Michel; Podevin, Guillaume; Cherel, Yan; Ferry, Nicolas; Roux, Françoise

    2012-01-01

     ; Case history and presentation: Two non-human primates (Macaca fascicularis) enrolled in an experimental protocol received a 25 μg hour−1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. Management and follow-up: Attempted reversal with naloxone was ineffective. After several hours of ventila...

  1. Fatal overdose after ingestion of a transdermal fentanyl patch in two non-human primates

    OpenAIRE

    Deschamps, Jack-Yves; Podevin, Guillaume; Cherel, Yan; Ferry, Nicolas

    2012-01-01

    Case history and presentation: Two non-human primates (Macaca fascicularis) enrolled in an experimental protocol received a 25 μg hour−1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis. Management and follow-up: Attempted reversal with naloxone was ineffective. After several hours of ventilatio...

  2. Isolation and characterization of adenoviruses persistently shed from the gastrointestinal tract of non-human primates.

    Directory of Open Access Journals (Sweden)

    Soumitra Roy

    2009-07-01

    Full Text Available Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans and macaques shed substantial quantities of infectious adenoviruses in stool. Shedding in stools from asymptomatic humans was found to be much less frequent, comparable to frequencies reported before. We purified and fully sequenced 30 novel adenoviruses from apes and 3 novel adenoviruses from macaques. Analyses of the new ape adenovirus sequences (as well as the 4 chimpanzee adenovirus sequences we have previously reported together with 22 complete adenovirus genomes available from GenBank revealed that (a the ape adenoviruses could clearly be classified into species corresponding to human adenovirus species B, C, and E, (b there was evidence for intraspecies recombination between adenoviruses, and (c the high degree of phylogenetic relatedness of adenoviruses across their various primate hosts provided evidence for cross species transmission events to have occurred in the natural history of B and E viruses. The high degree of asymptomatic shedding of live adenovirus in non-human primates and evidence for zoonotic transmissions warrants caution for primate handling and housing. Furthermore, the presence of persistent and/or latent adenovirus infections in the gut should be considered in the design and interpretation of human and non-human primate studies with adenovirus vectors.

  3. Investigation of sleep–wake rhythm in non-human primates without restraint during data collection

    Science.gov (United States)

    Ishikawa, Akiyoshi; Sakai, Keita; Maki, Takehiro; Mizuno, Yuri; Niimi, Kimie; Oda, Yasuhiro; Takahashi, Eiki

    2016-01-01

    To understand sleep mechanisms and develop treatments for sleep disorders, investigations using animal models are essential. The sleep architecture of rodents differs from that of diurnal mammals including humans and non-human primates. Sleep studies have been conducted in non-human primates; however, these sleep assessments were performed on animals placed in a restraint chair connected via the umbilical area to the recording apparatus. To avoid restraints, cables, and other stressful apparatuses and manipulations, telemetry systems have been developed. In the present study, sleep recordings in unrestrained cynomolgus monkeys (Macaca fascicularis) and common marmoset monkeys (Callithrix jacchus) were conducted to characterize normal sleep. For the analysis of sleep–wake rhythms in cynomolgus monkeys, telemetry electroencephalography (EEG), electromyography (EMG), and electrooculography (EOG) signals were used. For the analysis of sleep–wake rhythms in marmosets, telemetry EEG and EOG signals were used. Both monkey species showed monophasic sleep patterns during the dark phase. Although non-rapid eye movement (NREM) deep sleep showed higher levels at the beginning of the dark phase in cynomolgus monkeys, NREM deep sleep rarely occurred during the dark phase in marmosets. Our results indicate that the use of telemetry in non-human primate models is useful for sleep studies, and that the different NREM deep sleep activities between cynomolgus monkeys and common marmoset monkeys are useful to examine sleep functions. PMID:27760892

  4. Distinctiveness enhances long-term event memory in non-human primates, irrespective of reinforcement.

    Science.gov (United States)

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-08-01

    Non-human primates are capable of recalling events that occurred as long as 3 years ago, and are able to distinguish between similar events; akin to human memory. In humans, distinctiveness enhances memory for events, however, it is unknown whether the same occurs in non-human primates. As such, we tested three great ape species on their ability to remember an event that varied in distinctiveness. Across three experiments, apes witnessed a baiting event in which one of three identical containers was baited with food. After a delay of 2 weeks, we tested their memory for the location of the baited container. Apes failed to recall the baited container when the event was undistinctive (Experiment 1), but were successful when it was distinctive (Experiment 2), although performance was equally good in a less-distinctive condition. A third experiment (Experiment 3) confirmed that distinctiveness, independent of reinforcement, was a consistent predictor of performance. These findings suggest that distinctiveness may enhance memory for events in non-human primates in the same way as in humans, and provides further evidence of basic similarities between the ways apes and humans remember past events. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    W. Tecumseh Fitch

    2013-07-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  8. Human and non-human primate genomes share hotspots of positive selection.

    Directory of Open Access Journals (Sweden)

    David Enard

    2010-02-01

    Full Text Available Among primates, genome-wide analysis of recent positive selection is currently limited to the human species because it requires extensive sampling of genotypic data from many individuals. The extent to which genes positively selected in human also present adaptive changes in other primates therefore remains unknown. This question is important because a gene that has been positively selected independently in the human and in other primate lineages may be less likely to be involved in human specific phenotypic changes such as dietary habits or cognitive abilities. To answer this question, we analysed heterozygous Single Nucleotide Polymorphisms (SNPs in the genomes of single human, chimpanzee, orangutan, and macaque individuals using a new method aiming to identify selective sweeps genome-wide. We found an unexpectedly high number of orthologous genes exhibiting signatures of a selective sweep simultaneously in several primate species, suggesting the presence of hotspots of positive selection. A similar significant excess is evident when comparing genes positively selected during recent human evolution with genes subjected to positive selection in their coding sequence in other primate lineages and identified using a different test. These findings are further supported by comparing several published human genome scans for positive selection with our findings in non-human primate genomes. We thus provide extensive evidence that the co-occurrence of positive selection in humans and in other primates at the same genetic loci can be measured with only four species, an indication that it may be a widespread phenomenon. The identification of positive selection in humans alongside other primates is a powerful tool to outline those genes that were selected uniquely during recent human evolution.

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

    Science.gov (United States)

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

    2014-01-01

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

  10. Molecular phylogeny of anoplocephalid tapeworms (Cestoda: Anoplocephalidae) infecting humans and non-human primates.

    Science.gov (United States)

    Doležalová, Jana; Vallo, Peter; Petrželková, Klára J; Foitová, Ivona; Nurcahyo, Wisnu; Mudakikwa, Antoine; Hashimoto, Chie; Jirků, Milan; Lukeš, Julius; Scholz, Tomáš; Modrý, David

    2015-09-01

    Anoplocephalid tapeworms of the genus Bertiella Stiles and Hassall, 1902 and Anoplocephala Blanchard, 1848, found in the Asian, African and American non-human primates are presumed to sporadic ape-to-man transmissions. Variable nuclear (5.8S-ITS2; 28S rRNA) and mitochondrial genes (cox1; nad1) of isolates of anoplocephalids originating from different primates (Callicebus oenanthe, Gorilla beringei, Gorilla gorilla, Pan troglodytes and Pongo abelii) and humans from various regions (South America, Africa, South-East Asia) were sequenced. In most analyses, Bertiella formed a monophyletic group within the subfamily Anoplocephalinae, however, the 28S rRNA sequence-based analysis indicated paraphyletic relationship between Bertiella from primates and Australian marsupials and rodents, which should thus be regarded as different taxa. Moreover, isolate determined as Anoplocephala cf. gorillae from mountain gorilla clustered within the Bertiella clade from primates. This either indicates that A. gorillae deserves to be included into the genus Bertiella, or, that an unknown Bertiella species infects also mountain gorillas. The analyses allowed the genetic differentiation of the isolates, albeit with no obvious geographical or host-related patterns. The unexpected genetic diversity of the isolates studied suggests the existence of several Bertiella species in primates and human and calls for revision of the whole group, based both on molecular and morphological data.

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

    Directory of Open Access Journals (Sweden)

    Damiana F Ravasi

    Full Text Available 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.

  12. From sweeping to the caress: similarities and discrepancies between human and non-human primates' pleasant touch

    Directory of Open Access Journals (Sweden)

    Laura Clara Grandi

    2016-09-01

    Full Text Available 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.

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

    Science.gov (United States)

    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. © 2016 Wiley Periodicals, Inc.

  14. Cloning of non-human primates: the road "less traveled by".

    Science.gov (United States)

    Sparman, Michelle L; Tachibana, Masahito; Mitalipov, Shoukhrat M

    2010-01-01

    Early studies on cloning of non-human primates by nuclear transfer utilized embryonic blastomeres from preimplantation embryos which resulted in the reproducible birth of live offspring. Soon after, the focus shifted to employing somatic cells as a source of donor nuclei (somatic cell nuclear transfer, SCNT). However, initial efforts were plagued with inefficient nuclear reprogramming and poor embryonic development when standard SCNT methods were utilized. Implementation of several key SCNT modifications was critical to overcome these problems. In particular, a non-invasive method of visualizing the metaphase chromosomes during enucleation was developed to preserve the reprogramming capacity of monkey oocytes. These modifications dramatically improved the efficiency of SCNT, yielding high blastocyst development in vitro. To date, SCNT has been successfully used to derive pluripotent embryonic stem cells (ESCs) from adult monkey skin fibroblasts. These remarkable advances have the potential for development of human autologous ESCs and cures for many human diseases. Reproductive cloning of nonhuman primates by SCNT has not been achieved yet. We have been able to establish several pregnancies with SCNT embryos which, so far, did not progress to term. In this review, we summarize the approaches, obstacles and accomplishments of SCNT in a non-human primate model.

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

    Science.gov (United States)

    Zhang, Xiao-Liang; Pang, Wei; Hu, Xin-Tian; Li, Jia-Li; Yao, Yong-Gang; Zheng, Yong-Tang

    2014-11-18

    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.

  16. Daily feeding rhythm in proboscis monkeys: a preliminary comparison with other non-human primates.

    Science.gov (United States)

    Matsuda, Ikki; Akiyama, Yoshihiro; Tuuga, Augustine; Bernard, Henry; Clauss, Marcus

    2014-04-01

    In non-human primates, the daily feeding rhythm, i.e., temporal fluctuation in feeding activity across the day, has been described but has rarely received much analytical interpretation, though it may play a crucial part in understanding the adaptive significance of primate foraging strategies. This study is the first to describe the detailed daily feeding rhythm in proboscis monkeys (Nasalis larvatus) based on data collected from both riverbank and inland habitats. From May 2005 to May 2006, data on feeding behavior in a group of proboscis monkeys consisting of an alpha-male, six adult females and immatures was collected via continuous focal animal sampling technique in a forest along the Menanggul River, Sabah, Malaysia. In both the male and females, the highest peak of feeding activity was in the late afternoon at 15:00-17:00, i.e., shortly before sleeping. The differences in the feeding rhythm among the seasons appeared to reflect the time spent eating fruit and/or the availability of fruit; clearer feeding peaks were detected when the monkeys spent a relevant amount of time eating fruit, but no clear peak was detected when fruit eating was less frequent. The daily feeding rhythm was not strongly influenced by daily temperature fluctuations. When comparing the daily feeding rhythm of proboscis monkeys to that of other primates, one of the most common temporal patterns detected across primates was a feeding peak in the late afternoon, although it was impossible to demonstrate this statistically because of methodological differences among studies.

  17. [Symbol-based communication in non-human primates: a C. S. Peirce's semiotic analysis].

    Science.gov (United States)

    Queiroz, João

    2003-12-01

    Are (or were) there any other symbolic species? This question has been addressed by researchers from many different fields and is responsible for a historical controversy on the existence of a threshold between "symbolic creatures" vs "simple forms of language creatures". According to the mainstream ethology and comparative psychology only the Homo sapiens is cognitively equiped to produce and interpret symbols. Here, I introduce an empirically testable model of symbolic semiosis ("symbolic action of sign") supported by C.S.Peirce logical-phenomenological theory of categories. I suggest that a specific sign-user pattern of behavior, observed in non-human primate communication, indicate a transition from indexical to symbolic semiosis.

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

    Science.gov (United States)

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

    2014-02-01

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Protection of Non-Human Primates against Rabies with an Adenovirus Recombinant Vaccine

    Science.gov (United States)

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

    2014-01-01

    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. PMID:24503087

  20. Preference for Averageness in Faces Does Not Generalize to Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Olivia B. Tomeo

    2017-07-01

    Full Text Available Facial attractiveness is a long-standing topic of active study in both neuroscience and social science, motivated by its positive social consequences. Over the past few decades, it has been established that averageness is a major factor influencing judgments of facial attractiveness in humans. Non-human primates share similar social behaviors as well as neural mechanisms related to face processing with humans. However, it is unknown whether monkeys, like humans, also find particular faces attractive and, if so, which kind of facial traits they prefer. To address these questions, we investigated the effect of averageness on preferences for faces in monkeys. We tested three adult male rhesus macaques using a visual paired comparison (VPC task, in which they viewed pairs of faces (both individual faces, or one individual face and one average face; viewing time was used as a measure of preference. We did find that monkeys looked longer at certain individual faces than others. However, unlike humans, monkeys did not prefer the average face over individual faces. In fact, the more the individual face differed from the average face, the longer the monkeys looked at it, indicating that the average face likely plays a role in face recognition rather than in judgments of facial attractiveness: in models of face recognition, the average face operates as the norm against which individual faces are compared and recognized. Taken together, our study suggests that the preference for averageness in faces does not generalize to non-human primates.

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

    Directory of Open Access Journals (Sweden)

    Simone M Cinini

    2014-03-01

    Full Text Available 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 one or three 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 one and three weeks of isolation. After social isolation (one or three 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.

  2. Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos.

    Science.gov (United States)

    Tu, Zhuchi; Yang, Weili; Yan, Sen; Yin, An; Gao, Jinquan; Liu, Xudong; Zheng, Yinghui; Zheng, Jiezhao; Li, Zhujun; Yang, Su; Li, Shihua; Guo, Xiangyu; Li, Xiao-Jiang

    2017-02-03

    CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing.

  3. Promoting Cas9 degradation reduces mosaic mutations in non-human primate embryos

    Science.gov (United States)

    Tu, Zhuchi; Yang, Weili; Yan, Sen; Yin, An; Gao, Jinquan; Liu, Xudong; Zheng, Yinghui; Zheng, Jiezhao; Li, Zhujun; Yang, Su; Li, Shihua; Guo, Xiangyu; Li, Xiao-Jiang

    2017-01-01

    CRISPR-Cas9 is a powerful new tool for genome editing, but this technique creates mosaic mutations that affect the efficiency and precision of its ability to edit the genome. Reducing mosaic mutations is particularly important for gene therapy and precision genome editing. Although the mechanisms underlying the CRSIPR/Cas9-mediated mosaic mutations remain elusive, the prolonged expression and activity of Cas9 in embryos could contribute to mosaicism in DNA mutations. Here we report that tagging Cas9 with ubiquitin-proteasomal degradation signals can facilitate the degradation of Cas9 in non-human primate embryos. Using embryo-splitting approach, we found that shortening the half-life of Cas9 in fertilized zygotes reduces mosaic mutations and increases its ability to modify genomes in non-human primate embryos. Also, injection of modified Cas9 in one-cell embryos leads to live monkeys with the targeted gene modifications. Our findings suggest that modifying Cas9 activity can be an effective strategy to enhance precision genome editing. PMID:28155910

  4. A Chronically Implantable Bidirectional Neural Interface for Non-human Primates

    Directory of Open Access Journals (Sweden)

    Misako Komatsu

    2017-09-01

    Full Text Available Optogenetics has potential applications in the study of epilepsy and neuroprostheses, and for studies on neural circuit dynamics. However, to achieve translation to clinical usage, optogenetic interfaces that are capable of chronic stimulation and monitoring with minimal brain trauma are required. We aimed to develop a chronically implantable device for photostimulation of the brain of non-human primates. We used a micro-light-emitting diode (LED array with a flexible polyimide film. The array was combined with a whole-cortex electrocorticographic (ECoG electrode array for simultaneous photostimulation and recording. Channelrhodopsin-2 (ChR2 was virally transduced into the cerebral cortex of common marmosets, and then the device was epidurally implanted into their brains. We recorded the neural activity during photostimulation of the awake monkeys for 4 months. The neural responses gradually increased after the virus injection for ~8 weeks and remained constant for another 8 weeks. The micro-LED and ECoG arrays allowed semi-invasive simultaneous stimulation and recording during long-term implantation in the brains of non-human primates. The development of this device represents substantial progress in the field of optogenetic applications.

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

    Science.gov (United States)

    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

    2015-04-01

    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. 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. 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. 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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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

  7. A Comparison of Non-Human Primate Cytochrome P450 2D Members and the Implication in Drug Discovery.

    Science.gov (United States)

    He, Zhi-Xu; Chen, Xiao-Wu; Yang, Yinxue; Zhou, Shu-Feng

    2016-01-01

    Non-human primates are valuable animal models in drug discovery and biomedical research. Human CYP2D6 accounts for 1.3-4.3% of total hepatic CYP content in the liver, but is involved in the metabolism of more than 150 drugs. With the advancement of genomic sequencing and annotation, a panel of CYP2D genes have been cloned from non-human primates. This review highlights the similarities and differences of these CYP2D genes non-human primates. We conducted a structured PubMed search using a focused review question and proper inclusion/exclusion criteria. The quality of retrieved papers was assessed and briefed using standard tools and expert knowledge. Most studies on CYP expression in non-human primates have been carried out in the cynomolgus and Rhesus monkeys. Deduced amino acid sequences of primate CYP2D cDNAs share high sequence identity (93-96%) with human CYP2D6. The chimpanzee genome has CYP2D6 and 2D7 but bonobos only contain CYP2D6. The CYP2D6 gene is located on chromosome 22 in the chimpanzee genome (human CYP2D6 maps to chromosome 22q13.1), and on chromosome 10 in the genome of the Rhesus monkey. Cynomolgus monkey CYP2D17 and Japanese monkey 2D29 metabolize bufuralol and dextromethorphan. CYP2D17 metabolizes bufuralol and dextromethorphan, whereas CYP2D29 metabolizes bufuralol and debrisoquine. In addition, quinidine inhibits both cynomolgus monkey CYP2D17 and Japanese monkey 2D29. The CYP2D members from non-human primates show differential genomic contexts, catalytic activities toward substrates and inhibitory profiles. Further studies are warranted to elucidate the structural and functional features of CYP2D members in non-human primates and thus offer a solid base for the application of these animals in drug discovery.

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

    Directory of Open Access Journals (Sweden)

    Louis eLefebvre

    2013-06-01

    Full Text Available 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 moulded 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Z.Q. [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Greenberg, L. [Centers for Disease Control and Prevention, Atlanta, GA (United States); Ertl, H.C., E-mail: ertl@wistar.upenn.edu [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Rupprecht, C.E. [The Global Alliance for Rabies Control, Manhattan, KS (United States); Ross University School of Veterinary Medicine, Basseterre (Saint Kitts and Nevis)

    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.

  10. Prospects for genetically modified non-human primate models, including the common marmoset.

    Science.gov (United States)

    Sasaki, Erika

    2015-04-01

    Genetically modified mice have contributed much to studies in the life sciences. In some research fields, however, mouse models are insufficient for analyzing the molecular mechanisms of pathology or as disease models. Often, genetically modified non-human primate (NHP) models are desired, as they are more similar to human physiology, morphology, and anatomy. Recent progress in studies of the reproductive biology in NHPs has enabled the introduction of exogenous genes into NHP genomes or the alteration of endogenous NHP genes. This review summarizes recent progress in the production of genetically modified NHPs, including the common marmoset, and future perspectives for realizing genetically modified NHP models for use in life sciences research. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. Clinical veterinarian's perspective of non-human primate (NHP) use in drug safety studies.

    Science.gov (United States)

    Taylor, Katrina

    2010-01-01

    Owing to their size, cost, and availability, the cynomolgus macaque (Macaca fascicularis) has surpassed the rhesus macaque in its use as a non-human primate preclinical model for drug safety studies. There are three major regions where cynomolgus macaques are bred: China, Southeast Asia, and the island of Mauritius. Country of origin of the macaque is important, as disease status and background disease incidence in non-human primates from each of these sites can differ. Once a source of macaque has been decided, careful monitoring of the animal during breeding and by the importing vendor while the animals are in quarantine is important. During vendor quarantine, the animals should be monitored and evaluated for disease, response to tuberculosis testing, retroviral status, and both ecto- and endoparasites. After animals arrive at the test facility, additional quarantine and acclimation are important to ascertain health status further and to reduce stress on the animals, thereby providing a better research model. The type of caging, food, water, and enrichment should be carefully selected to best suit the needs of the study while working within Federal Regulations (i.e., Animal Welfare Act and Good Laboratory Practices). Careful prescreening by performing tests (such as physical, neurologic, and ophthalmologic examinations), complete blood count, biochemical profile, urinanalysis, electrocardiograms, and pulse oximetry is important when selecting the most appropriate animals for the study. After the in-life portion of the study begins, animals that present with clinical signs should be examined and an appropriate treatment course begun while maintaining study objectives. As many commonly used medications have immunomodulatory effects, having an understanding of the mechanism of action of test articles will aid in the appropriate choice of treatment of study animals. A tiered approach to the treatment of these animals is a conservative and usually acceptable approach.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)], E-mail: snai3212@uni.sydney.edu.au

    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 {sup 57}Co transmission point source with a 4% energy window. The optimal energy window for a {sup 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 {sup 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 [{sup 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 {sup 57}Co (4% energy window) or {sup 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.

  15. Biomarkers for non-human primate type-I hypersensitivity: antigen-specific immunoglobulin E assays.

    Science.gov (United States)

    Clark, Darcey; Shiota, Faith; Forte, Carla; Narayanan, Padma; Mytych, Daniel T; Hock, M Benjamin

    2013-06-28

    Immunoglobulin E (IgE) is the least abundant immunoglobulin in serum. However, development of an IgE immune response can induce IgE receptor-expressing cells to carry out potent effector functions. A reliable antigen-specific IgE biomarker method for use in non-human primate studies would facilitate (i) confirmation of Type-I hypersensitivity reactions during safety toxicology testing, and (ii) a better understanding of non-human primate models of allergic disease. We cloned and expressed a recombinant cynomolgus monkey IgE molecule in order to screen a panel of commercially available detection reagents raised against human IgE for cross-reactivity. The reagent most reactive to cynomolgus IgE was confirmed to be specific for IgE and did not bind recombinant cynomolgus monkey IgG1-4. A drug-specific IgE assay was developed on the MSD electrochemiluminescent (ECL) platform. The assay is capable of detecting 10 ng/mL drug-specific IgE. Importantly, the assay is able to detect IgE in the presence of excess IgG, the scenario likely to be present in a safety toxicology study. Using our ECL assay, we were able to confirm that serum from cynomolgus monkeys that had experienced clinical symptoms consistent with hypersensitivity responses contained IgE specific for a candidate therapeutic antibody. In addition, a bioassay for mast cell activation was developed using CD34(+)-derived cynomolgus monkey mast cells. This assay confirmed that plasma from animals identified as positive in the drug-specific IgE immunoassay contained biologically active IgE (i.e. could sensitize cultured mast cells), resulting in histamine release after exposure to the therapeutic antibody. These sensitive assays for Type-I hypersensitivity in the NHP can confirm that secondary events are downstream of immunogenicity. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

  17. Titi Monkeys as a Novel Non-Human Primate Model for the Neurobiology of Pair Bonding
.

    Science.gov (United States)

    Bales, Karen L; Arias Del Razo, Rocío; Conklin, Quinn A; Hartman, Sarah; Mayer, Heather S; Rogers, Forrest D; Simmons, Trenton C; Smith, Leigh K; Williams, Alexia; Williams, Donald R; Witczak, Lynea R; Wright, Emily C

    2017-09-01

    It is now widely recognized that social bonds are critical to human health and well-being. One of the most important social bonds is the attachment relationship between two adults, known as the pair bond. The pair bond involves many characteristics that are inextricably linked to quality of health, including providing a secure psychological base and acting as a social buffer against stress. The majority of our knowledge about the neurobiology of pair bonding comes from studies of a socially monogamous rodent, the prairie vole (Microtus ochrogaster), and from human imaging studies, which inherently lack control. Here, we first review what is known of the neurobiology of pair bonding from humans and prairie voles. We then present a summary of the studies we have conducted in titi monkeys (Callicebus cupreus)-a species of socially monogamous New World primates. Finally, we construct a neural model based on the location of neuropeptide receptors in the titi monkey brain, as well as the location of neural changes in our imaging studies, with some basic assumptions based on the prairie vole model. In this model, we emphasize the role of visual mating stimuli as well as contributions of the dopaminergic reward system and a strong role for the lateral septum. This model represents an important step in understanding the neurobiology of social bonds in non-human primates, which will in turn facilitate a better understanding of these mechanisms in humans.

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

    Science.gov (United States)

    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

  19. Modeling Zika plasma viral dynamics in non-human primates: insights into viral pathogenesis and antiviral strategies

    Energy Technology Data Exchange (ETDEWEB)

    Best, Katharine [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Guedj, Jeremie [Univ. of Paris (France). IAME; Madelain, Vincent [Univ. of Paris (France); de Lamballerie, Xavier [Aix-Marseille Univ. (France); L, So-Yonim [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Osuna, Christa E [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Whitney, James [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Perelson, Alan S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-24

    The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and neurological complications, prompting global concern. Here we present the first mathematical analysis of the within-host dynamics of plasma ZiKV burden in a non-human primate model, allowing for characterization of the growth and clearance of ZIKV within an individual macaque.

  20. Plasma and cerebrospinal fluid pharmacokinetics of the histone deacetylase inhibitor, belinostat (PXD101), in non-human primates

    DEFF Research Database (Denmark)

    Warren, K.E.; McCully, C.; Dvinge, H.

    2008-01-01

    is a novel, potent, pan-HDAC inhibitor with antiproliferative activity on a wide variety of tumor cell lines. We studied the cerebrospinal fluid (CSF) penetration of intravenous (IV) belinostat in a non-human primate model as a surrogate for blood:brain barrier penetration. DESIGN: Five adult rhesus monkeys...

  1. Utility, limitations and future of non-human primates for dengue research and vaccine development

    Directory of Open Access Journals (Sweden)

    Laura eWhite

    2014-09-01

    Full Text Available 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 antiviral drugs. The development of a dengue vaccine faces unique challenges. The 4 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 towards a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups.

  2. Utility, limitations, and future of non-human primates for dengue research and vaccine development.

    Science.gov (United States)

    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.

  3. Concealed fertility and extended female sexuality in a non-human primate (Macaca assamensis.

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    Ines Fürtbauer

    Full Text Available 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.

  4. Photoperiodic regime influences onset of lens opacities in a non-human primate.

    Science.gov (United States)

    Dubicanac, Marko; Strueve, Julia; Mestre-Frances, Nadine; Verdier, Jean-Michel; Zimmermann, Elke; Joly, Marine

    2017-01-01

    Opacities of the lens are typical age-related phenomena which have a high influence on photoreception and consequently circadian rhythm. In mouse lemurs, a small bodied non-human primate, a high incidence (more than 50% when >seven years) of cataracts has been previously described during aging. Previous studies showed that photoperiodically induced accelerated annual rhythms alter some of mouse lemurs' life history traits. Whether a modification of photoperiod also affects the onset of age dependent lens opacities has not been investigated so far. The aim of this study was therefore to characterise the type of opacity and the mouse lemurs' age at its onset in two colonies with different photoperiodic regimen. Two of the largest mouse lemur colonies in Europe were investigated: Colony 1 having a natural annual photoperiodic regime and Colony 2 with an induced accelerated annual cycle. A slit-lamp was used to determine opacities in the lens. Furthermore, a subset of all animals which showed no opacities in the lens nucleus in the first examination but developed first changes in the following examination were further examined to estimate the age at onset of opacities. In total, 387 animals were examined and 57 represented the subset for age at onset estimation. The first and most commonly observable opacity in the lens was nuclear sclerosis. Mouse lemurs from Colony 1 showed a delayed onset of nuclear sclerosis compared to mouse lemurs from Colony 2 (4.35 ± 1.50 years vs. 2.75 ± 0.99 years). For colony 1, the chronological age was equivalent to the number of seasonal cycles experienced by the mouse lemurs. For colony 2, in which seasonal cycles were accelerated by a factor of 1.5, mouse lemurs had experienced 4.13 ± 1.50 seasonal cycles in 2.75 ± 0.99 chronological years. Our study showed clear differences in age at the onset of nuclear sclerosis formation between lemurs kept under different photoperiodic regimes. Instead of measuring the chronological age

  5. Simian Foamy Virus in Non-Human Primates and Cross-Species Transmission to Humans in Gabon: An Emerging Zoonotic Disease in Central Africa?

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    Augustin Mouinga-Ondémé

    2013-06-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2012-01-12

    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.

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

    Science.gov (United States)

    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

  9. Perceptual learning in a non-human primate model of artificial vision.

    Science.gov (United States)

    Killian, Nathaniel J; Vurro, Milena; Keith, Sarah B; Kyada, Margee J; Pezaris, John S

    2016-11-22

    Visual perceptual grouping, the process of forming global percepts from discrete elements, is experience-dependent. Here we show that the learning time course in an animal model of artificial vision is predicted primarily from the density of visual elements. Three naïve adult non-human primates were tasked with recognizing the letters of the Roman alphabet presented at variable size and visualized through patterns of discrete visual elements, specifically, simulated phosphenes mimicking a thalamic visual prosthesis. The animals viewed a spatially static letter using a gaze-contingent pattern and then chose, by gaze fixation, between a matching letter and a non-matching distractor. Months of learning were required for the animals to recognize letters using simulated phosphene vision. Learning rates increased in proportion to the mean density of the phosphenes in each pattern. Furthermore, skill acquisition transferred from trained to untrained patterns, not depending on the precise retinal layout of the simulated phosphenes. Taken together, the findings suggest that learning of perceptual grouping in a gaze-contingent visual prosthesis can be described simply by the density of visual activation.

  10. Isolation of Anti-Ricin Protective Antibodies Exhibiting High Affinity from Immunized Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Tal Noy-Porat

    2016-03-01

    Full Text Available 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.

  11. Non-Human Primates Harbor Diverse Mammalian and Avian Astroviruses Including Those Associated with Human Infections.

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    Erik A Karlsson

    Full Text Available 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.

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

    Science.gov (United States)

    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

    2016-03-31

    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.

  13. Correlation between cerebral hemodynamic and perfusion pressure changes in non-human primates

    Science.gov (United States)

    Ruesch, A.; Smith, M. A.; Wollstein, G.; Sigal, I. A.; Nelson, S.; Kainerstorfer, J. M.

    2017-02-01

    The mechanism that maintains a stable blood flow in the brain despite changes in cerebral perfusion pressure (CPP), and therefore guaranties a constant supply of oxygen and nutrients to the neurons, is known as cerebral auto-regulation (CA). In a certain range of CPP, blood flow is mediated by a vasomotor adjustment in vascular resistance through dilation of blood vessels. CA is known to be impaired in diseases like traumatic brain injury, Parkinson's disease, stroke, hydrocephalus and others. If CA is impaired, blood flow and pressure changes are coupled and thee oxygen supply might be unstable. Lassen's blood flow auto-regulation curve describes this mechanism, where a plateau of stable blood flow in a specific range of CPP corresponds to intact auto-regulation. Knowing the limits of this plateau and maintaining CPP within these limits can improve patient outcome. Since CPP is influenced by both intracranial pressure and arterial blood pressure, long term changes in either can lead to auto-regulation impairment. Non-invasive methods for monitoring blood flow auto-regulation are therefore needed. We propose too use Near infrared spectroscopy (NIRS) too fill this need. NIRS is an optical technique, which measures microvascular changes in cerebral hemoglobin concentration. We performed experiments on non-human primates during exsanguination to demonstrate that thee limits of blood flow auto-regulation can be accessed with NIRS.

  14. Random amplification of polymorphic DNA reveals clonal relationships among enteropathogenic Escherichia coli isolated from non-human primates and humans

    Directory of Open Access Journals (Sweden)

    V.M. Carvalho

    2007-02-01

    Full Text Available Enteropathogenic Escherichia coli (EPEC strains are important agents of infantile diarrhea all over the world, gaining even greater importance in developing countries. EPEC have also been isolated from various animal species, but most isolates belong to serotypes that differ from those recovered from humans. However, it has been demonstrated that several isolates from non-human primates belong to the serogroups and/or serotypes related to those implicated in human disease. The objective of this study was to evaluate the genetic differences between thirteen strains isolated from non-human primates and the same number of strains isolated from human infections. Human isolates belonged to the same serogroup/serotype as the monkey strains and the evaluation was done by analysis of random amplified polymorphic DNA. Dendrogram analysis showed that there was no clustering between human and monkey strains. Human and non-human isolates of the EPEC serotypes O127:H40 and O128:H2 shared 90 and 87% of their bands, respectively, indicating strong genomic similarity between the strains, leading to the speculation that they may have arisen from the same pathogenic clone. To our knowledge, this study is the first one comparing genomic similarity between human and non-human primate strains and the results provide further evidence that monkey EPEC strains correlate with human EPEC, as suggested in a previous investigation.

  15. Preventive immunization of aged and juvenile non-human primates to beta-amyloid

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    Kofler Julia

    2012-05-01

    Full Text Available Abstract Background Immunization against beta-amyloid (Aβ is a promising approach for the treatment of Alzheimer’s disease, but the optimal timing for the vaccination remains to be determined. Preventive immunization approaches may be more efficacious and associated with fewer side-effects; however, there is only limited information available from primate models about the effects of preclinical vaccination on brain amyloid composition and the neuroinflammatory milieu. Methods Ten non-human primates (NHP of advanced age (18–26 years and eight 2-year-old juvenile NHPs were immunized at 0, 2, 6, 10 and 14 weeks with aggregated Aβ42 admixed with monophosphoryl lipid A as adjuvant, and monitored for up to 6 months. Anti-Aβ antibody levels and immune activation markers were assessed in plasma and cerebrospinal fluid samples before and at several time-points after immunization. Microglial activity was determined by [11C]PK11195 PET scans acquired before and after immunization, and by post-mortem immunohistochemical and real-time PCR evaluation. Aβ oligomer composition was assessed by immunoblot analysis in the frontal cortex of aged immunized and non-immunized control animals. Results All juvenile animals developed a strong and sustained serum anti-Aβ IgG antibody response, whereas only 80 % of aged animals developed detectable antibodies. The immune response in aged monkeys was more delayed and significantly weaker, and was also more variable between animals. Pre- and post-immunization [11C]PK11195 PET scans showed no evidence of vaccine-related microglial activation. Post-mortem brain tissue analysis indicated a low overall amyloid burden, but revealed a significant shift in oligomer size with an increase in the dimer:pentamer ratio in aged immunized animals compared with non-immunized controls (P  Conclusions Our results indicate that preventive Aβ immunization is a safe therapeutic approach lacking adverse CNS immune system

  16. Faster scaling of visual neurons in cortical areas relative to subcortical structures in non-human primate brains

    OpenAIRE

    Collins, C. E.; Leitch, D. B.; Wong, P.; Kaas, J. H.; Herculano-Houzel, Suzana

    2012-01-01

    Cortical expansion, both in absolute terms and in relation to subcortical structures, is considered a major trend in mammalian brain evolution with important functional implications, given that cortical computations should add complexity and flexibility to information processing. Here, we investigate the numbers of neurons that compose 4 structures in the visual pathway across 11 non-human primate species to determine the scaling relationships that apply to these structures and among them. We...

  17. Balantidium coli and other gastrointestinal parasites in captives non-human primates of the Rio de Janeiro, Brazil.

    Science.gov (United States)

    da Silva Barbosa, Alynne; Pissinatti, Alcides; Dib, Laís Verdan; de Siqueira, Mayara Perlingeiro; Cardozo, Matheus Lessa; Fonseca, Ana Beatriz Monteiro; de Barros Oliveira, Anderson; da Silva, Fábio Alves; Uchôa, Claudia M Antunes; Bastos, Otilio Machado Pereira; Amendoeira, Maria Regina Reis

    2015-02-01

    Parasites are agents of diarrhea in captive non-human primates (NHP). To broaden information about those etiological agents in captive animals in Brazil, gastrointestinal parasites in captive NHP were researched in nurturing Centers of Rio de Janeiro State. Fecal samples were collected from primates, of which 960 came from the Research Center (Cecal/Fiocruz) and 115 from the Primate Center (CPRJ/Inea). The study involved species of the New World (NW) primates and of the Old World (OW). The estimated prevalence was 56.7%, of which 91.3% presented protozoans and 7.4% presented helminths. Statistical difference between the nurturing centers occurred in the overall value of parasitosis and in the isolated frequency of Balantidium coli and Entamoeba sp., especially in the samples of OW primates living in Cecal. These results demonstrated the need for implements of sanitation programs in the sites for captive primates nurturing. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. IMPROVED METHODS FOR ACRYLIC-FREE IMPLANTS IN NON-HUMAN PRIMATES FOR NEUROSCIENCE RESEARCH.

    Science.gov (United States)

    Overton, Jacqueline A; Cooke, Dylan F; Goldring, Adam B; Lucero, Steven A; Weatherford, Conor; Recanzone, Gregg H

    2017-08-30

    Traditionally, head fixation devices and recording cylinders have been implanted in non-human primates (NHP) using dental acrylic, in spite of several shortcomings associated with acrylic. The use of more biocompatible materials such as titanium and PEEK is becoming more prevalent in NHP research. We describe a cost-effective set of procedures that maximizes the integration of headposts and recording cylinders with the animal's tissues while reducing surgery time. Nine rhesus monkeys were implanted with titanium headposts and one of these was also implanted with a recording chamber. In each case, a 3D printed replica of the skull was created based on computerized tomography scans. The titanium feet of the headposts were shaped and the skull thickness measured pre-operatively, reducing surgery time by up to 70%. The recording cylinder was manufactured to conform tightly to the skull, which was fastened to the skull with 4 screws and remained watertight for 8.5 months. We quantified the amount of regression of the skin edge at the headpost. We found a large degree of variability in the timing and extent of skin regression that could not be explained by any single recorded factor. However, there was not a single case of bone exposure: while skin retracted from the titanium, skin also remained adhered to the skull adjacent to those regions. The headposts remained fully functional and free of complications for the experimental life of each animal, several of which are still participating in experiments over 4 years after implant. Copyright © 2017, Journal of Neurophysiology.

  19. Alteration of daily and circadian rhythms following dopamine depletion in MPTP treated non-human primates.

    Directory of Open Access Journals (Sweden)

    Karim Fifel

    Full Text Available Disturbances of the daily sleep/wake cycle are common non-motor symptoms of Parkinson's disease (PD. However, the impact of dopamine (DA depletion on circadian rhythms in PD patients or non-human primate (NHP models of the disorder have not been investigated. We evaluated alterations of circadian rhythms in NHP following MPTP lesion of the dopaminergic nigro-striatal system. DA degeneration was assessed by in vivo PET ([(11C]-PE2I and post-mortem TH and DAT quantification. In a light∶dark cycle, control and MPTP-treated NHP both exhibit rest-wake locomotor rhythms, although DA-depleted NHP show reduced amplitude, decreased stability and increased fragmentation. In all animals, 6-sulphatoxymelatonin peaks at night and cortisol in early morning. When the circadian system is challenged by exposure to constant light, controls retain locomotor rest-wake and hormonal rhythms that free-run with stable phase relationships whereas in the DA-depleted NHP, locomotor rhythms are severely disturbed or completely abolished. The amplitude and phase relations of hormonal rhythms nevertheless remain unaltered. Use of a light-dark masking paradigm shows that expression of daily rest-wake activity in MPTP monkeys requires the stimulatory and inhibitory effects of light and darkness. These results suggest that following DA lesion, the central clock in the SCN remains intact but, in the absence of environmental timing cues, is unable to drive downstream rhythmic processes of striatal clock gene and dopaminergic functions that control locomotor output. These findings suggest that the circadian component of the sleep-wake disturbances in PD is more profoundly affected than previously assumed.

  20. Assessing the True Intraocular Pressure in the Non-human Primate.

    Science.gov (United States)

    McAllister, Faith; Harwerth, Ronald; Patel, Nimesh

    2018-02-01

    For glaucoma patients, high intraocular pressure (IOP) is a risk factor for progressive neuropathy. Similarly, animal models used to study the disease are based on an experimental elevation of IOP. Thus, accurate IOP measurements are important in characterizing experimental models and resulting effects. The purpose of the present study was to investigate IOP measurements in a non-human primate model of experimental glaucoma by comparing clinical tonometry (Tono-Pen and TonoVet) to the true IOP from intracameral manometry. A total of 17 rhesus macaque eyes from 12 animals were used for this study. Eleven eyes had no previous experimental intervention, whereas six eyes were at varying stages of laser-induced experimental glaucoma. IOPs were adjusted by inserting a needle in the anterior chamber that was attached to a pressure transducer and syringe pump system. The anterior chamber IOP was adjusted to values between 10 and 50 mmHg and corresponding measures with Tono-Pen and TonoVet were taken. The IOPs by TonoVet and Tono-Pen were linearly related over the range of pressures tested (slope = 0.68 normal/healthy and 0.72 experimental glaucoma). For the most, TonoVet measures overestimated IOP at all anterior chamber pressure settings (mean difference of 3.17 mmHg, 95% CI 12.53 to -4.74 normal and 3.90 mmHg, 95% CI 12.90 to -6.53 experimental glaucoma). In contrast, Tono-Pen measures overestimated IOP at lower IOPs and underestimated at higher IOP (slope = -0.26 normal and -0.21 experimental glaucoma). The TonoVet and Tono-Pen tonometers that are often used to assess IOP in both clinical and experimental settings generally reflect the status of IOP, but the results from this study suggest that the instruments need calibration with true anterior chamber pressure for accurate measures in experimental models of glaucoma.

  1. A Cage-Based Training System for Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Michaela D Curry

    2017-07-01

    Full Text Available Non-human primates (NHPs are widely-used experimental models in neurophysiological studies. Training on cognitive tasks prior to collecting neurophysiological data is an inseparable part of much of the research conducted using NHPs. Any improvement in the training method that reduces stress to the animal, increases the speed of training or improves performance on the task is of great potential value. We have designed, built and successfully utilized a fully portable cage-mountable system to train rhesus monkeys (Macaca mulatta. The flexibility and portability of both the animal interface and the control unit of this system would allow it to be used for a large variety of behavioral paradigms. Aside from experimental use, our system could potentially be used as a source of animal enrichment. We present the behavioral data collected using this method to train a visual working memory and a change detection task. Utilizing the in-cage training system allows the animal greater control over when and how long it chooses to work, rather than imposing a training schedule based on the availability of the experimenter. Using this method the animal learned to perform both behavioral tasks in a short amount of time. In some cases the animal would use the training system without the need for any water restriction. In addition to allowing voluntary, self-paced engagement with the task, this method has the advantage of being less disruptive to the monkey's social interactions, and presumably eliminating some of the stress occasioned by relocating for chair training. Although this system has the potential to ease and expedite the behavioral training of NHPs on a variety of tasks, here we provide only a demonstration of our cage-based training system using one NHP.

  2. Neuroanatomical study of the A11 diencephalospinal pathway in the non-human primate.

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    Quentin Barraud

    Full Text Available BACKGROUND: The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP. We therefore characterized the anatomy of this pathway in the NHP. METHODS AND FINDINGS: In situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group. CONCLUSION: The diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells.

  3. Neuroanatomical study of the A11 diencephalospinal pathway in the non-human primate.

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    Barraud, Quentin; Obeid, Ibrahim; Aubert, Incarnation; Barrière, Gregory; Contamin, Hugues; McGuire, Steve; Ravenscroft, Paula; Porras, Gregory; Tison, François; Bezard, Erwan; Ghorayeb, Imad

    2010-10-13

    The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP). We therefore characterized the anatomy of this pathway in the NHP. In situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG) into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group. The diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells.

  4. Do robots have goals? How agent cues influence action understanding in non-human primates.

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    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Non-human primate models of PD to test novel therapies.

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    Morissette, Marc; Di Paolo, Thérèse

    2017-04-08

    Non-human primate (NHP) models of Parkinson disease show many similarities with the human disease. They are very useful to test novel pharmacotherapies as reviewed here. The various NHP models of this disease are described with their characteristics including the macaque, the marmoset, and the squirrel monkey models. Lesion-induced and genetic models are described. There is no drug to slow, delay, stop, or cure Parkinson disease; available treatments are symptomatic. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-Dopa) still remains the gold standard symptomatic treatment of Parkinson. However, involuntary movements termed L-Dopa-induced dyskinesias appear in most patients after chronic treatment and may become disabling. Dyskinesias are very difficult to manage and there is only amantadine approved providing only a modest benefit. In this respect, NHP models have been useful to seek new drug targets, since they reproduce motor complications observed in parkinsonian patients. Therapies to treat motor symptoms in NHP models are reviewed with a discussion of their translational value to humans. Disease-modifying treatments tested in NHP are reviewed as well as surgical treatments. Many biochemical changes in the brain of post-mortem Parkinson disease patients with dyskinesias are reviewed and compare well with those observed in NHP models. Non-motor symptoms can be categorized into psychiatric, autonomic, and sensory symptoms. These symptoms are present in most parkinsonian patients and are already installed many years before the pre-motor phase of the disease. The translational usefulness of NHP models of Parkinson is discussed for non-motor symptoms.

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

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    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).

  7. Host responses to concurrent combined injuries in non-human primates

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    Matthew J. Bradley

    2017-11-01

    Full Text Available Abstract Background Multi-organ failure (MOF following trauma remains a significant cause of morbidity and mortality related to a poorly understood abnormal inflammatory response. We characterized the inflammatory response in a non-human primate soft tissue injury and closed abdomen hemorrhage and sepsis model developed to assess realistic injury patterns and induce MOF. Methods Adult male Mauritan Cynomolgus Macaques underwent laparoscopy to create a cecal perforation and non-anatomic liver resection along with a full-thickness flank soft tissue injury. Treatment consisted of a pre-hospital phase followed by a hospital phase after 120 minutes. Blood counts, chemistries, and cytokines/chemokines were measured throughout the study. Lung tissue inflammation/apoptosis was confirmed by mRNA quantitative real-time PCR (qPCR, H&E, myeloperoxidase (MPO and TUNEL staining was performed comparing age-matched uninjured controls to experimental animals. Results Twenty-one animals underwent the protocol. Mean percent hepatectomy was 64.4 ± 5.6; percent blood loss was 69.0 ± 12.1. Clinical evidence of end-organ damage was reflected by a significant elevation in creatinine (1.1 ± 0.03 vs. 1.9 ± 0.4, p=0.026. Significant increases in systemic levels of IL-10, IL-1ra, IL-6, G-CSF, and MCP-1 occurred (11-2986-fold by 240 minutes. Excessive pulmonary inflammation was evidenced by alveolar edema, congestion, and wall thickening (H&E staining. Concordantly, amplified accumulation of MPO leukocytes and significant pulmonary inflammation and pneumocyte apoptosis (TUNEL was confirmed using qRT-PCR. Conclusion We created a clinically relevant large animal multi-trauma model using laparoscopy that resulted in a significant systemic inflammatory response and MOF. With this model, we anticipate studying systemic inflammation and testing innovative therapeutic options.

  8. Suboptimal porcine endogenous retrovirus infection in non-human primate cells: implication for preclinical xenotransplantation.

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    Giada Mattiuzzo

    Full Text Available BACKGROUND: Porcine endogenous retrovirus (PERV poses a potential risk of zoonotic infection in xenotransplantation. Preclinical transplantation trials using non-human primates (NHP as recipients of porcine xenografts present the opportunity to assess the zoonosis risk in vivo. However, PERV poorly infects NHP cells for unclear reasons and therefore NHP may represent a suboptimal animal model to assess the risk of PERV zoonoses. We investigated the mechanism responsible for the low efficiency of PERV-A infection in NHP cells. PRINCIPAL FINDINGS: Two steps, cell entry and exit, were inefficient for the replication of high-titer, human-tropic A/C recombinant PERV. A restriction factor, tetherin, is likely to be responsible for the block to matured virion release, supported by the correlation between the levels of inhibition and tetherin expression. In rhesus macaque, cynomolgus macaque and baboon the main receptor for PERV entry, PERV-A receptor 1 (PAR-1, was found to be genetically deficient: PAR-1 genes in these species encode serine at amino acid 109 in place of the leucine in human PAR-1. This genetic defect inevitably impacts in vivo sensitivity to PERV infection of these species. In contrast, African green monkey (AGM PAR-1 is functional, but PERV infection is still poor. Although the mechanism is unclear, tunicamycin treatment, which removes N-glycosylated sugar chains, increases PERV infection, suggesting a possible role for the glycosylation of the receptors. CONCLUSIONS: Since cynomolgus macaque and baboon, species often used in pig-to-NHP xenotransplantation experiments, have a defective PAR-1, they hardly represent an ideal animal model to assess the risk of PERV transmission in xenotransplantation. Alternatively, NHP species, like AGM, whose both PARs are functional may represent a better model than baboon and cynomolgus macaque for PERV zoonosis in vivo studies.

  9. A wireless transmission neural interface system for unconstrained non-human primates

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    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.

  10. Adeno-associated virus type 6 is retrogradely transported in the non-human primate brain.

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    San Sebastian, W; Samaranch, L; Heller, G; Kells, A P; Bringas, J; Pivirotto, P; Forsayeth, J; Bankiewicz, K S

    2013-12-01

    We recently demonstrated that axonal transport of adeno-associated virus (AAV) is serotype-dependent. Thus, AAV serotype 2 (AAV2) is anterogradely transported (e.g., from cell bodies to nerve terminals) in both rat and non-human primate (NHP) brain. In contrast, AAV serotype 6 (AAV6) is retrogradely transported from terminals to neuronal cell bodies in the rat brain. However, the directionality of axonal transport of AAV6 in the NHP brain has not been determined. In this study, two Cynomolgus macaques received an infusion of AAV6 harboring green fluorescent protein (GFP) into the striatum (caudate and putamen) by magnetic resonance (MR)-guided convection-enhanced delivery. One month after infusion, immunohistochemical staining of brain sections revealed a striatal GFP expression that corresponded well with MR signal observed during gene delivery. As shown previously in rats, GFP expression was detected throughout the prefrontal, frontal and parietal cortex, as well as the substantia nigra pars compacta and thalamus, indicating retrograde transport of the vector in NHP. AAV6-GFP preferentially transduced neurons, although a few astrocytes were also transduced. Transduction of non-neuronal cells in the brain was associated with the upregulation of the major histocompatibility complex-II and lymphocytic infiltration as previously observed with AAV1 and AAV9. This contrasts with highly specific neuronal transduction in the rat brain. Retrograde axonal transport of AAV6 from a single striatal infusion permits efficient transduction of cortical neurons in significant tissue volumes that otherwise would be difficult to achieve.

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

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    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.

  12. Viral Kinetics of Primary Dengue Virus Infection in Non-Human Primates: A Systematic Review and Individual Pooled Analysis

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    Althouse, Benjamin M.; Durbin, Anna P.; Hanley, Kathryn A.; Halstead, Scott B.; Weaver, Scott C.; Cummings, Derek A. T.

    2014-01-01

    Viremia kinetics directly influence the clinical course and transmission dynamics of DENV, but many aspects of viral dynamics remain unknown. Non-human primates (NHP) have been used as a model system for DENV infection for decades. Here, we identify papers with experimentally-infected NHP and estimate the time to- and duration of viremia as well as estimate associations between these and serotype, inoculating dose, viremia assay, and species of NHP. We estimate the time to viremia in rhesus macaques to range from 2.63 to 3.32 days for DENV-2 and -1 and the duration to range from 3.13 to 5.13 days for DENV-4 and -2. We find no differences between non-human primates for time to viremia or duration, and a significant negative relationship between inoculating dose and duration of viremia. These results aide in understanding the transmission dynamics of sylvatic DENV non-human primates, an issue of growing importance as dengue vaccines become available. PMID:24606701

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

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    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.

  14. Guidelines for the prevention and control of tuberculosis in non-human primates: recommendations of the European Primate Veterinary Association Working Group on Tuberculosis.

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    Bushmitz, Moshe; Lecu, Alex; Verreck, Frank; Preussing, Ellen; Rensing, Susanne; Mätz-Rensing, Kerstin

    2009-02-01

    Effective tuberculosis (TB) control requires accurate diagnostic methods but the tuberculin skin test has serious limitations. Both false-negative and false-positive reactions are common, resulting in the spread of the infection and devastating TB outbreaks. Results of questionnaire surveys concerning TB testing practices in primate housing facilities showed great differences in testing practices. Although there was some uniformity regarding the sites of application, the amounts of tuberculin used and the time intervals for retesting, a great deal of variety was revealed considering the types of tuberculin preparations, the interpretation of tests and the susceptibility of animals. Here, we summarize the most common practices as regards TB control and prevention for non-human primates, and attempt to establish a uniform guideline based upon our experience with primate husbandry and care programmes as well as recent developments in the literature. The present guideline represents a consensus recommendation intending to harmonize the existing protocols.

  15. Non-human primate antibody response to mosquito salivary proteins: Implications for dengue virus transmission in Puerto Rico.

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    Hemme, Ryan R; Poole-Smith, B Katherine; Hunsperger, Elizabeth A; Felix, Gilberto E; Horiuchi, Kalanthe; Biggerstaff, Brad J; Lopez-Ortiz, Ricardo; Barrera, Roberto

    2016-12-01

    An important step to incriminate a mosquito as a vector of a disease pathogen is finding evidence of direct contact between the mosquito and humans. Typically, this is accomplished through landing/biting catches, or host blood meal analysis in engorged mosquitoes via immunologic assays. An alternate approach is to identify the presence of specific mosquito anti-saliva protein antibodies in the blood of exposed hosts. Following the discovery of dengue infected, free roaming non-human primates in Puerto Rico, we investigated which mosquito species had bitten these primates using a serologic assay. Serum samples from 20 patas monkeys (Erythrocebus patas) and two rhesus macaques (Macaca mulatta) were used to evaluate mosquito bite exposure to Aedes aegypti, Aedes mediovittatus, Aedes taeniorhynchus, and Culex quinquefasciatus mosquitoes. Of 22 non-human primates examined 20 (90%), 17 (77%), 13 (59%), and 7 (31%) were positive for exposure to Ae. mediovittatus, Cx. quinquefasciatus, Ae. taeniorhynchus, and Ae. aegypti, respectively. Our findings indicated that free-roaming primates in Puerto Rico were exposed to the bites of one proven dengue vector, Ae. aegypti and one potential dengue vector, Ae. mediovittatus. Published by Elsevier B.V.

  16. Do non-human primates cooperate? Evidences of motor coordination during a joint action task in macaque monkeys.

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    Visco-Comandini, Federica; Ferrari-Toniolo, Simone; Satta, Eleonora; Papazachariadis, Odysseas; Gupta, Rajnish; Nalbant, Laura Elena; Battaglia-Mayer, Alexandra

    2015-09-01

    Humans are intensively social primates, therefore many of their actions are dedicated to communication and interaction with other individuals. Despite the progress in understanding the cognitive and neural processes that allow humans to perform cooperative actions, in non-human primates only few studies have investigated the ability to interact with a partner in order to reach a common goal. These studies have shown that in naturalistic conditions animals engage in various types of social behavior that involve forms of mutual coordination and cooperation. However, little is known on the capacity of non-human primates to actively cooperate in a controlled experimental setting, which allows full characterization of the motor parameters underlying individual action and their change during motor cooperation. To this aim, we analyzed the behavior of three pairs of macaque monkeys trained to perform solo and joint-actions by exerting a force on an isometric joystick, as to move an individual or a common cursor toward visual targets on a screen. We found that during cooperation monkeys reciprocally adapt their behavior by changing the parameters that define the spatial and temporal aspects of their action, as to fine tune their joint effort, and maximize their common performance. Furthermore the results suggest that when acting together the movement parameters that specify each actor's behavior are not only modulated during execution, but also during planning. These findings provide the first quantitative description of action coordination in non-human primates during the performance of a joint action task. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Thickness, phase retardation, birefringence, and reflectance of the retinal nerve fiber layer in normal and glaucomatous non-human primates.

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    Dwelle, Jordan; Liu, Shuang; Wang, Bingqing; McElroy, Austin; Ho, Derek; Markey, Mia K; Milner, Thomas; Rylander, H Grady

    2012-07-01

    We identified candidate optical coherence tomography (OCT) markers for early glaucoma diagnosis. Time variation of retinal nerve fiber layer (RNFL) thickness, phase retardation, birefringence, and reflectance using polarization sensitive optical coherence tomography (PS-OCT) were measured in three non-human primates with induced glaucoma in one eye. We characterized time variation of RNFL thickness, phase retardation, birefringence, and reflectance with elevated intraocular pressure (IOP). One eye of each of three non-human primates was laser treated to increase IOP. Each primate was followed for a 30-week period. PS-OCT measurements were recorded at weekly intervals. Reflectance index (RI) is introduced to characterize RNFL reflectance. Associations between elevated IOP and RNFL thickness, phase retardation, birefringence, and reflectance were characterized in seven regions (entire retina, inner and outer rings, and nasal, temporal, superior and inferior quadrants) by linear and non-linear mixed-effects models. Elevated IOP was achieved in three non-human primate eyes with an average increase of 13 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in the nasal region (P = 0.0002), decreased RNFL phase retardation in the superior (P = 0.046) and inferior (P = 0.021) regions, decreased RNFL birefringence in the nasal (P = 0.002) and inferior (P = 0.029) regions, and loss of RNFL reflectance in the outer rings (P = 0.018). When averaged over the entire retinal area, only RNFL reflectance showed a significant decrease (P = 0.028). Of the measured parameters, decreased RNFL reflectance was the most robust correlate with glaucomatous damage. Candidate cellular mechanisms are considered for decreased RNFL reflectance, including mitochondrial dysfunction and retinal ganglion cell apoptosis.

  18. Efficient derivation of multipotent neural stem/progenitor cells from non-human primate embryonic stem cells.

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    Hiroko Shimada

    Full Text Available The common marmoset (Callithrix jacchus is a small New World primate that has been used as a non-human primate model for various biomedical studies. We previously demonstrated that transplantation of neural stem/progenitor cells (NS/PCs derived from mouse and human embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs promote functional locomotor recovery of mouse spinal cord injury models. However, for the clinical application of such a therapeutic approach, we need to evaluate the efficacy and safety of pluripotent stem cell-derived NS/PCs not only by xenotransplantation, but also allotransplantation using non-human primate models to assess immunological rejection and tumorigenicity. In the present study, we established a culture method to efficiently derive NS/PCs as neurospheres from common marmoset ESCs. Marmoset ESC-derived neurospheres could be passaged repeatedly and showed sequential generation of neurons and astrocytes, similar to that of mouse ESC-derived NS/PCs, and gave rise to functional neurons as indicated by calcium imaging. Although marmoset ESC-derived NS/PCs could not differentiate into oligodendrocytes under default culture conditions, these cells could abundantly generate oligodendrocytes by incorporating additional signals that recapitulate in vivo neural development. Moreover, principal component analysis of microarray data demonstrated that marmoset ESC-derived NS/PCs acquired similar gene expression profiles to those of fetal brain-derived NS/PCs by repeated passaging. Therefore, marmoset ESC-derived NS/PCs may be useful not only for accurate evaluation by allotransplantation of NS/PCs into non-human primate models, but are also applicable to analysis of iPSCs established from transgenic disease model marmosets.

  19. Gastrostomy tube placement for long-term oral drug administration in non-human primates.

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    Kim, Jong-Min; Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Jung-Sik; Yoon, Il-Hee; Jeong, Won-Young; Lee, Ga-Eul; Kim, Min-Sun; Kim, Ju-Eun; Park, Chung-Gyu

    2017-03-01

    Non-human primates (NHPs) are often used as recipients in preclinical transplantation research that in most cases involves administration of various drugs including immunosuppressants. Long-term oral drug administration, particularly tacrolimus, is challenging in the transplant recipient NHPs. Oral drug administration method using the mixture of drug and fruit juice has been used in NHPs, but this is not always effective in all monkeys. To those monkeys who are poorly compliant, oral drug administration in restraint or administration using gastrostomy tube should be necessary. The aim of this study was to compare the efficacy of between oral drug administration in restraint and administration using gastrostomy tube and to report complications and solutions to overcome the problems related to gastrostomy tube for long-term oral drug dosing in rhesus monkeys. Fifteen of 4- to 5-year-old male and female healthy rhesus monkeys weighing 5.0-6.8 kg were used as recipients for porcine pancreatic islet transplantation. Oral drug administration in restraint was used for four monkeys, and gastrostomy tube was placed to other 11 monkeys (8-French Feeding tube, n=6; Tri-Funnel Replacement Gastrostomy tube, n=5). Oral immunosuppressive drugs such as sirolimus and tacrolimus were administered through the tube. The efficacy and the extent of ease for administration and related complications were compared between two groups. The complication of gastrostomy included a transient inflammation in the skin and peritonitis caused by a leakage around implantation site (one case), which could be overcome by changing suture method and tube type to interlocking box suture and Tri-Funnel Replacement Gastrostomy tube, respectively. Despite these complications, oral drug administration using gastrostomy tube allowed us to perform accurate dosage of drug administration and to reduce the stress that both the monkey and the researcher may experience. Taken together, this study showed that

  20. Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

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    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

  1. Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. A sexually dimorphic peptidergic system in the lower spinal cord controlling penile function in non-human primates.

    Science.gov (United States)

    Ito, T; Oti, T; Takanami, K; Satoh, K; Ueda, Y; Sakamoto, T; Sakamoto, H

    2017-09-12

    Experimental animal study. Although a population of gastrin-releasing peptide (GRP) neurons in the lumbar spinal cord has an important role in erection and ejaculation in rats, little information exists on this GRP system in primates. To identify the male-specific GRP system in the primate spinal cord, we studied the lumbosacral cord in macaque monkeys as a non-human primate model. University laboratory in Japan. To determine the gene sequence of GRP precursors, the rhesus macaque monkey genomic sequence data were searched, followed by phylogenetic analysis. Subsequently, immunocytochemical analysis for GRP was performed in the monkey spinal cord. We have used bioinformatics to identify the ortholog gene for GRP precursor in macaque monkeys. Phylogenetic analysis suggested that primate prepro-GRP is separated from that of other mammalian species and clustered to an independent branch as primates. Immunocytochemistry for GRP further demonstrated that male-dominant sexual dimorphism was found in the spinal GRP system in monkeys as in rodents. We have demonstrated in macaque monkeys that the GRP system in the lower spinal cord shows male-specific dimorphism and may have an important role in penile functions not only in rodents but also in primates. Tissues of Nihonzaru (Japanese macaque monkeys) were provided in part by National Institutes of Natural Sciences (NINS) through the National Bio-Resource Project (NBRP) of the MEXT, Japan. This work was supported in part by KAKENHI from the Japan Society for the Promotion of Science (JSPS) (to KT; 15KK0343, 15J40220 and HS; 15K15202, 15KK0257, 15H05724).Spinal Cord advance online publication, 12 September 2017; doi:10.1038/sc.2017.105.

  4. Concealed fertility and extended female sexuality in a non-human primate (Macaca assamensis)

    National Research Council Canada - National Science Library

    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...

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

    OpenAIRE

    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 stu...

  6. First report of yellow fever virus in non-human primates in the State of Parana, Brazil

    Directory of Open Access Journals (Sweden)

    Marcos Vinicius Tranquilin

    2013-07-01

    Full Text Available Sylvatic yellow fever is a zoonosis associated mainly with wild animals, especially those in the genus Alouatta, that act as the source of infection. Once infected, these animals pass the disease on to humans by way of an infected mosquito belonging to the genera Aedes, Haemagogus, or Sabethes. The present study is the first report of a case of yellow fever in non-human primates (NHP in the State of Paraná, Brazil. After the case was diagnosed, several prophylactic measures were adopted to prevent outbreaks of the disease in humans.

  7. Social learning, culture and the 'socio-cultural brain' of human and non-human primates.

    Science.gov (United States)

    Whiten, Andrew; van de Waal, Erica

    2017-11-01

    Noting important recent discoveries, we review primate social learning, traditions and culture, together with associated findings about primate brains. We survey our current knowledge of primate cultures in the wild, and complementary experimental diffusion studies testing species' capacity to sustain traditions. We relate this work to theories that seek to explain the enlarged brain size of primates as specializations for social intelligence, that have most recently extended to learning from others and the cultural transmission this permits. We discuss alternative theories and review a variety of recent findings that support cultural intelligence hypotheses for primate encephalization. At a more fine-grained neuroscientific level we focus on the underlying processes of social learning, especially emulation and imitation. Here, our own and others' recent research has established capacities for bodily imitation in both monkeys and apes, results that are consistent with a role for the mirror neuron system in social learning. We review important convergences between behavioural findings and recent non-invasive neuroscientific studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Encapsulating Non-Human Primate Multipotent Stromal Cells in Alginate via High Voltage for Cell-Based Therapies and Cryopreservation

    Science.gov (United States)

    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

  9. Good gibbons and evil macaques: a historical review on cognitive features of non-human primates in Chinese traditional culture.

    Science.gov (United States)

    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.

  10. Molecular Detection of Plasmodium malariae/Plasmodium brasilianum in Non-Human Primates in Captivity in Costa Rica.

    Science.gov (United States)

    Fuentes-Ramírez, Alicia; Jiménez-Soto, Mauricio; Castro, Ruth; Romero-Zuñiga, Juan José; Dolz, Gaby

    2017-01-01

    One hundred and fifty-two blood samples of non-human primates of thirteen rescue centers in Costa Rica were analyzed to determine the presence of species of Plasmodium using thick blood smears, semi-nested multiplex polymerase chain reaction (SnM-PCR) for species differentiation, cloning and sequencing for confirmation. Using thick blood smears, two samples were determined to contain the Plasmodium malariae parasite, with SnM-PCR, a total of five (3.3%) samples were positive to P. malariae, cloning and sequencing confirmed both smear samples as P. malariae. One sample amplified a larger and conserved region of 18S rDNA for the genus Plasmodium and sequencing confirmed the results obtained microscopically and through SnM-PCR tests. Sequencing and construction of a phylogenetic tree of this sample revealed that the P. malariae/P. brasilianum parasite (GenBank KU999995) found in a howler monkey (Alouatta palliata) is identical to that recently reported in humans in Costa Rica. The SnM-PCR detected P. malariae/P. brasilianum parasite in different non-human primate species in captivity and in various regions of the southern Atlantic and Pacific coast of Costa Rica. The similarity of the sequences of parasites found in humans and a monkey suggests that monkeys may be acting as reservoirs of P.malariae/P. brasilianum, for which reason it is important, to include them in control and eradication programs.

  11. High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Hey-Cunningham, A J [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Lehnert, W [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Kench, P L [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Kassiou, M [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Banati, R [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia); Meikle, S R [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)

    2007-11-21

    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 mm{sup 3} FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm{sup 3}) and 3D reprojection (3DRP) (5.9-9.1 mm{sup 3}). A pilot {sup 18}F-2-fluoro-2-deoxy-d-glucose ([{sup 18}F]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.

  12. Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Roqueline A. G. M. F. Aversi-Ferreira

    2014-01-01

    Full Text Available 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.

  13. Energetics of feeding, social behavior, and life history in non-human primates.

    Science.gov (United States)

    Emery Thompson, Melissa

    2017-05-01

    Energy is a variable of key importance to a wide range of research in primate behavioral ecology, life history, and conservation. However, obtaining detailed data on variation in energetic condition, and its biological consequences, has been a considerable challenge. In the past 20years, tremendous strides have been made towards non-invasive methods for monitoring the physiology of animals in their natural environment. These methods provide detailed, individualized data about energetic condition, as well as energy allocations to growth, reproduction, and somatic health. In doing so, they add much-needed resolution by which to move beyond correlative studies to research programs that can discriminate causes from effects and disaggregate multiple correlated features of the social and physical environment. In this review, I describe the conceptual and methodological approaches for studying primate energetics. I then discuss the core questions about primate feeding ecology, social behavior, and life history that can benefit from physiological studies, highlighting the ways in which recent research has done so. Among these are studies that test, and often refute, common assumptions about how feeding ecology shapes primate biology, and those that reveal proximate associations between energetics and reproductive strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Sources of variation in hair cortisol in wild and captive non-human primates.

    Science.gov (United States)

    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. Published by Elsevier GmbH.

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

    Directory of Open Access Journals (Sweden)

    Travis May

    Full Text Available 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.

  16. An Evaluation of Twenty Years of EU Framework Programme-funded Immune-mediated Inflammatory Translational Research in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Krista Geraldine Haanstra

    2016-11-01

    Full Text Available Ageing western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which often no effective treatments exist, resulting in increasing health care expenditure. Despite high investments in drug development, the number of promising new drug candidates decreases. We propose that preclinical research in non-human primate can help to bridge the gap between drug discovery and drug prescription.Translational research covers various stages of drug development of which pre-clinical efficacy tests in valid animal models is usually the last stage. Pre-clinical research in non-human primates may be essential in the evaluation of new drugs or therapies when a relevant rodent model is not available. Non-human primate models for life-threatening or severely debilitating diseases in humans are available at the Biomedical Primate Research Centre (BPRC. These have been instrumental in translational research for several decades.In order to stimulate European health research and innovation from bench to bedside, the European Commission (EC has invested heavily in access to non-human primate research for more than 20 years. BPRC has hosted European users in a series of transnational access programs covering a wide range of research areas with the common theme being immune-mediated inflammatory disorders. We present an overview of the results and give an account of the studies performed as part of European Union Framework Programme (EU FP-funded translational non-human primate research performed at the BPRC. The data illustrate value of translational non-human primate research for the development of new therapies and emphasize the importance of EU FP funding

  17. Rabies in humans and non-human in the state of Pará, Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Marcus Emanuel Barroncas Fernandes

    Full Text Available We evaluate the relationship of positive cases of rabies with the continuing expansion of livestock production, and analyse the trends of this zoonosis in human population in the state of Pará, Brazilian Amazon. The distribution of rabies cases was recorded between 1999 and 2004. Of 148 cases of rabies, 21% were in humans and 79% in non-human mammals. The rapid growth in livestock numbers seems to be associated with the increase of positive cases in bovine livestock transmitted by vampire bats. This idea is supported by positive and significant relationship of both events in time (p < 0.01, but failed when spatial distribution among regions of the state was considered. However, rabies cases tend to occur toward the northeastern of the state of Pará, where rabies cases are proportionally five times greater than other mesoregions, suggesting that increased livestock production may influence the increase of this zoonosis.

  18. Rabies in humans and non-human in the state of Pará, Brazilian Amazon

    Directory of Open Access Journals (Sweden)

    Marcus Emanuel Barroncas Fernandes

    2013-04-01

    Full Text Available We evaluate the relationship of positive cases of rabies with the continuing expansion of livestock production, and analyse the trends of this zoonosis in human population in the state of Pará, Brazilian Amazon. The distribution of rabies cases was recorded between 1999 and 2004. Of 148 cases of rabies, 21% were in humans and 79% in non-human mammals. The rapid growth in livestock numbers seems to be associated with the increase of positive cases in bovine livestock transmitted by vampire bats. This idea is supported by positive and significant relationship of both events in time (p < 0.01, but failed when spatial distribution among regions of the state was considered. However, rabies cases tend to occur toward the northeastern of the state of Pará, where rabies cases are proportionally five times greater than other mesoregions, suggesting that increased livestock production may influence the increase of this zoonosis.

  19. Evolution of invasive placentation with special reference to non-human primates

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Pijnenborg, Robert

    2011-01-01

    It is now possible to view human placentation in an evolutionary context because advances in molecular phylogenetics provide a reliable scenario for the evolution of mammals. Perhaps the most striking finding is the uniqueness of human placenta. The lower primates have non-invasive placentae...... and even tarsiers and New World monkeys show restricted trophoblast invasion. Moreover, a truly villous placenta occurs only in Old World monkeys and great apes. The two latter groups of haplorhine primates show varying degrees of trophoblast-uterine interaction, including differences in the extent...... of decidualization, formation and disintegration of a cytotrophoblastic shell, degree of interstitial trophoblast invasion and depth of trophoblast invasion into spiral arteries. Recently, the occurrence of human-like deep invasion was confirmed in gorillas and chimpanzees. As the still enigmatic disease of pre...

  20. Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

    Science.gov (United States)

    Almeida, Marco A B; Cardoso, Jader da C; Dos Santos, Edmilson; da Fonseca, Daltro F; Cruz, Laura L; Faraco, Fernando J C; Bercini, Marilina A; Vettorello, Kátia C; Porto, Mariana A; Mohrdieck, Renate; Ranieri, Tani M S; Schermann, Maria T; Sperb, Alethéa F; Paz, Francisco Z; Nunes, Zenaida M A; Romano, Alessandro P M; Costa, Zouraide G; Gomes, Silvana L; Flannery, Brendan

    2014-03-01

    In Brazil, epizootics among New World monkey species may indicate circulation of yellow fever (YF) virus and provide early warning of risk to humans. Between 1999 and 2001, the southern Brazilian state of Rio Grande do Sul initiated surveillance for epizootics of YF in non-human primates to inform vaccination of human populations. Following a YF outbreak, we analyzed epizootic surveillance data and assessed YF vaccine coverage, timeliness of implementation of vaccination in unvaccinated human populations. From October 2008 through June 2009, circulation of YF virus was confirmed in 67 municipalities in Rio Grande do Sul State; vaccination was recommended in 23 (34%) prior to the outbreak and in 16 (24%) within two weeks of first epizootic report. In 28 (42%) municipalities, vaccination began more than two weeks after first epizootic report. Eleven (52%) of 21 laboratory-confirmed human YF cases occurred in two municipalities with delayed vaccination. By 2010, municipalities with confirmed YF epizootics reported higher vaccine coverage than other municipalities that began vaccination. In unvaccinated human populations timely response to epizootic events is critical to prevent human yellow fever cases.

  1. Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

    Directory of Open Access Journals (Sweden)

    Marco A B Almeida

    2014-03-01

    Full Text Available In Brazil, epizootics among New World monkey species may indicate circulation of yellow fever (YF virus and provide early warning of risk to humans. Between 1999 and 2001, the southern Brazilian state of Rio Grande do Sul initiated surveillance for epizootics of YF in non-human primates to inform vaccination of human populations. Following a YF outbreak, we analyzed epizootic surveillance data and assessed YF vaccine coverage, timeliness of implementation of vaccination in unvaccinated human populations. From October 2008 through June 2009, circulation of YF virus was confirmed in 67 municipalities in Rio Grande do Sul State; vaccination was recommended in 23 (34% prior to the outbreak and in 16 (24% within two weeks of first epizootic report. In 28 (42% municipalities, vaccination began more than two weeks after first epizootic report. Eleven (52% of 21 laboratory-confirmed human YF cases occurred in two municipalities with delayed vaccination. By 2010, municipalities with confirmed YF epizootics reported higher vaccine coverage than other municipalities that began vaccination. In unvaccinated human populations timely response to epizootic events is critical to prevent human yellow fever cases.

  2. Non-human Primate Schlafen11 Inhibits Production of Both Host and Viral Proteins.

    Directory of Open Access Journals (Sweden)

    Alex C Stabell

    2016-12-01

    Full Text Available Schlafen11 (encoded by the SLFN11 gene has been shown to inhibit the accumulation of HIV-1 proteins. We show that the SLFN11 gene is under positive selection in simian primates and is species-specific in its activity against HIV-1. The activity of human Schlafen11 is relatively weak compared to that of some other primate versions of this protein, with the versions encoded by chimpanzee, orangutan, gibbon, and marmoset being particularly potent inhibitors of HIV-1 protein production. Interestingly, we find that Schlafen11 is functional in the absence of infection and reduces protein production from certain non-viral (GFP and even host (Vinculin and GAPDH transcripts. This suggests that Schlafen11 may just generally block protein production from non-codon optimized transcripts. Because Schlafen11 is an interferon-stimulated gene with a broad ability to inhibit protein production from many host and viral transcripts, its role may be to create a general antiviral state in the cell. Interestingly, the strong inhibitors such as marmoset Schlafen11 consistently block protein production better than weak primate Schlafen11 proteins, regardless of the virus or host target being analyzed. Further, we show that the residues to which species-specific differences in Schlafen11 potency map are distinct from residues that have been targeted by positive selection. We speculate that the positive selection of SLFN11 could have been driven by a number of different factors, including interaction with one or more viral antagonists that have yet to be identified.

  3. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates

    Science.gov (United States)

    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.

  4. A multi-site array for combined local electrochemistry and electrophysiology in the non-human primate brain.

    Science.gov (United States)

    Disney, Anita A; McKinney, Collin; Grissom, Larry; Lu, Xuekun; Reynolds, John H

    2015-11-30

    Currently, the primary technique employed in circuit-level study of the brain is electrophysiology, recording local field or action potentials (LFPs or APs). However most communication between neurons is chemical and the relationship between electrical activity within neurons and chemical signaling between them is not well understood in vivo, particularly for molecules that signal at least in part by non-synaptic transmission. We describe a multi-contact array and accompanying head stage circuit that together enable concurrent electrophysiological and electrochemical recording. The array is small (<200 μm) and can be assembled into a device of arbitrary length. It is therefore well-suited for use in all major in vivo model systems in neuroscience, including non-human primates where the large brain and need for daily insertion and removal of recording devices places particularly strict demands on design. We present a protocol for array fabrication. We then show that a device built in the manner described can record LFPs and perform enzyme-based amperometric detection of choline in the awake macaque monkey. Comparison with existing methods Existing methods allow single mode (electrophysiology or electrochemistry) recording. This system is designed for concurrent, dual-mode recording. It is also the only system designed explicitly to meet the challenges of recording in non-human primates. Our system offers the possibility for conducting in vivo studies in a range of species that examine the relationship between the electrical activity of neurons and their chemical environment, with exquisite spatial and temporal precision. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Effects of Caloric Restriction on Cardiovascular Aging in Non-human Primates and Humans

    Science.gov (United States)

    Cruzen, Christina; Colman, Ricki J.

    2009-01-01

    Synopsis Approximately one in three Americans has some form of cardiovascular disease (CVD), accounting for one of every 2.8 deaths in the United States in 2004. Two of the major risk factors for CVD are advancing age and obesity. An intervention able to positively impact both aging and obesity, such as caloric restriction (CR), may prove extremely useful in the fight against CVD. CR is the only environmental or lifestyle intervention that has repeatedly been shown to increase maximum life span and to retard aging in laboratory rodents. In this article, we review evidence that CR in nonhuman primates and humans has a positive effect on risk factors for CVD. PMID:19944270

  6. History, citoarchitecture and neurophysiology of human and non human primates' parietal lobe: A review

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    Tales Alexandre Aversi-Ferreira

    Full Text Available Abstract This strict localizationism had and still has its importance for the development of Neurosciences, since the analysis of changes in mental processes resulting from brain damage became the basis for understanding the brain organization. The human parietal cortex is a highly differentiated structure, consisting of citoarchitectonically defined subareas that are connected to other cortical and subcortical areas. Patients with lesions in the parietal cortex develop various types of neuropsychological manifestations, depending on the specific location of the lesion and the corresponding hemisphere and these lesions in this lobe do not cause modal specific disturbances. The establishment of homologies between the parietal region in humans and primates can be of great contribution in trying to unravel the various functions and complexity of this area.

  7. Characterizing eye movement behaviors and kinematics of non-human primates during virtual navigation tasks.

    Science.gov (United States)

    Corrigan, Benjamin W; Gulli, Roberto A; Doucet, Guillaume; Martinez-Trujillo, Julio C

    2017-10-01

    Virtual environments (VE) allow testing complex behaviors in naturalistic settings by combining highly controlled visual stimuli with spatial navigation and other cognitive tasks. They also allow for the recording of eye movements using high-precision eye tracking techniques, which is important in electrophysiological studies examining the response properties of neurons in visual areas of nonhuman primates. However, during virtual navigation, the pattern of retinal stimulation can be highly dynamic which may influence eye movements. Here we examine whether and how eye movement patterns change as a function of dynamic visual stimulation during virtual navigation tasks, relative to standard oculomotor tasks. We trained two rhesus macaques to use a joystick to navigate in a VE to complete two tasks. To contrast VE behavior with classic measurements, the monkeys also performed a simple Cued Saccade task. We used a robust algorithm for rapid classification of saccades, fixations, and smooth pursuits. We then analyzed the kinematics of saccades during all tasks, and specifically during different phases of the VE tasks. We found that fixation to smooth pursuit ratios were smaller in VE tasks (4:5) compared to the Cued Saccade task (7:1), reflecting a more intensive use of smooth pursuit to foveate targets in VE than in a standard visually guided saccade task or during spontaneous fixations. Saccades made to rewarded targets (exploitation) tended to have increased peak velocities compared to saccades made to unrewarded objects (exploration). VE exploitation saccades were 6% slower than saccades to discrete targets in the Cued Saccade task. Virtual environments represent a technological advance in experimental design for nonhuman primates. Here we provide a framework to study the ways that eye movements change between and within static and dynamic displays.

  8. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease

    DEFF Research Database (Denmark)

    Hallett, Penelope J; Deleidi, Michela; Astradsson, Arnar

    2015-01-01

    Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primat...

  9. Energy expenditure in chow-fed female non-human primates of various weights.

    Science.gov (United States)

    Rising, Russell; Signaevsky, Maxim; Rosenblum, Leonard A; Kral, John G; Lifshitz, Fima

    2008-11-17

    Until now no technology has been available to study energy metabolism in monkeys. The objective of this study was to determine daily energy expenditures (EE) and respiratory quotients (RQ) in female monkeys of various body weights and ages. 16 socially reared Bonnet Macaque female monkeys [5.5 +/- 1.4 kg body weight, modified BMI (length measurement from head to base of the tail) = 28.8 +/- 6.7 kg/crown-rump length, m2 and 11.7 +/- 4.6 years] were placed in the primate Enhanced Metabolic Testing Activity Chamber (Model 3000a, EMTAC Inc. Santa Barbara, CA) for 22-hour measurements of EE (kcal/kg) and RQ (VCO2/VO2). All were fed monkey chow (4.03 kcal/g) ad-libitum under a 12/12 hour light/dark cycle. Metabolic data were corrected for differences in body weight. Results were divided into day (8-hours), dark (12 hours) and morning (2-hours) periods. Data analysis was conducted utilizing SPSS (Version 13). Modified BMI negatively correlated with 22-hour energy expenditure in all monkeys (r = -0.80, p 23 kcal/kg). There were reductions (p 30). The obese group had lower EE (p weight.

  10. Baby on board: olfactory cues indicate pregnancy and fetal sex in a non-human primate

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    Crawford, Jeremy Chase; Drea, Christine M.

    2015-01-01

    Olfactory cues play an integral, albeit underappreciated, role in mediating vertebrate social and reproductive behaviour. These cues fluctuate with the signaller's hormonal condition, coincident with and informative about relevant aspects of its reproductive state, such as pubertal onset, change in season and, in females, timing of ovulation. Although pregnancy dramatically alters a female's endocrine profiles, which can be further influenced by fetal sex, the relationship between gestation and olfactory cues is poorly understood. We therefore examined the effects of pregnancy and fetal sex on volatile genital secretions in the ring-tailed lemur (Lemur catta), a strepsirrhine primate possessing complex olfactory mechanisms of reproductive signalling. While pregnant, dams altered and dampened their expression of volatile chemicals, with compound richness being particularly reduced in dams bearing sons. These changes were comparable in magnitude with other, published chemical differences among lemurs that are salient to conspecifics. Such olfactory ‘signatures’ of pregnancy may help guide social interactions, potentially promoting mother–infant recognition, reducing intragroup conflict or counteracting behavioural mechanisms of paternity confusion; cues that also advertise fetal sex may additionally facilitate differential sex allocation. PMID:25716086

  11. Temporal and Spatial Categorization in Human and Non-Human Primates

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    Juan Carlos eMendez

    2011-09-01

    Full Text Available It has been proposed that a functional overlap exists in the brain for temporal and spatial information processing. To test this, we designed two relative categorization tasks in which human subjects and a Rhesus monkey had to assign time intervals or distances to a ‘short’ or ‘long’ category according to varying prototypes. The performance of both species was analyzed using psychometric techniques that showed that they may have similar perceptual, memory and/or decision mechanisms, specially for the estimation of time intervals. We also did a correlation analysis with human subjects’ psychometric thresholds and the results imply that indeed, temporal and spatial information categorization share neural substrates. However, not all of the tested distances and intervals correlated with each other, suggesting the existence of sub-circuits that process restricted ranges of distances and intervals. A different analysis was done on the monkey data, in which the influence of the previous categorical prototypes was measured on the task currently being performed. Again, we found a significant interaction between previous and current interval and distance categorization. Overall, the present paper points towards common or at least partially overlapped neural circuits for temporal and spatial categorization in primates.

  12. The relevance of non-human primate and rodent malaria models for humans

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    Riley Eleanor

    2011-02-01

    Full Text Available Abstract At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material.

  13. Non-human primate model of Kaposi's sarcoma-associated herpesvirus infection.

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    Heesoon Chang

    2009-10-01

    Full Text Available Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 was first identified in Kaposi's sarcoma (KS lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. In response to this need for an animal model of KSHV infection, we have explored whether common marmosets can be experimentally infected with human KSHV. Here, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj, a New World primate. Marmosets infected with recombinant KSHV rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. KSHV DNA and latent nuclear antigen (LANA were readily detected in the peripheral blood mononuclear cells (PBMCs and various tissues of infected marmosets. Remarkably, one orally infected marmoset developed a KS-like skin lesion with the characteristic infiltration of leukocytes by spindle cells positive for KSHV DNA and proteins. These results demonstrate that human KSHV infects common marmosets, establishes an efficient persistent infection, and occasionally leads to a KS-like skin lesion. This is the first animal model to significantly elaborate the important aspects of KSHV infection in humans and will aid in the future design of vaccines against KSHV and anti-viral therapies targeting KSHV coinfected tumor cells.

  14. Energy expenditure in chow-fed female non-human primates of various weights

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    Kral John G

    2008-11-01

    Full Text Available Abstract Background Until now no technology has been available to study energy metabolism in monkeys. The objective of this study was to determine daily energy expenditures (EE and respiratory quotients (RQ in female monkeys of various body weights and ages. Methods 16 socially reared Bonnet Macaque female monkeys [5.5 ± 1.4 kg body weight, modified BMI (length measurement from head to base of the tail = 28.8 ± 6.7 kg/crown-rump length, m2 and 11.7 ± 4.6 years] were placed in the primate Enhanced Metabolic Testing Activity Chamber (Model 3000a, EMTAC Inc. Santa Barbara, CA for 22-hour measurements of EE (kcal/kg and RQ (VCO2/VO2. All were fed monkey chow (4.03 kcal/g ad-libitum under a 12/12 hour light/dark cycle. Metabolic data were corrected for differences in body weight. Results were divided into day (8-hours, dark (12 hours and morning (2-hours periods. Data analysis was conducted utilizing SPSS (Version 13. Results Modified BMI negatively correlated with 22-hour energy expenditure in all monkeys (r = -0.80, p 23 kcal/kg. There were reductions (p 30. The obese group had lower EE (p Conclusion The EMTAC proved to be a valuable tool for metabolic measurements in monkeys. The accuracy and sensitivity of the instrument allowed detection of subtle metabolic changes in relation to energy intake. Moreover, there is an association between a reduction of energy expenditure and a gain in body weight.

  15. Functional Imaging of the Non-Human Primate Placenta With Endogenous BOLD Contrast

    Science.gov (United States)

    Schabel, M.C.; Roberts, V.H.J.; Lo, J. O.; Platt, S.; Grant, K. A.

    2015-01-01

    Purpose To characterize spatial patterns of T2∗ in the rhesus macaque placenta, to correlate these patterns with placental perfusion determined using dynamic contrast enhanced (DCE)-MRI, and to evaluate the potential for using the blood oxygen level-dependent (BOLD) effect to quantify placental perfusion without the use of exogenous contrast reagent. Methods Magnetic resonance imaging was performed on three pregnant rhesus macaques at gestational day 110. Multi-echo spoiled gradient echo measurements were used to compute maps of T2∗. Spatial maxima in these maps were compared with foci of early enhancement determined by DCE-MRI. Results Local maxima in T2∗ maps are strongly correlated with spiral arteries identified by DCE-MRI, with mean spatial separations ranging from 2.34 to 6.11 mm in the three animals studied. Spatial patterns of R2∗(=1∕T2∗) within individual placental lobules can be quantitatively analyzed using a simple model to estimate fetal arterial oxyhemoglobin concentration [Hbo,f] and a parameter viPS/Φ, reflecting oxygen transport to the fetus. Estimated mean values of [Hbo,f] ranged from 4.25 mM to 4.46 mM, while viPS/Φ ranged from 2.80×105 cm−3 to 1.61×106 cm−3. Conclusions Maternal spiral arteries show strong spatial correlation with foci of extended T2∗ observed in the primate placenta. A simple model of oxygen transport accurately describes the spatial dependence of R2∗ within placental lobules and enables assessment of placental function and oxygenation without requiring administration of an exogenous contrast reagent. PMID:26599502

  16. 3D printing and modelling of customized implants and surgical guides for non-human primates.

    Science.gov (United States)

    Chen, Xing; Possel, Jessy K; Wacongne, Catherine; van Ham, Anne F; Klink, P Christiaan; Roelfsema, Pieter R

    2017-07-15

    Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium. Here, we present a low-cost method of creating customized 3D-printed cranial implants that are tailored to the anatomy of individual animals. We performed pre-surgical computed tomography (CT) and magnetic resonance (MR) scans to generate three-dimensional (3D) models of the skull and brain. We then used 3D modelling software to design implantable head posts, chambers, and a pedestal anchorage base, as well as craniotomy guides to aid us during surgery. Prototypes were made from plastic or resin, while implants were 3D-printed in titanium. The implants underwent post-processing and received a coating of osteocompatible material to promote bone integration. Their tailored fit greatly facilitated surgical implantation, and eliminated the gap between the implant and the bone. To date, our implants remain robust and well-integrated with the skull. Commercial-off-the-shelf solutions typically come with a uniform, flat base, preventing them from sitting flush against the curved surface of the skull. This leaves gaps for fluid and tissue ingress, increasing the risk of microbial infection and tissue inflammation, as well as implant loss. The use of 3D printing technology enabled us to quickly and affordably create unique, complex designs, avoiding the constraints levied by traditional production methods, thereby boosting experimental success and improving the wellbeing of the animals. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  17. Multisensory integration in non-human primates during a sensory-motor task

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    Florian eLanz

    2013-11-01

    Full Text Available Daily our central nervous system receives inputs via several sensory modalities, processes them and integrates information in order to produce a suitable behaviour. The amazing part is that such a multisensory integration brings all information into a unified percept. An approach to start investigating this property is to show that perception is better and faster when multimodal stimuli are used as compared to unimodal stimuli. This forms the first part of the present study conducted in a non-human primate’s model (n=2 engaged in a detection sensory-motor task where visual and auditory stimuli were displayed individually or simultaneously. The measured parameters were the reaction time (RT between stimulus and onset of arm movement, successes and errors percentages, as well as the evolution as a function of time of these parameters with training. As expected, RTs were shorter when the subjects were exposed to combined stimuli. The gains for both subjects were around 20 and 40 msec, as compared with the auditory and visual stimulus alone, respectively. Moreover the number of correct responses increased in response to bimodal stimuli. We interpreted such multisensory advantage through redundant signal effect which decreases perceptual ambiguity, increases speed of stimulus detection and improves performance accuracy.The second part of the study presents single unit recordings derived from the premotor cortex (PM of the same subjects during the sensory-motor task. Response patterns to sensory/multisensory stimulation are documented and specific type proportions are reported. Characterization of bimodal neurons indicates a mechanism of audio-visual integration possibly through a decrease of inhibition. Nevertheless the neural processing leading to faster motor response from PM as a polysensory association cortical area remains still unclear.

  18. Sleep deprivation impairs spatial retrieval but not spatial learning in the non-human primate grey mouse lemur.

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    Anisur Rahman

    Full Text Available A bulk of studies in rodents and humans suggest that sleep facilitates different phases of learning and memory process, while sleep deprivation (SD impairs these processes. Here we tested the hypothesis that SD could alter spatial learning and memory processing in a non-human primate, the grey mouse lemur (Microcebus murinus, which is an interesting model of aging and Alzheimer's disease (AD. Two sets of experiments were performed. In a first set of experiments, we investigated the effects of SD on spatial learning and memory retrieval after one day of training in a circular platform task. Eleven male mouse lemurs aged between 2 to 3 years were tested in three different conditions: without SD as a baseline reference, 8 h of SD before the training and 8 h of SD before the testing. The SD was confirmed by electroencephalographic recordings. Results showed no effect of SD on learning when SD was applied before the training. When the SD was applied before the testing, it induced an increase of the amount of errors and of the latency prior to reach the target. In a second set of experiments, we tested the effect of 8 h of SD on spatial memory retrieval after 3 days of training. Twenty male mouse lemurs aged between 2 to 3 years were tested in this set of experiments. In this condition, the SD did not affect memory retrieval. This is the first study that documents the disruptive effects of the SD on spatial memory retrieval in this primate which may serve as a new validated challenge to investigate the effects of new compounds along physiological and pathological aging.

  19. Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates

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    Unzu Carmen

    2012-06-01

    Full Text Available Abstract Background Adeno-associated vectors (rAAV have been used to attain long-term liver gene expression. In humans, the cellular immune response poses a serious obstacle for transgene persistence while neutralizing humoral immunity curtails re-administration. Porphobilinogen deaminase (PBGD haploinsufficiency (acute intermittent porphyria benefits from liver gene transfer in mouse models and clinical trials are about to begin. In this work, we sought to study in non-human primates the feasibility of repeated gene-transfer with intravenous administration of rAAV5 vectors under the effects of an intensive immunosuppressive regimen and to analyze its ability to circumvent T-cell immunity and thereby prolong transgene expression. Methods Three female Macaca fascicularis were intravenously injected with 1x1013 genome copies/kg of rAAV5 encoding the human PBGD. Mycophenolate mofetil (MMF, anti-thymocyte immunoglobulin, methylprednisolone, tacrolimus and rituximab were given in combination during 12 weeks to block T- and B-cell mediated adaptive immune responses in two macaques. Immunodeficient and immunocompetent mice were intravenously injected with 5x1012 genome copies/kg of rAAV5-encoding luciferase protein. Forty days later MMF, tacrolimus and rituximab were daily administrated to ascertain whether the immunosuppressants or their metabolites could interfere with transgene expression. Results Macaques given a rAAV5 vector encoding human PBGD developed cellular and humoral immunity against viral capsids but not towards the transgene. Anti-AAV humoral responses were attenuated during 12 weeks but intensely rebounded following cessation of the immunosuppressants. Accordingly, subsequent gene transfer with a rAAV5 vector encoding green fluorescent protein was impossible. One macaque showed enhanced PBGD expression 25 weeks after rAAV5-pbgd administration but overexpression had not been detected while the animal was under immunosuppression. As

  20. Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation.

    Science.gov (United States)

    Rose, Destanie R; Careaga, Milo; Van de Water, Judy; McAllister, Kim; Bauman, Melissa D; Ashwood, Paul

    2017-07-01

    Infection during pregnancy can lead to activation of the maternal immune system and has been associated with an increased risk of having an offspring later diagnosed with a neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD) or schizophrenia (SZ). Most maternal immune activation (MIA) studies to date have been in rodents and usually involve the use of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). However, since NDD are based on behavioral changes, a model of MIA in non-human primates could potentially provide data that helps illuminate complex behavioral and immune outputs in human NDD. In this study twenty-one pregnant rhesus macaques were either given three injections over 72 hours of poly I:C-LC, a double stranded RNA analog (viral mimic), or saline as a control. Injections were given near the end of the first trimester or near the end of the second trimester to determine if there were differences in immune output due to the timing of MIA.An additional three non-treated animals were used as controls. The offspring were followed until 4 years of age, with blood collected at the end of their first (year 1) and fourth (year 4) years to assess dynamic cellular immune function. Induced responses from peripheral immune cells were measured using multiplex assays.At one year of age, MIA exposed offspring displayed elevated production of innate inflammatory cytokines including: interleukin (IL)-1β, IL-6, IL-12p40, and tumor necrosis factor (TNF)α at baseline and following stimulation. At four years of age, the MIA exposed offspring continued to display elevated IL-1β, and there was also a pattern of an increased production of T-cell helper type (TH)-2 cytokines, IL-4 and IL-13. Throughout this time period, the offspring of MIA treated dams exhibited altered behavioral phenotypes including increased stereotyped behaviors. During the first two years, stereotyped behaviors were associated with innate cytokine production

  1. Detection of HEV-specific antibodies in four non-human primate species, including great apes, from different zoos in Germany.

    Science.gov (United States)

    Spahr, C; Knauf-Witzens, T; Dähnert, L; Enders, M; Müller, M; Johne, R; Ulrich, R G

    2018-01-01

    The hepatitis E virus (HEV) has been described in humans and various animal species in different regions of the world. However, the knowledge on natural HEV infection in non-human primates and the corresponding risk of zoonotic transmission is scarce. To determine whether primates in captivity are affected by HEV infection, we investigated 259 individual sera of clinically healthy non-human primates of 14 species from nine German zoos. Using a commercial double-antigen-sandwich ELISA and a commercial IgG ELISA, 10 animals (3·9%) reacted positive in at least one assay. Three ape species and one Old World monkey species were among the seropositive animals: bonobo (Pan paniscus), gorilla (Gorilla gorilla gorilla), lar gibbon (Hylobates lar) and drill (Mandrillus leucophaeus). Testing for anti-HEV-IgM antibodies by commercial ELISA and for viral RNA by reverse-transcription real-time polymerase chain reaction resulted in negative results for all animals indicating the absence of acute HEV infections. In the past, no clinical signs of hepatitis were recorded for the seropositive animals. The results suggest that non-human primates in zoos can get naturally and subclinically infected with HEV or related hepeviruses. Future studies should evaluate potential sources and transmission routes of these infections and their impact on human health.

  2. Isolation and maintenance of Balantidium coli (Malmsteim, 1857) cultured from fecal samples of pigs and non-human primates.

    Science.gov (United States)

    Barbosa, Alynne da Silva; Bastos, Otilio Machado Pereira; Uchôa, Claudia M Antunes; Pissinatti, Alcides; Ferreira Filho, Paulo Ricardo; Dib, Lais Verdan; Azevedo, Eduarda Peixoto; de Siqueira, Mayara Perlingeiro; Cardozo, Matheus Lessa; Amendoeira, Maria Regina Reis

    2015-06-15

    Balantidium coli is a protozoa that can determine dysentery in humans, pigs and non-human primates having zoonotic potential. The lack of standardization in isolation and maintenance hinders the development of research on its biology and epidemiology. This study is aimed to standardize the isolation and maintenance of this parasite from animal feces, in culture medium, Pavlova modified. From 2012 to 2014, 1905 fecal samples were collected from captive animals of Rio de Janeiro. Were selected for isolation samples with a minimum of 10 trophozoites and/or 30 cysts of B. coli, totaling 88 pigs, 26 Cynomolgus and 90 rhesus macaques. In the presence of cysts, the sample was homogenized in saline solution, 500 μL was removed and inoculated into culture medium. The material that contained trophozoites the inoculum was made from 240 μL of fecal solution. All inoculate tubes with the subcultures were kept at 36°C, and sterile rice starch was always added to the medium. The parasites isolate from pigs, 34%, and from Cynomolgus 38.4% were maintained in vitro for a period of more than 24 months. These procedures proved to be adequate for isolation and maintenance of B. coli from different animals, they were found to be inexpensive and easy to perform. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Non-ABO blood group systems phenotyping in non-human primates for blood banking laboratory and xenotransplantation.

    Science.gov (United States)

    Ramis, G; Martínez-Alarcon, L; Quereda, J J; Mrowiec, A; Funes, C; Ríos, A; Ramírez, P; Muñoz, A; Majado, M J

    2013-04-01

    Some biomedical research procedures, such as organ xenotransplantation, usually require intensive hemotherapy. Knowledge of the whole phenotype of blood donor and graft could be useful in the field of xenotransplantation. Human and simian-type categories of blood groups have been established and they can be tested by standard methods used for human blood grouping. The aim of this work was to study the incidence of non-ABO blood group systems in different species of non-human primates, which are employed in biomedical research. The phenotype of Rh, Lewis, Kidd, Kell, MNSs, Lutheran, P and Duffy antigens was investigated in olive baboon (n = 48), chacma baboon (n = 9), Guinea baboon (n = 14), Rhesus macaque (n = 38) and squirrel monkey (n = 30) by using commercial microtyping cards. Kell, Lutheran, Kidd and Duffy antigens have been detected in all species, Rh in squirrel monkey, MNSs in rhesus macaque and squirrel monkey, and Lewis in baboon and rhesus macaque. There were differences in frequency and haemagglutination scores between species regardless of their gender and age. The main differences were found in squirrel monkey when compared with baboons and macaques. This typing system provides a tool to assess the presence of antigens in animals used for experimental procedures, such as xenotransplantation and xenotransfusion.

  4. Apo-AII is an elevated biomarker of chronic non-human primate ethanol self-administration.

    Science.gov (United States)

    Freeman, Willard M; Gooch, Randy S; Lull, Melinda E; Worst, Travis J; Walker, Stephen J; Xu, Arron S L; Green, Heather; Pierre, Peter J; Grant, Kathleen A; Vrana, Kent E

    2006-01-01

    Serum protein profiles were examined in naïve, ethanol self-administering and ethanol abstinent cynomolgus monkeys (Macaca fasicularis) to search for differences in protein expression which could possibly serve as biomarkers of heavy ethanol consumption. Surface-enhanced laser desorption ionization time-of-flight (SELDI-ToF) mass spectrometry was used for proteomic profiling of serum. Two proteins were identified by SELDI-ToF to be increased in ethanol self-administering compared with abstinent animals. These proteins were identified to be apolipoprotein AI (Apo-AI) and apolipoprotein AII (Apo-AII) by peptide mass fingerprinting and comparison with spectra of purified human Apo-AI and AII proteins. Immunoblot analysis of Apo-AI and Apo-AII was performed on a separate group of animals (within-animal ethanol-naïve and self-administering) and confirmed a statistically significant increase in Apo-AII, while Apo-AI was unchanged. An open proteomic screen of serum and confirmation in a separate set of animals found Apo-AII to be increased in the serum of ethanol self-administering monkeys. These results are consistent with previous clinical studies of human ethanol consumption and serum apolipoprotein expression. Moreover, these results validate the use of non-human primates as a model organism for proteomic analysis of ethanol self-administration biomarkers.

  5. Safety and Efficacy of the Complement Inhibitor AMY-101 in a Natural Model of Periodontitis in Non-human Primates

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    Tetsuhiro Kajikawa

    2017-09-01

    Full Text Available Periodontitis is a chronic inflammatory disease associated with overactivation of the complement system. Recent preclinical studies suggest that host-modulation therapies may contribute to effective treatment of human periodontitis, which may lead to loss of teeth and function if untreated. We previously showed that locally administered AMY-101 (Cp40, a peptidic inhibitor of the central complement component C3, can inhibit naturally occurring periodontitis in non-human primates (NHPs when given once a week. This study was undertaken to determine the local safety of increasing doses of the drug as well as its efficacy when given at a reduced frequency or after systemic administration. Our findings have determined a local dose of AMY-101 (0.1 mg/site that is free of local irritation and effective when given once every 3 weeks. Moreover, a daily subcutaneous dose of AMY-101 (4 mg/kg bodyweight was protective against NHP periodontitis, suggesting that patients treated for systemic disorders (e.g., paroxysmal nocturnal hemoglobinuria can additionally benefit in terms of improved periodontal condition. In summary, AMY-101 appears to be a promising candidate drug for the adjunctive treatment of human periodontitis, a notion that merits investigation in human clinical trials.

  6. Biological Differences in rAAV Transduction of Airway Epithelia in Humans and in Old World Non-human Primates.

    Science.gov (United States)

    Liu, Xiaoming; Luo, Meihui; Trygg, Cyndi; Yan, Ziying; Lei-Butters, Diana C M; Smith, Carolina I; Fischer, Anne C; Munson, Keith; Guggino, William B; Bunnell, Bruce A; Engelhardt, John F

    2007-12-01

    Non-human primates (NHPs) are considered to be among the most relevant animal models for pre-clinical testing of human therapies, on the basis of their close evolutionary relatedness to humans in terms of organ cell biology and physiology. In this study, we sought to investigate whether NHP models accurately reflect the effectiveness of recombinant adeno-associated virus (rAAV)-mediated gene delivery to the airway in humans. In order to do this, we utilized an identical model system of differentiated airway epithelia from Indian Rhesus monkeys and from humans, cultured at an air-liquid interface (ALI). In addition to assessing the biology of rAAV-mediated transduction for three serotypes, we characterized the bioelectric properties as a reference for biological similarities and differences between the cell cultures from the two species. Our results demonstrate that airway epithelia from NHPs and humans have very similar Na(+) and Cl(-) transport properties. In contrast, rAAV transduction of airway epithelia of NHPs demonstrated significant differences to those in humans with regard to the efficiency of apical and/or basal transduction with three rAAV serotypes (AAV1, AAV2, AAV5). These findings suggest that the IndianRhesusmonkey may not be the best model for preclinical testing of rAAV-mediated gene therapy to the airway in humans.

  7. Multilocus genotyping of Giardia duodenalis in captive non-human primates in Sichuan and Guizhou provinces, Southwestern China.

    Directory of Open Access Journals (Sweden)

    Zhijun Zhong

    Full Text Available Giardia duodenalis is a common human and animal pathogen. It has been increasingly reported in wild and captive non-human primates (NHPs in recent years. However, multilocus genotyping information for G. duodenalis infecting NHPs in southwestern China is limited. In the present study, the prevalence and multilocus genotypes (MLGs of G. duodenalis in captive NHPs in southwestern China were determined. We examined 207 fecal samples from NHPs in Sichuan and Guizhou provinces, and 16 specimens were positive for G. duodenalis. The overall infection rate was 7.7%, and only assemblage B was identified. G. duodenalis was detect positive in northern white-cheeked gibbon (14/36, 38.9%, crab-eating macaque (1/60, 1.7% and rhesus macaques (1/101, 0.9%. Multilocus sequence typing based on beta-giardin (bg, triose phosphate isomerase (tpi and glutamate dehydrogenase (gdh revealed nine different assemblage B MLGs (five known genotypes and four novel genotypes. Based on a phylogenetic analysis, one potentially zoonotic genotype of MLG SW7 was identified in a northern white-cheeked gibbon. A high degree of genetic diversity within assemblage B was observed in captive northern white-cheeked gibbons in Southwestern China, including a potentially zoonotic genotype, MLG SW7. To the best of our knowledge, this is the first report using a MLGs approach to identify G. duodenalis in captive NHPs in Southwestern China.

  8. Blood-Brain Barrier Opening in Behaving Non-Human Primates via Focused Ultrasound with Systemically Administered Microbubbles

    Science.gov (United States)

    Downs, Matthew E.; Buch, Amanda; Karakatsani, Maria Eleni; Konofagou, Elisa E.; Ferrera, Vincent P.

    2015-10-01

    Over the past fifteen years, focused ultrasound coupled with intravenously administered microbubbles (FUS) has been proven an effective, non-invasive technique to open the blood-brain barrier (BBB) in vivo. Here we show that FUS can safely and effectively open the BBB at the basal ganglia and thalamus in alert non-human primates (NHP) while they perform a behavioral task. The BBB was successfully opened in 89% of cases at the targeted brain regions of alert NHP with an average volume of opening 28% larger than prior anesthetized FUS procedures. Safety (lack of edema or microhemorrhage) of FUS was also improved during alert compared to anesthetized procedures. No physiological effects (change in heart rate, motor evoked potentials) were observed during any of the procedures. Furthermore, the application of FUS did not disrupt reaching behavior, but in fact improved performance by decreasing reaction times by 23 ms, and significantly decreasing touch error by 0.76 mm on average.

  9. Future of liver transplantation: non-human primates for patient-specific organs from induced pluripotent stem cells.

    Science.gov (United States)

    Sanal, Madhusudana Girija

    2011-08-28

    Strategies to fill the huge gap in supply versus demand of human organs include bioartificial organs, growing humanized organs in animals, cell therapy, and implantable bioengineered constructs. Reproducing the complex relations between different cell types, generation of adequate vasculature, and immunological complications are road blocks in generation of bioengineered organs, while immunological complications limit the use of humanized organs produced in animals. Recent developments in induced pluripotent stem cell (iPSC) biology offer a possibility of generating human, patient-specific organs in non-human primates (NHP) using patient-derived iPSC and NHP-derived iPSC lacking the critical developmental genes for the organ of interest complementing a NHP tetraploid embryo. The organ derived in this way will have the same human leukocyte antigen (HLA) profile as the patient. This approach can be curative in genetic disorders as this offers the possibility of gene manipulation and correction of the patient's genome at the iPSC stage before tetraploid complementation. The process of generation of patient-specific organs such as the liver in this way has the great advantage of making use of the natural signaling cascades in the natural milieu probably resulting in organs of great quality for transplantation. However, the inexorable scientific developments in this direction involve several social issues and hence we need to educate and prepare society in advance to accept the revolutionary consequences, good, bad and ugly.

  10. Consequences of early adverse rearing experience(EARE) on development: insights from non-human primate studies.

    Science.gov (United States)

    Zhang, Bo

    2017-01-18

    Early rearing experiences are important in one's whole life, whereas early adverse rearing experience(EARE) is usually related to various physical and mental disorders in later life. Although there were many studies on human and animals, regarding the effect of EARE on brain development, neuroendocrine systems, as well as the consequential mental disorders and behavioral abnormalities, the underlying mechanisms remain unclear. Due to the close genetic relationship and similarity in social organizations with humans, non-human primate(NHP) studies were performed for over 60 years. Various EARE models were developed to disrupt the early normal interactions between infants and mothers or peers. Those studies provided important insights of EARE induced effects on the physiological and behavioral systems of NHPs across life span, such as social behaviors(including disturbance behavior, social deficiency, sexual behavior, etc), learning and memory ability, brain structural and functional developments(including influences on neurons and glia cells, neuroendocrine systems, e.g., hypothalamic-pituitary-adrenal(HPA) axis, etc). In this review, the effects of EARE and the underlying epigenetic mechanisms were comprehensively summarized and the possibility of rehabilitation was discussed.

  11. Placental growth factor reduces blood pressure in a uteroplacental ischemia model of preeclampsia in non-human primates

    Science.gov (United States)

    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

    2016-01-01

    An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia due to endothelial dysfunction. Circulating sFLT-1 (soluble fms-like tyrosine kinase 1) increases and PlGF (placental growth factor) reduces prior to 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 non-human primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of an 182 day pregnancy). Two weeks after uteroplacental ischemia (UPI), rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100μg/kg/day) for 5 days. Blood pressure (BP) was monitored by intra-arterial radiotelemetry, sFLT-1 and PlGF by ELISA. UPI resulted in experimental preeclampsia evidenced by increased BP, proteinuria and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after UPI. rhPlGF reduced SBP in the treated group (-5.2mmHg+0.8mmHg;from 132.6+6.6mmHg to 124.1+7.6mmHg) compared to an increase in SBP in controls (6.5mmHg+3mmHg; from 131.3+1.5mmHg to 138.6+1.5mmHg). Proteinuria reduced in the treated group (-72.7±55.7mg/mmol) but increased in the control group. Circulating sFLT-1 was not affected by the administration of PlGF, however a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference in 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

  12. New STLV-3 strains and a divergent SIVmus strain identified in non-human primate bushmeat in Gabon

    Directory of Open Access Journals (Sweden)

    Liégeois Florian

    2012-03-01

    Full Text Available Abstract Background Human retroviral infections such as Human Immunodeficiency Virus (HIV or Human T-cell Lymphotropic Virus (HTLV are the result of simian zoonotic transmissions through handling and butchering of Non-Human Primates (NHP or by close contact with pet animals. Recent studies on retroviral infections in NHP bushmeat allowed for the identification of numerous Simian Immunodeficiency Viruses (SIV and Simian T-cell Lymphotropic Viruses (STLV to which humans are exposed. Nevertheless, today, data on simian retroviruses at the primate/hunter interface remain scarce. We conducted a pilot study on 63 blood and/or tissues samples derived from NHP bushmeat seized by the competent authorities in different locations across the country. Results SIV and STLV were detected by antibodies to HIV and HTLV antigens, and PCRs were performed on samples with an HIV or/and HTLV-like or indeterminate profile. Fourteen percent of the samples cross-reacted with HIV antigens and 44% with HTLV antigens. We reported STLV-1 infections in five of the seven species tested. STLV-3 infections, including a new STLV-3 subtype, STLV-1 and -3 co-infections, and triple SIV, STLV-1, STLV-3 infections were observed in red-capped mangabeys (C.torquatus. We confirmed SIV infections by PCR and sequence analyses in mandrills, red-capped mangabeys and showed that mustached monkeys in Gabon are infected with a new SIV strain basal to the SIVgsn/mus/mon lineage that did not fall into the previously described SIVmus lineages reported from the corresponding species in Cameroon. The same monkey (subspecies can thus be carrier of, at least, three distinct SIVs. Overall, the minimal prevalence observed for both STLV and SIV natural infections were 26.9% and 11.1% respectively. Conclusions Overall, these data, obtained from a restricted sampling, highlight the need for further studies on simian retroviruses in sub-Saharan Africa to better understand their evolutionary history and to

  13. A consensus envelope protein domain III can induce neutralizing antibody responses against serotype 2 of dengue virus in non-human primates.

    Science.gov (United States)

    Chen, Hsin-Wei; Liu, Shih-Jen; Li, Yi-Shiuan; Liu, Hsueh-Hung; Tsai, Jy-Ping; Chiang, Chen-Yi; Chen, Mei-Yu; Hwang, Chyi-Sing; Huang, Chin-Cheng; Hu, Hui-Mei; Chung, Han-Hsuan; Wu, Sze-Hsien; Chong, Pele; Leng, Chih-Hsiang; Pan, Chien-Hsiung

    2013-07-01

    We have previously demonstrated that vaccination with a subunit dengue vaccine containing a consensus envelope domain III with aluminum phosphate elicits neutralizing antibodies against all four serotypes of dengue virus in mice. In this study, we evaluated the immunogenicity of the subunit dengue vaccine in non-human primates. After vaccination, monkeys that received the subunit vaccine with aluminum phosphate developed a significantly strong and long-lasting antibody response. A specific T cell response with cytokine production was also induced, and this correlated with the antibody response. Additionally, neutralizing antibodies against serotype 2 were detected in two of three monkeys. The increase in serotype-2-specific antibody titers and avidity observed in these two monkeys suggested that a serotype-2-biased antibody response occurs. These data provide evidence that a protective neutralizing antibody response was successfully elicited in non-human primates by the dengue subunit vaccine with aluminum phosphate adjuvant.

  14. Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a mouse and a non-human primate tuberculosis model

    DEFF Research Database (Denmark)

    Billeskov, Rolf; Christensen, Jan Pravsgaard; Aagaard, Claus

    2013-01-01

    a significant positive correlation with protection at week 6 post infection, whereas the opposite was observed for post infection CD4 T cells producing only IFN-γ. Moreover, as a BCG booster vaccine in a clinically relevant non-human primate TB model, the H28/H28 vaccine strategy induced a slightly more......-γ single producing CD4 T cell subsets correlated with protection in the mouse TB model. Moreover, our data demonstrated that the H28 vaccine antigen was able to induce strong protection in both a mouse and a non-human primate TB model......., in mice vaccinated with adjuvanted recombinant H28 alone (H28/H28) we observed the highest production of IL-2 per single cell and the highest frequency of antigen specific TNF-α/IL-2 expressing CD4 T cells pre and post infection. Interestingly, TNF-α/IL-2 expressing central memory-like CD4 T cells showed...

  15. A Prophylactic Multivalent Vaccine Against Different Filovirus Species is Immunogenic and Provides Protection from Lethal Infections of Ebolavirus and Marburgvirus Species in Non-Human Primates

    Science.gov (United States)

    2016-12-22

    1985;54(1): 30-37. Coltart CE, Johnson AM, Whitty CJ. Role of healthcare workers in early epidemic spread of Ebola: policy implications of...Lethal Infections of Ebolavirus and Marburgvirus Species in Non-human Primates Short title 70 characters Immunogenicity and Protection of a...filovirus species has been prompted by sporadic but large outbreaks of Ebolavirus and Marburgvirus infections . A good prophylactic vaccine should be able

  16. Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates

    DEFF Research Database (Denmark)

    Straarup, Ellen Marie; Fisker, Niels; Hedtjärn, Maj

    2010-01-01

    -high-density lipoprotein (non-HDL) cholesterol without increasing serum liver toxicity markers. The data presented here show that oligonucleotide length as a parameter needs to be considered in the design of antisense oligonucleotide and that potent short oligonucleotides with sufficient target affinity can be generated...... using the LNA chemistry. Conclusively, we present a 13-mer LNA oligonucleotide with therapeutic potential that produce beneficial cholesterol lowering effect in non-human primates....

  17. The physiological effect of human grooming on the heart rate and the heart rate variability of laboratory non-human primates: a pilot study in male rhesus monkeys

    OpenAIRE

    Laura Clara Grandi; Hiroaki eIshida

    2015-01-01

    Grooming is a widespread, essential and complex behavior with social and affiliative valence in the non-human primate world. Its impact at the autonomous nervous system level has been studied during allogrooming among monkeys living in a semi-naturalistic environment. For the first time, we investigated the effect of human grooming to monkey in a typical experimental situation inside laboratory. We analyzed the autonomic response of male monkeys groomed by a familiar human (experimenter), in ...

  18. A Recommended Laparoscopic Procedure for Implantation of Microcapsules in the Peritoneal Cavity of Non-human Primates

    Science.gov (United States)

    Qi, Meirigeng; Lacik, Igor; Kolláriková, Gabriela; Strand, Berit L; Formo, Kjetil; Wang, Yong; Marchese, Enza; Mendoza-Elias, Joshua E.; Kinzer, Katie P.; Gatti, Francesca; Paushter, Daniel; Patel, Sonny; Oberholzer, Jose

    2013-01-01

    Background The anatomical spatial distribution of microencapsulated islets transplanted into the peritoneal cavity of large animals remains a relatively unexplored area of study. In this study, we developed a new implantation approach using laparoscopy in order to avoid microcapsule amalgamation. This approach constitutes a clinically relevant method, which can be used to evaluate the distribution and in vivo biocompatibility of various types of transplanted microcapsules in the future. Materials and Methods Two healthy baboons were implanted intraperitoneally with microencapsulated islets through mini-laparotomy and observed at 76 days after implantation. Nine baboons underwent laparoscopic implantation of approximately 80,000 empty microcapsules. Microcapsule distribution was observed by laparoscopic camera during and after implantation at 1, 2, and 4 weeks. At each time point, microcapsules were retrieved and evaluated with brightfield microscopy and histological analysis. Results Mini-laparotomic implantation resulted in microcapusle aggregation in both baboons. In contrast, laparoscopic implantation resulted in even distribution of microcapsules throughout the peritoneum without sedimentation to the Douglas space in all animals. In 8 out of 9 animals, retrieved microcapsules were evenly distributed in the peritoneal cavity and presented with no pericapsular overgrowth and easily washed out during laparoscopic procedure. The one exception was attributed to microcapsule contamination with blood from the abdominal wall following trocar insertion. Conclusions Laparoscopic implantation of microcapsules in non-human primates can be successfully performed and prevents microcapsule aggregation. Given the current widespread clinical application of laparoscopy, we propose that this presented laparoscopy technique could be applied in future clinical trials of microencapsulated islet transplantation. PMID:21435661

  19. Induction of humoural and cellular immunity by immunisation with HCV particle vaccine in a non-human primate model.

    Science.gov (United States)

    Yokokawa, Hiroshi; Higashino, Atsunori; Suzuki, Saori; Moriyama, Masaki; Nakamura, Noriko; Suzuki, Tomohiko; Suzuki, Ryosuke; Ishii, Koji; Kobiyama, Kouji; Ishii, Ken J; Wakita, Takaji; Akari, Hirofumi; Kato, Takanobu

    2018-02-01

    Although HCV is a major cause of chronic liver disease worldwide, there is currently no prophylactic vaccine for this virus. Thus, the development of an HCV vaccine that can induce both humoural and cellular immunity is urgently needed. To create an effective HCV vaccine, we evaluated neutralising antibody induction and cellular immune responses following the immunisation of a non-human primate model with cell culture-generated HCV (HCVcc). To accomplish this, 10 common marmosets were immunised with purified, inactivated HCVcc in combination with two different adjuvants: the classically used aluminum hydroxide (Alum) and the recently established adjuvant: CpG oligodeoxynucleotide (ODN) wrapped by schizophyllan (K3-SPG). The coadministration of HCVcc with K3-SPG efficiently induced immune responses against HCV, as demonstrated by the production of antibodies with specific neutralising activity against chimaeric HCVcc with structural proteins from multiple HCV genotypes (1a, 1b, 2a and 3a). The induction of cellular immunity was also demonstrated by the production of interferon-γ mRNA in spleen cells following stimulation with the HCV core protein. These changes were not observed following immunisation with HCVcc/Alum preparation. No vaccination-related abnormalities were detected in any of the immunised animals. The current preclinical study demonstrated that a vaccine included both HCVcc and K3-SPG induced humoural and cellular immunity in marmosets. Vaccination with this combination resulted in the production of antibodies exhibiting cross-neutralising activity against multiple HCV genotypes. Based on these findings, the vaccine created in this study represents a promising, potent and safe prophylactic option against HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells.

    Directory of Open Access Journals (Sweden)

    Shanaz A Ghandhi

    Full Text Available We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60-100 days, corresponding to computed tomography (CT and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.

  1. An inter-laboratory retrospective analysis of immunotoxicological endpoints in non-human primates: T-cell-dependent antibody responses.

    Science.gov (United States)

    Lebrec, Hervé; Cowan, Laine; Lagrou, Michelle; Krejsa, Cecile; Neradilek, Moni B; Polissar, Nayak L; Black, Lauren; Bussiere, Jeanine

    2011-01-01

    The Immunotoxicology Technical Committee of HESI sponsored a retrospective analysis of T-cell-dependent antibody responses in non-human primates (NHP). Antibody responses to keyhole limpet hemocyanin (KLH), tetanus toxoid (TT), and/or sheep red blood cells (SRBC) in 178 NHP (from 8 sponsors, 13 testing sites, 30 studies) were statistically analyzed. Rates of positive or negative anti-KLH, -TT, and -SRBC primary and secondary IgM and IgG responses were compared. The influence of gender, country of origin, and previous immunization with a different antigen on response rate and kinetics of anti-KLH and anti-TT responses were analyzed. In addition, the magnitude of the antibody responses and the impact of the above-mentioned factors were analyzed. In addition, based upon the inter-individual variability of the peak response values, power calculations were conducted. The analysis demonstrated that the rates of positive responses were similar between the two genders, were high for KLH, SRBC, and TT challenges by 21 days following immunization (87, 100, and 84%, respectively, for IgGs) and did not include statistically significant differences based on NHP country of origin. Mean peak secondary responses were greater than peak primary responses; the magnitude of the response to KLH was increased by incomplete Freund's adjuvant (IFA). Gender had little effect on the magnitude and variability of these responses. KLH and TT were associated with similar inter-animal variability, whereas in some situations KLH responses were less variable than responses to SRBC. The data suggested that inter-animal variability with KLH was similar with or without IFA. Power analysis illustrated that animal group sizes of typical standard toxicology studies (generally ≤ 4/sex) are likely to detect only fairly large treatment effects. However, combining males and females, when appropriate, will improve the power: an N of 8 to 12 could detect ≤ 3.1-fold differences in anti-KLH IgG responses.

  2. Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator

    Science.gov (United States)

    Connolly, Allison T.; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B.; Vitek, Jerrold L.; Johnson, Matthew D.

    2015-12-01

    Objective. Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach. Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results. LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10-30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30-60 s, but there was no correlation with beta band power. Significance. This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology.

  3. Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator.

    Science.gov (United States)

    Connolly, Allison T; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B; Vitek, Jerrold L; Johnson, Matthew D

    2015-12-01

    Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10-30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects' limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30-60 s, but there was no correlation with beta band power. This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject's symptomatology.

  4. Differential neurophysiological effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS) in non-human primates.

    Science.gov (United States)

    Cycowicz, Yael M; Luber, Bruce; Spellman, Timothy; Lisanby, Sarah H

    2008-07-01

    Magnetic seizure therapy (MST) is under development as a means of reducing the side effects of electroconvulsive therapy (ECT) through enhanced control over patterns of seizure induction and spread. We previously reported that chronic treatment with MST resulted in less impairment in cognitive function than electroconvulsive shock (ECS) in a non-human primate model of convulsive therapy. Here we present quantitative analyses of ictal expression and post-ictal suppression following ECS, MST, and anesthesia-alone sham in the same model to test whether differential neurophysiological characteristics of the seizures could be identified. Rhesus monkeys received 4 weeks of daily treatment with ECS, MST, and anesthesia-alone sham in a counterbalanced order separated by a recovery period. Both ECS and MST were given bilaterally at 2.5 x seizure threshold. Neurophysiological characteristics were derived from two scalp EEG electrode recording sites during and immediately following the ictal period, and were compared to sham treatment. EEG power within four frequencies (delta, theta, alpha and beta) was calculated. Our results support earlier findings from intracerebral electrode recordings demonstrating that MST- and ECS- induced seizures elicit differential patterns of EEG activation. Specifically, we found that ECS shows significantly more marked ictal expression, and more intense post-ictal suppression than MST in the theta, alpha, and beta frequency bands (Ps MST were indistinguishable in the delta frequency band during both ictal and post-ictal periods. These results demonstrate that magnetic seizure induction can result in seizures that differ in some neurophysiological respects compared with ECS, but that these modalities share some aspects of seizure expression. The clinical significance of these similarities and differences awaits clinical correlation.

  5. Non-human primate skull effects on the cavitation detection threshold of FUS-induced blood-brain barrier opening

    Science.gov (United States)

    Wu, Shih-Ying; Tung, Yao-Sheng; Marquet, Fabrice; Chen, Cherry C.; Konofagou, Elisa E.

    2012-11-01

    Microbubble (MB)-assisted focused ultrasound is a promising technique for delivering drugs to the brain by noninvasively and transiently opening the blood-brain barrier (BBB), and monitoring BBB opening using passive cavitation detection (PCD) is critical in detecting its occurrence, extent as well as assessing its mechanism. One of the main obstacles in achieving those objectives in large animals is the transcranial attenuation. To study the effects, the cavitation response through the in-vitro non-human primate (NHP) skull was investigated. In-house manufactured lipid-shelled MB (medium diameter: 4-5 um) were injected into a 4-mm channel of a phantom below a degassed monkey skull. A hydrophone confocally aligned with the FUS transducer served as PCD during sonication (frequency: 0.50 MHz, peak rarefactional pressures: 0.05-0.60 MPa, pulse length: 100 cycles, PRF: 10 Hz, duration: 2 s) for four cases: water without skull, water with skull, MB without skull and MB with skull. A 5.1-MHz linear-array transducer was also used to monitor the MB disruption. The frequency spectra, spectrograms, stable cavitation dose (SCD) and inertial cavitation dose (ICD) were quantified. Results showed that the onset of stable cavitation and inertial cavitation in the experiments occurred at 50 kPa, and was detectable throught the NHP skull since the both the detection thresholds for stable cavitation and inertial cavitation remained unchanged compared to the non-skull case, and the SCD and ICD acquired transcranially may not adequately represent the true extent of stable and inertial cavitation due to the skull attenuation.

  6. Demonstration of a setup for chronic optogenetic stimulation and recording across cortical areas in non-human primates

    Science.gov (United States)

    Yazdan-Shahmorad, Azadeh; Diaz-Botia, Camilo; Hanson, Tim; Ledochowitsch, Peter; Maharabiz, Michel M.; Sabes, Philip N.

    2015-03-01

    Although several studies have shown the feasibility of using optogenetics in non-human primates (NHP), reliable largescale chronic interfaces have not yet been reported for such studies in NHP. Here we introduce a chronic setup that permits repeated, daily optogenetic stimulation and large-scale recording from the same sites in NHP cortex. The setup combines optogenetics with a transparent artificial dura (AD) and high-density micro-electrocorticography (μECoG). To obtain expression across large areas of cortex, we infused AAV5-CamKIIa-C1V1-EYFP viral vector using an infusion technique based on convection-enhanced delivery (CED) in primary somatosensory (S1) and motor (M1) cortices. By epifluorescent imaging through AD we were able to confirm high levels of expression covering about 110 mm2 of S1 and M1. We then incorporated a 192-channel μECoG array spanning 192 mm2 into the AD for simultaneous electrophysiological recording during optical stimulation. The array consists of patterned Pt-Au-Pt metal traces embedded in ~10 μm Parylene-C insulator. The parylene is sufficiently transparent to allow minimally attenuated optical access for optogenetic stimulation. The array was chronically implanted over the opsin-expressing areas in M1 and S1 for over two weeks. Optical stimulation was delivered via a fiber optic placed on the surface of the AD. With this setup, we recorded reliable evoked activity following light stimulation at several locations. Similar responses were recorded across tens of days, however a decline in the light-evoked signal amplitude was observed during this period due to the growth of dural tissue over the array. These results show the feasibility of a chronic interface for combined largescale optogenetic stimulation and cortical recordings across days.

  7. Engineering an endothelialized vascular graft: a rational approach to study design in a non-human primate model.

    Directory of Open Access Journals (Sweden)

    Deirdre E J Anderson

    Full Text Available After many years of research, small diameter, synthetic vascular grafts still lack the necessary biologic integration to perform ideally in clinical settings. Endothelialization of vascular grafts has the potential to improve synthetic graft function, and endothelial outgrowth cells (EOCs are a promising autologous cell source. Yet no work has established the link between endothelial cell functions and outcomes of implanted endothelialized grafts. This work utilized steady flow, oscillatory flow, and tumor necrosis factor stimulation to alter EOC phenotype and enable the formulation of a model to predict endothelialized graft performance. To accomplish this, EOC in vitro expression of coagulation and inflammatory markers was quantified. In parallel, in non-human primate (baboon models, the platelet and fibrinogen accumulation on endothelialized grafts were quantified in an ex vivo shunt, or the tissue ingrowth on implanted grafts were characterized after 1mth. Oscillatory flow stimulation of EOCs increased in vitro coagulation markers and ex vivo platelet accumulation. Steady flow preconditioning did not affect platelet accumulation or intimal hyperplasia relative to static samples. To determine whether in vitro markers predict implant performance, a linear regression model of the in vitro data was fit to platelet accumulation data-correlating the markers with the thromboprotective performance of the EOCs. The model was tested against implant intimal hyperplasia data and found to correlate strongly with the parallel in vitro analyses. This research defines the effects of flow preconditioning on EOC regulation of coagulation in clinical vascular grafts through parallel in vitro, ex vivo, and in vivo analyses, and contributes to the translatability of in vitro tests to in vivo clinical graft performance.

  8. Prevalence of gastrointestinal parasites in captive non-human primates of twenty-four zoological gardens in China.

    Science.gov (United States)

    Li, Mei; Zhao, Bo; Li, Bo; Wang, Qiang; Niu, Lili; Deng, Jiabo; Gu, Xiaobin; Peng, Xuerong; Wang, Tao; Yang, Guangyou

    2015-06-01

    Captive primates are susceptible to gastrointestinal (GIT) parasitic infections, which are often zoonotic and can contribute to morbidity and mortality. Fecal samples were examined by the means of direct smear, fecal flotation, fecal sedimentation, and fecal cultures. Of 26.51% (317/1196) of the captive primates were diagnosed gastrointestinal parasitic infections. Trichuris spp. were the most predominant in the primates, while Entamoeba spp. were the most prevalent in Old World monkeys (P primates and the safety of animal keepers and visitors. © 2015 The Authors. Journal of Medical Primatology Published by John Wiley & Sons Ltd.

  9. Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson's Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque

    National Research Council Canada - National Science Library

    James B Koprich; Tom H Johnston; Gabriela Reyes; Vanessa Omana; Jonathan M Brotchie

    2016-01-01

      Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration...

  10. Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates.

    Science.gov (United States)

    Kotterman, M A; Yin, L; Strazzeri, J M; Flannery, J G; Merigan, W H; Schaffer, D V

    2015-02-01

    Gene delivery vectors based on adeno-associated viruses (AAV) have exhibited promise in both preclinical disease models and human clinical trials for numerous disease targets, including the retinal degenerative disorders Leber's congenital amaurosis and choroideremia. One general challenge for AAV is that preexisting immunity, as well as subsequent development of immunity following vector administration, can severely inhibit systemic AAV vector gene delivery. However, the role of neutralizing antibodies (NABs) in AAV transduction of tissues considered to be immune privileged, such as the eye, is unclear in large animals. Intravitreal AAV administration allows for broad retinal delivery, but is more susceptible to interactions with the immune system than subretinal administration. To assess the effects of systemic anti-AAV antibody levels on intravitreal gene delivery, we quantified the anti-AAV antibodies present in sera from non-human primates before and after intravitreal injections with various AAV capsids. Analysis showed that intravitreal administration resulted in an increase in anti-AAV antibodies regardless of the capsid serotype, transgene or dosage of virus injected. For monkeys injected with wild-type AAV2 and/or an AAV2 mutant, the variable that most significantly affected the production of anti-AAV2 antibodies was the amount of virus delivered. In addition, post-injection antibody titers were highest against the serotype administered, but the antibodies were also cross-reactive against other AAV serotypes. Furthermore, NAB levels in serum correlated with those in vitreal fluid, demonstrating both that this route of administration exposes AAV capsid epitopes to the adaptive immune system and that serum measurements are predictive of vitreous fluid NAB titers. Moreover, the presence of preexisting NAB titers in the serum of monkeys correlated strongly (R=0.76) with weak, decaying or no transgene expression following intravitreal administration of AAV

  11. Plasma and cerebrospinal fluid pharmacokinetics of select chemotherapeutic agents following intranasal delivery in a non-human primate model.

    Science.gov (United States)

    League-Pascual, James C; Lester-McCully, Cynthia M; Shandilya, Shaefali; Ronner, Lukas; Rodgers, Louis; Cruz, Rafael; Peer, Cody J; Figg, William D; Warren, Katherine E

    2017-05-01

    The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure. Intravenous (IV) temozolomide (TMZ), oral (PO) valproic acid, and PO perifosine were administered to adult male rhesus macaques. The animals received a single dose of each agent systemically and intranasally in separate experiments, with each animal acting as his own control. The dose of the agents administered systemically was the human equivalent of a clinically appropriate dose, while the intranasal dose was the maximum achievable dose based on the volume limitation of 1 mL. Multiple serial paired plasma and CSF samples were collected and quantified using a validated uHPLC/tandem mass spectrometry assay after each drug administration. Pharmacokinetic parameters were estimated using non-compartmental analysis. CSF penetration was calculated from the ratio of areas under the concentration-time curves for CSF and plasma (AUCCSF:plasma). Intranasal administration was feasible and tolerable for all agents with no significant toxicities observed. For TMZ, the degrees of CSF drug penetration after intranasal and IV administration were 36 (32-57) and 22 (20-41)%, respectively. Although maximum TMZ drug concentration in the CSF (Cmax) was lower after intranasal

  12. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study.

    Science.gov (United States)

    Geisbert, Thomas W; Lee, Amy C H; Robbins, Marjorie; Geisbert, Joan B; Honko, Anna N; Sood, Vandana; Johnson, Joshua C; de Jong, Susan; Tavakoli, Iran; Judge, Adam; Hensley, Lisa E; Maclachlan, Ian

    2010-05-29

    We previously showed that small interfering RNAs (siRNAs) targeting the Zaire Ebola virus (ZEBOV) RNA polymerase L protein formulated in stable nucleic acid-lipid particles (SNALPs) completely protected guineapigs when administered shortly after a lethal ZEBOV challenge. Although rodent models of ZEBOV infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. We therefore assessed the efficacy of modified non-immunostimulatory siRNAs in a uniformly lethal non-human primate model of ZEBOV haemorrhagic fever. A combination of modified siRNAs targeting the ZEBOV L polymerase (EK-1 mod), viral protein (VP) 24 (VP24-1160 mod), and VP35 (VP35-855 mod) were formulated in SNALPs. A group of macaques (n=3) was given these pooled anti-ZEBOV siRNAs (2 mg/kg per dose, bolus intravenous infusion) after 30 min, and on days 1, 3, and 5 after challenge with ZEBOV. A second group of macaques (n=4) was given the pooled anti-ZEBOV siRNAs after 30 min, and on days 1, 2, 3, 4, 5, and 6 after challenge with ZEBOV. Two (66%) of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected. The treatment regimen in the second study was well tolerated with minor changes in liver enzymes that might have been related to viral infection. This complete postexposure protection against ZEBOV in non-human primates provides a model for the treatment of ZEBOV-induced haemorrhagic fever. These data show the potential of RNA interference as an effective postexposure treatment strategy for people infected with Ebola virus, and suggest that this strategy might also be useful for treatment of other emerging viral infections. Defense Threat Reduction Agency. Copyright 2010 Elsevier Ltd. All rights reserved.

  13. Induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus

    CSIR Research Space (South Africa)

    Ripamonti, U

    2008-01-01

    Full Text Available proteins of the transforming growth factor-β(TGF-β) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis...

  14. A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.

    Science.gov (United States)

    Choi, Jin Huk; Jonsson-Schmunk, Kristina; Qiu, Xiangguo; Shedlock, Devon J; Strong, Jim; Xu, Jason X; Michie, Kelly L; Audet, Jonathan; Fernando, Lisa; Myers, Mark J; Weiner, David; Bajrovic, Irnela; Tran, Lilian Q; Wong, Gary; Bello, Alexander; Kobinger, Gary P; Schafer, Stephen C; Croyle, Maria A

    2015-08-03

    As the Ebola outbreak in West Africa continues and cases appear in the United States and other countries, the need for long-lasting vaccines to preserve global health is imminent. Here, we evaluate the long-term efficacy of a respiratory and sublingual (SL) adenovirus-based vaccine in non-human primates in two phases. In the first, a single respiratory dose of 1.4×10(9) infectious virus particles (ivp)/kg of Ad-CAGoptZGP induced strong Ebola glycoprotein (GP) specific CD8+ and CD4+ T cell responses and Ebola GP-specific antibodies in systemic and mucosal compartments and was partially (67%) protective from challenge 62 days after immunization. The same dose given by the SL route induced Ebola GP-specific CD8+ T cell responses similar to that of intramuscular (IM) injection, however, the Ebola GP-specific antibody response was low. All primates succumbed to infection. Three primates were then given the vaccine in a formulation that improved the immune response to Ebola in rodents. Three primates were immunized with 2.0×10(10) ivp/kg of vaccine by the SL route. Diverse populations of polyfunctional Ebola GP-specific CD4+ and CD8+ T cells and significant anti-Ebola GP antibodies were present in samples collected 150 days after respiratory immunization. The formulated vaccine was fully protective against challenge 21 weeks after immunization. While diverse populations of Ebola GP-specific CD4+ T cells were produced after SL immunization, antibodies were not neutralizing and the vaccine was unprotective. To our knowledge, this is the first time that durable protection from a single dose respiratory adenovirus-based Ebola vaccine has been demonstrated in primates.

  15. Hidden population structure and cross-species transmission of whipworms (Trichuris sp. in humans and non-human primates in Uganda.

    Directory of Open Access Journals (Sweden)

    Ria R Ghai

    2014-10-01

    Full Text Available Whipworms (Trichuris sp. are a globally distributed genus of parasitic helminths that infect a diversity of mammalian hosts. Molecular methods have successfully resolved porcine whipworm, Trichuris suis, from primate whipworm, T. trichiura. However, it remains unclear whether T. trichiura is a multi-host parasite capable of infecting a wide taxonomic breadth of primate hosts or a complex of host specific parasites that infect one or two closely related hosts.We examined the phylogenetic structure of whipworms in a multi-species community of non-human primates and humans in Western Uganda, using both traditional microscopy and molecular methods. A newly developed nested polymerase chain reaction (PCR method applied to non-invasively collected fecal samples detected Trichuris with 100% sensitivity and 97% specificity relative to microscopy. Infection rates varied significantly among host species, from 13.3% in chimpanzees (Pan troglodytes to 88.9% in olive baboons (Papio anubis. Phylogenetic analyses based on nucleotide sequences of the Trichuris internal transcribed spacer regions 1 and 2 of ribosomal DNA revealed three co-circulating Trichuris groups. Notably, one group was detected only in humans, while another infected all screened host species, indicating that whipworms from this group are transmitted among wild primates and humans.Our results suggest that the host range of Trichuris varies by taxonomic group, with some groups showing host specificity, and others showing host generality. In particular, one Trichuris taxon should be considered a multi-host pathogen that is capable of infecting wild primates and humans. This challenges past assumptions about the host specificity of this and similar helminth parasites and raises concerns about animal and human health.

  16. Social networks dynamics revealed by temporal analysis: An example in a non-human primate (Macaca sylvanus) in "La Forêt des Singes".

    Science.gov (United States)

    Sosa, Sebastian; Zhang, Peng; Cabanes, Guénaël

    2017-06-01

    This study applied a temporal social network analysis model to describe three affiliative social networks (allogrooming, sleep in contact, and triadic interaction) in a non-human primate species, Macaca sylvanus. Three main social mechanisms were examined to determine interactional patterns among group members, namely preferential attachment (i.e., highly connected individuals are more likely to form new connections), triadic closure (new connections occur via previous close connections), and homophily (individuals interact preferably with others with similar attributes). Preferential attachment was only observed for triadic interaction network. Triadic closure was significant in allogrooming and triadic interaction networks. Finally, gender homophily was seasonal for allogrooming and sleep in contact networks, and observed in each period for triadic interaction network. These individual-based behaviors are based on individual reactions, and their analysis can shed light on the formation of the affiliative networks determining ultimate coalition networks, and how these networks may evolve over time. A focus on individual behaviors is necessary for a global interactional approach to understanding social behavior rules and strategies. When combined, these social processes could make animal social networks more resilient, thus enabling them to face drastic environmental changes. This is the first study to pinpoint some of the processes underlying the formation of a social structure in a non-human primate species, and identify common mechanisms with humans. The approach used in this study provides an ideal tool for further research seeking to answer long-standing questions about social network dynamics. © 2017 Wiley Periodicals, Inc.

  17. Time- and radiation-dose dependent changes in the plasma proteome after total body irradiation of non-human primates: Implications for biomarker selection.

    Directory of Open Access Journals (Sweden)

    Stephanie D Byrum

    Full Text Available Acute radiation syndrome (ARS is a complex multi-organ disease resulting from total body exposure to high doses of radiation. Individuals can be exposed to total body irradiation (TBI in a number of ways, including terrorist radiological weapons or nuclear accidents. In order to determine whether an individual has been exposed to high doses of radiation and needs countermeasure treatment, robust biomarkers are needed to estimate radiation exposure from biospecimens such as blood or urine. In order to identity such candidate biomarkers of radiation exposure, high-resolution proteomics was used to analyze plasma from non-human primates following whole body irradiation (Co-60 at 6.7 Gy and 7.4 Gy with a twelve day observation period. A total of 663 proteins were evaluated from the plasma proteome analysis. A panel of plasma proteins with characteristic time- and dose-dependent changes was identified. In addition to the plasma proteomics study reported here, we recently identified candidate biomarkers using urine from these same non-human primates. From the proteomic analysis of both plasma and urine, we identified ten overlapping proteins that significantly differentiate both time and dose variables. These shared plasma and urine proteins represent optimal candidate biomarkers of radiation exposure.

  18. PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates.

    Science.gov (United States)

    Thompson, W Clayton; Zhou, Yingjiang; Talukdar, Saswata; Musante, Cynthia J

    2016-08-01

    PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure.

  19. Development of the first marmoset-specific DNA microarray (EUMAMA: a new genetic tool for large-scale expression profiling in a non-human primate

    Directory of Open Access Journals (Sweden)

    Waegele Brigitte

    2007-06-01

    Full Text Available Abstract Background The common marmoset monkey (Callithrix jacchus, a small non-endangered New World primate native to eastern Brazil, is becoming increasingly used as a non-human primate model in biomedical research, drug development and safety assessment. In contrast to the growing interest for the marmoset as an animal model, the molecular tools for genetic analysis are extremely limited. Results Here we report the development of the first marmoset-specific oligonucleotide microarray (EUMAMA containing probe sets targeting 1541 different marmoset transcripts expressed in hippocampus. These 1541 transcripts represent a wide variety of different functional gene classes. Hybridisation of the marmoset microarray with labelled RNA from hippocampus, cortex and a panel of 7 different peripheral tissues resulted in high detection rates of 85% in the neuronal tissues and on average 70% in the non-neuronal tissues. The expression profiles of the 2 neuronal tissues, hippocampus and cortex, were highly similar, as indicated by a correlation coefficient of 0.96. Several transcripts with a tissue-specific pattern of expression were identified. Besides the marmoset microarray we have generated 3215 ESTs derived from marmoset hippocampus, which have been annotated and submitted to GenBank [GenBank: EF214838 – EF215447, EH380242 – EH382846]. Conclusion We have generated the first marmoset-specific DNA microarray and demonstrated its use to characterise large-scale gene expression profiles of hippocampus but also of other neuronal and non-neuronal tissues. In addition, we have generated a large collection of ESTs of marmoset origin, which are now available in the public domain. These new tools will facilitate molecular genetic research into this non-human primate animal model.

  20. Computational simulation of convection-enhanced drug delivery in the non-human primate brainstem: a simple model predicting the drug distribution.

    Science.gov (United States)

    Sugiyama, Shin-Ichiro; Saito, Ryuta; Funamoto, Kenichi; Nakayama, Toshio; Sonoda, Yukihiko; Yamashita, Yoji; Inoue, Tomoo; Kumabe, Toshihiro; Hayase, Toshiyuki; Tominaga, Teiji

    2013-10-01

    Convection-enhanced delivery (CED) is a technique that delivers therapeutic agents directly and effectively into the brain parenchyma. Application of CED is now under investigation as a new treatment for various diseases. Diffuse brainstem glioma is one of the important candidates that could be targeted with CED. Especially when targeting brainstem lesions, prediction of drug distribution prior to CED will be necessary. This study evaluated the computational simulation of CED in the primate brainstem using a simplified model. Three in vivo experiments infusing gadolinium solution into the non-human primate brainstem were analyzed. T1-weighted magnetic resonance (MR) images were acquired during infusion of a total of 300 μl gadolinium solution. Computational simulation reconstructed the surface geometry of the brainstem from the MR images. The volume of the whole structure was meshed by grid generating software. Under the assumptions that the brainstem surface was rigid and the interior was filled with cerebrospinal fluid, the equations of continuity and Darcy's law were solved within a computational fluid dynamics package using a finite volume method. The results of computational simulations were compared with those of the in vivo experiments. The distribution volume (Vd) in the simulations corresponded well with the in vivo experiments. Under the condition without massive 'catheter back flow', computational simulations predicted almost 70% of the Vd of the in vivo experiments. The simplified computational simulations were consistent with the experiments in vivo. The methodology used in this study can be applied to predict convective drug distribution in the primate brainstem.

  1. The role and contributions of systems biology to the non-human primate model of influenza pathogenesis and vaccinology.

    Science.gov (United States)

    Baskin, Carole

    2013-01-01

    Nonhuman primates have proven to be valuable models in the study of seasonal and highly pathogenic influenza virus infections, prophylaxis, and therapy. Due to their close genetic relationship to humans, these animals share anatomic, postural, physiological, and immune features with us of key importance when it comes to progression and mitigation of respiratory infections. Their lower susceptibility to natural influenza infection even presents an advantage in the laboratory setting because of the need for immunologically naïve animals, and since nonhuman primates are relatively genetically diverse within one species, their study provides an essential complement to the body of knowledge acquired with inbred animal models. However, ethical and cost considerations typically result in smaller experiments and a need to look at additional levels of biological information in order to maximize insights gained from these studies. Systems biology is a powerful tool for this purpose, because it provides a much needed wide angle view of complex interactions taking places in organisms which are more than the sum of their parts. This chapter will describe the extent to which functional genomics and proteomics have successfully integrated with other, more traditional tools in the areas of clinical presentation, pathology, and immunology during influenza infections in nonhuman primates. It will also describe the unique contributions systems biology has made to our understanding of host-virus interactions, as well as response to vaccination and antiviral therapy.

  2. Initial characterization of a PDE10A selective positron emission tomography tracer [11C]AMG 7980 in non-human primates.

    Science.gov (United States)

    Hwang, Dah-Ren; Hu, Essa; Rumfelt, Shannon; Easwaramoorthy, Balu; Castrillon, John; Davis, Carl; Allen, Jennifer R; Chen, Hang; Treanor, James; Abi-Dargham, Anissa; Slifstein, Mark

    2014-04-01

    Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the breakdown of cyclic nucleotides which are important secondary messengers in the central nervous system. Inhibition of PDE10A has been identified as a potential therapeutic target for treatment of various neuropsychiatric disorders. To assist the drug development program, we have identified a selective PDE10A PET tracer, [(11)C]AMG 7980, for imaging PDE10A distribution using positron emission tomography. [(11)C]AMG 7980 was prepared in a one-pot, two-step reaction. Dynamic PET scans were performed in non-human primates following a bolus or bolus plus constant infusion tracer injection paradigm. Regions-of-interest were defined on individuals' MRIs and transferred to the co-registered PET images. Data were analyzed using Logan graphical analysis with metabolite-corrected input function, the simplified reference tissue model (SRTM) method and occupancy plots. A benchmark PDE10A inhibitor was used to demonstrate PDE10A-specific binding. [(11)C]AMG 7980 was prepared with a mean specific activity of 99 ± 74 GBq/μmol (n=10) and a synthesis time of 45 min. Specific binding of the tracer was localized to the striatum and globus pallidus (GP) and low in other brain regions. Thalamus was used as the reference tissue to derive binding potentials (BPND). The BPND for caudate, putamen, and GP were 0.23, 0.65, 0.51, respectively by the graphical method, and 0.42, 0.76, and 0.75 from the SRTM method. A dose dependent decrease of BPND was observed with the pre-treatment of a PDE10A inhibitor. A bolus plus infusion injection paradigm yielded similar results. [(11)C]AMG 7980 has been successfully used for imaging PDE10A in non-human primate brain. Despite the fast brain kinetics it can be used to measure target occupancy of PDE10A inhibitors in non-human primates and potentially applicable to humans. Copyright © 2014. Published by Elsevier Inc.

  3. Cycle-Triggered Cortical Stimulation during Slow Wave Sleep Facilitates Learning a BMI Task: A Case Report in a Non-Human Primate.

    Science.gov (United States)

    Rembado, Irene; Zanos, Stavros; Fetz, Eberhard E

    2017-01-01

    Slow wave sleep (SWS) has been identified as the sleep stage involved in consolidating newly acquired information. A growing body of evidence has shown that delta (1-4 Hz) oscillatory activity, the characteristic electroencephalographic signature of SWS, is involved in coordinating interaction between the hippocampus and the neocortex and is thought to take a role in stabilizing memory traces related to a novel task. This case report describes a new protocol that uses neuroprosthetics training of a non-human primate to evaluate the effects of surface cortical electrical stimulation triggered from SWS cycles. The results suggest that stimulation phase-locked to SWS oscillatory activity promoted learning of the neuroprosthetic task. This protocol could be used to elucidate mechanisms of synaptic plasticity underlying off-line learning during sleep and offers new insights into the role of brain oscillations in information processing and memory consolidation.

  4. HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo.

    Directory of Open Access Journals (Sweden)

    Charlotte V Hobbs

    Full Text Available We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination, but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts.

  5. Activation of TrkB with TAM-163 results in opposite effects on body weight in rodents and non-human primates.

    Science.gov (United States)

    Perreault, Mylène; Feng, Guo; Will, Sarah; Gareski, Tiffany; Kubasiak, David; Marquette, Kimberly; Vugmeyster, Yulia; Unger, Thaddeus J; Jones, Juli; Qadri, Ariful; Hahm, Seung; Sun, Ying; Rohde, Cynthia M; Zwijnenberg, Raphael; Paulsen, Janet; Gimeno, Ruth E

    2013-01-01

    Strong genetic data link the Tyrosine kinase receptor B (TrkB) and its major endogenous ligand brain-derived neurotrophic factor (BDNF) to the regulation of energy homeostasis, with loss-of-function mutations in either gene causing severe obesity in both mice and humans. It has previously been reported that peripheral administration of the endogenous TrkB agonist ligand neurotrophin-4 (NT-4) profoundly decreases food intake and body weight in rodents, while paradoxically increasing these same parameters in monkeys. We generated a humanized TrkB agonist antibody, TAM-163, and characterized its therapeutic potential in several models of type 2 diabetes and obesity. In vitro, TAM-163 bound to human and rodent TrkB with high affinity, activated all aspects of the TrkB signaling cascade and induced TrkB internalization and degradation in a manner similar to BDNF. In vivo, peripheral administration of TAM-163 decreased food intake and/or body weight in mice, rats, hamsters, and dogs, but increased food intake and body weight in monkeys. The magnitude of weight change was similar in rodents and non-human primates, occurred at doses where there was no appreciable penetration into deep structures of the brain, and could not be explained by differences in exposures between species. Rather, peripherally administered TAM-163 localized to areas in the hypothalamus and the brain stem located outside the blood-brain barrier in a similar manner between rodents and non-human primates, suggesting differences in neuroanatomy across species. Our data demonstrate that a TrkB agonist antibody, administered peripherally, causes species-dependent effects on body weight similar to the endogenous TrkB ligand NT-4. The possible clinical utility of TrkB agonism in treating weight regulatory disorder, such as obesity or cachexia, will require evaluation in man.

  6. Activation of TrkB with TAM-163 results in opposite effects on body weight in rodents and non-human primates.

    Directory of Open Access Journals (Sweden)

    Mylène Perreault

    Full Text Available Strong genetic data link the Tyrosine kinase receptor B (TrkB and its major endogenous ligand brain-derived neurotrophic factor (BDNF to the regulation of energy homeostasis, with loss-of-function mutations in either gene causing severe obesity in both mice and humans. It has previously been reported that peripheral administration of the endogenous TrkB agonist ligand neurotrophin-4 (NT-4 profoundly decreases food intake and body weight in rodents, while paradoxically increasing these same parameters in monkeys. We generated a humanized TrkB agonist antibody, TAM-163, and characterized its therapeutic potential in several models of type 2 diabetes and obesity. In vitro, TAM-163 bound to human and rodent TrkB with high affinity, activated all aspects of the TrkB signaling cascade and induced TrkB internalization and degradation in a manner similar to BDNF. In vivo, peripheral administration of TAM-163 decreased food intake and/or body weight in mice, rats, hamsters, and dogs, but increased food intake and body weight in monkeys. The magnitude of weight change was similar in rodents and non-human primates, occurred at doses where there was no appreciable penetration into deep structures of the brain, and could not be explained by differences in exposures between species. Rather, peripherally administered TAM-163 localized to areas in the hypothalamus and the brain stem located outside the blood-brain barrier in a similar manner between rodents and non-human primates, suggesting differences in neuroanatomy across species. Our data demonstrate that a TrkB agonist antibody, administered peripherally, causes species-dependent effects on body weight similar to the endogenous TrkB ligand NT-4. The possible clinical utility of TrkB agonism in treating weight regulatory disorder, such as obesity or cachexia, will require evaluation in man.

  7. Knowledge-Guided Robust MRI Brain Extraction for Diverse Large-Scale Neuroimaging Studies on Humans and Non-Human Primates

    Science.gov (United States)

    Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Geng, Xiujuan; Guo, Lei; Shen, Dinggang

    2014-01-01

    Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness. PMID:24489639

  8. Knowledge-guided robust MRI brain extraction for diverse large-scale neuroimaging studies on humans and non-human primates.

    Science.gov (United States)

    Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Geng, Xiujuan; Guo, Lei; Shen, Dinggang

    2014-01-01

    Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55 ∼ 90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18 ∼ 96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5 ∼ 18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness.

  9. Sotrastaurin (AEB071) alone and in combination with cyclosporine A prolongs survival times of non-human primate recipients of life-supporting kidney allografts.

    Science.gov (United States)

    Bigaud, Marc; Wieczorek, Grazyna; Beerli, Christian; Audet, Maxime; Blancher, Antoine; Heusser, Christoph; Morris, Randall E; Wagner, Jürgen

    2012-01-27

    Sotrastaurin (STN), a novel oral protein kinase C inhibitor that inhibits early T-cell activation, was assessed in non-human primate recipients of life-supporting kidney allografts. Cynomolgus monkey recipients of life-supporting kidney allografts were treated orally with STN alone or in combination with cyclosporine A (CsA). STN monotherapy at 50 mg/kg once daily prolonged recipient survival times to the predefined endpoint of 29 days (n=2); when given at 25 mg/kg twice daily, the median survival time (MST) was 27 days (n=4). Neither once-daily monotherapy of STN 20 mg/kg nor CsA 20 mg/kg was effective (MST 6 days [n=2] and 7 days [n=5], respectively). In combination, however, STN 20 mg/kg and CsA 20 mg/kg prolonged MST to more than 100 days (n=5). By combining lower once-daily doses of STN (7 or 2 mg/kg) with CsA (20 mg/kg), MST was more than 100 (n=3) and 22 days (n=2), respectively. Neither in single-dose pharmacokinetic studies nor the transplant recipients were STN or CsA blood levels for combined treatment greater than when either drug was administered alone. STN blood levels in transplant recipients during combination therapy were dose related (20 mg/kg, 30-182 ng/mL; 7 mg/kg, 7-41 ng/mL; and 2 mg/kg, 3-5 ng/mL). STN at a daily dose of up to 20 mg/kg was relatively well tolerated. STN prolonged survival times of non-human primate kidney allograft recipients both as monotherapy and most effectively in combination with CsA. Pharmacokinetic interactions were not responsible for the potentiation of immunosuppressive efficacy by coadministering STN and CsA.

  10. A high density of human communication-associated genes in chromosome 7q31-q36: differential expression in human and non-human primate cortices.

    Science.gov (United States)

    Schneider, E; Jensen, L R; Farcas, R; Kondova, I; Bontrop, R E; Navarro, B; Fuchs, E; Kuss, A W; Haaf, T

    2012-01-01

    The human brain is distinguished by its remarkable size, high energy consumption, and cognitive abilities compared to all other mammals and non-human primates. However, little is known about what has accelerated brain evolution in the human lineage. One possible explanation is that the appearance of advanced communication skills and language has been a driving force of human brain development. The phenotypic adaptations in brain structure and function which occurred on the way to modern humans may be associated with specific molecular signatures in today's human genome and/or transcriptome. Genes that have been linked to language, reading, and/or autism spectrum disorders are prime candidates when searching for genes for human-specific communication abilities. The database and genome-wide expression analyses we present here revealed a clustering of such communication-associated genes (COAG) on human chromosomes X and 7, in particular chromosome 7q31-q36. Compared to the rest of the genome, we found a high number of COAG to be differentially expressed in the cortices of humans and non-human primates (chimpanzee, baboon, and/or marmoset). The role of X-linked genes for the development of human-specific cognitive abilities is well known. We now propose that chromosome 7q31-q36 also represents a hot spot for the evolution of human-specific communication abilities. Selective pressure on the T cell receptor beta locus on chromosome 7q34, which plays a pivotal role in the immune system, could have led to rapid dissemination of positive gene variants in hitchhiking COAG. Copyright © 2012 S. Karger AG, Basel.

  11. Saccades during visual exploration align hippocampal 3-8 Hz rhythms in human and non-human primates

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    Kari L Hoffman

    2013-08-01

    Full Text Available Visual exploration in primates depends on saccadic eye movements that cause alternations of neural suppression and enhancement. This modulation extends beyond retinotopic areas, and is thought to facilitate perception; yet saccades may also influence brain regions critical for forming memories of these exploratory episodes. The hippocampus, for example, shows oscillatory activity that is generally associated with encoding of information. Whether or how hippocampal oscillations are influenced by eye movements is unknown. We recorded the neural activity in the human and macaque hippocampus during visual scene search. Across species, saccadic eye movements were associated with a time-limited alignment of a low-frequency (3-8 Hz rhythm. The phase alignment depended on the task and not only on eye movements per se, and the frequency band was not a direct consequence of saccade rate. Hippocampal theta-frequency oscillations are produced by other mammals during repetitive exploratory behaviors, including whisking, sniffing, echolocation and locomotion. The present results may reflect a similar yet distinct primate homologue supporting active perception during exploration.

  12. Prevalence of ESBLs and PMQR genes in fecal Escherichia coli isolated from the non-human primates in six zoos in China.

    Science.gov (United States)

    Wang, Yang; He, Tao; Han, Jing; Wang, Juan; Foley, Steven L; Yang, Guangyou; Wan, Shuangxiu; Shen, Jianzhong; Wu, Congming

    2012-09-14

    The aim of this study is to characterize the prevalence of extended-spectrum β-lactamases (ESBLs) and plasmid-mediated quinolone resistance (PMQR) genes in Escherichia coli from captive non-human primates. A total of 206 E. coli isolates were collected from primates in six zoos in China in 2009 and their susceptibility to 10 antimicrobials were tested by broth microdilution. The susceptibility patterns of E. coli strains varied greatly among different zoos reflecting different backgrounds of antimicrobial usage. Both the ESBL-encoding genes and the PMQR genes were detected by PCR. Of the 206 strains, 65 (32%) were confirmed as phenotypic ESBL producers with bla(CTX-M) (27%, bla(CTX-M-15), n=31, bla(CTX-M-3), n=23 and bla(CTX-M-14), n=2) mainly mediating the ESBL phenotype. qnrS1 (18%, n=36) and oqxAB (15%, n=31) were the predominant PMQR genes and the prevalence of PMQR genes was much higher among phenotypic ESBL producers than that among phenotypic non-ESBL producers from any zoo. Notably, the PMQR genes qnrS1 and oqxAB and β-lactamase genes bla(TEM-1) and bla(CTX-M-3) were found together in 23 E. coli isolates in two zoos in Shanghai. PFGE analysis of these 23 isolates demonstrated nearly identical PFGE profiles (similarity matrix >97%) indicating this specific E. coli genotype was prevalent in these two zoos. To the best of our knowledge, this is the first report of these four genes coexisting in an E. coli genotype and the first report of antimicrobial resistance profiles in E. coli isolated from primates in China. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Of mice and monkeys: using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders

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    Watson Karli K

    2012-07-01

    Full Text Available Abstract The autism spectrum disorders (ASDs arise from a diverse array of genetic and environmental origins that disrupt the typical developmental trajectory of neural connectivity and synaptogenesis. ASDs are marked by dysfunctional social behavior and cognition, among other deficits. Greater understanding of the biological substrates of typical social behavior in animal models will further our understanding of the etiology of ASDs. Despite the precision and tractability of molecular genetics models of ASDs in rodents, these organisms lack the complexity of human social behavior, thus limiting their impact on understanding ASDs to basic mechanisms. Non-human primates (NHPs provide an attractive, complementary model for ASDs, due in part to the complexity and dynamics of social structures, reliance on vision for social signaling, and deep homology in brain circuitry mediating social behavior and reward. This knowledge is based on a rich literature, compiled over 50 years of observing primate behavior in the wild, which, in the case of rhesus macaques, is complemented by a large body of research characterizing neuronal activity during cognitive behavior. Several recent developments in this field are directly relevant to ASDs, including how the brain represents the perceptual features of social stimuli, how social information influences attention processes in the brain, and how the value of social interaction is computed. Because the symptoms of ASDs may represent extreme manifestations of traits that vary in intensity within the general population, we will additionally discuss ways in which nonhuman primates also show variation in social behavior and reward sensitivity. In cases where variation in species-typical behavior is analogous to similar variations in human behavior, we believe that study of the neural circuitry underlying this variation will provide important insights into the systems-level mechanisms contributing to ASD pathology.

  14. Anatomical Organization of Urocortin 3-Synthesizing Neurons and Immunoreactive Terminals in the Central Nervous System of Non-Human Primates [Sapajus spp.

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    Daniella S. Battagello

    2017-07-01

    Full Text Available Urocortin 3 (UCN3 is a neuropeptide member of the corticotropin-releasing factor (CRF peptide family that acts as a selective endogenous ligand for the CRF, subtype 2 (CRF2 receptor. Immunohistochemistry and in situ hybridization data from rodents revealed UCN3-containing neurons in discrete regions of the central nervous system (CNS, such as the medial preoptic nucleus, the rostral perifornical area (PFA, the medial nucleus of the amygdala and the superior paraolivary nucleus. UCN3-immunoreactive (UCN3-ir terminals are distributed throughout regions that mostly overlap with regions of CRF2 messenger RNA (mRNA expression. Currently, no similar mapping exists for non-human primates. To better understand the role of this neuropeptide, we aimed to study the UCN3 distribution in the brains of New World monkeys of the Sapajus genus. To this end, we analyzed the gene and peptide sequences in these animals and performed immunohistochemistry and in situ hybridization to identify UCN3 synthesis sites and to determine the distribution of UCN3-ir terminals. The sequencing of the Sapajus spp. UCN3-coding gene revealed 88% and 65% identity to the human and rat counterparts, respectively. Additionally, using a probe generated from monkey cDNA and an antiserum raised against human UCN3, we found that labeled cells are mainly located in the hypothalamic and limbic regions. UCN3-ir axons and terminals are primarily distributed in the ventromedial hypothalamic nucleus (VMH and the lateral septal nucleus (LS. Our results demonstrate that UCN3-producing neurons in the CNS of monkeys are phylogenetically conserved compared to those of the rodent brain, that the distribution of fibers agrees with the distribution of CRF2 in other primates and that there is anatomical evidence for the participation of UCN3 in neuroendocrine control in primates.

  15. Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Croy, Carrie Hughes; Dencker, Ditte

    2015-01-01

    Cholinergic, muscarinic receptor agonists exhibit functional dopamine antagonism and muscarinic receptors have been suggested as possible future targets for the treatment of schizophrenia and drug abuse. The muscarinic ligand (5R,6R)-6-(3-butylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane...... (BuTAC) exhibits high affinity for muscarinic receptors with no or substantially less affinity for a large number of other receptors and binding sites, including the dopamine receptors and the dopamine transporter. In the present study, we wanted to examine the possible antipsychotic-like effects...... of BuTAC in primates. To this end, we investigated the effects of BuTAC on d-amphetamine-induced behaviour in antipsychotic-naive Cebus paella monkeys. Possible adverse events of BuTAC, were evaluated in the same monkeys as well as in monkeys sensitized to antipsychotic-induced extrapyramidal side...

  16. EVOLUCIÓN DEL CONFLICTO SOCIAL Y DE SU RESOLUCIÓN EN PRIMATES NO HUMANOS Evolution of Social Conflict and its Resolution in Non Human Primates

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    ALBA LETICIA PÉREZ RUIZ

    Full Text Available El propósito de este trabajo es analizar, desde una aproximación evolutiva, el comportamiento social de los primates, para explorar el significado del conflicto agresivo y de la reconciliación como su principal mecanismo de resolución dentro del contexto social intraespecífico. La vida en un grupo social de primates implica costos y beneficios para los miembros del grupo. Además, la convivencia en grupo permite el desarrollo de relaciones sociales complejas entre los miembros del grupo. Dado que la socialización genera competencia y conflictos que pueden implicar comportamientos agresivos, la agresión es costosa no solo en términos de gasto de energía y relaciones sociales sino también en términos de daño físico. Con base en esto, la selección natural deberá favorecer la agresión solo en los casos en los que el valor de los beneficios sea mayor que el de los costos. La agresión impone costos tanto al agresor como al receptor de la agresión. Por ello, es de esperar que la selección natural favorecerá a los individuos que disminuyan los costos de la agresión, pero al mismo tiempo favorecerá a los individuos que usen -adecuadamente- los episodios agonistas para ganar acceso a los recursos o para resolver conflictos en su favor. El conflicto generado entre los oponentes por un episodio agresivo puede implicar altos costos en términos de vínculos sociales, de ahí que hayan evolucionado distintos mecanismos de resolución de conflicto, como es el caso del comportamiento reconciliatorio, donde la cooperación tiene un importante papel como causa y consecuencia de la reconciliación.The purpose of this article is to analyze, from an evolutionary approach, the social behavior of primates, to explore the meaning of aggressive conflict and reconciliation, its main mechanism of resolution, within an intraspecific social context. Life among a primate social group supposes costs and benefits to its members. Group life allows as well

  17. Effects of the alpha-2 adrenoceptor agonist guanfacine on attention and working memory in aged non-human primates.

    Science.gov (United States)

    Decamp, Emmanuel; Clark, Kathryn; Schneider, Jay S

    2011-09-01

    Alpha-2 adrenergic receptors are potential targets for ameliorating cognitive deficits associated with aging as well as certain pathologies such as attention deficit disorder, schizophrenia and Parkinson's disease. Although the alpha-2 agonist guanfacine has been reported to improve working memory in aged primates, it has been difficult to assess the extent to which these improvements may be related to drug effects on attention and/or memory processes involved in task performance. The present study investigated effects of guanfacine on specific attention and memory tasks in aged monkeys. Four Rhesus monkeys (18-21 years old) performed a sustained attention (continuous performance) task and spatial working memory task (self-ordered spatial search) that has minimal demands on attention. Effects of a low (0.0015 mg/kg) and high (0.5 mg/kg) dose of gunafacine were examined. Low-dose guanfacine improved performance on the attention task [i.e. decreased omission errors by 50.8 ± 4.3% (P = 0.001) without an effect on commission errors] but failed to improve performance on the spatial working memory task. The high dose of guanfacine had no effects on either task. Guanfacine may have a preferential effect on some aspects of attention in normal aged monkeys and in doing so may also improve performance on other tasks, including some working memory tasks that have relatively high attention demands. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  18. Examination of the direct effects of metabolic factors on somatotrope function in a non-human primate model, Papio anubis.

    Science.gov (United States)

    Luque, Raul M; Gahete, Manuel D; Valentine, Rudy J; Kineman, Rhonda D

    2006-08-01

    In humans, circulating GH levels are increased in catabolic states and suppressed in obesity. In both extremes, normalization of the metabolic environment normalizes GH release, leading to the conclusion that changes in metabolic hormones and/or metabolites promote changes in GH synthesis and release. Metabolic regulation of GH secretion can be mediated centrally by modulation of hypothalamic GHRH and somatostatin input to the pituitary and/or by direct regulation of pituitary somatotrope function. Although data are available showing glucocorticoids, free fatty acids (FFA), IGF-I, and insulin have direct effects on rat somatotrope function, little information is available regarding the direct pituitary effects of these metabolic factors in primates. Therefore, this study examined the effects of glucocorticoids (dexamethasone (0.1-100 nM) and hydrocortisone (10 nM)), FFA (oleic and linoleic acid, 100 and 400 microM each), IGF-I (0.5-50 nM), and insulin (0.5-50 nM) on GH release and GH, GHRH-receptor (GHRH-R) and ghrelin-receptor (GHS-R) mRNA levels, in primary pituitary cell cultures of baboons (Papio anubis) after 24 h treatment. A commercial ELISA kit was used to determine the amount of GH released into the media, while quantitative real-time reverse transcription-PCR was used to determine mRNA levels. To design species-specific primers for baboon GH, GHRH-R, GHS-R, insulin receptor (INSR), IGF-I receptor (IGF-IR), pituitary-specific transcription factor-1 (Pit-1), and cyclophilin A (used as a housekeeping gene) cDNA, sequence data for each baboon transcript were obtained and this data were submitted to Genbank. Glucocorticoids, FFA, insulin and IGF-I treatment did not significantly alter the expression of Pit-1, a transcription factor essential for normal somatotrope development and function. However, as previously reported in the rat, glucocorticoids increased, while FFA, IGF-I and insulin decreased GH release in baboon pituitary cell cultures, where changes in

  19. Patterns of microRNA expression in non-human primate cells correlate with neoplastic development in vitro.

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    Belete Teferedegne

    Full Text Available MicroRNAs (miRNAs are small noncoding RNAs that negatively regulate gene expression post-transcriptionally. They play a critical role in developmental and physiological processes and have been implicated in the pathogenesis of several diseases including cancer. To identify miRNA signatures associated with different stages of neoplastic development, we examined the expression profile of 776 primate miRNAs in VERO cells (a neoplastically transformed cell line being used for the manufacture of viral vaccines, progenitor primary African green monkey kidney (pAGMK cells, and VERO cell derivatives: spontaneously immortalized, non-tumorigenic, low-passage VERO cells (10-87 LP; tumorigenic, high-passage VERO cells (10-87 HP; and a cell line (10-87 T derived from a 10-87 HP cell tumor xenograft in athymic nude mice. When compared with pAGMK cells, the majority of miRNAs were expressed at lower levels in 10-87 LP, 10-87 HP, and 10-87 T cells. We identified 10 up-regulated miRNAs whose level of expression correlated with VERO cell evolution from a non-tumorigenic phenotype to a tumorigenic phenotype. The overexpression of miR-376a and the polycistronic cluster of miR-376a, miR-376b and miR-376c conferred phenotypic changes to the non-tumorigenic 10-87 LP cells that mimic the tumorigenic 10-87 HP cells. Thirty percent of miRNAs that were components of the identified miRNAs in our spontaneously transformed AGMK cell model are also dysregulated in a variety of human tumors. These results may prove to be relevant to the biology of neoplastic development. In addition, one or more of these miRNAs could be biomarkers for the expression of a tumorigenic phenotype.

  20. Patterns of microRNA expression in non-human primate cells correlate with neoplastic development in vitro.

    Science.gov (United States)

    Teferedegne, Belete; Murata, Haruhiko; Quiñones, Mariam; Peden, Keith; Lewis, Andrew M

    2010-12-22

    MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression post-transcriptionally. They play a critical role in developmental and physiological processes and have been implicated in the pathogenesis of several diseases including cancer. To identify miRNA signatures associated with different stages of neoplastic development, we examined the expression profile of 776 primate miRNAs in VERO cells (a neoplastically transformed cell line being used for the manufacture of viral vaccines), progenitor primary African green monkey kidney (pAGMK) cells, and VERO cell derivatives: spontaneously immortalized, non-tumorigenic, low-passage VERO cells (10-87 LP); tumorigenic, high-passage VERO cells (10-87 HP); and a cell line (10-87 T) derived from a 10-87 HP cell tumor xenograft in athymic nude mice. When compared with pAGMK cells, the majority of miRNAs were expressed at lower levels in 10-87 LP, 10-87 HP, and 10-87 T cells. We identified 10 up-regulated miRNAs whose level of expression correlated with VERO cell evolution from a non-tumorigenic phenotype to a tumorigenic phenotype. The overexpression of miR-376a and the polycistronic cluster of miR-376a, miR-376b and miR-376c conferred phenotypic changes to the non-tumorigenic 10-87 LP cells that mimic the tumorigenic 10-87 HP cells. Thirty percent of miRNAs that were components of the identified miRNAs in our spontaneously transformed AGMK cell model are also dysregulated in a variety of human tumors. These results may prove to be relevant to the biology of neoplastic development. In addition, one or more of these miRNAs could be biomarkers for the expression of a tumorigenic phenotype.

  1. Social and emotional values of sounds influence human (Homo sapiens and non-human primate (Cercopithecus campbelli auditory laterality.

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    Muriel Basile

    Full Text Available The last decades evidenced auditory laterality in vertebrates, offering new important insights for the understanding of the origin of human language. Factors such as the social (e.g. specificity, familiarity and emotional value of sounds have been proved to influence hemispheric specialization. However, little is known about the crossed effect of these two factors in animals. In addition, human-animal comparative studies, using the same methodology, are rare. In our study, we adapted the head turn paradigm, a widely used non invasive method, on 8-9-year-old schoolgirls and on adult female Campbell's monkeys, by focusing on head and/or eye orientations in response to sound playbacks. We broadcast communicative signals (monkeys: calls, humans: speech emitted by familiar individuals presenting distinct degrees of social value (female monkeys: conspecific group members vs heterospecific neighbours, human girls: from the same vs different classroom and emotional value (monkeys: contact vs threat calls; humans: friendly vs aggressive intonation. We evidenced a crossed-categorical effect of social and emotional values in both species since only "negative" voices from same class/group members elicited a significant auditory laterality (Wilcoxon tests: monkeys, T = 0 p = 0.03; girls: T = 4.5 p = 0.03. Moreover, we found differences between species as a left and right hemisphere preference was found respectively in humans and monkeys. Furthermore while monkeys almost exclusively responded by turning their head, girls sometimes also just moved their eyes. This study supports theories defending differential roles played by the two hemispheres in primates' auditory laterality and evidenced that more systematic species comparisons are needed before raising evolutionary scenario. Moreover, the choice of sound stimuli and behavioural measures in such studies should be the focus of careful attention.

  2. Dyslipidemic Diet-Induced Monocyte “Priming” and Dysfunction in Non-Human Primates Is Triggered by Elevated Plasma Cholesterol and Accompanied by Altered Histone Acetylation

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    John D. Short

    2017-08-01

    Full Text Available Monocytes and the recruitment of monocyte-derived macrophages into sites of inflammation play a key role in atherogenesis and other chronic inflammatory diseases linked to cardiometabolic syndrome and obesity. Previous studies from our group have shown that metabolic stress promotes monocyte priming, i.e., enhanced adhesion and accelerated chemotaxis of monocytes in response to chemokines, both in vitro and in dyslipidemic LDLR−/− mice. We also showed that metabolic stress-induced monocyte dysfunction is, at least to a large extent caused by the S-glutathionylation, inactivation, and subsequent degradation of mitogen-activated protein kinase phosphatase 1. Here, we analyzed the effects of a Western-style, dyslipidemic diet (DD, which was composed of high levels of saturated fat, cholesterol, and simple sugars, on monocyte (dysfunction in non-human primates (NHPs. We found that similar to mice, a DD enhances monocyte chemotaxis in NHP within 4 weeks, occurring concordantly with the onset of hypercholesterolemia but prior to changes in triglycerides, blood glucose, monocytosis, or changes in monocyte subset composition. In addition, we identified transitory decreases in the acetylation of histone H3 at the lysine residues 18 and 23 in metabolically primed monocytes, and we found that monocyte priming was correlated with the acetylation of histone H3 at lysine 27 after an 8-week DD regimen. Our data show that metabolic stress promotes monocyte priming and hyper-chemotactic responses in NHP. The histone modifications accompanying monocyte priming in primates suggest a reprogramming of the epigenetic landscape, which may lead to dysregulated responses and functionalities in macrophages derived from primed monocytes that are recruited to sites of inflammation.

  3. Diverse captive non-human primates with phytanic acid-deficient diets rich in plant products have substantial phytanic acid levels in their red blood cells

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    Moser Ann B

    2013-02-01

    Full Text Available Abstract Background Humans and rodents with impaired phytanic acid (PA metabolism can accumulate toxic stores of PA that have deleterious effects on multiple organ systems. Ruminants and certain fish obtain PA from the microbial degradation of dietary chlorophyll and/or through chlorophyll-derived precursors. In contrast, humans cannot derive PA from chlorophyll and instead normally obtain it only from meat, dairy, and fish products. Results Captive apes and Old world monkeys had significantly higher red blood cell (RBC PA levels relative to humans when all subjects were fed PA-deficient diets. Given the adverse health effects resulting from PA over accumulation, we investigated the molecular evolution of thirteen PA metabolism genes in apes, Old world monkeys, and New world monkeys. All non-human primate (NHP orthologs are predicted to encode full-length proteins with the marmoset Phyh gene containing a rare, but functional, GA splice donor dinucleotide. Acox2, Scp2, and Pecr sequences had amino acid positions with accelerated substitution rates while Amacr had significant variation in evolutionary rates in apes relative to other primates. Conclusions Unlike humans, diverse captive NHPs with PA-deficient diets rich in plant products have substantial RBC PA levels. The favored hypothesis is that NHPs can derive significant amounts of PA from the degradation of ingested chlorophyll through gut fermentation. If correct, this raises the possibility that RBC PA levels could serve as a biomarker for evaluating the digestive health of captive NHPs. Furthermore, the evolutionary rates of the several genes relevant to PA metabolism provide candidate genetic adaptations to NHP diets.

  4. Giardia duodenalis assemblages and Entamoeba species infecting non-human primates in an Italian zoological garden: zoonotic potential and management traits

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    Di Cave David

    2011-10-01

    Full Text Available Abstract Background Giardia duodenalis and Entamoeba spp. are among the most common intestinal human protozoan parasites worldwide and they are frequently reported in captive non-human primates (NHP. From a public health point of view, infected animals in zoos constitute a risk for animal caretakers and visitors. In this study we carried out the molecular identification of G. duodenalis and Entamoeba spp. from nine species of primates housed in the zoological garden of Rome, to better ascertain their occurrence and zoonotic potential. Results G. duodenalis was found only in Lemur catta (47.0%. Entamoeba spp. were detected in all species studied, with the exception of Eulemur macaco and Varecia rubra. The number of positive pools ranged from 5.9% in L. catta to 81.2% in Mandrillus sphinx; in Pan troglodytes the observed prevalence was 53.6%. A mixed Entamoeba-Giardia infection was recorded only in one sample of L. catta. All G. duodenalis isolates belonged to the zoonotic assemblage B, sub assemblage BIV. Three Entamoeba species were identified: E. hartmanni, E. coli and E. dispar. Conclusions Our results highlight the importance of regularly testing animals kept in zoos for the diagnosis of zoonotic parasites, in order to evaluate their pathogenic role in the housed animals and the zoonotic risk linked to their presence. A quick detection of the arrival of pathogens into the enclosures could also be a prerequisite to limit their spread into the structure via the introduction of specific control strategies. The need for molecular identification of some parasite species/genotype in order to better define the zoonotic risk is also highlighted.

  5. Evaluation of Dose and Safety of AAV7m8 and AAV8BP2 in the Non-Human Primate Retina.

    Science.gov (United States)

    Ramachandran, Pavitra S; Lee, Vivian; Wei, Zhangyong; Song, Ji Yun; Casal, Giulia; Cronin, Therese; Willett, Keirnan; Huckfeldt, Rachel; Morgan, Jessica I W; Aleman, Tomas S; Maguire, Albert M; Bennett, Jean

    2017-02-01

    Within the next decade, we will see many gene therapy clinical trials for eye diseases, which may lead to treatments for thousands of visually impaired people around the world. To target retinal diseases that affect specific cell types, several recombinant adeno-associated virus (AAV) serotypes have been generated and used successfully in preclinical mouse studies. Because there are numerous anatomic and physiologic differences between the eyes of mice and "men" and because surgical delivery approaches and immunologic responses also differ between these species, this study evaluated the transduction characteristics of two promising new serotypes, AAV7m8 and AAV8BP2, in the retinas of animals that are most similar to those of humans: non-human primates (NHPs). We report that while AAV7m8 efficiently targets a variety of cell types by subretinal injection in NHPs, transduction after intravitreal delivery was mostly restricted to the inner retina at lower doses that did not induce an immune response. AAV8BP2 targets the cone photoreceptors efficiently but bipolar cells inefficiently by subretinal injection. Additionally, transduction by both serotypes in the anterior chamber of the eye and the optic pathway of the brain was observed post-intravitreal delivery. Finally, we assessed immunogenicity, keeping in mind that these AAV capsids may be used in future clinical trials. We found that AAV8BP2 had a better safety profile compared with AAV7m8, even at the highest doses administered. These studies underscore the differences in AAV transduction between mice and primates, highlighting the importance of careful evaluation of therapeutic vectors in NHPs prior to moving to clinical trials.

  6. Neuromodulation of Prefrontal Cortex in Non-Human Primates by Dopaminergic Receptors during Rule-Guided Flexible Behavior and Cognitive Control

    Science.gov (United States)

    Vijayraghavan, Susheel; Major, Alex J.; Everling, Stefan

    2017-01-01

    The prefrontal cortex (PFC) is indispensable for several higher-order cognitive and executive capacities of primates, including representation of salient stimuli in working memory (WM), maintenance of cognitive task set, inhibition of inappropriate responses and rule-guided flexible behavior. PFC networks are subject to robust neuromodulation from ascending catecholaminergic systems. Disruption of these systems in PFC has been implicated in cognitive deficits associated with several neuropsychiatric disorders. Over the past four decades, a considerable body of work has examined the influence of dopamine on macaque PFC activity representing spatial WM. There has also been burgeoning interest in neuromodulation of PFC circuits involved in other cognitive functions of PFC, including representation of rules to guide flexible behavior. Here, we review recent neuropharmacological investigations conducted in our laboratory and others of the role of PFC dopamine receptors in regulating rule-guided behavior in non-human primates. Employing iontophoresis, we examined the effects of local manipulation of dopaminergic subtypes on neuronal activity during performance of rule-guided pro- and antisaccades, an experimental paradigm sensitive to PFC integrity, wherein deficits in performance are reliably observed in many neuropsychiatric disorders. We found dissociable effects of dopamine receptors on neuronal activity for rule representation and oculomotor responses and discuss these findings in the context of prior studies that have examined the role of dopamine in spatial delayed response tasks, attention, target selection, abstract rules, visuomotor learning and reward. The findings we describe here highlight the common features, as well as heterogeneity and context dependence of dopaminergic neuromodulation in regulating the efficacy of cognitive functions of PFC in health and disease. PMID:29259545

  7. Resveratrol Metabolism in a Non-Human Primate, the Grey Mouse Lemur (Microcebus murinus), Using Ultra-High-Performance Liquid Chromatography–Quadrupole Time of Flight

    Science.gov (United States)

    Menet, Marie-Claude; Marchal, Julia; Dal-Pan, Alexandre; Taghi, Méryam; Nivet-Antoine, Valérie; Dargère, Delphine; Laprévote, Olivier; Beaudeux, Jean-Louis; Aujard, Fabienne; Epelbaum, Jacques; Cottart, Charles-Henry

    2014-01-01

    The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg−1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism. PMID:24663435

  8. Resveratrol metabolism in a non-human primate, the grey mouse lemur (Microcebus murinus, using ultra-high-performance liquid chromatography-quadrupole time of flight.

    Directory of Open Access Journals (Sweden)

    Marie-Claude Menet

    Full Text Available The grey mouse lemur (Microcebus murinus is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg-1 of oral resveratrol by ultra-high performance liquid chromatography (UHPLC, coupled to a quadrupole-time-of-flight (Q-TOF mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives. The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism.

  9. The induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus

    Science.gov (United States)

    Ripamonti, U; Richter, P W; Nilen, R W N; Renton, L

    2008-01-01

    Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/p-tricalcium phosphate (HA/β-TCP) biomimetic matrices. HA/β-TCP biomimetic matrices in a pre-sinter ratio (wt%) of 40/60 and 20/80, respectively, were sintered and implanted in the rectus abdominis and in calvarial defects of four adult baboons. The post-sinter phase content ratios were 19/81 and 4/96, respectively. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices with substantial bone formation by induction and resorption/dissolution of the implanted matrices. One year after implantation in calvarial defects, 4/96 biphasic biomimetic constructs showed prominent induction of bone formation with significant dissolution of the implanted scaffolds. The implanted smart biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor-β(TGF-β) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis are regulators of bone formation by induction. The concavities assembled in HA/β-TCP biomimetic bioceramics are endowed with multifunctional pleiotropic self-assembly capacities initiating and promoting angiogenesis and bone formation by induction. Resident mesenchymal cells differentiate into osteoblastic cell lines expressing, secreting and embedding osteogenic soluble molecular signals of the TGF-β superfamily within the concavities of the biomimetic matrices initiating bone formation as a secondary response. PMID:18363843

  10. Giardia duodenalis assemblages and Entamoeba species infecting non-human primates in an Italian zoological garden: zoonotic potential and management traits.

    Science.gov (United States)

    Berrilli, Federica; Prisco, Cristina; Friedrich, Klaus G; Di Cerbo, Pilar; Di Cave, David; De Liberato, Claudio

    2011-10-12

    Giardia duodenalis and Entamoeba spp. are among the most common intestinal human protozoan parasites worldwide and they are frequently reported in captive non-human primates (NHP). From a public health point of view, infected animals in zoos constitute a risk for animal caretakers and visitors. In this study we carried out the molecular identification of G. duodenalis and Entamoeba spp. from nine species of primates housed in the zoological garden of Rome, to better ascertain their occurrence and zoonotic potential. G. duodenalis was found only in Lemur catta (47.0%). Entamoeba spp. were detected in all species studied, with the exception of Eulemur macaco and Varecia rubra. The number of positive pools ranged from 5.9% in L. catta to 81.2% in Mandrillus sphinx; in Pan troglodytes the observed prevalence was 53.6%. A mixed Entamoeba-Giardia infection was recorded only in one sample of L. catta. All G. duodenalis isolates belonged to the zoonotic assemblage B, sub assemblage BIV. Three Entamoeba species were identified: E. hartmanni, E. coli and E. dispar. Our results highlight the importance of regularly testing animals kept in zoos for the diagnosis of zoonotic parasites, in order to evaluate their pathogenic role in the housed animals and the zoonotic risk linked to their presence. A quick detection of the arrival of pathogens into the enclosures could also be a prerequisite to limit their spread into the structure via the introduction of specific control strategies. The need for molecular identification of some parasite species/genotype in order to better define the zoonotic risk is also highlighted.

  11. Radiosynthesis and initial characterization of a PDE10A specific PET tracer [18F]AMG 580 in non-human primates.

    Science.gov (United States)

    Hwang, Dah-Ren; Hu, Essa; Allen, Jennifer R; Davis, Carl; Treanor, James; Miller, Silke; Chen, Hang; Shi, Bingzhi; Narayanan, Tanjorie K; Barret, Olivier; Alagille, David; Yu, Zhigang; Slifstein, Mark

    2015-08-01

    Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the breakdown of cyclic nucleotides which are important second messengers for neurotransmission. Inhibition of PDE10A has been identified as a potential target for treatment of various neuropsychiatric disorders. To assist drug development, we have identified a selective PDE10A positron emission tomography (PET) tracer, AMG 580. We describe here the radiosynthesis of [(18)F]AMG 580 and in vitro and in vivo characterization results. The potency and selectivity were determined by in vitro assay using [(3)H]AMG 580 and baboon brain tissues. [(18)F]AMG 580 was prepared by a 1-step [(18)F]fluorination procedure. Dynamic brain PET scans were performed in non-human primates. Regions-of-interest were defined on individuals' MRIs and transferred to the co-registered PET images. Data were analyzed using two tissue compartment analysis (2TC), Logan graphical (Logan) analysis with metabolite-corrected input function and the simplified reference tissue model (SRTM) method. A PDE10A inhibitor and unlabeled AMG 580 were used to demonstrate the PDE10A specificity. KD was estimated by Scatchard analysis of high and low affinity PET scans. AMG 580 has an in vitro KD of 71.9 pM. Autoradiography showed specific uptake in striatum. Mean activity of 121 ± 18 MBq was used in PET studies. In Rhesus, the baseline BPND for putamen and caudate was 3.38 and 2.34, respectively, via 2TC, and 3.16, 2.34 via Logan, and 2.92, and 2.01 via SRTM. A dose dependent decrease of BPND was observed by the pre-treatment with a PDE10A inhibitor. In baboons, 0.24 mg/kg dose of AMG 580 resulted in about 70% decrease of BPND. The in vivo KD of [(18)F]AMG 580 was estimated to be around 0.44 nM in baboons. [(18)F]AMG 580 is a selective and potent PDE10A PET tracer with excellent specific striatal binding in non-human primates. It warrants further evaluation in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a mouse and a non-human primate tuberculosis model.

    Directory of Open Access Journals (Sweden)

    Rolf Billeskov

    Full Text Available Here we report for the first time on the immunogenicity and protective efficacy of a vaccine strategy involving the adjuvanted fusion protein "H28" (consisting of Ag85B-TB10.4-Rv2660c and Modified Vaccinia Virus Ankara expressing H28. We show that a heterologous prime-boost regimen involving priming with H28 in a Th1 adjuvant followed by boosting with H28 expressed by MVA (H28/MVA28 induced the highest percentage of IFN-γ expressing T cells, the highest production of IFN-γ per single cell and the highest induction of CD8 T cells compared to either of the vaccines given alone. In contrast, in mice vaccinated with adjuvanted recombinant H28 alone (H28/H28 we observed the highest production of IL-2 per single cell and the highest frequency of antigen specific TNF-α/IL-2 expressing CD4 T cells pre and post infection. Interestingly, TNF-α/IL-2 expressing central memory-like CD4 T cells showed a significant positive correlation with protection at week 6 post infection, whereas the opposite was observed for post infection CD4 T cells producing only IFN-γ. Moreover, as a BCG booster vaccine in a clinically relevant non-human primate TB model, the H28/H28 vaccine strategy induced a slightly more prominent reduction of clinical disease and pathology for up to one year post infection compared to H28/MVA28. Taken together, our data showed that the adjuvanted subunit and MVA strategies led to different T cell subset combinations pre and post infection and that TNF-α/IL-2 double producing but not IFN-γ single producing CD4 T cell subsets correlated with protection in the mouse TB model. Moreover, our data demonstrated that the H28 vaccine antigen was able to induce strong protection in both a mouse and a non-human primate TB model.

  13. Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex.

    Science.gov (United States)

    Suner, Selim; Fellows, Matthew R; Vargas-Irwin, Carlos; Nakata, Gordon Kenji; Donoghue, John P

    2005-12-01

    related signals for neural prostheses, as well as for fundamental research applications, can be reliably obtained for long time periods using a monolithic microelectrode array in primate MI and potentially from other cortical areas as well.

  14. Omega-3 fatty acids from fish oil lower anxiety, improve cognitive functions and reduce spontaneous locomotor activity in a non-human primate.

    Directory of Open Access Journals (Sweden)

    Nina Vinot

    Full Text Available Omega-3 (ω3 polyunsaturated fatty acids (PUFA are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus, a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group. Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05, while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001, a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty

  15. Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

    Science.gov (United States)

    Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

    2017-12-01

    The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

  16. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates

    Science.gov (United States)

    Doloff, Joshua C.; Veiseh, Omid; Vegas, Arturo J.; Tam, Hok Hei; Farah, Shady; Ma, Minglin; Li, Jie; Bader, Andrew; Chiu, Alan; Sadraei, Atieh; Aresta-Dasilva, Stephanie; Griffin, Marissa; Jhunjhunwala, Siddharth; Webber, Matthew; Siebert, Sean; Tang, Katherine; Chen, Michael; Langan, Erin; Dholokia, Nimit; Thakrar, Raj; Qi, Meirigeng; Oberholzer, Jose; Greiner, Dale L.; Langer, Robert; Anderson, Daniel G.

    2017-06-01

    Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization. Interestingly, colony stimulating factor-1 receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, reactive oxygen species production and phagocytosis. Our results indicate that targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.

  17. An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

    Science.gov (United States)

    Vailas, Arthur C.; Martinez, Daniel A.

    1999-01-01

    Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, media] gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

  18. Ebola virus genome plasticity as a marker of its passaging history: a comparison of in vitro passaging to non-human primate infection.

    Directory of Open Access Journals (Sweden)

    Jeffrey R Kugelman

    Full Text Available To identify polymorphic sites that could be used as biomarkers of Ebola virus passage history, we repeatedly amplified Ebola virus (Kikwit variant in vitro and in vivo and performed deep sequencing analysis of the complete genomes of the viral subpopulations. We then determined the sites undergoing selection during passage in Vero E6 cells. Four locations within the Ebola virus Kikwit genome were identified that together segregate cell culture-passaged virus and virus obtained from infected non-human primates. Three of the identified sites are located within the glycoprotein gene (GP sequence: the poly-U (RNA editing site at position 6925, as well as positions 6677, and 6179. One site was found in the VP24 gene at position 10833. In all cases, in vitro and in vivo, both populations (majority and minority variants were maintained in the viral swarm, with rapid selections occurring after a few passages or infections. This analysis approach will be useful to differentiate whether filovirus stocks with unknown history have been passaged in cell culture and may support filovirus stock standardization for medical countermeasure development.

  19. Multiple signaling pathways convey central and peripheral signals to regulate pituitary function: Lessons from human and non-human primate models.

    Science.gov (United States)

    Vázquez-Borrego, M C; Gahete, M D; Martínez-Fuentes, A J; Fuentes-Fayos, A C; Castaño, J P; Kineman, R D; Luque, R M

    2018-03-05

    The anterior pituitary gland is a key organ involved in the control of multiple physiological functions including growth, reproduction, metabolism and stress. These functions are controlled by five distinct hormone-producing pituitary cell types that produce growth hormone (somatotropes), prolactin (lactotropes), adrenocorticotropin (corticotropes), thyrotropin (thyrotropes) and follicle stimulating hormone/luteinizing hormone (gonadotropes). Classically, the synthesis and release of pituitary hormones was thought to be primarily regulated by central (neuroendocrine) signals. However, it is now becoming apparent that factors produced by pituitary hormone targets (endocrine and non-endocrine organs) can feedback directly to the pituitary to adjust pituitary hormone synthesis and release. Therefore, pituitary cells serve as sensors to integrate central and peripheral signals in order to fine-tune whole-body homeostasis, although it is clear that pituitary cell regulation is species-, age- and sex-dependent. The purpose of this review is to provide a comprehensive, general overview of our current knowledge of both central and peripheral regulators of pituitary cell function and associated intracellular mechanisms, focusing on human and non-human primates. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. A retrospective evaluation of species-specific sensitivity for neurological signs in toxicological studies: Is the dog more sensitive than the non-human primate?

    Science.gov (United States)

    Backes, Kathrin; Lorenz, Helga; Laplanche, Loic; Hudzik, Thomas J; Potschka, Heidrun; Hempel, Katja

    2016-01-22

    Selection of the appropriate non-rodent species in preclinical programs is crucial for good translatability and human safety. There is no data available in the literature which provides exact comparison of dog and non-human primate (NHP) sensitivity regarding neurological signs in toxicological studies. We performed a retrospective analysis of 174 toxicity studies with 15 neuroscience substances. Neurological signs in dogs and NHPs were evaluated in correlation to exposure data. Overall incidence of substance induced convulsions was similar in both species and no gender differences were observed. The reported liability of beagles to spontaneous convulsions was not confirmed in our studies. The symptom tremor showed the best inter-species translatability. The current toxicological study design does not include exposure assessment at the time-point of neurological signs, therefore, we propose to include additional toxicokinetic samples. Our analysis revealed factors including housing, handling, and behavior, which prevents direct species comparison. In addition only one non-rodent species is routinely tested in development programs, therefore data for both species is rare. We however, had sufficient data which enabled comparison for one compound. In the spirit of 3Rs further examples should be evaluated. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Structural architecture of the social network of a non-human primate (Macaca sylvanus): a study of its topology in La Forêt des Singes, Rocamadour.

    Science.gov (United States)

    Sosa, Sebastian

    2014-01-01

    For a decade, technological or natural networks have appeared to have a common mathematical architecture. This type of architecture has a node connectivity which follows a power law distribution. This architecture confers to these networks a resistance property to the loss of nodes. Such properties are advantageous for evolutional networks through time. Thus, this architecture can be expected in animal social networks. Another characteristic commonly met concerns the structuration of the network into communities by the mechanism of assortative mixing by vertex degree (i.e. by the number of ties individuals have). Such a structure is a reflection of evolutional mechanisms: the preferential attachment and the triadic closure processes. Using recent analytical techniques on an affiliative social network in a non-human primate species (Macaca sylvanus), we analysed the mathematical architecture and its properties. We demonstrate that in spite of the use of a recent protocol supposed to permit this type of analysis, the type of distribution cannot be clearly determined, encouraging us to carefully interpret the results obtained until then. Nevertheless, we observed interesting properties of the network at an ecological and evolutional level with network resilience that allows a cohesive society to be maintained even when faced with a catastrophe (high predation, epidemic).

  2. Generation and characterization of large-particle aerosols using a center flow tangential aerosol generator with a non-human-primate, head-only aerosol chamber.

    Science.gov (United States)

    Bohannon, J Kyle; Lackemeyer, Matthew G; Kuhn, Jens H; Wada, Jiro; Bollinger, Laura; Jahrling, Peter B; Johnson, Reed F

    2015-01-01

    Aerosol droplets or particles produced from infected respiratory secretions have the potential to infect another host through inhalation. These respiratory particles can be polydisperse and range from 0.05 to 500 µm in diameter. Animal models of infection are generally established to facilitate the potential licensure of candidate prophylactics and/or therapeutics. Consequently, aerosol-based animal infection models are needed to properly study and counter airborne infections. Ideally, experimental aerosol exposure should reliably result in animal disease that faithfully reproduces the modeled human disease. Few studies have been performed to explore the relationship between exposure particle size and induced disease course for infectious aerosol particles. The center flow tangential aerosol generator (CenTAG™) produces large-particle aerosols capable of safely delivering a variety of infectious aerosols to non-human primates (NHPs) within a Class III Biological Safety Cabinet (BSC) for establishment or refinement of NHP infectious disease models. Here, we report the adaptation of this technology to the Animal Biosafety Level 4 (ABSL-4) environment for the future study of high-consequence viral pathogens and the characterization of CenTAG™-created sham (no animal, no virus) aerosols using a variety of viral growth media and media supplements.

  3. Cross-species and tissue variations in cyanide detoxification rates in rodents and non-human primates on protein-restricted diet.

    Science.gov (United States)

    Kimani, S; Moterroso, V; Morales, P; Wagner, J; Kipruto, S; Bukachi, F; Maitai, C; Tshala-Katumbay, D

    2014-04-01

    We sought to elucidate the impact of diet, cyanide or cyanate exposure on mammalian cyanide detoxification capabilities (CDC). Male rats (~8 weeks old) (N=52) on 75% sulfur amino acid (SAA)-deficient diet were treated with NaCN (2.5mg/kg bw) or NaOCN (50mg/kg bw) for 6 weeks. Macaca fascicularis monkeys (~12 years old) (N=12) were exclusively fed cassava for 5 weeks. CDC was assessed in plasma, or spinal cord, or brain. In rats, NaCN induced seizures under SAA-restricted diet whereas NaOCN induced motor deficits. No deficits were observed in non-human primates. Under normal diet, the CDC were up to ~80× faster in the nervous system (14 ms to produce one μmol of thiocyanate from the detoxification of cyanide) relative to plasma. Spinal cord CDC was impaired by NaCN, NaOCN, or SAA deficiency. In M. fascicularis, plasma CDC changed proportionally to total proteins (r=0.43; pcyanide may result from a "multiple hit" by the toxicity of cyanide or its cyanate metabolite, the influences of dietary deficiencies, and the tissue variations in CDC. Chronic dietary reliance on cassava may cause metabolic derangement including poor CDC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Testing the H56 Vaccine Delivered in 4 Different Adjuvants as a BCG-Booster in a Non-Human Primate Model of Tuberculosis.

    Science.gov (United States)

    Billeskov, Rolf; Tan, Esterlina V; Cang, Marjorie; Abalos, Rodolfo M; Burgos, Jasmin; Pedersen, Bo Vestergaard; Christensen, Dennis; Agger, Else Marie; Andersen, Peter

    2016-01-01

    The search for new and improved tuberculosis (TB) vaccines has focused on IFN-γ both for selecting antigens and for evaluating vaccine delivery strategies. The essential role of IFN-γ in endogenous host protection is well established, but it is still uncertain whether this also holds true for vaccine protection. Here we evaluate the H56 fusion protein vaccine as a BCG booster in a non-human primate (NHP) model of TB that closely recapitulates human TB pathogenesis. To date, only a handful of novel adjuvants have been tested in the NHP model of TB, and therefore we administered H56 in 3 novel cationic liposome adjuvants of increasing immunogenicity (CAF01, CAF04, CAF05) and compared them to H56 in the IC31® adjuvant previously reported to promote protection in this model. The individual clinical parameters monitored during infection (weight, ESR, X-ray) all correlated with survival, and boosting BCG with H56 in all adjuvants resulted in better survival rates compared to BCG alone. The adjuvants promoted IFN-γ-responses of increasing intensity as measured by ELISPOT in the peripheral blood, but the level of vaccine-specific IFN-γ production did not correlate with or predict disease outcome. This study's main outcome underscores the importance of the choice of adjuvant for TB subunit vaccines, and secondly it highlights the need for better correlates of protection in preclinical models of TB.

  5. Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates

    Science.gov (United States)

    Thompson, Jacqueline R.; Valleau, Jeanette C.; Barling, Ashley N.; Franco, Juliana G.; DeCapo, Madison; Bagley, Jennifer L.; Sullivan, Elinor L.

    2017-01-01

    Perinatal exposure to maternal obesity and high-fat diet (HFD) consumption not only poses metabolic risks to offspring but also impacts brain development and mental health. Using a non-human primate model, we observed a persistent increase in anxiety in juvenile offspring exposed to a maternal HFD. Postweaning HFD consumption also increased anxiety and independently increased stereotypic behaviors. These behavioral changes were associated with modified cortisol stress response and impairments in the development of the central serotonin synthesis, with altered tryptophan hydroxylase-2 mRNA expression in the dorsal and median raphe. Postweaning HFD consumption decreased serotonergic immunoreactivity in area 10 of the prefrontal cortex. These results suggest that perinatal exposure to HFD consumption programs development of the brain and endocrine system, leading to behavioral impairments associated with mental health and neurodevelopmental disorders. Also, an early nutritional intervention (consumption of the control diet at weaning) was not sufficient to ameliorate many of the behavioral changes, such as increased anxiety, that were induced by maternal HFD consumption. Given the level of dietary fat consumption and maternal obesity in developed nations these findings have important implications for the mental health of future generations. PMID:28785241

  6. Targeting accuracy and closing timeline of the microbubble-enhanced focused ultrasound blood-brain barrier opening in non-human primates

    Science.gov (United States)

    Marquet, Fabrice; Tung, Yao-Sheng; Teichert, Tobias; Wu, Shih-Ying; Wang, Shutao; Downs, Matthew; Ferrera, Vincent P.; Konofagou, Elisa E.

    2012-11-01

    The delivery of drugs to specific neural targets faces two fundamental problems: Most drugs do not cross the blood-brain barrier and those that do spread to all parts of the brain. To date there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier disruption using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500 kHz spherical transducer ultrasound setup for use in the non-human primate. Using this system for selective blood-brain barrier disruption is technically no more challenging than positioning a TMS coil, and does not rely on MRI-guided targeting or expensive phased array ultrasound systems. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. Here we tested the accuracy of the system by targeting the caudate nucleus of the basal ganglia in two macaque monkeys. Our results show that average in-plane error of the system is on the order of 2 mm and targeting error in depth, i.e., along the ultrasound path, is even smaller and averaged 1.2 mm. In summary, targeting accuracy of our system is good enough to enable the selective delivery of drugs to specific sub-structures of the basal ganglia.

  7. Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

    Science.gov (United States)

    Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

    2016-09-07

    Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Poxvirus antigen staining of immune cells as a biomarker to predict disease outcome in monkeypox and cowpox virus infection in non-human primates.

    Directory of Open Access Journals (Sweden)

    Haifeng Song

    Full Text Available Infection of non-human primates (NHPs such as rhesus and cynomolgus macaques with monkeypox virus (MPXV or cowpox virus (CPXV serve as models to study poxvirus pathogenesis and to evaluate vaccines and anti-orthopox therapeutics. Intravenous inoculation of macaques with high dose of MPXV (>1-2×10(7 PFU or CPXV (>10(2 PFU results in 80% to 100% mortality and 66 to 100% mortality respectively. Here we report that NHPs with positive detection of poxvirus antigens in immune cells by flow cytometric staining, especially in monocytes and granulocytes succumbed to virus infection and that early positive pox staining is a strong predictor for lethality. Samples from four independent studies were analyzed. Eighteen NHPs from three different experiments were inoculated with two different MPXV strains at lethal doses. Ten NHPs displayed positive pox-staining and all 10 NHPs reached moribund endpoint. In contrast, none of the three NHPs that survived anticipated lethal virus dose showed apparent virus staining in the monocytes and granulocytes. In addition, three NHPs that were challenged with a lethal dose of MPXV and received cidofovir treatment were pox-antigen negative and all three NHPs survived. Furthermore, data from a CPXV study also demonstrated that 6/9 NHPs were pox-antigen staining positive and all 6 NHPs reached euthanasia endpoint, while the three survivors were pox-antigen staining negative. Thus, we conclude that monitoring pox-antigen staining in immune cells can be used as a biomarker to predict the prognosis of virus infection. Future studies should focus on the mechanisms and implications of the pox-infection of immune cells and the correlation between pox-antigen detection in immune cells and disease progression in human poxviral infection.

  9. AdHu5Ag85A Respiratory Mucosal Boost Immunization Enhances Protection against Pulmonary Tuberculosis in BCG-Primed Non-Human Primates.

    Science.gov (United States)

    Jeyanathan, Mangalakumari; Shao, Zhongqi; Yu, Xuefeng; Harkness, Robin; Jiang, Rong; Li, Junqiang; Xing, Zhou; Zhu, Tao

    2015-01-01

    Persisting high global tuberculosis (TB) morbidity and mortality and poor efficacy of BCG vaccine emphasizes an urgent need for developing effective novel boost vaccination strategies following parenteral BCG priming in humans. Most of the current lead TB vaccine candidates in the global pipeline were developed for parenteral route of immunization. Compelling evidence indicates respiratory mucosal delivery of vaccine to be the most effective way to induce robust local mucosal protective immunity against pulmonary TB. However, despite ample supporting evidence from various animal models, there has been a lack of evidence supporting the safety and protective efficacy of respiratory mucosal TB vaccination in non-human primates (NHP) and humans. By using a rhesus macaque TB model we have evaluated the safety and protective efficacy of a recombinant human serotype 5 adenovirus-based TB vaccine (AdHu5Ag85A) delivered via the respiratory mucosal route. We show that mucosal AdHu5Ag85A boost immunization was safe and well tolerated in parenteral BCG-primed rhesus macaques. A single AdHu5Ag85A mucosal boost immunization in BCG-primed rhesus macaques enhanced the antigen-specific T cell responses. Boost immunization significantly improved the survival and bacterial control following M.tb challenge. Furthermore, TB-related lung pathology and clinical outcomes were lessened in BCG-primed, mucosally boosted animals compared to control animals. Thus, for the first time we show that a single respiratory mucosal boost immunization with a novel TB vaccine enhances protection against pulmonary TB in parenteral BCG-primed NHP. Our study provides the evidence for the protective potential of AdHu5Ag85A as a respiratory mucosal boost TB vaccine for human application.

  10. Coordinated defects in hepatic long chain fatty acid metabolism and triglyceride accumulation contribute to insulin resistance in non-human primates.

    Directory of Open Access Journals (Sweden)

    Subhash Kamath

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by accumulation of triglycerides (TG in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant.To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR and lean insulin sensitive (IS baboons in relation with hepatic and peripheral insulin sensitivity.Twenty baboons with varying grades of adiposity were studied. Hepatic (liver and peripheral (mainly muscle insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance.Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA was greater than saturated (LC-SFA fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons.Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans.

  11. A rapid immunization strategy with a live attenuated tetravalent dengue vaccine elicits protective neutralizing antibody responses in non-human primates

    Directory of Open Access Journals (Sweden)

    Yuping eAmbuel

    2014-06-01

    Full Text Available Dengue viruses (DENVs cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine (TDV that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2 and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3 and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0 at two different anatomical locations with a needle-free disposable syringe jet injection (DSJI delivery devices (PharmaJet in non-human primates (NHP. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (two months later vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3 and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post- challenge. RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas.

  12. Successful Repeated Hepatic Gene Delivery in Mice and Non-human Primates Achieved by Sequential Administration of AAV5ch and AAV1.

    Science.gov (United States)

    Majowicz, Anna; Salas, David; Zabaleta, Nerea; Rodríguez-Garcia, Estefania; González-Aseguinolaza, Gloria; Petry, Harald; Ferreira, Valerie

    2017-08-02

    In the gene therapy field, re-administration of adeno-associated virus (AAV) is an important topic because a decrease in therapeutic protein expression might occur over time. However, an efficient re-administration with the same AAV serotype is impossible due to serotype-specific, anti-AAV neutralizing antibodies (NABs) that are produced after initial AAV treatment. To address this issue, we explored the feasibility of using chimeric AAV serotype 5 (AAV5ch) and AAV1 for repeated liver-targeted gene delivery. To develop a relevant model, we immunized animals with a high dose of AAV5ch-human secreted embryonic alkaline phosphatase (hSEAP) that generates high levels of anti-AAV5ch NAB. Secondary liver transduction with the same dose of AAV1-human factor IX (hFIX) in the presence of high levels of anti-AAV5ch NAB proved to be successful because expression/activity of both reporter transgenes was observed. This is the first time that two different transgenes are shown to be produced by non-human primate (NHP) liver after sequential administration of clinically relevant doses of both AAV5ch and AAV1. The levels of transgene proteins achieved after delivery with AAV5ch and AAV1 illustrate the possibility of both serotypes for liver targeting. Furthermore, transgene DNA and RNA biodistribution patterns provided insight into the potential cause of decrease or loss of transgene protein expression over time in NHPs. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  13. Versatile, modular 3D microelectrode arrays for neuronal ensemble recordings: from design to fabrication, assembly, and functional validation in non-human primates

    Science.gov (United States)

    Barz, F.; Livi, A.; Lanzilotto, M.; Maranesi, M.; Bonini, L.; Paul, O.; Ruther, P.

    2017-06-01

    Objective. Application-specific designs of electrode arrays offer an improved effectiveness for providing access to targeted brain regions in neuroscientific research and brain machine interfaces. The simultaneous and stable recording of neuronal ensembles is the main goal in the design of advanced neural interfaces. Here, we describe the development and assembly of highly customizable 3D microelectrode arrays and demonstrate their recording performance in chronic applications in non-human primates. Approach. System assembly relies on a microfabricated stacking component that is combined with Michigan-style silicon-based electrode arrays interfacing highly flexible polyimide cables. Based on the novel stacking component, the lead time for implementing prototypes with altered electrode pitches is minimal. Once the fabrication and assembly accuracy of the stacked probes have been characterized, their recording performance is assessed during in vivo chronic experiments in awake rhesus macaques (Macaca mulatta) trained to execute reaching-grasping motor tasks. Main results. Using a single set of fabrication tools, we implemented three variants of the stacking component for electrode distances of 250, 300 and 350 µm in the stacking direction. We assembled neural probes with up to 96 channels and an electrode density of 98 electrodes mm-2. Furthermore, we demonstrate that the shank alignment is accurate to a few µm at an angular alignment better than 1°. Three 64-channel probes were chronically implanted in two monkeys providing single-unit activity on more than 60% of all channels and excellent recording stability. Histological tissue sections, obtained 52 d after implantation from one of the monkeys, showed minimal tissue damage, in accordance with the high quality and stability of the recorded neural activity. Significance. The versatility of our fabrication and assembly approach should significantly support the development of ideal interface geometries for a broad

  14. Effects of dietary resveratrol on the sleep-wake cycle in the non-human primate gray mouse lemur (Microcebus murinus).

    Science.gov (United States)

    Pifferi, F; Rahman, A; Languille, S; Auffret, A; Babiloni, C; Blin, O; Lamberty, Y; Richardson, J C; Aujard, F

    2012-04-01

    Converging evidence shows that the non-human primate gray mouse lemur (Microcebus murinus) is ideal for the study of the aging process and for testing the effects of new therapies and dietary interventions on age-associated pathologies. One such dietary supplement is resveratrol (RSV), a dietary polyphenolic compound with several positive effects on metabolic functions and longevity. However, little is known about the effect of RSV on the lemur sleep-wake cycle, which reflects mammalian brain function and health. In the present study, the authors investigated this effect by comparing sleep-wake cycles in adult lemurs based on electroencephalographic (EEG) rhythms. The effect of short-term RSV supplementation on the sleep-wake cycle of mouse lemurs was evaluated in entrained conditions (long-day photoperiods, light:dark 14:10). After 3 wks of RSV supplementation, the animals exhibited a significantly increased proportion of active-wake time, occurring mainly during the resting phase of the sleep-wake cycle (+163%). The increase in active-wake time with RSV supplementation was accompanied by a significant reduction of both paradoxical sleep (-95%) and slow-wave sleep (-38%). These changes mainly occurred during the resting phase of the sleep-wake cycle (RSV supplementation induced negligible changes in active-wake time during the active phase of the sleep-wake cycle). The present data suggest that RSV may be a potent regulator of sleep-wake rhythms and could be of major interest in the study of sleep perturbations associated with aging and neuropathology.

  15. Characterization of Enteroviruses from non-human primates in cameroon revealed virus types widespread in humans along with candidate new types and species.

    Directory of Open Access Journals (Sweden)

    Serge Alain Sadeuh-Mba

    Full Text Available Enteroviruses (EVs infecting African Non-Human Primates (NHP are still poorly documented. This study was designed to characterize the genetic diversity of EVs among captive and wild NHP in Cameroon and to compare this diversity with that found in humans. Stool specimens were collected in April 2008 in NHP housed in sanctuaries in Yaounde and neighborhoods. Moreover, stool specimens collected from wild NHP from June 2006 to October 2008 in the southern rain forest of Cameroon were considered. RNAs purified directly from stool samples were screened for EVs using a sensitive RT-nested PCR targeting the VP1 capsid coding gene whose nucleotide sequence was used for molecular typing. Captive chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla were primarily infected by EV types already reported in humans in Cameroon and elsewhere: Coxsackievirus A13 and A24, Echovirus 15 and 29, and EV-B82. Moreover EV-A119, a novel virus type recently described in humans in central and west Africa, was also found in a captive Chimpanzee. EV-A76, which is a widespread virus in humans, was identified in wild chimpanzees, thus suggesting its adaptation and parallel circulation in human and NHP populations in Cameroon. Interestingly, some EVs harbored by wild NHP were genetically distinct from all existing types and were thus assigned as new types. One chimpanzee-derived virus was tentatively assigned as EV-J121 in the EV-J species. In addition, two EVs from wild monkeys provisionally registered as EV-122 and EV-123 were found to belong to a candidate new species. Overall, this study indicates that the genetic diversity of EVs among NHP is more important than previously known and could be the source of future new emerging human viral diseases.

  16. Reversible femtosecond laser-assisted myopia correction: a non-human primate study of lenticule re-implantation after refractive lenticule extraction.

    Directory of Open Access Journals (Sweden)

    Andri K Riau

    Full Text Available LASIK (laser-assisted in situ keratomileusis is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx utilizes solely a femtosecond laser (FSL to incise an intrastromal refractive lenticule (RL, which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors.

  17. Characterization of Enteroviruses from Non-Human Primates in Cameroon Revealed Virus Types Widespread in Humans along with Candidate New Types and Species

    Science.gov (United States)

    Sadeuh-Mba, Serge Alain; Bessaud, Maël; Joffret, Marie-Line; Endegue Zanga, Marie-Claire; Balanant, Jean; Mpoudi Ngole, Eitel; Njouom, Richard; Reynes, Jean-Marc; Delpeyroux, Francis; Rousset, Dominique

    2014-01-01

    Enteroviruses (EVs) infecting African Non-Human Primates (NHP) are still poorly documented. This study was designed to characterize the genetic diversity of EVs among captive and wild NHP in Cameroon and to compare this diversity with that found in humans. Stool specimens were collected in April 2008 in NHP housed in sanctuaries in Yaounde and neighborhoods. Moreover, stool specimens collected from wild NHP from June 2006 to October 2008 in the southern rain forest of Cameroon were considered. RNAs purified directly from stool samples were screened for EVs using a sensitive RT-nested PCR targeting the VP1 capsid coding gene whose nucleotide sequence was used for molecular typing. Captive chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) were primarily infected by EV types already reported in humans in Cameroon and elsewhere: Coxsackievirus A13 and A24, Echovirus 15 and 29, and EV-B82. Moreover EV-A119, a novel virus type recently described in humans in central and west Africa, was also found in a captive Chimpanzee. EV-A76, which is a widespread virus in humans, was identified in wild chimpanzees, thus suggesting its adaptation and parallel circulation in human and NHP populations in Cameroon. Interestingly, some EVs harbored by wild NHP were genetically distinct from all existing types and were thus assigned as new types. One chimpanzee-derived virus was tentatively assigned as EV-J121 in the EV-J species. In addition, two EVs from wild monkeys provisionally registered as EV-122 and EV-123 were found to belong to a candidate new species. Overall, this study indicates that the genetic diversity of EVs among NHP is more important than previously known and could be the source of future new emerging human viral diseases. PMID:25079078

  18. Induction of alpha-synuclein pathology in the enteric nervous system of the rat and non-human primate results in gastrointestinal dysmotility and transient CNS pathology.

    Science.gov (United States)

    Manfredsson, Fredric P; Luk, Kelvin C; Benskey, Matthew J; Gezer, Aysegul; Garcia, Joanna; Kuhn, Nathan C; Sandoval, Ivette M; Patterson, Joseph R; O'Mara, Alana; Yonkers, Reid; Kordower, Jeffrey H

    2018-04-01

    Alpha-Synuclein (α-syn) is by far the most highly vetted pathogenic and therapeutic target in Parkinson's disease. Aggregated α-syn is present in sporadic Parkinson's disease, both in the central nervous system (CNS) and peripheral nervous system (PNS). The enteric division of the PNS is of particular interest because 1) gastric dysfunction is a key clinical manifestation of Parkinson's disease, and 2) Lewy pathology in myenteric and submucosal neurons of the enteric nervous system (ENS) has been referred to as stage zero in the Braak pathological staging of Parkinson's disease. The presence of Lewy pathology in the ENS and the fact that patients often experience enteric dysfunction before the onset of motor symptoms has led to the hypothesis that α-syn pathology starts in the periphery, after which it spreads to the CNS via interconnected neural pathways. Here we sought to directly test this hypothesis in rodents and non-human primates (NHP) using two distinct models of α-syn pathology: the α-syn viral overexpression model and the preformed fibril (PFF) model. Subjects (rat and NHP) received targeted enteric injections of PFFs or adeno-associated virus overexpressing the Parkinson's disease associated A53T α-syn mutant. Rats were evaluated for colonic motility monthly and sacrificed at 1, 6, or 12 months, whereas NHPs were sacrificed 12 months following inoculation, after which the time course and spread of pathology was examined in all animals. Rats exhibited a transient GI phenotype that resolved after four months. Minor α-syn pathology was observed in the brainstem (dorsal motor nucleus of the vagus and locus coeruleus) 1 month after PFF injections; however, no pathology was observed at later time points (nor in saline or monomer treated animals). Similarly, a histopathological analysis of the NHP brains revealed no pathology despite the presence of robust α-syn pathology throughout the ENS which persisted for the entirety of the study (12

  19. The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates

    Science.gov (United States)

    Wang, Jing; Tricoche, Nancy; Du, Lanying; Hunter, Meredith; Zhan, Bin; Goud, Gaddam; Didier, Elizabeth S.; Liu, Jing; Lu, Lu; Marx, Preston A.; Jiang, Shibo; Lustigman, Sara

    2012-01-01

    Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant. PMID

  20. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides.

    Science.gov (United States)

    Rayner, Katey J; Esau, Christine C; Hussain, Farah N; McDaniel, Allison L; Marshall, Stephanie M; van Gils, Janine M; Ray, Tathagat D; Sheedy, Frederick J; Goedeke, Leigh; Liu, Xueqing; Khatsenko, Oleg G; Kaimal, Vivek; Lees, Cynthia J; Fernandez-Hernando, Carlos; Fisher, Edward A; Temel, Ryan E; Moore, Kathryn J

    2011-10-19

    Cardiovascular disease remains the leading cause of mortality in westernized countries, despite optimum medical therapy to reduce the levels of low-density lipoprotein (LDL)-associated cholesterol. The pursuit of novel therapies to target the residual risk has focused on raising the levels of high-density lipoprotein (HDL)-associated cholesterol in order to exploit its atheroprotective effects. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of lipid metabolism and are thus a new class of target for therapeutic intervention. MicroRNA-33a and microRNA-33b (miR-33a/b) are intronic miRNAs whose encoding regions are embedded in the sterol-response-element-binding protein genes SREBF2 and SREBF1 (refs 3-5), respectively. These miRNAs repress expression of the cholesterol transporter ABCA1, which is a key regulator of HDL biogenesis. Recent studies in mice suggest that antagonizing miR-33a may be an effective strategy for raising plasma HDL levels and providing protection against atherosclerosis; however, extrapolating these findings to humans is complicated by the fact that mice lack miR-33b, which is present only in the SREBF1 gene of medium and large mammals. Here we show in African green monkeys that systemic delivery of an anti-miRNA oligonucleotide that targets both miR-33a and miR-33b increased hepatic expression of ABCA1 and induced a sustained increase in plasma HDL levels over 12 weeks. Notably, miR-33 antagonism in this non-human primate model also increased the expression of miR-33 target genes involved in fatty acid oxidation (CROT, CPT1A, HADHB and PRKAA1) and reduced the expression of genes involved in fatty acid synthesis (SREBF1, FASN, ACLY and ACACA), resulting in a marked suppression of the plasma levels of very-low-density lipoprotein (VLDL)-associated triglycerides, a finding that has not previously been observed in mice. These data establish, in a model that is highly relevant to humans, that pharmacological inhibition

  1. Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments.

    Science.gov (United States)

    Bassett, Leanne; Troncy, Eric; Pouliot, Mylene; Paquette, Dominique; Ascah, Alexis; Authier, Simon

    2014-01-01

    required by regulators. Non-human primates represent an important model in seizure liability assessments given similarities to humans and a high translational potential. Copyright © 2014. Published by Elsevier Inc.

  2. Organ Doses Associated with Partial-Body Irradiation with 2.5% Bone Marrow Sparing of the Non-Human Primate: A Retrospective Study.

    Science.gov (United States)

    Prado, C; MacVittie, T J; Bennett, A W; Kazi, A; Farese, A M; Prado, K

    2017-12-01

    A partial-body irradiation model with approximately 2.5% bone marrow sparing (PBI/BM2.5) was established to determine the radiation dose-response relationships for the prolonged and delayed multi-organ effects of acute radiation exposure. Historically, doses reported to the entire body were assumed to be equal to the prescribed dose at some defined calculation point, and the dose-response relationship for multi-organ injury has been defined relative to the prescribed dose being delivered at this point, e.g., to a point at mid-depth at the level of the xiphoid of the non-human primate (NHP). In this retrospective-dose study, the true distribution of dose within the major organs of the NHP was evaluated, and these doses were related to that at the traditional dose-prescription point. Male rhesus macaques were exposed using the PBI/BM2.5 protocol to a prescribed dose of 10 Gy using 6-MV linear accelerator photons at a rate of 0.80 Gy/min. Point and organ doses were calculated for each NHP from computed tomography (CT) scans using heterogeneous density data. The prescribed dose of 10.0 Gy to a point at midline tissue assuming homogeneous media resulted in 10.28 Gy delivered to the prescription point when calculated using the heterogeneous CT volume of the NHP. Respective mean organ doses to the volumes of nine organs, including the heart, lung, bowel and kidney, were computed. With modern treatment planning systems, utilizing a three-dimensional reconstruction of the NHP's CT images to account for the variations in body shape and size, and using density corrections for each of the tissue types, bone, water, muscle and air, accurate determination of the differences in dose to the NHP can be achieved. Dose and volume statistics can be ascertained for any body structure or organ that has been defined using contouring tools in the planning system. Analysis of the dose delivered to critical organs relative to the total-body target dose will permit a more definitive analysis

  3. The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein

  4. The adjuvanticity of an O. volvulus-derived rOv-ASP-1 protein in mice using sequential vaccinations and in non-human primates.

    Science.gov (United States)

    Wang, Jing; Tricoche, Nancy; Du, Lanying; Hunter, Meredith; Zhan, Bin; Goud, Gaddam; Didier, Elizabeth S; Liu, Jing; Lu, Lu; Marx, Preston A; Jiang, Shibo; Lustigman, Sara

    2012-01-01

    Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.

  5. Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells.

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    Yu Cong

    2016-05-01

    Full Text Available Humans infected with yellow fever virus (YFV, a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM and dendritic cells (MoDC from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.

  6. MOLECULAR TYPING OF Giardia duodenalis ISOLATES FROM NONHUMAN PRIMATES HOUSED IN A BRAZILIAN ZOO

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    Erica Boarato David

    2014-01-01

    Full Text Available Giardia infections in captive nonhuman primates (NHP housed at a Brazilian zoo were investigated in order to address their zoonotic potential. Fresh fecal samples were collected from the floors of 22 enclosures where 47 primates of 18 different species were housed. The diagnosis of intestinal parasites after concentration by sedimentation and flotation methods revealed the following parasites and their frequencies: Giardia (18%; Entamoeba spp. (18%; Endolimax nana (4.5%; Iodamoeba spp. (4.5%; Oxyurid (4.5% and Strongylid (4.5%. Genomic DNA extracted from all samples was processed by PCR methods in order to amplify fragments of gdh and tpi genes of Giardia. Amplicons were obtained from samples of Ateles belzebuth, Alouatta caraya, Alouatta fusca and Alouatta seniculus. Clear sequences were only obtained for the isolates from Ateles belzebuth (BA1, Alouatta fusca (BA2 and Alouatta caraya (BA3. According to the phenetic analyses of these sequences, all were classified as assemblage A. For the tpi gene, all three isolates were grouped into sub-assemblage AII (BA1, BA2 and BA3 whereas for the gdh gene, only BA3 was sub-assemblage AII, and the BA1 and BA2 were sub-assemblage AI. Considering the zoonotic potential of the assemblage A, and that the animals of the present study show no clinical signs of infection, the data obtained here stresses that regular coproparasitological surveys are necessary to implement preventive measures and safeguard the health of the captive animals, of their caretakers and of people visiting the zoological gardens.

  7. Effect of body mass distribution on the ontogeny of positional behaviors in non-human primates: Longitudinal follow-up of infant captive olive baboons (Papio anubis).

    Science.gov (United States)

    Druelle, François; Aerts, Peter; Berillon, Gilles

    2016-11-01

    The diversity of primates' positional capabilities is unique among mammals. Indeed, they exhibit a daily repertoire composed of various locomotor and postural modes that may be linked to their particular morphological pattern. Because ontogeny undergoes parallel behavioral and morphological modifications, it may be useful to investigate the biomechanical consequences of the changing body shape. We, therefore, collected accurate quantitative and longitudinal data on positional behaviors, body mass distribution patterns, activities, and environment on a sample of six infant olive baboons, Papio anubis. These baboons are kept at the Primatology Station of the CNRS, France, where they live within the same social group. Individual behaviors were quantified using the focal sampling method. The body mass distribution was estimated according to a geometric model based on direct external measurements. Multivariate analysis enabled us to analyze the interactions between the data. Our results show that body mass distribution changes together with the ontogenetic changes in positional behaviors. At an early age, individuals have distally heavy segment masses in the limbs and an important fraction of the behavioral repertoire involves efficient grasping abilities. At the end of infancy, the same individuals have relatively more mass in proximal segments of the limbs and the proportion of quadrupedal walking is significantly higher while other climbing and suspensory behaviors decreased substantially. The present study experimentally confirms the association between body mass distribution and the positional repertoire of primates. These relationships, when interpreted in the context of basic biomechanical concepts, may improve our understanding of primate locomotion. We discuss further the implications of these functional relationships when modeling the evolutionary pathway of primates. Am. J. Primatol. 78:1201-1221, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley

  8. Energy expenditure evaluation in humans and non-human primates by SenseWear Armband. Validation of energy expenditure evaluation by SenseWear Armband by direct comparison with indirect calorimetry.

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    Francesca Casiraghi

    Full Text Available INTRODUCTION: The purpose of this study was to compare and validate the use of SenseWear Armband (SWA placed on the arm (SWA ARM and on the back (SWA BACK in healthy humans during resting and a cycle-ergometer exercise and to evaluate the SWA to estimate Resting Energy Expenditure (REE and Total Energy Expenditure (TEE in healthy baboons. METHODS: We studied 26 (15F/11M human subjects wearing SWA in two different anatomical sites (arm and back during resting and a cycle-ergometer test and directly compared these results with indirect calorimetry evaluation (IC, performed at the same time. We then inserted the SWA in a metabolic jacket for baboons and evaluated the TEE and REE in free living condition for 6 days in 21 (8F/13M non-human primates. RESULTS: In humans we found a good correlation between SWA place on the ARM and on the BACK with IC during the resting experiment (1.1±0.3 SWAs, 1±0.2 IC kcal/min and a slight underestimation in the SWAs data compared with IC during the cycle-ergometer exercise (5±1.9 SWA ARM, 4.5±1.5 SWA BACK and 5.4±2.1 IC kcal/min. In the non-human primate (baboons experiment SWA estimated a TEE of 0.54±0.009 kcal/min during free living and a REE of 0.82±0.06 kcal/min. CONCLUSION: SWA, an extremely simple and inexpensive apparatus, provides quite accurate measurements of energy expenditure in humans and in baboons. Energy expenditure data obtained with SWA are highly correlated with the data obtained with "gold standard", IC, in humans.

  9. Systems biology discoveries using non-human primate pluripotent stem and germ cells: novel gene and genomic imprinting interactions as well as unique expression patterns.

    Science.gov (United States)

    Ben-Yehudah, Ahmi; Easley, Charles A; Hermann, Brian P; Castro, Carlos; Simerly, Calvin; Orwig, Kyle E; Mitalipov, Shoukhrat; Schatten, Gerald

    2010-08-05

    The study of pluripotent stem cells has generated much interest in both biology and medicine. Understanding the fundamentals of biological decisions, including what permits a cell to maintain pluripotency, that is, its ability to self-renew and thereby remain immortal, or to differentiate into multiple types of cells, is of profound importance. For clinical applications, pluripotent cells, including both embryonic stem cells and adult stem cells, have been proposed for cell replacement therapy for a number of human diseases and disorders, including Alzheimer's, Parkinson's, spinal cord injury and diabetes. One challenge in their usage for such therapies is understanding the mechanisms that allow the maintenance of pluripotency and controlling the specific differentiation into required functional target cells. Because of regulatory restrictions and biological feasibilities, there are many crucial investigations that are just impossible to perform using pluripotent stem cells (PSCs) from humans (for example, direct comparisons among panels of inbred embryonic stem cells from prime embryos obtained from pedigreed and fertile donors; genomic analysis of parent versus progeny PSCs and their identical differentiated tissues; intraspecific chimera analyses for pluripotency testing; and so on). However, PSCs from nonhuman primates are being investigated to bridge these knowledge gaps between discoveries in mice and vital information necessary for appropriate clinical evaluations. In this review, we consider the mRNAs and novel genes with unique expression and imprinting patterns that were discovered using systems biology approaches with primate pluripotent stem and germ cells.

  10. Epigenetic status of H19/IGF2 and SNRPN imprinted genes in aborted and successfully derived embryonic stem cell lines in non-human primates

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    Florence Wianny

    2016-05-01

    Full Text Available The imprinted genes of primate embryonic stem cells (ESCs often show altered DNA methylation. It is unknown whether these alterations emerge while deriving the ESCs. Here we studied the methylation patterns of two differentially methylated regions (DMRs, SNRPN and H19/IGF2 DMRs, during the derivation of monkey ESCs. We show that the SNRPN DMR is characteristically methylated at maternal alleles, whereas the H19/IGF2 DMR is globally highly methylated, with unusual methylation on the maternal alleles. These methylation patterns remain stable from the early stages of ESC derivation to late passages of monkey ESCs and following differentiation. Importantly, the methylation status of H19/IGF2 DMR and the expression levels of IGF2, H19, and DNMT3B mRNAs in early embryo-derived cells were correlated with their capacity to generate genuine ESC lines. Thus, we propose that these markers could be useful to predict the outcomes of establishing an ESC line in primates.

  11. Improved cell therapy protocols for Parkinson's disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons

    DEFF Research Database (Denmark)

    Sundberg, Maria; Bogetofte, Helle; Lawson, Tristan

    2013-01-01

    survived in the striatum of one primate without any immunosuppression. These neural cell grafts contained FOXA2/TH-positive neurons in the graft site. This is an important proof of concept for the feasibility and safety of iPSC-derived cell transplantation therapies in the future....... of safety and efficacy of stem cell-derived DA neurons. The aim of this study was to improve the safety of human- and non-human primate iPSC (PiPSC)-derived DA neurons. According to our results, NCAM(+) /CD29(low) sorting enriched VM DA neurons from pluripotent stem cell-derived neural cell populations....... NCAM(+) /CD29(low) DA neurons were positive for FOXA2/TH and EN1/TH and this cell population had increased expression levels of FOXA2, LMX1A, TH, GIRK2, PITX3, EN1, NURR1 mRNA compared to unsorted neural cell populations. PiPSC-derived NCAM(+) /CD29(low) DA neurons were able to restore motor function...

  12. Effects of acute administration of donepezil or memantine on sleep-deprivation-induced spatial memory deficit in young and aged non-human primate grey mouse lemurs (Microcebus murinus).

    Science.gov (United States)

    Rahman, Anisur; Lamberty, Yves; Schenker, Esther; Cella, Massimo; Languille, Solène; Bordet, Régis; Richardson, Jill; Pifferi, Fabien; Aujard, Fabienne

    2017-01-01

    The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD) is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON) and the N-methyl-D-aspartate antagonist memantine (MEM) provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation. The non-human primate grey mouse lemur (Microcebus murinus) is increasingly used in aging research, but there is no published results related to the impact of known pharmacological treatments on age-related cognitive impairment observed in this primate. In the present study we investigated the effects of DON and MEM on sleep-deprivation (SD)-induced memory impairment in young and aged male mouse lemurs. In particular, spatial memory impairment was evaluated using a circular platform task after 8 h of total SD. Acute single doses of DON or MEM (0.1 and 1mg/kg) or vehicle were administered intraperitoneally 3 h before the cognitive task during the SD procedure. Results indicated that both doses of DON were able to prevent the SD-induced deficits in retrieval of spatial memory as compared to vehicle-treated animals, both in young and aged animals Likewise, MEM show a similar profile at 1 mg/kg but not at 0.1mg/kg. Taken together, these results indicate that two widely used drugs for mitigating cognitive deficits in AD were partially effective in sleep deprived mouse lemurs, which further support the translational potential of this animal model. Our findings demonstrate the utility of this primate model for further testing cognitive enhancing drugs in development for AD or other neuropsychiatric conditions.

  13. Effects of acute administration of donepezil or memantine on sleep-deprivation-induced spatial memory deficit in young and aged non-human primate grey mouse lemurs (Microcebus murinus)

    Science.gov (United States)

    Rahman, Anisur; Lamberty, Yves; Schenker, Esther; Cella, Massimo; Languille, Solène; Bordet, Régis; Richardson, Jill

    2017-01-01

    The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD) is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON) and the N-methyl-D-aspartate antagonist memantine (MEM) provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation. The non-human primate grey mouse lemur (Microcebus murinus) is increasingly used in aging research, but there is no published results related to the impact of known pharmacological treatments on age-related cognitive impairment observed in this primate. In the present study we investigated the effects of DON and MEM on sleep-deprivation (SD)—induced memory impairment in young and aged male mouse lemurs. In particular, spatial memory impairment was evaluated using a circular platform task after 8 h of total SD. Acute single doses of DON or MEM (0.1 and 1mg/kg) or vehicle were administered intraperitoneally 3 h before the cognitive task during the SD procedure. Results indicated that both doses of DON were able to prevent the SD-induced deficits in retrieval of spatial memory as compared to vehicle-treated animals, both in young and aged animals Likewise, MEM show a similar profile at 1 mg/kg but not at 0.1mg/kg. Taken together, these results indicate that two widely used drugs for mitigating cognitive deficits in AD were partially effective in sleep deprived mouse lemurs, which further support the translational potential of this animal model. Our findings demonstrate the utility of this primate model for further testing cognitive enhancing drugs in development for AD or other neuropsychiatric conditions. PMID:28922421

  14. Effects of acute administration of donepezil or memantine on sleep-deprivation-induced spatial memory deficit in young and aged non-human primate grey mouse lemurs (Microcebus murinus.

    Directory of Open Access Journals (Sweden)

    Anisur Rahman

    Full Text Available The development of novel therapeutics to prevent cognitive decline of Alzheimer's disease (AD is facing paramount difficulties since the translational efficacy of rodent models did not resulted in better clinical results. Currently approved treatments, including the acetylcholinesterase inhibitor donepezil (DON and the N-methyl-D-aspartate antagonist memantine (MEM provide marginal therapeutic benefits to AD patients. There is an urgent need to develop a predictive animal model that is phylogenetically proximal to humans to achieve better translation. The non-human primate grey mouse lemur (Microcebus murinus is increasingly used in aging research, but there is no published results related to the impact of known pharmacological treatments on age-related cognitive impairment observed in this primate. In the present study we investigated the effects of DON and MEM on sleep-deprivation (SD-induced memory impairment in young and aged male mouse lemurs. In particular, spatial memory impairment was evaluated using a circular platform task after 8 h of total SD. Acute single doses of DON or MEM (0.1 and 1mg/kg or vehicle were administered intraperitoneally 3 h before the cognitive task during the SD procedure. Results indicated that both doses of DON were able to prevent the SD-induced deficits in retrieval of spatial memory as compared to vehicle-treated animals, both in young and aged animals Likewise, MEM show a similar profile at 1 mg/kg but not at 0.1mg/kg. Taken together, these results indicate that two widely used drugs for mitigating cognitive deficits in AD were partially effective in sleep deprived mouse lemurs, which further support the translational potential of this animal model. Our findings demonstrate the utility of this primate model for further testing cognitive enhancing drugs in development for AD or other neuropsychiatric conditions.

  15. High consumption of primates by pumas and ocelots in a remnant of the Brazilian Atlantic Forest

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    JL Santos

    Full Text Available We studied the diet of the ocelot and puma during the years 2007 and 2008 at the Feliciano Miguel Abdala Reserve, in Minas Gerais, south-eastern Brazil. We collected 49 faecal samples (scats from cats, and identified the species of cat from 23 of them by the analysis of the microstructure patterns of hairs found in their faeces: 17 scats of the puma (Puma concolor and six of the ocelot (Leopardus pardalis. In the puma scats, we identified three species of primates (Brachyteles hypoxanthus, Alouatta guariba and Sapajus nigritus, the remains of which were found in eight of 17 collected (47.1%, representing 26.7% of items consumed. For the ocelot, we detected capuchin monkey (S. nigritus remains in three of the six scats (50%, accounting for 18.7% of items consumed by ocelot. We were unable to identify the cat species in the remaining 26 faecal samples, but we were able to analyse the food items present. Primates were found in five of these 26 faeces (19.2% and represented 10.2% of the items found. Although the sample size is limited, our results indicate a relatively high consumption of primates by felines. We believe that this high predation may be the result of the high local density of primates as well as the greater exposure to the risks of predation in fragmented landscapes, which tends to increase the incidence of the primates using the ground.

  16. Diversity and prevalence of gastrointestinal parasites in seven non-human primates of the Taï National Park, Côte d’Ivoire

    Science.gov (United States)

    Kouassi, Roland Yao Wa; McGraw, Scott William; Yao, Patrick Kouassi; Abou-Bacar, Ahmed; Brunet, Julie; Pesson, Bernard; Bonfoh, Bassirou; N’goran, Eliezer Kouakou; Candolfi, Ermanno

    2015-01-01

    Parasites and infectious diseases are well-known threats to primate populations. The main objective of this study was to provide baseline data on fecal parasites in the cercopithecid monkeys inhabiting Côte d’Ivoire’s Taï National Park. Seven of eight cercopithecid species present in the park were sampled: Cercopithecus diana, Cercopithecus campbelli, Cercopithecus petaurista, Procolobus badius, Procolobus verus, Colobus polykomos, and Cercocebus atys. We collected 3142 monkey stool samples between November 2009 and December 2010. Stool samples were processed by direct wet mount examination, formalin-ethyl acetate concentration, and MIF (merthiolate, iodine, formalin) concentration methods. Slides were examined under microscope and parasite identification was based on the morphology of cysts, eggs, and adult worms. A total of 23 species of parasites was recovered including 9 protozoa (Entamoeba coli, Entamoeba histolytica/dispar, Entamoeba hartmanni, Endolimax nana, Iodamoeba butschlii, Chilomastix mesnili, Giardia sp., Balantidium coli, and Blastocystis sp.), 13 nematodes (Oesophagostomum sp., Ancylostoma sp., Anatrichosoma sp., Capillariidae Gen. sp. 1, Capillariidae Gen. sp. 2, Chitwoodspirura sp., Subulura sp., spirurids [cf Protospirura muricola], Ternidens sp., Strongyloides sp., Trichostrongylus sp., and Trichuris sp.), and 1 trematode (Dicrocoelium sp.). Diversity indices and parasite richness were high for all monkey taxa, but C. diana, C. petaurista, C. atys, and C. campbelli exhibited a greater diversity of parasite species and a more equitable distribution. The parasitological data reported are the first available for these cercopithecid species within Taï National Park. PMID:25619957

  17. Diversity and prevalence of gastrointestinal parasites in seven non-human primates of the Taï National Park, Côte d'Ivoire.

    Science.gov (United States)

    Kouassi, Roland Yao Wa; McGraw, Scott William; Yao, Patrick Kouassi; Abou-Bacar, Ahmed; Brunet, Julie; Pesson, Bernard; Bonfoh, Bassirou; N'goran, Eliezer Kouakou; Candolfi, Ermanno

    2015-01-01

    Parasites and infectious diseases are well-known threats to primate populations. The main objective of this study was to provide baseline data on fecal parasites in the cercopithecid monkeys inhabiting Côte d'Ivoire's Taï National Park. Seven of eight cercopithecid species present in the park were sampled: Cercopithecus diana, Cercopithecus campbelli, Cercopithecus petaurista, Procolobus badius, Procolobus verus, Colobus polykomos, and Cercocebus atys. We collected 3142 monkey stool samples between November 2009 and December 2010. Stool samples were processed by direct wet mount examination, formalin-ethyl acetate concentration, and MIF (merthiolate, iodine, formalin) concentration methods. Slides were examined under microscope and parasite identification was based on the morphology of cysts, eggs, and adult worms. A total of 23 species of parasites was recovered including 9 protozoa (Entamoeba coli, Entamoeba histolytica/dispar, Entamoeba hartmanni, Endolimax nana, Iodamoeba butschlii, Chilomastix mesnili, Giardia sp., Balantidium coli, and Blastocystis sp.), 13 nematodes (Oesophagostomum sp., Ancylostoma sp., Anatrichosoma sp., Capillariidae Gen. sp. 1, Capillariidae Gen. sp. 2, Chitwoodspirura sp., Subulura sp., spirurids [cf Protospirura muricola], Ternidens sp., Strongyloides sp., Trichostrongylus sp., and Trichuris sp.), and 1 trematode (Dicrocoelium sp.). Diversity indices and parasite richness were high for all monkey taxa, but C. diana, C. petaurista, C. atys, and C. campbelli exhibited a greater diversity of parasite species and a more equitable distribution. The parasitological data reported are the first available for these cercopithecid species within Taï National Park. © R.W.Y. Kouassi et al., published by EDP Sciences, 2015.

  18. Effect of image registration on longitudinal analysis of retinal nerve fiber layer thickness of non-human primates using Optical Coherence Tomography (OCT).

    Science.gov (United States)

    Liu, Shuang; Datta, Anjali; Ho, Derek; Dwelle, Jordan; Wang, Daifeng; Milner, Thomas E; Rylander, Henry Grady; Markey, Mia K

    2015-01-01

    In this paper we determined the benefits of image registration on estimating longitudinal retinal nerve fiber layer thickness (RNFLT) changes. RNFLT maps around the optic nerve head (ONH) of healthy primate eyes were measured using Optical Coherence Tomography (OCT) weekly for 30 weeks. One automatic algorithm based on mutual information (MI) and the other semi-automatic algorithm based on log-polar transform cross-correlation using manually segmented blood vessels (LPCC_MSBV), were used to register retinal maps longitudinally. We compared the precision and recall between manually segmented image pairs for the two algorithms using a linear mixed effects model. We found that the precision calculated between manually segmented image pairs following registration by LPCC_MSBV algorithm is significantly better than the one following registration by MI algorithm (p registration. RNFLT of clock hours 1, 2, and 10 showed significant change over 30 weeks (p = 0.0058, 0.0054, and 0.0298 for clock hours 1, 2 and 10 respectively) without registration, but stayed constant over time with registration. The LPCC_MSBV provides better registration of RNFLT maps recorded on different dates than the automatic MI algorithm. Registration of RNFLT maps can improve clinical analysis of glaucoma progression.

  19. Diversity and prevalence of gastrointestinal parasites in seven non-human primates of the Taï National Park, Côte d’Ivoire

    Directory of Open Access Journals (Sweden)

    Kouassi Roland Yao Wa

    2015-01-01

    Full Text Available Parasites and infectious diseases are well-known threats to primate populations. The main objective of this study was to provide baseline data on fecal parasites in the cercopithecid monkeys inhabiting Côte d’Ivoire’s Taï National Park. Seven of eight cercopithecid species present in the park were sampled: Cercopithecus diana, Cercopithecus campbelli, Cercopithecus petaurista, Procolobus badius, Procolobus verus, Colobus polykomos, and Cercocebus atys. We collected 3142 monkey stool samples between November 2009 and December 2010. Stool samples were processed by direct wet mount examination, formalin-ethyl acetate concentration, and MIF (merthiolate, iodine, formalin concentration methods. Slides were examined under microscope and parasite identification was based on the morphology of cysts, eggs, and adult worms. A total of 23 species of parasites was recovered including 9 protozoa (Entamoeba coli, Entamoeba histolytica/dispar, Entamoeba hartmanni, Endolimax nana, Iodamoeba butschlii, Chilomastix mesnili, Giardia sp., Balantidium coli, and Blastocystis sp., 13 nematodes (Oesophagostomum sp., Ancylostoma sp., Anatrichosoma sp., Capillariidae Gen. sp. 1, Capillariidae Gen. sp. 2, Chitwoodspirura sp., Subulura sp., spirurids [cf Protospirura muricola], Ternidens sp., Strongyloides sp., Trichostrongylus sp., and Trichuris sp., and 1 trematode (Dicrocoelium sp.. Diversity indices and parasite richness were high for all monkey taxa, but C. diana, C. petaurista, C. atys, and C. campbelli exhibited a greater diversity of parasite species and a more equitable distribution. The parasitological data reported are the first available for these cercopithecid species within Taï National Park.

  20. Apports nutritionnels, dépense et bilan énergétiques chez l’homme et les primates non-humains : aspects méthodologiques Nutritional intakes, energy expenditure and energy balance in human and non-human primates: methodological aspects

    Directory of Open Access Journals (Sweden)

    Laurent Tarnaud

    2011-02-01

    intègrent des approches quantitatives dont la précision dépend des populations étudiées et des conditions de terrain. L'approche comportementale est le plus souvent complétée par des analyses réalisées en laboratoire et pouvant nécessiter des équipements lourds et des personnels qualifiés. La présente revue a donc pour objectif d'orienter le(s choix du chercheur en fonction de sa thématique de recherche et des conditions de son étude. Le choix de la ou des techniques sera nécessairement le fruit d’un compromis entre la précision, la faisabilité et le coût des études.This paper presents field methods and laboratory techniques used to evaluate food intake, energy and nutrient input, activity patterns, energy expenditure, and body energy storage in human and non-human primates. The aim is to review both traditional techniques and recent advances in the methods designed to investigate energetic parameters in an anthropobiological perspective. Although most of human habits and behaviours are regarded as culturally determined, Homo as a species share with non-human primates a number of psycho-physiological features originating from biological adaptations and close phylogenetic relationships. Therefore, determining the mechanisms involved in the energetic dynamics in non-human primates may contribute to identify some of these shared biological bases. In this respect, several methods in the field of energetics are applicable to both humans and non-human primates bringing out the similarities of approaches. Besides interspecific comparisons that provide a background to assess the evolution of energy strategies among primates, contrasting the energy fluxes at the population or group level highlights the range of bio-cultural adjustments of humans and non-human primate species to their social and natural environment.The present review distinguishes methods according to the energetic parameters the researcher wishes to describe and quantify: food intake

  1. Phenotypic Features of Circulating Leukocytes from Non-human Primates Naturally Infected with Trypanosoma cruzi Resemble the Major Immunological Findings Observed in Human Chagas Disease.

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    Renato Sathler-Avelar

    2016-01-01

    Full Text Available Cynomolgus macaques (Macaca fascicularis represent a feasible model for research on Chagas disease since natural T. cruzi infection in these primates leads to clinical outcomes similar to those observed in humans. However, it is still unknown whether these clinical similarities are accompanied by equivalent immunological characteristics in the two species. We have performed a detailed immunophenotypic analysis of circulating leukocytes together with systems biology approaches from 15 cynomolgus macaques naturally infected with T. cruzi (CH presenting the chronic phase of Chagas disease to identify biomarkers that might be useful for clinical investigations.Our data established that CH displayed increased expression of CD32+ and CD56+ in monocytes and enhanced frequency of NK Granzyme A+ cells as compared to non-infected controls (NI. Moreover, higher expression of CD54 and HLA-DR by T-cells, especially within the CD8+ subset, was the hallmark of CH. A high level of expression of Granzyme A and Perforin underscored the enhanced cytotoxicity-linked pattern of CD8+ T-lymphocytes from CH. Increased frequency of B-cells with up-regulated expression of Fc-γRII was also observed in CH. Complex and imbricate biomarker networks demonstrated that CH showed a shift towards cross-talk among cells of the adaptive immune system. Systems biology analysis further established monocytes and NK-cell phenotypes and the T-cell activation status, along with the Granzyme A expression by CD8+ T-cells, as the most reliable biomarkers of potential use for clinical applications.Altogether, these findings demonstrated that the similarities in phenotypic features of circulating leukocytes observed in cynomolgus macaques and humans infected with T. cruzi further supports the use of these monkeys in preclinical toxicology and pharmacology studies applied to development and testing of new drugs for Chagas disease.

  2. Synthesis and PET evaluation of the translocator protein (18 kDa) (T.S.P.O.) ligand [{sup 11}C]D.P.A.-715 in rat and non-human primate

    Energy Technology Data Exchange (ETDEWEB)

    Creelman, A.; Mcgregor, I.; Kassiou, M. [Sydney Univ., NSW (Australia); Thominiaux, C.; Chauveau, F.; Kuhnast, B.; Boutin, H.; Hantraye, P.; Tavitian, B.; Dolle, F. [Service Hospitalier Frederic Joliot 91 - Orsay (France); Fulton, R.; Henderson, D. [RPAH, NSW (Australia); Selleri, S. [Firenze Univ. (Italy)

    2008-02-15

    The translocator protein (18 kDa) (T.S.P.O.), formerly known as the peripheral benzodiazepine receptor (P.B.R.), is over expressed upon micro-glial activation. This study involved the evaluation of the pyrazolo-pyrimidine D.P.A.-715 (T.S.P.O. Ki = 16.4 nM) in behavioural studies and the radiolabelled form, [{sup 11}C]D.P.A.-715, in healthy non-human primate and A.M.P.A.-lesioned rats as a model of activated micro-glia using PET. The in vivo anxiolytic effects of D.P.A.-715 were assessed using the social interaction test which represents social anxiety in humans. [{sup 11}C]D.P.A.-715 was prepared using [{sup 11}C]CH{sub 3}I as the labelling intermediate from the phenolic precursor of D.P.A.-715 using T.B.A.H. and D.M.F. followed by H.P.L.C.. The non-human primate distribution studies were performed using a clinical PET scanner, and A.M.P.A.-lesioned rats using micro PET. Blocking studies were conducted using P.K.11195 (5 mg/kg).In the social interaction test a significant overall effect for the duration of time spent in general investigation, adjacent lying and rearing was observed. Post hoc analysis revealed a significantly greater time spent in general investigation and adjacent lying in the 20 mg/kg D.P.A.-715 treatment group compared to vehicle treated rats. The average non-decay corrected radiochemical yield of [{sup 11}C]D.P.A.-715 was 0.27 {+-} 0.05% with an average specific activity of 16.32 {+-} 4.01 GBq/mmol. The PET distribution studies revealed poor brain uptake. Pre-treatment with P.K.1195 resulted in no change of in the uptake of the radioligand, which suggests that brain uptake is representative of non-specific binding. In agreement with these results, the brain uptake in the A.M.P.A. lesioned model, depicted no significant differences between the lesioned striatum and the non-lesioned contralateral striatum. Although D.P.A.-715 does possess anxiolytic properties in vivo, [{sup 11}C]D.P.A.-715 does not possess the required properties for further

  3. Effects of a purified krill oil phospholipid rich in long-chain omega-3 fatty acids on cardiovascular disease risk factors in non-human primates with naturally occurring diabetes type-2 and dyslipidemia.

    Science.gov (United States)

    Hals, Petter-Arnt; Wang, Xiaoli; Xiao, Yong-Fu

    2017-01-17

    High serum levels of cholesterol, in particular low-density lipoprotein cholesterol, are considered a significant risk factor for development of cardiovascular disease. Therefore, rigorous treatment regimens with statins and other pharmaceuticals have been used extensively to reduce elevated cholesterol levels. Literature data have not clearly concluded whether long-chain omega-3 fatty acids reduce, increase or leave circulating cholesterol unaffected. In the present study a novel krill-oil derived preparation of omega-3 rich phospholipids, mainly phosphatidylcholine, was administered orally at increasing doses for 12 weeks to dyslipidemic non-human primates, and cholesterols and several other risk factors for cardiovascular disease were measured before, during and after treatment. Six dyslipidemic non-human primates suffering from naturally occurring diabetes type-2 were included, three in a vehicle control group and three being treated with the omega-3 rich phospholipid preparation. The control and test items were given daily by gavage and the doses of the test item were 50, 150 and 450 mg phospholipids/kg/day. Each dose level was given for 4 weeks. Plasma concentrations of the omega-3 fatty acids were measured in connection with change in dose and the omega-3 index in erythrocytes was determined bi-weekly. Blood lipids, apolipoproteins and diabetes, inflammatory and safety biomarkers were determined either weekly, biweekly or every 4 weeks. For the blood lipids and apolipoproteins, control-adjusted mean values are presented while absolute values are presented for the other parameters. Due to the low number of animals in each group, no statistical analyses were done. The only detectable effects measured during dosing with the lowest dose were an increase in HDL-cholesterol and apolipoprotein A1. The intermediate and high doses decreased total cholesterol, LDL-cholesterol, apolipoprotein B100 and triglycerides and increased HDL-cholesterol and apolipoprotein A

  4. The time course of erythrocyte membrane fatty acid concentrations during and after treatment of non-human primates with increasing doses of an omega-3 rich phospholipid preparation derived from krill-oil.

    Science.gov (United States)

    Hals, Petter-Arnt; Wang, Xiaoli; Piscitelli, Fabiana; Di Marzo, Vincenzo; Xiao, Yong-Fu

    2017-01-21

    A commonly used measure to reflect the intake of the long-chain omega-3 fatty acids EPA and DHA is the omega-3 index, defined as the sum of EPA + DHA as % of total fatty acids in erythrocyte membrane. When the omega-3 index changes it follows that the relative fractions of other fatty acids in the membrane are also changed. In the present study, increasing doses of a preparation of omega-3 rich phospholipids extracted from krill oil were administered orally to non-human primates for 12 weeks and the time course of EPA, DHA and 22 other fatty acids in erythrocytes was determined bi-weekly during treatment and for 8 weeks after cessation of treatment. Plasma concentrations of six endocannabinoid-type mediators being downstream metabolites of some fatty acids analyzed in erythrocytes were also determined. Six diabetic, dyslipidemic non-human primates were included, three in a vehicle control group and three being treated with the omega-3 rich phospholipid preparation. The vehicle control and test items were given daily by gavage and the test item doses were 50, 150 and 450 mg phospholipids/kg/day. Each dose level was given for four weeks. Blood was sampled at baseline and thereafter bi-weekly. Fatty acids were determined in erythrocytes by methylation followed by gas-chromatography. Endocannabinoids and endocannabinoid-like mediators were analyzed in plasma by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. The treatment resulted in a dose-related increase in the fraction of EPA and DHA in erythrocyte membranes and a dose-related decrease of other poly-unsaturated fatty acids, in particular omega-6 polyunsaturated fatty acids. Erythrocyte concentrations of saturated fatty acids remained unchanged throughout the experiment. Plasma concentrations of endocannabinoids and endocannabinoid-like mediators changed accordingly as those being downstream arachidonic acid decreased, downstream of the saturated palmitic and oleic acids

  5. Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice.

    Science.gov (United States)

    Chopra, Pankaj; Papale, Ligia A; White, Andrew T J; Hatch, Andrea; Brown, Ryan M; Garthwaite, Mark A; Roseboom, Patrick H; Golos, Thaddeus G; Warren, Stephen T; Alisch, Reid S

    2014-02-13

    Methylation on the fifth position of cytosine (5-mC) is an essential epigenetic mark that is linked to both normal neurodevelopment and neurological diseases. The recent identification of another modified form of cytosine, 5-hydroxymethylcytosine (5-hmC), in both stem cells and post-mitotic neurons, raises new questions as to the role of this base in mediating epigenetic effects. Genomic studies of these marks using model systems are limited, particularly with array-based tools, because the standard method of detecting DNA methylation cannot distinguish between 5-mC and 5-hmC and most methods have been developed to only survey the human genome. We show that non-human data generated using the optimization of a widely used human DNA methylation array, designed only to detect 5-mC, reproducibly distinguishes tissue types within and between chimpanzee, rhesus, and mouse, with correlations near the human DNA level (R(2) > 0.99). Genome-wide methylation analysis, using this approach, reveals 6,102 differentially methylated loci between rhesus placental and fetal tissues with pathways analysis significantly overrepresented for developmental processes. Restricting the analysis to oncogenes and tumor suppressor genes finds 76 differentially methylated loci, suggesting that rhesus placental tissue carries a cancer epigenetic signature. Similarly, adapting the assay to detect 5-hmC finds highly reproducible 5-hmC levels within human, rhesus, and mouse brain tissue that is species-specific with a hierarchical abundance among the three species (human > rhesus > mouse). Annotation of 5-hmC with respect to gene structure reveals a significant prevalence in the 3'UTR and an association with chromatin-related ontological terms, suggesting an epigenetic feedback loop mechanism for 5-hmC. Together, these data show that this array-based methylation assay is generalizable to all mammals for the detection of both 5-mC and 5-hmC, greatly improving the utility of mammalian model systems

  6. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    Science.gov (United States)

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. Placental impairment likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol that links altered placental function to impaired fetal development remain areas of active research. Recently, we developed magnetic resonance imaging techniques in nonhuman primates to characterize placental blood oxygenation through measurements of T2* and perfusion using dynamic contrast-enhanced magnetic resonance imaging. The objective of this study was to evaluate the effects of first-trimester alcohol exposure on macaque placental function and to characterize fetal brain development in vivo. Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (n=6) and ethanol exposed (n=6). Animals were trained to self-administer orally either 1.5 g/kg/d of a 4% ethanol solution (equivalent to 6 drinks/d) or an isocaloric control fluid from preconception until gestational day 60 (term is G168). All animals underwent Doppler ultrasound scanning followed by magnetic resonance imaging that consisted of T2* and dynamic contrast-enhanced measurements. Doppler ultrasound scanning was used to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow and placental volume blood flow. After noninvasive imaging, animals underwent cesarean delivery for placenta collection and fetal necropsy at gestational day 110 (n=6) or 135 (n=6). Fetal weight and biparietal diameter were significantly smaller in ethanol-exposed animals compared with control animals at gestational day 110. By Doppler ultrasound scanning, placental volume blood flow was significantly lower (P=.04) at gestational day 110 in ethanol-exposed vs control animals. A significant reduction in placental blood flow was evident by dynamic contrast-enhanced magnetic resonance imaging. As we demonstrated recently, T2* values vary

  7. Anesthetic management in intrauterine surgery to evaluate an experimental model of myelomeningocele in non human primates (Macaca mulatta Anestesia em cirurgia intra-uterina para avaliar um modelo experimental de mielomeningocele em primatas não humanos (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Alfonso Galván-Montaño

    2010-06-01

    Full Text Available PURPOSE: Evaluate the anesthetic management in intrauterine surgery to induce myelomeningocele in non human primates Macaca mulatta. METHODS: A total of nine fetuses had intrauterine surgery; laminectomy was performed on them in L5 and L6. The studied variables were: maternal death, fetus death, cardiac frequency, respiratory frequency, arterial pressure, temperature, and oxygen saturation. RESULTS: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature. CONCLUSION: No maternal or fetal deaths occurred; the only variable that was reported below the normal ranges was temperature.OBJETIVO: Avaliar o manejo anestésico em cirurgia intra-uterina para induzir mielomeningocelo em primatas não humanos, Macaca mulatta. MÉTODOS: Operaram-se um total de nove fetos in útero que foram submetidos à laminectomia em L5 e L6. As variáveis a estudar foram mortes maternas ou fetais, freqüência cardíaca e respiratória, pressão arterial, temperatura e saturação de oxigênio. RESULTADOS: Não se apresentaram mortes maternas ou fetais, a temperatura se manteve abaixo dos 36°C, não tendo repercussões no bem-estar dos macacos. CONCLUSÃO: Não ocorreu nenhum óbito materno ou fetal, sendo que a única variável abaixo do normal foi a temperatura.

  8. Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson's Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque.

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    James B Koprich

    Full Text Available Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 1012 gp/ml, this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform.

  9. Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson’s Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque

    Science.gov (United States)

    Koprich, James B.; Johnston, Tom H.; Reyes, Gabriela; Omana, Vanessa; Brotchie, Jonathan M.

    2016-01-01

    Recent failures in clinical trials for disease modification in Parkinson’s disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 1012 gp/ml), this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform. PMID:27902767

  10. Towards a Non-Human Primate Model of Alpha-Synucleinopathy for Development of Therapeutics for Parkinson's Disease: Optimization of AAV1/2 Delivery Parameters to Drive Sustained Expression of Alpha Synuclein and Dopaminergic Degeneration in Macaque.

    Science.gov (United States)

    Koprich, James B; Johnston, Tom H; Reyes, Gabriela; Omana, Vanessa; Brotchie, Jonathan M

    2016-01-01

    Recent failures in clinical trials for disease modification in Parkinson's disease have highlighted the need for a non-human primate model of the synucleinopathy underpinning dopaminergic neuron degeneration. The present study was defined to begin the development of such a model in cynomolgus macaque. We have validated surgical and vector parameters to define a means to provide a robust over-expression of alpha-synuclein which is associated with Lewy-like pathology and robust degeneration of the nigrostriatal pathway. Thus, an AAV1/2 vector incorporating strong transcription and transduction regulatory elements was used to deliver the gene for the human A53T mutation of alpha-synuclein. When injected into 4 sites within each substantia nigra (7 μl per site, 1.7 x 1012 gp/ml), this vector provided expression lasting at least 4 months, and a 50% loss of nigral dopaminergic neurons and a 60% reduction in striatal dopamine. Further studies will be required to develop this methodology into a validated model of value as a drug development platform.

  11. Quantitative Expression Analysis of APP Pathway and Tau Phosphorylation-Related Genes in the ICV STZ-Induced Non-Human Primate Model of Sporadic Alzheimer’s Disease

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    Sang-Je Park

    2015-01-01

    Full Text Available The accumulation and aggregation of misfolded proteins in the brain, such as amyloid-β (Aβ and hyperphosphorylated tau, is a neuropathological hallmark of Alzheimer’s disease (AD. Previously, we developed and validated a novel non-human primate model for sporadic AD (sAD research using intracerebroventricular administration of streptozotocin (icv STZ. To date, no characterization of AD-related genes in different brain regions has been performed. Therefore, in the current study, the expression of seven amyloid precursor protein (APP pathway-related and five tau phosphorylation-related genes was investigated by quantitative real-time PCR experiments, using two matched-pair brain samples from control and icv STZ-treated cynomolgus monkeys. The genes showed similar expression patterns within the control and icv STZ-treated groups; however, marked differences in gene expression patterns were observed between the control and icv STZ-treated groups. Remarkably, other than β-secretase (BACE1 and cyclin-dependent kinase 5 (CDK5, all the genes tested showed similar expression patterns in AD models compared to controls, with increased levels in the precuneus and occipital cortex. However, significant changes in gene expression patterns were not detected in the frontal cortex, hippocampus, or posterior cingulate. Based on these results, we conclude that APP may be cleaved via the general metabolic mechanisms of increased α- and γ-secretase levels, and that hyperphosphorylation of tau could be mediated by elevated levels of tau protein kinase, specifically in the precuneus and occipital cortex.

  12. Strontium-90 Biokinetics from Simulated Wound Intakes in Non-human Primates Compared with Combined Model Predictions from National Council on Radiation Protection and Measurements Report 156 and International Commission on Radiological Protection Publication 67.

    Science.gov (United States)

    Allen, Mark B; Brey, Richard R; Gesell, Thomas; Derryberry, Dewayne; Poudel, Deepesh

    2016-01-01

    This study had a goal to evaluate the predictive capabilities of the National Council on Radiation Protection and Measurements (NCRP) wound model coupled to the International Commission on Radiological Protection (ICRP) systemic model for 90Sr-contaminated wounds using non-human primate data. Studies were conducted on 13 macaque (Macaca mulatta) monkeys, each receiving one-time intramuscular injections of 90Sr solution. Urine and feces samples were collected up to 28 d post-injection and analyzed for 90Sr activity. Integrated Modules for Bioassay Analysis (IMBA) software was configured with default NCRP and ICRP model transfer coefficients to calculate predicted 90Sr intake via the wound based on the radioactivity measured in bioassay samples. The default parameters of the combined models produced adequate fits of the bioassay data, but maximum likelihood predictions of intake were overestimated by a factor of 1.0 to 2.9 when bioassay data were used as predictors. Skeletal retention was also over-predicted, suggesting an underestimation of the excretion fraction. Bayesian statistics and Monte Carlo sampling were applied using IMBA to vary the default parameters, producing updated transfer coefficients for individual monkeys that improved model fit and predicted intake and skeletal retention. The geometric means of the optimized transfer rates for the 11 cases were computed, and these optimized sample population parameters were tested on two independent monkey cases and on the 11 monkeys from which the optimized parameters were derived. The optimized model parameters did not improve the model fit in most cases, and the predicted skeletal activity produced improvements in three of the 11 cases. The optimized parameters improved the predicted intake in all cases but still over-predicted the intake by an average of 50%. The results suggest that the modified transfer rates were not always an improvement over the default NCRP and ICRP model values.

  13. Generation of complement molecular complex C5b-9 (C5b-9) in response to poly-traumatic hemorrhagic shock and evaluation of C5 cleavage inhibitors in non-human primates.

    Science.gov (United States)

    Paredes, R Madelaine; Reyna, Sarah; Vernon, Philip; Tadaki, Douglas K; Dallelucca, Jurandir J; Sheppard, Forest

    2018-01-01

    Severe trauma initiates a systemic inflammatory cascade and that involves early activation of complement and cleavage of C5 into C5a (anaphylatoxin) and C5b (C5b-9 membrane attack complex). We examined activation of C5 in non-human primate (NHP) models of hemorrhagic shock. Blood plasma concentrations of C5b-9 were significantly increased in NHPs in response to hemorrhage alone and were further increased with the addition of tissue trauma. The onset of increased C5 cleavage was accelerated in NHPs that experienced decompensated poly-traumatic hemorrhagic shock. Next, to identify an effective inhibitor of NHP C5 cleavage in vitro, as a first step in the development of a potential therapy, three inhibitors of human C5 cleavage and hemolysis were tested in vitro. NHP C5 cleavage and complement-mediated hemolysis were successfully inhibited by pre-treatment of serum samples with a small, inhibitory peptide RA101348. Commercially-available C5 inhibitory antibodies were found to exhibit species-specific efficacy in vitro. Quidel's A217 antibody demonstrated dose-dependent inhibition of C5 cleavage and hemolysis in NHP samples, whereas LGM-Eculizumab only inhibited complement-mediated hemolysis in human samples. This study shows that complement activation in NHPs following experimental poly-traumatic hemorrhagic shock is consistent with clinical reports, and that cleavage of C5 and complement-mediated hemolysis can be effectively inhibited in vitro using a small peptide inhibitor. Taken together, these findings offer a clinically-relevant vehicle and a potential strategy for treatment of hemorrhagic shock with poly-traumatic injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Biodistribution and Radiation Dosimetry of the Integrin Marker 64Cu-BaBaSar-RGD2 Determined from Whole-Body PET/CT in a Non-human Primate

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    Shuanglong Liu

    2017-10-01

    Full Text Available Introduction:64Cu-BaBaSar-RGD2 is a positron emission radiotracer taken up by integrin αvβ3, which is overexpressed in many malignancies. The aim of this study was to evaluate the biodistribution of 64Cu-BaBaSar-RGD2 in a non-human primate with positron emission tomography (PET and to estimate the absorbed doses in major organs for human.Materials and Methods: Whole-body PET imaging was done on a Siemens Biograph scanner with a male macaque monkey. After an i.v. injection of 13.1–19.7 MBq/kg of 64Cu-BaBaSar-RGD2, whole body scan was collected for a total duration of 180 min. Attenuation and scatter corrections were applied to reconstructions of the whole-body emission scan. After image reconstruction, three-dimensional volumes of interest (VOI were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves (TACs for each VOI were obtained, and residence times of each organ were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the standard human model in OLINDA/EXM software.Results: Injection of 64Cu-BaBaSar-RGD2 was well-tolerated in the macaque monkey, with no serious tracer-related adverse events observed. 64Cu-BaBaSar-RGD2 was cleared rapidly from the blood pool, with a 12.1-min biological half-life. Increased 64Cu-BaBaSar-RGD2 uptake was observed in the kidneys, and bladder, with mean percentage injected dose (ID% values at 1 h after injection ~35.50 ± 6.47 and 36.89 ± 5.48, respectively. The calculated effective dose was 15.30 ± 2.21 μSv/MBq, and the kidneys had the highest absorbed dose at 108.43 ± 16.41 μGy/MBq using the non-voiding model. For an injected activity of 925 MBq 64Cu for human, the effective dose would be 14.2 ± 2.1 mSv.Discussion: Due to the limited availability of the primates, we evaluated 64Cu-BaBaSar-RGD2 in the same monkey using three imaging sessions. Measured absorbed doses and effective doses of

  15. Identification and utilization of inter-species conserved (ISC probesets on Affymetrix human GeneChip® platforms for the optimization of the assessment of expression patterns in non human primate (NHP samples

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    Arnold Alma

    2004-10-01

    Full Text Available Abstract Background While researchers have utilized versions of the Affymetrix human GeneChip® for the assessment of expression patterns in non human primate (NHP samples, there has been no comprehensive sequence analysis study undertaken to demonstrate that the probe sequences designed to detect human transcripts are reliably hybridizing with their orthologs in NHP. By aligning probe sequences with expressed sequence tags (ESTs in NHP, inter-species conserved (ISC probesets, which have two or more probes complementary to ESTs in NHP, were identified on human GeneChip® platforms. The utility of human GeneChips® for the assessment of NHP expression patterns can be effectively evaluated by analyzing the hybridization behaviour of ISC probesets. Appropriate normalization methods were identified that further improve the reliability of human GeneChips® for interspecies (human vs NHP comparisons. Results ISC probesets in each of the seven Affymetrix GeneChip® platforms (U133Plus2.0, U133A, U133B, U95Av2, U95B, Focus and HuGeneFL were identified for both monkey and chimpanzee. Expression data was generated from peripheral blood mononuclear cells (PBMCs of 12 human and 8 monkey (Indian origin Rhesus macaque samples using the Focus GeneChip®. Analysis of both qualitative detection calls and quantitative signal intensities showed that intra-species reproducibility (human vs. human or monkey vs. monkey was much higher than interspecies reproducibility (human vs. monkey. ISC probesets exhibited higher interspecies reproducibility than the overall expressed probesets. Importantly, appropriate normalization methods could be leveraged to greatly improve interspecies correlations. The correlation coefficients between human (average of 12 samples and monkey (average of 8 Rhesus macaque samples are 0.725, 0.821 and 0.893 for MAS5.0 (Microarray Suite version 5.0, dChip and RMA (Robust Multi-chip Average normalization method, respectively. Conclusion It is

  16. Yellow fever epizootics in non-human primates, São Paulo state, Brazil, 2008-2009 Epizootias de febre amarela em primatas não humanos no estado de São Paulo, Brasil, 2008-2009

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    Eduardo Stramandinoli Moreno

    2013-02-01

    Full Text Available Since 2000, the expansion of Sylvatic Yellow Fever (YF has been observed in the southeast of Brazil, being detected in areas considered silent for decades. Epizootics in non-human primates (NHPs are considered sentinel events for the detection of human cases. It is important to report epizootic events that could have impact on the conservation status of susceptible species. We describe the epizootics in NHPs, notified in state of São Paulo, Brazil, between September 2008 to August 2009. Ninety-one epizootic events, involving 147 animals, were reported in 36 counties. Samples were obtained from 65 animals (44.2%. Most of the epizootics (46.6% were reported between March and April, the same period during which human cases of YF occurred in the state. Biological samples were collected from animals found dead and were sent to Instituto Adolfo Lutz, in São Paulo. Two samples, collected in two counties without an indication for YF vaccination, were positive for the virus. Another 48 animals were associated with YF by clinical-epidemiological linkage with laboratory confirmed cases. Because the disease in human and NHPs occurred in the same period, the detection of the virus in NHPs did not work as sentinel, but aided in the delineation of new areas of risk.Desde 2000, vem sendo observada a expansão da febre amarela (FA no Sudeste do Brasil, sendo detectados casos em áreas consideradas silenciosas por décadas. Epizootias em primatas não humanos (NHPs são considerados eventos sentinela para a detecção de casos humanos. É importante relatar eventos epizoóticos que podem ter impacto sobre o estado de conservação de espécies sensíveis. Descrevemos as epizootias, notificadas em NHPs no estado de São Paulo, Brasil, entre setembro de 2008 a agosto de 2009. Noventa e um eventos epizoóticos, envolvendo 147 animais, foram notificados em 36 municípios. As amostras foram obtidas a partir de 65 animais (44,2%. A maioria das epizootias (46,6% foram

  17. Multimedia in Anthropology: A Guide to the Nonhuman Primates.

    Science.gov (United States)

    Burton, Frances D.

    This paper describes a primatology project using computer assisted learning and interactive multimedia to help students at the University of Toronto (Canada) learn about non-human primates. The purpose of the interactive program is to present the "natural history" of the majority of the 200-plus species of non-human primates in constant…

  18. Simian malaria in the Brazilian Atlantic forest: first description of natural infection of capuchin monkeys (Cebinae subfamily) by Plasmodium simium.

    Science.gov (United States)

    de Alvarenga, Denise Anete Madureira; de Pina-Costa, Anielle; de Sousa, Taís Nóbrega; Pissinatti, Alcides; Zalis, Mariano G; Suaréz-Mutis, Martha C; Lourenço-de-Oliveira, Ricardo; Brasil, Patrícia; Daniel-Ribeiro, Cláudio Tadeu; de Brito, Cristiana Ferreira Alves

    2015-02-18

    In Brazil, two species of Plasmodium have been described infecting non-human primates, Plasmodium brasilianum and Plasmodium simium. These species are morphologically, genetically and immunologically indistinguishable from the human Plasmodium malariae and Plasmodium vivax parasites, respectively. Plasmodium simium has been observed naturally infecting monkeys of the genera Alouatta and Brachyteles in a restricted area of the Atlantic Forest in the south and southeast regions of Brazil. However, its reported geographical distribution and the diversity of its vertebrate hosts may be underestimated, since available data were largely based on analyses by microscopic examination of peripheral blood, a method with limited sensitivity, considering the potential sub-patent feature of these infections. The present study describes, for the first time, the natural infection of P. simium in capuchin monkeys from the Brazilian Atlantic Forest. Blood samples from 30 non-human primates belonging to nine species kept in the Primate Centre of Rio de Janeiro were collected. Fragments of spleen and liver from one dead monkey found in the neighborhoods of the Primate Centre were also analysed. Molecular diagnosis was performed by nested PCR (18SSU rRNA) and the amplified fragment was sequenced. Thirty per cent of the captive animals were infected with P. simium and/or P. brasilianum. The dead monkey tested positive for DNA of P. simium. For the first time, Cebinae primates (two specimens of genus Cebus and two of genus Sapajos) were found naturally infected by P. simium. The infection was confirmed by sequencing a small fragment of 18SSU rRNA. The results highlight the possibility of infection by P. simium in other species of non-human primates whose impact could be significant for the malaria epidemiology among non-human primates and, if it becomes clear that this P. simium is able to infect monkeys and, eventually, man, also for the maintenance of transmission of human malaria in

  19. Ethics of primate use

    OpenAIRE

    Prescott, M J

    2010-01-01

    This article provides an overview of the ethical issues raised by the use of non-human primates (NHPs) in research involving scientific procedures which may cause pain, suffering, distress or lasting harm. It is not an exhaustive review of the literature and views on this subject, and it does not present any conclusions about the moral acceptability or otherwise of NHP research. Rather the aim has been to identify the ethical issues involved and to provide guidance on how th...

  20. A non-human primate model for gluten sensitivity.

    Directory of Open Access Journals (Sweden)

    Michael T Bethune

    2008-02-01

    Full Text Available Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity.Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity.When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse.Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.

  1. Arcobacter butzleri isolated from a diarrhoeic non-human primate.

    Science.gov (United States)

    Higgins, R; Messier, S; Daignault, D; Lorange, M

    1999-01-01

    The bacteriological examination of a faecal specimen from a 20-year-old female rhesus macaque (Macaca mulatta) with diarrhoeal illness revealed the presence of a large number of a relatively new enteric pathogen, Arcobacter butzleri. The animal was from a closed colony of about 60 females, some of them were showing intermittent diarrhoea possibly related to Giardia spp. Conditions for the isolation and identification of A. butzleri are reported, as well as discussions about its role as a primary pathogen and its zoonotic potential.

  2. Promoting Autoimmune Diabetes in Non-Human Primates

    Science.gov (United States)

    2014-04-01

    the mediastinum. After the completion of total thymectomy, hemostasis is obtained by electrocautery. If necessary, one or 2 small drains ( Jackson ...obtained by pressure. Small drains ( Jackson -pratt or equivalent) were not considered necessary for checking post-operative bleeding since no fluid...the second monkey ( Percy , #150-11), in contrast to the 70% removal in the first one (Leo, #149-11). The close to complete removal of the thymus enable

  3. Spontaneous and experimental malignancies in non-human primates.

    Science.gov (United States)

    Lapin, Boris A; Yakovleva, Lelita A

    2014-04-01

    Contrary to earlier established opinion that tumors in monkeys are found rarely, now the large material confirms that monkey tumors are frequent phenomenon. Tumor incidence clearly increases with age. Frequencies of benign and malignant tumors of various locations and histogenesis are slightly different. Tumors of hematopoietic system are the most frequent. Sporadic cases and enzootic outbreaks of lymphomas are described for different kinds of monkeys, including apes, and probably are caused by viruses. Two viruses were isolated by us from sick monkeys - the retrovirus C-type STLV-1 and the herpes virus papio HVP. Inoculation of virus cultures into monkeys and rabbits induces neoplasms. Monkey neoplasms can be induced by exposure to various chemical agents, and by oncogenic and non-oncogenic viruses. There is no strict species specificity of tumor viruses. The role of polyoma viruses in neoplasms etiology is discussed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium.

    Science.gov (United States)

    Faust, Christina; Dobson, Andrew P

    2015-12-01

    Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence-absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

  5. Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium

    Directory of Open Access Journals (Sweden)

    Christina Faust

    2015-12-01

    Full Text Available Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

  6. Percussive technology in human evolution: an introduction to a comparative approach in fossil and living primates.

    Science.gov (United States)

    de la Torre, Ignacio; Hirata, Satoshi

    2015-11-19

    Percussive technology is part of the behavioural suite of several fossil and living primates. Stone Age ancestors used lithic artefacts in pounding activities, which could have been most important in the earliest stages of stone working. This has relevant evolutionary implications, as other primates such as chimpanzees and some monkeys use stone hammer-and-anvil combinations to crack hard-shelled foodstuffs. Parallels between primate percussive technologies and early archaeological sites need to be further explored in order to assess the emergence of technological behaviour in our evolutionary line, and firmly establish bridges between Primatology and Archaeology. What are the anatomical, cognitive and ecological constraints of percussive technology? How common are percussive activities in the Stone Age and among living primates? What is their functional significance? How similar are archaeological percussive tools and those made by non-human primates? This issue of Phil. Trans. addresses some of these questions by presenting case studies with a wide chronological, geographical and disciplinary coverage. The studies presented here cover studies of Brazilian capuchins, captive chimpanzees and chimpanzees in the wild, research on the use of percussive technology among modern humans and recent hunter-gatherers in Australia, the Near East and Europe, and archaeological examples of this behaviour from a million years ago to the Holocene. In summary, the breadth and depth of research compiled here should make this issue of Philosophical Transactions of the Royal Society B, a landmark step forward towards a better understanding of percussive technology, a unique behaviour shared by some modern and fossil primates. © 2015 The Author(s).

  7. Pathogenesis of Varicelloviruses in primates

    Science.gov (United States)

    Ouwendijk, Werner J.D.; Verjans, Georges M.G.M.

    2014-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. PMID:25255989

  8. Pathogenesis of varicelloviruses in primates.

    Science.gov (United States)

    Ouwendijk, Werner J D; Verjans, Georges M G M

    2015-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Strongyloides cebus (Nematoda: Strongyloididae) in Lagothrix cana (Primates: Atelidae) from the Brazilian Amazon: aspects of clinical presentation, anatomopathology, treatment, and parasitic biology.

    Science.gov (United States)

    Mati, Vitor Luís Tenório; Ferreira Junior, Francisco Carlos; Pinto, Hudson Alves; de Melo, Alan Lane

    2013-12-01

    Abstract :  Seven cases of parasitism by Strongyloides cebus were identified in Lagothrix cana from Brazil. Aspects of the clinical presentation, treatment, pathology, and parasitic biology of these infections are described. Moderate to severe disease was observed, requiring hospitalization of 3 primates, and diarrhea was the most common clinical sign described. One L. cana individual died, for which ulcerative enteritis was the major finding upon histopathological analysis. The use of ivermectin in these atelids was safe and effective against the parasite. Parallel attempts to experimentally infect gerbils with the parasite failed. Lagothrix cana is presented as a new host for S. cebus. The evidence that Strongyloides infections are common in nonhuman primates under free-living conditions, and even more prevalent in captive animals, likely represents a neglected problem.

  10. Ethics of primate use

    Science.gov (United States)

    Prescott, M. J.

    2010-11-01

    This article provides an overview of the ethical issues raised by the use of non-human primates (NHPs) in research involving scientific procedures which may cause pain, suffering, distress or lasting harm. It is not an exhaustive review of the literature and views on this subject, and it does not present any conclusions about the moral acceptability or otherwise of NHP research. Rather the aim has been to identify the ethical issues involved and to provide guidance on how these might be addressed, in particular by carefully examining the scientific rationale for NHP use, implementing fully the 3Rs principle of Russell and Burch (1959) and applying a robust "harm-benefit assessment" to research proposals involving NHPs.

  11. Criteria for feasibility, health and welfare assessment of requirement to use second and subsequent generations of non-human primates or animals from self-sustaining colonies in research Critères d’évaluation de la faisabilité, de l’incidence sanitaire et des répercussions sur le bien-être animal, relatifs à l'obligation future d'utiliser des primates non humains issus uniquement des animaux de deuxième génération et plus ou des animaux provenant de colonies d'élevage auto-entretenues pour la recherche expérimentale

    Directory of Open Access Journals (Sweden)

    David Smith

    2011-10-01

    Full Text Available The European Directive 2010/63/EU on the protection of animals used for scientific purposes requires that a feasibility study must be conducted by the European Commission to determine if all sourcing of non-human primates from parents bred in captivity (F2 or from self-sustaining colonies can be achieved. This study should also include an assessment of animal health and welfare. Prior to the initiation of the European Commission’s study, it was considered by EFPIA and FELASA that the criteria to be used in the feasibility, health and welfare assessment should be established by experts to help expedite such a study. This paper identifies those criteria which may be useful in making policy decisions on the confirmation or reconsideration of the timetable for implementation of the F2 requirement. A key requirement before a number of criteria can be assessed is the generation of base-line data relating to the supply and future demand of non-human primates and the health and welfare status of current breeding colonies supplying the European market. Three groups of criteria have been indentified, namely feasibility, science and research and welfare. Within each group, a number of parameters are defined and their rationale for inclusion, together with suggested information points, is discussed.La directive européenne 2010/63/EU sur la protection des animaux utilisés à des fins scientifiques exige qu'une étude de faisabilité soit conduite par la Commission européenne afin de déterminer si l’approvisionnement en primates non-humains à partir de géniteurs élevés en captivité (F2 ou de colonies d'élevage autosuffisantes, peut être possible. Cette étude devra également inclure une évaluation de la santé des animaux et de leur bien-être. Avant le début de cette étude par la Commission européenne, l'EFPIA et FELASA ont estimé que les critères à utiliser pour les évaluations de la faisabilité, de la santé des animaux et du bien

  12. A human model for primate personality

    Science.gov (United States)

    2017-01-01

    In this article, I review the literature to determine how successful the latent trait theory model of personality from differential psychology has been for studying personality in non-human primates. The evidence for the success of this model is quite good, and offers insights and directions for personality research in primates and other animals. This, I conclude, stems from (i) the human trait model's simplicity, and (ii) the fact that the human differential model of personality developed in the face of harsh criticism, which led researchers to test and refine their models. PMID:29021170

  13. A human model for primate personality.

    Science.gov (United States)

    Weiss, Alexander

    2017-10-11

    In this article, I review the literature to determine how successful the latent trait theory model of personality from differential psychology has been for studying personality in non-human primates. The evidence for the success of this model is quite good, and offers insights and directions for personality research in primates and other animals. This, I conclude, stems from (i) the human trait model's simplicity, and (ii) the fact that the human differential model of personality developed in the face of harsh criticism, which led researchers to test and refine their models. © 2017 The Author(s).

  14. Evolution of microRNA in primates.

    Science.gov (United States)

    McCreight, Jennifer C; Schneider, Sean E; Wilburn, Damien B; Swanson, Willie J

    2017-01-01

    MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny. Hundreds of miRNA were validated, and the number of species with experimentally validated miRNA was tripled. These species include a sister taxon to humans (bonobo) and basal primates (aye-aye, mouse lemur, galago). Consistent with previous studies, we found the seed region and mature miRNA to be highly conserved across primates, with overall structural conservation of the pre-miRNA hairpin. However, there were a number of interesting exceptions, including a seed shift due to structural changes in miR-501. We also identified an increase in the number of miR-320 paralogs throughout primate evolution. Many of these non-conserved miRNA appear to regulate neuronal processes, illustrating the importance of investigating miRNA to learn more about human evolution.

  15. Evolution of microRNA in primates.

    Directory of Open Access Journals (Sweden)

    Jennifer C McCreight

    Full Text Available MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny. Hundreds of miRNA were validated, and the number of species with experimentally validated miRNA was tripled. These species include a sister taxon to humans (bonobo and basal primates (aye-aye, mouse lemur, galago. Consistent with previous studies, we found the seed region and mature miRNA to be highly conserved across primates, with overall structural conservation of the pre-miRNA hairpin. However, there were a number of interesting exceptions, including a seed shift due to structural changes in miR-501. We also identified an increase in the number of miR-320 paralogs throughout primate evolution. Many of these non-conserved miRNA appear to regulate neuronal processes, illustrating the importance of investigating miRNA to learn more about human evolution.

  16. Primates´ socio-cognitive abilities: What kind of comparisons makes sense?

    DEFF Research Database (Denmark)

    Byrnit, Jill

    2015-01-01

    presented an experimental paradigm with which to examine the use of referential gestures in non-human primates: the object-choice task. Since then, numerous object-choice studies have been made, not only with primates but also with a range of other animal taxa. Surprisingly, several non-primate species...... are testing animals on experimental paradigms that do not take into account what are the challenges of their natural habitat....

  17. Why does multiple sclerosis only affect human primates?

    NARCIS (Netherlands)

    't Hart, Bert A.

    Background: Multiple sclerosis (MS) develops exclusively in humans. Non-human primates are resistant against MS, although they are highly susceptible to the MS animal model, experimental autoimmune encephalomyelitis (EAE). Unravelling of the cause(s) underlying this discrepancy is highly relevant as

  18. Biology of primate relaxin: A paracrine signal in early pregnancy?

    Directory of Open Access Journals (Sweden)

    Hayes Eric S

    2004-06-01

    Full Text Available Abstract Relaxin is a peptide hormone that exerts numerous effects in a variety of tissues across a broad range of species. Although first identified more than 75 years ago interest in relaxin biology has waxed and waned over the years consistent with peaks and troughs of new experimental data on its wide-ranging biological effects and advances in relaxin enabling technologies. Recent insights into species-dependent differences in relaxin biology during pregnancy have once again stimulated a relative surge of interest in the study of relaxin's reproductive biology. Identification and pharmacological characterization of orphaned relaxin receptors and exploration of its paracrine effects on pregnancy using genomic and proteomic technologies have succeeded in fueling current interest in relaxin research. Primates and non-primate vertebrates exhibit very disparate profiles of relaxin genomics, proteomics and functional biology. Non-human primates appear to exhibit a very close similarity to humans with respect to relaxin reproductive biology but the similarities and subtle differences are only just beginning to be understood. We, and others, have shown that relaxin produces significant changes to the non-human primate endometrium during the peri-implantation period that are consistent with relaxin's long perceived role as a paracrine modulator of pregnancy. The purpose of this review is to summarize the reproductive biology of relaxin in non-human primates with a specific emphasis on the paracrine role of ovarian and endometrial relaxin during embryo implantation and early pregnancy.

  19. Primate photopigments and primate color vision.

    OpenAIRE

    Jacobs, G H

    1996-01-01

    The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys...

  20. Scaling of free-ranging primate energetics with body mass predicts low energy expenditure in humans.

    Science.gov (United States)

    Simmen, Bruno; Darlu, Pierre; Hladik, Claude Marcel; Pasquet, Patrick

    2015-01-01

    Studies of how a mammal's daily energy expenditure scales with its body mass suggest that humans, whether Westerners, agro-pastoralists, or hunter-gatherers, all have much lower energy expenditures for their body mass than other mammals. However, non-human primates also differ from other mammals in several life history traits suggestive of low energy use. Judging by field metabolic rates of free-ranging strepsirhine and haplorhine primates with different lifestyle and body mass, estimated using doubly labeled water, primates have lower energy expenditure than other similar-sized eutherian mammals. Daily energy expenditure in humans fell along the regression line of non-human primates. The results suggest that thrifty energy use could be an ancient strategy of primates. Although physical activity is a major component of energy balance, our results suggest a need to revise the basis for establishing norms of energy expenditure in modern humans. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Annotation of primate miRNAs by high throughput sequencing of small RNA libraries

    Directory of Open Access Journals (Sweden)

    Dannemann Michael

    2012-03-01

    Full Text Available Abstract Background In addition to genome sequencing, accurate functional annotation of genomes is required in order to carry out comparative and evolutionary analyses between species. Among primates, the human genome is the most extensively annotated. Human miRNA gene annotation is based on multiple lines of evidence including evidence for expression as well as prediction of the characteristic hairpin structure. In contrast, most miRNA genes in non-human primates are annotated based on homology without any expression evidence. We have sequenced small-RNA libraries from chimpanzee, gorilla, orangutan and rhesus macaque from multiple individuals and tissues. Using patterns of miRNA expression in conjunction with a model of miRNA biogenesis we used these high-throughput sequencing data to identify novel miRNAs in non-human primates. Results We predicted 47 new miRNAs in chimpanzee, 240 in gorilla, 55 in orangutan and 47 in rhesus macaque. The algorithm we used was able to predict 64% of the previously known miRNAs in chimpanzee, 94% in gorilla, 61% in orangutan and 71% in rhesus macaque. We therefore added evidence for expression in between one and five tissues to miRNAs that were previously annotated based only on homology to human miRNAs. We increased from 60 to 175 the number miRNAs that are located in orthologous regions in humans and the four non-human primate species studied here. Conclusions In this study we provide expression evidence for homology-based annotated miRNAs and predict de novo miRNAs in four non-human primate species. We increased the number of annotated miRNA genes and provided evidence for their expression in four non-human primates. Similar approaches using different individuals and tissues would improve annotation in non-human primates and allow for further comparative studies in the future.

  2. Detection of anti-Toxoplasma gondii antibodies in experimentally and naturally infected non-human primates by Indirect Fluorescence Assay (IFA and indirect ELISA Detecção de anticorpos anti-Toxoplasma gondii por meio das técnicas de Imunofluorescência Indireta e ELISA Indireto em primatas experimentalmente e naturalmente infectados

    Directory of Open Access Journals (Sweden)

    Andréa Bouer

    2010-03-01

    Full Text Available The Indirect Fluorescence Assay (IFA and the indirect ELISA were comparatively used to detect IgG and IgM antibodies for Toxoplasma gondii in experimentally and naturally infected primates. In the experimentally infected group, antibodies of diagnostic value were detected at day 9 post-infection (PI with the IFA (IgG and IgM and with IgG-ELISA. IgM-ELISA detected antibodies for T. gondii starting at day 3 PI until the end of the experiment (102 days PI. Of the 209 naturally infected sera tested, from many zoos of State of Sao Paulo, 64.59 and 67.94% were positive in the IgG-IFA test and IgG-ELISA respectively. IgM-ELISA test detected seropositivity in 52.63% of the sera although IgM-IFA test detected it in only in 0.96% of the samples. The differential toxoplasmosis diagnosis was accomplished with Neospora caninum by IFA, observing 61 (29.2% seropositive animals for this parasite and 149 (70.8% negative. Sixty animals were positive for both T. gondii and N. caninum. Pneumonia, splenomegaly, and intestinal ulcers were macroscopically observed. Unremarkable interstitial pneumonia, enteritis, colitis, splenitis, and glomerulitis were microscopically observed. The immunohistochemical stain could not detect the presence of T. gondii in the tissues of the animals infected experimentally.Detectou-se anticorpos das classes IgG e IgM anti-Toxoplasma gondii em primatas experimentalmente e naturalmente infectados, utilizando-se como técnicas comparativas a RIFI e o ELISA-teste. No grupo dos primatas experimentalmente infectados, anticorpos de valor diagnóstico foram detectados a partir do 9º dia de infecção tanto na RIFI (IgG e IgM como no ELISA-IgG. O ELISA IgM detectou anticorpos a partir do 3º dia de infecção até o final do experimento (102 dias pós-infecção. Dos 209 soros dos primatas naturalmente infectados, de diversos zoológicos do Estado de São Paulo, 64,59 e 67,94% mostraram-se positivos na RIFI-IgG e no ELISA-IgG, respectivamente. O

  3. "Abraços de mono": elos perdidos e encontros intersubjetivos em etnografia com primatólogos no Brasil

    Directory of Open Access Journals (Sweden)

    Guilherme José da Silva e Sá

    2010-04-01

    Full Text Available A partir de pesquisa etnográfica junto a um grupo de primatólogos atuando em um fragmento da Mata Atlântica mineira, proponho tratar de algumas questões caras à antropologia da ciência, em especial daquela que da perspectiva etnológica se interessa pelas relações entre humanos e não humanos e pelas dinâmicas cosmológicas de atuação deste coletivo. Neste trabalho dedico-me à analise das formas de construção da imagem e agenciamento dos primatas estudados [conhecidos como "muriquis" ou "mono-carvoeiros"] que permeiam o discurso-cultura dos pesquisadores. Procura-se apresentar este coletivo de humanos e não humanos mapeando suas relações e variações dispostas na circulação de imagens, comportamentos e performances transespecíficas.Based on ethnographic fieldwork with a team of primatologists working in a small area of Brazilian Atlantic Forest, this paper engages with some of the classical issues in the anthropology of science, especially the ethnological interest in the relations between humans and non-humans and the cosmological dynamics that shape this collective. The paper focuses on how the image and agency of the primates is constructed (woolly-spider monkeys known as ‘muriquis' or ‘mono-carvoeiros' and also analyzes their appropriation by primatological discourse-culture. As well as tracing the relations forming this collective of humans and non-humans, the text maps the variations composed of images, behaviours and transpecific performances.

  4. Recent advances in primate nutritional ecology.

    Science.gov (United States)

    Righini, Nicoletta

    2017-04-01

    Nutritional ecology seeks to explain, in an ecological and evolutionary context, how individuals choose, acquire, and process food to satisfy their nutritional requirements. Historically, studies of primate feeding ecology have focused on characterizing diets in terms of the botanical composition of the plants consumed. Further, dietary studies have demonstrated how patch and food choice in relation to time spent foraging and feeding are influenced by the spatial and temporal distribution of resources and by social factors such as feeding competition, dominance, or partner preferences. From a nutritional perspective, several theories including energy and protein-to-fiber maximization, nutrient mixing, and toxin avoidance, have been proposed to explain the food choices of non-human primates. However, more recently, analytical frameworks such as nutritional geometry have been incorporated into primatology to explore, using a multivariate approach, the synergistic effects of multiple nutrients, secondary metabolites, and energy requirements on primate food choice. Dietary strategies associated with nutrient balancing highlight the tradeoffs that primates face in bypassing or selecting particular feeding sites and food items. In this Special Issue, the authors bring together a set of studies focusing on the nutritional ecology of a diverse set of primate taxa characterized by marked differences in dietary emphasis. The authors present, compare, and discuss the diversity of strategies used by primates in diet selection, and how species differences in ecology, physiology, anatomy, and phylogeny can affect patterns of nutrient choice and nutrient balancing. The use of a nutritionally explicit analytical framework is fundamental to identify the nutritional requirements of different individuals of a given species, and through its application, direct conservation efforts can be applied to regenerate and protect specific foods and food patches that offer the opportunity of a

  5. Forest structure drives global diversity of primates.

    Science.gov (United States)

    Gouveia, Sidney F; Villalobos, Fabricio; Dobrovolski, Ricardo; Beltrão-Mendes, Raone; Ferrari, Stephen F

    2014-11-01

    Geographic gradients in the species richness of non-human primates have traditionally been attributed to the variation in forest productivity (related to precipitation levels), although an all-inclusive, global-scale analysis has never been conducted. We perform a more comprehensive test on the role of precipitation and biomass production and propose an alternative hypothesis - the variation in vertical structure of forest habitats as measured by forest canopy height - in determining primate species richness on a global scale. Considering the potential causal relationships among precipitation, productivity and forest structure, we arranged these variables within a path framework to assess their direct and indirect associations with the pattern of primate species richness using structural equation modelling. The analysis also accounted for the influence of spatial autocorrelation in the relationships and assessed possible historical differences among biogeographical regions. The path coefficients indicate that forest canopy height (used as a proxy for vertical forest structure) is a better predictor of primate species richness than either precipitation or productivity on both global and continental scales. The only exception was Asia, where precipitation prevailed, albeit independently from productivity or forest structure. The influence of spatially structured processes varied markedly among biogeographical regions. Our results challenge the traditional rainfall-based viewpoint in favour of forest distribution and structure as primary drivers of primate species richness, which aggregate potential effects from both climatic factors and habitat complexity. These findings may support predictions of the impact of forest removal on primate species richness. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

  6. Evolution of the hepcidin gene in primates

    Directory of Open Access Journals (Sweden)

    Tossi Alessandro

    2008-03-01

    Full Text Available Abstract Background Hepcidin/LEAP-1 is an iron regulatory hormone originally identified as an antimicrobial peptide. As part of a systematic analysis of the evolution of host defense peptides in primates, we have sequenced the orthologous gene from 14 species of non-human primates. Results The sequence of the mature peptide is highly conserved amongst all the analyzed species, being identical to the human one in great apes and gibbons, with a single residue conservative variation in Old-World monkeys and with few substitutions in New-World monkeys. Conclusion Our analysis indicates that hepcidin's role as a regulatory hormone, which involves interaction with a conserved receptor (ferroportin, may result in conservation over most of its sequence, with the exception of the stretch between residues 15 and 18, which in New-World monkeys (as well as in other mammals shows a significant variation, possibly indicating that this structural region is involved in other functions.

  7. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    ) article 'Visualizing the mind: Looking at Titian's Flaying of Marsyas', addressing features of the painting not commented on by Hart, and supplementing Hart's (Kleinian) theoretical frame by involving Didier Anzieu's 'skin ego', Slavoj Zizek's concept of the 'non-human', Giorgio Agamben's term...

  8. Why primate models matter.

    Science.gov (United States)

    Phillips, Kimberley A; Bales, Karen L; Capitanio, John P; Conley, Alan; Czoty, Paul W; 't Hart, Bert A; Hopkins, William D; Hu, Shiu-Lok; Miller, Lisa A; Nader, Michael A; Nathanielsz, Peter W; Rogers, Jeffrey; Shively, Carol A; Voytko, Mary Lou

    2014-09-01

    Research involving nonhuman primates (NHPs) has played a vital role in many of the medical and scientific advances of the past century. NHPs are used because of their similarity to humans in physiology, neuroanatomy, reproduction, development, cognition, and social complexity-yet it is these very similarities that make the use of NHPs in biomedical research a considered decision. As primate researchers, we feel an obligation and responsibility to present the facts concerning why primates are used in various areas of biomedical research. Recent decisions in the United States, including the phasing out of chimpanzees in research by the National Institutes of Health and the pending closure of the New England Primate Research Center, illustrate to us the critical importance of conveying why continued research with primates is needed. Here, we review key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research. © 2014 Wiley Periodicals, Inc.

  9. Rethinking primate origins again.

    Science.gov (United States)

    Sussman, Robert W; Tab Rasmussen, D; Raven, Peter H

    2013-02-01

    In 1974, Cartmill introduced the theory that the earliest primate adaptations were related to their being visually oriented predators active on slender branches. Given more recent data on primate-like marsupials, nocturnal prosimians, and early fossil primates, and the context in which these primates first appeared, this theory has been modified. We hypothesize that our earliest primate relatives were likely exploiting the products of co-evolving angiosperms, along with insects attracted to fruits and flowers, in the slender supports of the terminal branch milieu. This has been referred to as the primate/angiosperm co-evolution theory. Cartmill subsequently posited that: "If the first euprimates had grasping feet and blunt teeth adapted for eating fruit, but retained small divergent orbits…" then the angiosperm coevolution theory would have support. The recent discovery of Carpolestes simpsoni provides this support. In addition, new field data on small primate diets, and a new theory concerning the visual adaptations of primates, have provided further evidence supporting the angiosperm coevolution theory. © 2012 Wiley Periodicals, Inc.

  10. Property in Nonhuman Primates

    Science.gov (United States)

    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…

  11. Comparative primate neurobiology and the evolution of brain language systems.

    Science.gov (United States)

    Rilling, James K

    2014-10-01

    Human brain specializations supporting language can be identified by comparing human with non-human primate brains. Comparisons with chimpanzees are critical in this endeavor. Human brains are much larger than non-human primate brains, but human language capabilities cannot be entirely explained by brain size. Human brain specializations that potentially support our capacity for language include firstly, wider cortical minicolumns in both Broca's and Wernicke's areas compared with great apes; secondly, leftward asymmetries in Broca's area volume and Wernicke's area minicolumn width that are not found in great apes; and thirdly, arcuate fasciculus projections beyond Wernicke's area to a region of expanded association cortex in the middle and inferior temporal cortex involved in processing word meaning. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Primate paternal care: interactions between biology and social experience

    Science.gov (United States)

    Storey, Anne E.; Ziegler, Toni E.

    2016-01-01

    We review recent research on the roles of hormones and social experiences on the development of paternal care in humans and non-human primates. Generally, lower concentrations of testosterone and higher concentrations of oxytocin are associated with greater paternal responsiveness. Hormonal changes prior to the birth appear to be important in preparation for fatherhood and changes after the birth are related to how much time fathers spend with offspring and whether they provide effective care. Prolactin may facilitate approach and the initiation of infant care, and in some biparental non-human primates, it affects body mass regulation. Glucocorticoids are involved in coordinating reproductive and parental behavior between mates. New research involving intranasal oxytocin and neuropeptide receptor polymorphisms may help us understand individual variation in paternal responsiveness. This area of research, integrating both biological factors and the role of early and adult experience, has the potential to suggest individually designed interventions that can strengthen relationships between fathers and their offspring. PMID:26253726

  13. Theories about evolutionary origins of human hepatitis B virus in primates and humans

    Directory of Open Access Journals (Sweden)

    Breno Frederico de Carvalho Dominguez Souza

    Full Text Available Introduction: The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. Objective: To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. Methods: This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. Results: The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly B virus in basal sister-relationship to the Old monkey human hepatitis World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory

  14. Theories about evolutionary origins of human hepatitis B virus in primates and humans.

    Science.gov (United States)

    Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix; Lima, Renato Santos de; Rosário, Mila de Oliveira Hughes Veiga do; Netto, Eduardo Martins

    2014-01-01

    The human hepatitis B virus causes acute and chronic hepatitis and is considered one of the most serious human health issues by the World Health Organization, causing thousands of deaths per year. There are similar viruses belonging to the Hepadnaviridae family that infect non-human primates and other mammals as well as some birds. The majority of non-human primate virus isolates were phylogenetically close to the human hepatitis B virus, but like the human genotypes, the origins of these viruses remain controversial. However, there is a possibility that human hepatitis B virus originated in primates. Knowing whether these viruses might be common to humans and primates is crucial in order to reduce the risk to humans. To review the existing knowledge about the evolutionary origins of viruses of the Hepadnaviridae family in primates. This review was done by reading several articles that provide information about the Hepadnaviridae virus family in non-human primates and humans and the possible origins and evolution of these viruses. The evolutionary origin of viruses of the Hepadnaviridae family in primates has been dated back to several thousand years; however, recent analyses of genomic fossils of avihepadnaviruses integrated into the genomes of several avian species have suggested a much older origin of this genus. Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the '90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate

  15. Skin Allograft Acceptance with Anti-CD154 in a Non-Human Primate Model

    National Research Council Canada - National Science Library

    Elster, Eric; Tadaki, Douglas

    2004-01-01

    Traditional burn wound management involves application of topical antimicrobial agents with frequent dressing changes for superficial partial thickness burns and early excision and grafting of deep...

  16. Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates

    Science.gov (United States)

    Smits, Saskia L.; de Lang, Anna; van den Brand, Judith M. A.; Leijten, Lonneke M.; van IJcken, Wilfred F.; Eijkemans, Marinus J. C.; van Amerongen, Geert; Kuiken, Thijs; Andeweg, Arno C.; Osterhaus, Albert D. M. E.; Haagmans, Bart L.

    2010-01-01

    The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI. PMID:20140198

  17. Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST

    Science.gov (United States)

    Alterations in hypothalamic–pituitary–adrenal axis function contribute to many of the adverse behavioral effects of chronic voluntary alcohol drinking, including alcohol dependence and mood disorders; limbic brain structures such as the bed nucleus of the stria termin...

  18. Differential mechanical response and microstructural organization between non-human primate femoral and carotid arteries

    Science.gov (United States)

    Raykin, Julia; Li, Haiyan; Gleason, Rudolph L.

    2014-01-01

    Unique anatomic locations and physiologic functions predispose different arteries to varying mechanical responses and pathologies. However, the underlying causes of these mechanical differences are not well understood. The objective of this study was to first identify structural differences in the arterial matrix that would account for the mechanical differences between healthy femoral and carotid arteries and second to utilize these structural observations to perform a microstructurally motivated constitutive analysis. Femoral and carotid arteries were subjected to cylindrical biaxial loading and their microstructure was quantified using two-photon microscopy. The femoral arteries were found to be less compliant than the carotid arteries at physiologic loads, consistent with previous studies, despite similar extracellular compositions of collagen and elastin (P > 0.05). The femoral arteries exhibited significantly less circumferential dispersion of collagen fibers (P arteries. Elastin transmural distribution, in vivo axial stretch, and opening angles were also found to be distinctly different between the arteries. Lastly, we modeled the arteries’ mechanical behaviors using a microstructural-based, distributed collagen fiber constitutive model. With this approach, the material parameters of the model were solved using the experimental microstructural observations. The findings of this study support an important role for microstructural organization in arterial stiffness. PMID:24532266

  19. MHC matching improves engraftment of iPSC-derived neurons in non-human primates.

    Science.gov (United States)

    Morizane, Asuka; Kikuchi, Tetsuhiro; Hayashi, Takuya; Mizuma, Hiroshi; Takara, Sayuki; Doi, Hisashi; Mawatari, Aya; Glasser, Matthew F; Shiina, Takashi; Ishigaki, Hirohito; Itoh, Yasushi; Okita, Keisuke; Yamasaki, Emi; Doi, Daisuke; Onoe, Hirotaka; Ogasawara, Kazumasa; Yamanaka, Shinya; Takahashi, Jun

    2017-08-30

    The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting.Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched iPSC-derived neurons provide better engraftment in the brain, with a lower immune response and higher survival of the transplanted neurons.

  20. Spatial and temporal disparity in signals and maskers affects signal detection in non-human primates.

    Science.gov (United States)

    Rocchi, Francesca; Dylla, Margit E; Bohlen, Peter A; Ramachandran, Ramnarayan

    2017-02-01

    Detection thresholds for auditory stimuli (signals) increase in the presence of maskers. Natural environments contain maskers/distractors that can have a wide range of spatiotemporal properties relative to the signal. While these parameters have been well explored psychophysically in humans, they have not been well explored in animal models, and their neuronal underpinnings are not well understood. As a precursor to the neuronal measurements, we report the effects of systematically varying the spatial and temporal relationship between signals and noise in macaque monkeys (Macaca mulatta and Macaca radiata). Macaques detected tones masked by noise in a Go/No-Go task in which the spatiotemporal relationships between the tone and noise were systematically varied. Masked thresholds were higher when the masker was continuous or gated on and off simultaneously with the signal, and lower when the continuous masker was turned off during the signal. A burst of noise caused higher masked thresholds if it completely temporally overlapped with the signal, whereas partial overlap resulted in lower thresholds. Noise durations needed to be at least 100 ms before significant masking could be observed. Thresholds for short duration tones were significantly higher when the onsets of signal and masker coincided compared to when the signal was presented during the steady state portion of the noise (overshoot). When signal and masker were separated in space, masked signal detection thresholds decreased relative to when the masker and signal were co-located (spatial release from masking). Masking release was larger for azimuthal separations than for elevation separations. These results in macaques are similar to those observed in humans, suggesting that the specific spatiotemporal relationship between signal and masker determine threshold in natural environments for macaques in a manner similar to humans. These results form the basis for future investigations of neuronal correlates and mechanisms of masking. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Late ophthalmological complications after total body irradiation in non-human primates

    Science.gov (United States)

    Niemer-Tucker, M. M.; Sterk, C. C.; de Wolff-Rouendaal, D.; Lee, A. C.; Lett, J. T.; Cox, A.; Emmanouilidis-van der Spek, K.; Davelaar, J.; Lambooy, A. C.; Mooy, C. M.; hide

    1999-01-01

    PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

  2. Scatter correction for large non-human primate brain imaging using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo-Variawa, S; Lehnert, W; Banati, R B; Meikle, S R, E-mail: snai3212@uni.sydney.edu.au [Discipline of Medical Radiation Sciences, Faculty of Health Sciences, University of Sydney, PO Box 170, Lidcombe, NSW 1825, Sydney (Australia)

    2011-04-07

    The baboon is well suited to pre-clinical evaluation of novel radioligands for positron emission tomography (PET). We have previously demonstrated the feasibility of using a high resolution animal PET scanner for this application in the baboon brain. However, the non-homogenous distribution of tissue density within the head may give rise to photon scattering effects that reduce contrast and compromise quantitative accuracy. In this study, we investigated the magnitude and distribution of scatter contributing to the final reconstructed image and its variability throughout the baboon brain using phantoms and Monte Carlo simulated data. The scatter fraction is measured up to 36% at the centre of the brain for a wide energy window (350-650 keV) and 19% for a narrow (450-650 keV) window. We observed less than 3% variation in the scatter fraction throughout the brain and found that scattered events arising from radioactivity outside the field of view contribute less than 1% of measured coincidences. In a contrast phantom, scatter and attenuation correction improved contrast recovery compared with attenuation correction on its own and reduced bias to less than 10% at the expense of the reduced signal-to-noise ratio. We conclude that scatter correction is a necessary step for ensuring high quality measurements of the radiotracer distribution in the baboon brain with a microPET scanner, while it is not necessary to model out of field of view scatter or a spatially variant scatter function.

  3. Performance Correlates of Social Behavior and Organization in Non-Human Primates.

    Science.gov (United States)

    1982-04-01

    juveniles and infants of both sexes in roughly the same proportions as are found in the wild (Angst, 1975). Matriarchies were kept intact as much as...order in the matriarchies of both troops. In T-Troop, the dominant matriarchy was that of Quail,’ a female born in 1961. 60 0-I E- 0 <Co-r4 0CL 0 r0 4-4...4 to U) lr U r- r-4 (-4 0 OCCI:4-~ - LI HE- Q.-I. Ln U)C) H to 0. 00 - ----- --- 61 Although Quail’s matriarchy was dominant over that of the other

  4. UTILIZING SPECTRAL TRANSCRANIAL DOPPLER TO CHARACTERIZE CEREBRAL HEMODYNAMICS IN A NON-HUMAN PRIMATE (RHESUS MACAQUE)

    Science.gov (United States)

    2017-05-16

    RHESUS MACAQUE) G. ANDREW PRATT III, MS; JACOB J. GLASER, MD FACS, CDR, MC USN; FOREST R. SHEPPARD, MD FACS, CDR, MC USN EXPEDITIONARY AND TRAUMA ...second only to traumatic brain injuries1. A retrospective analysis by Eastridge et al. 2012 evaluated the outcomes of wounded military personnel...cannulated to facilitate blood sampling and continuous blood pressure monitoring. The left femoral artery was cannulated to facilitate the trauma

  5. Effects of anesthesia on resting state BOLD signals in white matter of non-human primates.

    Science.gov (United States)

    Wu, Tung-Lin; Wang, Feng; Anderson, Adam W; Chen, Li Min; Ding, Zhaohua; Gore, John C

    2016-11-01

    Resting state functional magnetic resonance imaging (rsfMRI) has been widely used to measure functional connectivity between cortical regions of the brain. However, there have been minimal reports of bold oxygenation level dependent (BOLD) signals in white matter, and even fewer attempts to detect resting state connectivity. Recently, there has been growing evidence that suggests that reliable detection of white matter BOLD signals may be possible. We have previously shown that nearest neighbor inter-voxel correlations of resting state BOLD signal fluctuations in white matter are anisotropic and can be represented by a functional correlation tensor, but the biophysical origins of these signal variations are not clear. We aimed to assess whether MRI signal fluctuations in white matter vary for different baseline levels of neural activity. We performed imaging studies on live squirrel monkeys under different levels of isoflurane anesthesia at 9.4T. We found 1) the fractional power (0.01-0.08Hz) in white matter was between 60 to 75% of the level in gray matter; 2) the power in both gray and white matter low frequencies decreased monotonically in similar manner with increasing levels of anesthesia; 3) the distribution of fractional anisotropy values of the functional tensors in white matter were significantly higher than those in gray matter; and 4) the functional tensor eigenvalues decreased with increasing level of anesthesia. Our results suggest that as anesthesia level changes baseline neural activity, white matter signal fluctuations behave similarly to those in gray matter, and functional tensors in white matter are affected in parallel. Published by Elsevier Inc.

  6. [The influence of dehydroepiandrosterone (DHEA) on the behavior in old non-human primates].

    Science.gov (United States)

    Goncharov, N P; Katsiia, G V; Dzhokua, A A; Barkaia, V S; Kulava, Z V; Mikvabia, Z Ia

    2014-01-01

    At present time there is a lack of satisfactory understanding of how DHEA affects cognition and nervous system function. Aim of the present study to evaluate effects of long-term DH EA administration of physiological doses on the Higher Brain Activity (HBA) in rhesus macaques (RM) at the limits of their biological age. The study included 9 male RM aged 24-30 years. Five of them were given im injections of DHEA (1 mg/kg each two days for 3 months). 4 control monkeys were administered the vehicle alone. Cortisol, testosterone, and free thyroxin were measured by chemiluminescent immunoassay. HBA was studied by classical motor-food conditioning (to estimate long-term memory) and by determining delayed response time (a measure of short-term memory). RM had to respond to a positive signal (1000 Hz) and no bar-pressing was required in response to a negative signal (400 Hz). MR were free to move in the cage during the experiment. Their behavior was tested before, within 1, 2, 3 months of DHEA administration and 3 months after its termination. The HBA increased of all 5 RM within 1, 2, and 3 month after the beginning of DHEA administration. Both long- and short-term memory stably improved while response time decreased from 5 to 1-1.5 s. The behavior of RM changed radically from passive one to enhanced motor activity and food motivation. These effects of DHEA persisted as long as 3 months after DHEA treatment. During DHEA treatment the steady tendency to rising in a blood concentrations of a free thyroxine, testosterone and DHEA was observed. DHEA administration caused a rise in testosterone, free thyroxin levels and DHEAS levels. In three months after DHEA treatment the hairs lost in the old monkeys was restored and this effect remained within one years of observation. Conclusion. Administration of physiological doses of DHEA to old RM induced a stable increase of Higher Brain Activity with harmonization of excitation and inhibition processes; radically enhanced motor and food activity; completely restored body hairiness which already remained within one year.

  7. Histological evaluation of a chronically-implanted electrocorticographic electrode grid in a non-human primate

    Science.gov (United States)

    Degenhart, Alan D.; Eles, James; Dum, Richard; Mischel, Jessica L.; Smalianchuk, Ivan; Endler, Bridget; Ashmore, Robin C.; Tyler-Kabara, Elizabeth C.; Hatsopoulos, Nicholas G.; Wang, Wei; Batista, Aaron P.; Cui, X. Tracy

    2016-08-01

    Objective. Electrocorticography (ECoG), used as a neural recording modality for brain-machine interfaces (BMIs), potentially allows for field potentials to be recorded from the surface of the cerebral cortex for long durations without suffering the host-tissue reaction to the extent that it is common with intracortical microelectrodes. Though the stability of signals obtained from chronically implanted ECoG electrodes has begun receiving attention, to date little work has characterized the effects of long-term implantation of ECoG electrodes on underlying cortical tissue. Approach. We implanted and recorded from a high-density ECoG electrode grid subdurally over cortical motor areas of a Rhesus macaque for 666 d. Main results. Histological analysis revealed minimal damage to the cortex underneath the implant, though the grid itself was encapsulated in collagenous tissue. We observed macrophages and foreign body giant cells at the tissue-array interface, indicative of a stereotypical foreign body response. Despite this encapsulation, cortical modulation during reaching movements was observed more than 18 months post-implantation. Significance. These results suggest that ECoG may provide a means by which stable chronic cortical recordings can be obtained with comparatively little tissue damage, facilitating the development of clinically viable BMI systems.

  8. The translational value of non-human primates in preclinical research on infection and immunopathology

    NARCIS (Netherlands)

    't Hart, Bert A.; Bogers, Willy M.; Haanstra, Krista G.; Verreck, Frank A.; Kocken, Clemens H.

    2015-01-01

    The immune system plays a central role in the defense against environmental threats - such as infection with viruses, parasites or bacteria - but can also be a cause of disease, such as in the case of allergic or autoimmune disorders. In the past decades the impressive development of biotechnology

  9. Comparison of Non-Human Primate and Human Whole Blood Tissue Gene Expression Profiles

    Science.gov (United States)

    2005-03-01

    studies have used rhesus, chimpanzee, gorilla, or orangutan RNA, but to date no gene expression profiling studies are available that use AGM or cynomologus...previous work has been published using human genechips to study NHPs, particularly rhesus, chimpanzee, gorilla, and orangutan (Uddin et al., 2004; Kayo

  10. Novel Serum Proteomic Signatures in a Non-Human Primate Model of Retinal Injury

    Science.gov (United States)

    2011-01-01

    Macaca mulatta GN=HOXB1 PE=3 SV=1 DB=sp 4 4 1 2 1.407795 0.760907 P62503 Epididymal -specific lipocalin-6 OS=Macaca mulatta GN=LCN6 PE=2 SV=1 DB=sp 3 4...0.958837 A0N066 Antithrombin III OS=Macaca mulatta PE=2 SV=1 DB=tr 26 647 6 6 0.936358 0.431947 B2NJ31 Sperm -associated antigen 9 OS=Macaca mulatta GN...Macaca mulatta GN=Mamu-B PE=3 SV=1 DB=tr 3 3 0 2 Treated only 0.128662 Q6S9I4 Sperm protein associated with the nucleus OS=Macaca mulatta GN=SPANXN PE

  11. Cytokine expression in malaria-infected non-human primate placentas

    African Journals Online (AJOL)

    Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM) leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment ...

  12. The Temporal Dynamics of Regularity Extraction in Non-Human Primates

    Science.gov (United States)

    Minier, Laure; Fagot, Joël; Rey, Arnaud

    2016-01-01

    Extracting the regularities of our environment is one of our core cognitive abilities. To study the fine-grained dynamics of the extraction of embedded regularities, a method combining the advantages of the artificial language paradigm (Saffran, Aslin, & Newport, [Saffran, J. R., 1996]) and the serial response time task (Nissen & Bullemer,…

  13. Cytokine expression in malaria-infected non-human primate placentas

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    M.M. Gicheru

    2012-06-01

    Full Text Available Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis-Plasmodium knowlesi (P. knowlesi H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA. Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-α and interleukin 12 (IL-12. Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-γ levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.

  14. Early target cells of measles virus after aerosol infection of non-human primates.

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    Ken Lemon

    2011-01-01

    Full Text Available Measles virus (MV is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150, which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP, based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS. Cynomolgus macaques were infected with a high dose of rMV(KSEGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n = 3 per time point and infected (EGFP(+ cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP(+ cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia.

  15. Early Target Cells of Measles Virus after Aerosol Infection of Non-Human Primates

    Science.gov (United States)

    Mesman, Annelies W.; McQuaid, Stephen; van Amerongen, Geert; Yüksel, Selma; Ludlow, Martin; Rennick, Linda J.; Kuiken, Thijs; Rima, Bertus K.; Geijtenbeek, Teunis B. H.; Osterhaus, Albert D. M. E.; Duprex, W. Paul; de Swart, Rik L.

    2011-01-01

    Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMVKSEGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n = 3 per time point) and infected (EGFP+) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP+ cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia. PMID:21304593

  16. Social learning of vocal structure in a nonhuman primate?

    Directory of Open Access Journals (Sweden)

    Lemasson Alban

    2011-12-01

    Full Text Available Abstract Background Non-human primate communication is thought to be fundamentally different from human speech, mainly due to vast differences in vocal control. The lack of these abilities in non-human primates is especially striking if compared to some marine mammals and bird species, which has generated somewhat of an evolutionary conundrum. What are the biological roots and underlying evolutionary pressures of the human ability to voluntarily control sound production and learn the vocal utterances of others? One hypothesis is that this capacity has evolved gradually in humans from an ancestral stage that resembled the vocal behavior of modern primates. Support for this has come from studies that have documented limited vocal flexibility and convergence in different primate species, typically in calls used during social interactions. The mechanisms underlying these patterns, however, are currently unknown. Specifically, it has been difficult to rule out explanations based on genetic relatedness, suggesting that such vocal flexibility may not be the result of social learning. Results To address this point, we compared the degree of acoustic similarity of contact calls in free-ranging Campbell's monkeys as a function of their social bonds and genetic relatedness. We calculated three different indices to compare the similarities between the calls' frequency contours, the duration of grooming interactions and the microsatellite-based genetic relatedness between partners. We found a significantly positive relation between bond strength and acoustic similarity that was independent of genetic relatedness. Conclusion Genetic factors determine the general species-specific call repertoire of a primate species, while social factors can influence the fine structure of some the call types. The finding is in line with the more general hypothesis that human speech has evolved gradually from earlier primate-like vocal communication.

  17. Allelic lineages of the ficolin genes (FCNs are passed from ancestral to descendant primates.

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    Tina Hummelshøj

    Full Text Available The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host cells and are able to activate the lectin pathway of the complement system. In humans, three ficolin genes have been identified: FCN1, FCN2 and FCN3, which encode ficolin-1, ficolin-2 and ficolin-3, respectively. Rodents have only two ficolins designated ficolin-A and ficolin-B that are closely related to human ficolin-1, while the rodent FCN3 orthologue is a pseudogene. Ficolin-2 and ficolin-3 have so far only been observed in humans. Thus, we performed a systematic investigation of the FCN genes in non-human primates. The exons and intron-exon boundaries of the FCN1-3 genes were sequenced in the following primate species: chimpanzee, gorilla, orangutan, rhesus macaque, cynomolgus macaque, baboon and common marmoset. We found that the exon organisation of the FCN genes was very similar between all the non-human primates and the human FCN genes. Several variations in the FCN genes were found in more than one primate specie suggesting that they were carried from one species to another including humans. The amino acid diversity of the ficolins among human and non-human primate species was estimated by calculating the Shannon entropy revealing that all three proteins are generally highly conserved. Ficolin-1 and ficolin-2 showed the highest diversity, whereas ficolin-3 was more conserved. Ficolin-2 and ficolin-3 were present in non-human primate sera with the same characteristic oligomeric structures as seen in human serum. Taken together all the FCN genes show the same characteristics in lower and higher primates. The existence of trans-species polymorphisms suggests that different FCN allelic lineages may be passed from ancestral to descendant species.

  18. Primate cranial diversity.

    Science.gov (United States)

    Fleagle, John G; Gilbert, Christopher C; Baden, Andrea L

    2010-08-01

    Many studies in primate and human evolution focus on aspects of cranial morphology to address issues of systematics, phylogeny, and functional anatomy. However, broad analyses of cranial diversity within Primates as an Order are notably absent. In this study, we present a 3D geometric morphometric analysis of primate cranial morphology, providing a multivariate comparison of the major patterns of cranial shape change during primate evolution and quantitative assessments of cranial diversity among different clades. We digitized a set of 18 landmarks designed to capture overall cranial shape on male and female crania representing 66 genera of living primates. The landmark data were aligned using a Generalized Procrustes Analysis and then subjected to a principal components analysis to identify the major axes of cranial variation. Cranial diversity among clades was compared using multivariate measurements of variance. The first principal component axis reflects differences in cranial flexion, orbit size and orientation, and relative neurocranial volume. In general, it separates strepsirrhines from anthropoids. The second axis reflects differences in relative cranial height and snout length and primarily describes differences among anthropoids. Eulemur, Mandrillus, Pongo, and Homo are among the extremes in cranial shape. Anthropoids, catarrhines, and haplorhines show a higher variance than prosimians or strepsirrhines. Hominoids show the highest variance in cranial shape among extant primate clades, and much of this diversity is driven by the unique cranium of Homo sapiens. Copyright 2010 Wiley-Liss, Inc.

  19. 77 FR 7109 - Establishment of User Fees for Filovirus Testing of Nonhuman Primate Liver Samples

    Science.gov (United States)

    2012-02-10

    ... rulemaking. Laboratory testing of suspected NHPs and early detection of infected animals within the... offering this same service in the future. The testing of non-human primate samples is necessary to prevent... HUMAN SERVICES 42 CFR Part 71 RIN 0920-AA47 Establishment of User Fees for Filovirus Testing of Nonhuman...

  20. 77 FR 6971 - Establishment of User Fees for Filovirus Testing of Nonhuman Primate Liver Samples

    Science.gov (United States)

    2012-02-10

    ... rulemaking. Laboratory testing of suspected NHPs and early detection of infected animals within the... offering this same service in the future. The testing of non-human primate samples is necessary to prevent... HUMAN SERVICES 42 CFR Part 71 RIN 0920-AA47 Establishment of User Fees for Filovirus Testing of Nonhuman...

  1. Primate taxonomy: species and conservation.

    Science.gov (United States)

    Rylands, Anthony B; Mittermeier, Russell A

    2014-01-01

    Primatology as a discrete branch of science involving the study of primate behavior and ecology took off in the 1960s after discovery of the importance of primates as models for biomedical research and the realization that primates provide insights into the evolutionary history of humans. Osman Hill's unfortunately incomplete monograph series on the comparative anatomy and taxonomy of the primates(1) and the Napiers' 1967 A Handbook of Living Primates(2) recorded the world's view of primate diversity at this time. This taxonomy remained the baseline for nearly three decades, with the diversity of each genus being represented by some species, but extensively as subspecies. Copyright © 2014 Wiley Periodicals, Inc.

  2. Hands of early primates.

    Science.gov (United States)

    Boyer, Doug M; Yapuncich, Gabriel S; Chester, Stephen G B; Bloch, Jonathan I; Godinot, Marc

    2013-12-01

    Questions surrounding the origin and early evolution of primates continue to be the subject of debate. Though anatomy of the skull and inferred dietary shifts are often the focus, detailed studies of postcrania and inferred locomotor capabilities can also provide crucial data that advance understanding of transitions in early primate evolution. In particular, the hand skeleton includes characteristics thought to reflect foraging, locomotion, and posture. Here we review what is known about the early evolution of primate hands from a comparative perspective that incorporates data from the fossil record. Additionally, we provide new comparative data and documentation of skeletal morphology for Paleogene plesiadapiforms, notharctines, cercamoniines, adapines, and omomyiforms. Finally, we discuss implications of these data for understanding locomotor transitions during the origin and early evolutionary history of primates. Known plesiadapiform species cannot be differentiated from extant primates based on either intrinsic hand proportions or hand-to-body size proportions. Nonetheless, the presence of claws and a different metacarpophalangeal [corrected] joint form in plesiadapiforms indicate different grasping mechanics. Notharctines and cercamoniines have intrinsic hand proportions with extremely elongated proximal phalanges and digit rays relative to metacarpals, resembling tarsiers and galagos. But their hand-to-body size proportions are typical of many extant primates (unlike those of tarsiers, and possibly Teilhardina, which have extremely large hands). Non-adapine adapiforms and omomyids exhibit additional carpal features suggesting more limited dorsiflexion, greater ulnar deviation, and a more habitually divergent pollex than observed plesiadapiforms. Together, features differentiating adapiforms and omomyiforms from plesiadapiforms indicate increased reliance on vertical prehensile-clinging and grasp-leaping, possibly in combination with predatory behaviors in

  3. Prosocial primates: selfish and unselfish motivations

    Science.gov (United States)

    de Waal, Frans B. M.; Suchak, Malini

    2010-01-01

    Non-human primates are marked by well-developed prosocial and cooperative tendencies as reflected in the way they support each other in fights, hunt together, share food and console victims of aggression. The proximate motivation behind such behaviour is not to be confused with the ultimate reasons for its evolution. Even if a behaviour is ultimately self-serving, the motivation behind it may be genuinely unselfish. A sharp distinction needs to be drawn, therefore, between (i) altruistic and cooperative behaviour with knowable benefits to the actor, which may lead actors aware of these benefits to seek them by acting cooperatively or altruistically and (ii) altruistic behaviour that offers the actor no knowable rewards. The latter is the case if return benefits occur too unpredictably, too distantly in time or are of an indirect nature, such as increased inclusive fitness. The second category of behaviour can be explained only by assuming an altruistic impulse, which—as in humans—may be born from empathy with the recipient's need, pain or distress. Empathy, a proximate mechanism for prosocial behaviour that makes one individual share another's emotional state, is biased the way one would predict from evolutionary theories of cooperation (i.e. by kinship, social closeness and reciprocation). There is increasing evidence in non-human primates (and other mammals) for this proximate mechanism as well as for the unselfish, spontaneous nature of the resulting prosocial tendencies. This paper further reviews observational and experimental evidence for the reciprocity mechanisms that underlie cooperation among non-relatives, for inequity aversion as a constraint on cooperation and on the way defection is dealt with. PMID:20679114

  4. Impending extinction crisis of the world's primates: Why primates matter.

    Science.gov (United States)

    Estrada, Alejandro; Garber, Paul A; Rylands, Anthony B; Roos, Christian; Fernandez-Duque, Eduardo; Di Fiore, Anthony; Nekaris, K Anne-Isola; Nijman, Vincent; Heymann, Eckhard W; Lambert, Joanna E; Rovero, Francesco; Barelli, Claudia; Setchell, Joanna M; Gillespie, Thomas R; Mittermeier, Russell A; Arregoitia, Luis Verde; de Guinea, Miguel; Gouveia, Sidney; Dobrovolski, Ricardo; Shanee, Sam; Shanee, Noga; Boyle, Sarah A; Fuentes, Agustin; MacKinnon, Katherine C; Amato, Katherine R; Meyer, Andreas L S; Wich, Serge; Sussman, Robert W; Pan, Ruliang; Kone, Inza; Li, Baoguo

    2017-01-01

    Nonhuman primates, our closest biological relatives, play important roles in the livelihoods, cultures, and religions of many societies and offer unique insights into human evolution, biology, behavior, and the threat of emerging diseases. They are an essential component of tropical biodiversity, contributing to forest regeneration and ecosystem health. Current information shows the existence of 504 species in 79 genera distributed in the Neotropics, mainland Africa, Madagascar, and Asia. Alarmingly, ~60% of primate species are now threatened with extinction and ~75% have declining populations. This situation is the result of escalating anthropogenic pressures on primates and their habitats-mainly global and local market demands, leading to extensive habitat loss through the expansion of industrial agriculture, large-scale cattle ranching, logging, oil and gas drilling, mining, dam building, and the construction of new road networks in primate range regions. Other important drivers are increased bushmeat hunting and the illegal trade of primates as pets and primate body parts, along with emerging threats, such as climate change and anthroponotic diseases. Often, these pressures act in synergy, exacerbating primate population declines. Given that primate range regions overlap extensively with a large, and rapidly growing, human population characterized by high levels of poverty, global attention is needed immediately to reverse the looming risk of primate extinctions and to attend to local human needs in sustainable ways. Raising global scientific and public awareness of the plight of the world's primates and the costs of their loss to ecosystem health and human society is imperative.

  5. Unlike fellows - a review of primate-non-primate associations.

    Science.gov (United States)

    Heymann, Eckhard W; Hsia, Shin S

    2015-02-01

    Throughout many regions of the tropics, non-primate animals - mainly birds and mammals - have been observed to follow primate groups and to exploit dropped food and flushed prey. The anecdotal nature of most of the numerous reports on these primate-non-primate associations (PNPAs) may obscure the biological significance of such associations. We review the existing literature and test predictions concerning the influence of primate traits (body size, activity patterns, dietary strategies, habitat, group size) on the occurrence of PNPAs. Furthermore, we examine the influence of non-primates' dietary strategies on the occurrence of PNPAs, and the distribution of benefits and costs. We detected a strong signal in the geographic distribution of PNPAs, with a larger number of such associations in the Neotropics compared to Africa and Asia. Madagascar lacks PNPAs altogether. Primate body size, activity patterns, habitat and dietary strategies as well as non-primate dietary strategies affect the occurrence of PNPAs, while primate group size did not play a role. Benefits are asymmetrically distributed and mainly accrue to non-primates. They consist of foraging benefits through the consumption of dropped leaves and fruits and flushed prey, and anti-predation benefits through eavesdropping on primate alarm calls and vigilance. Where quantitative information is available, it has been shown that benefits for non-primates can be substantial. The majority of PNPAs can thus be categorized as cases of commensalism, while mutualism is very rare. Our review provides evidence that the ecological function of primates extends beyond their manifold interactions with plants, but may remain underestimated. © 2014 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

  6. Primate dietary ecology in the context of food mechanical properties.

    Science.gov (United States)

    Coiner-Collier, Susan; Scott, Robert S; Chalk-Wilayto, Janine; Cheyne, Susan M; Constantino, Paul; Dominy, Nathaniel J; Elgart, Alison A; Glowacka, Halszka; Loyola, Laura C; Ossi-Lupo, Kerry; Raguet-Schofield, Melissa; Talebi, Mauricio G; Sala, Enrico A; Sieradzy, Pawel; Taylor, Andrea B; Vinyard, Christopher J; Wright, Barth W; Yamashita, Nayuta; Lucas, Peter W; Vogel, Erin R

    2016-09-01

    Substantial variation exists in the mechanical properties of foods consumed by primate species. This variation is known to influence food selection and ingestion among non-human primates, yet no large-scale comparative study has examined the relationships between food mechanical properties and feeding strategies. Here, we present comparative data on the Young's modulus and fracture toughness of natural foods in the diets of 31 primate species. We use these data to examine the relationships between food mechanical properties and dietary quality, body mass, and feeding time. We also examine the relationship between food mechanical properties and categorical concepts of diet that are often used to infer food mechanical properties. We found that traditional dietary categories, such as folivory and frugivory, did not faithfully track food mechanical properties. Additionally, our estimate of dietary quality was not significantly correlated with either toughness or Young's modulus. We found a complex relationship among food mechanical properties, body mass, and feeding time, with a potential interaction between median toughness and body mass. The relationship between mean toughness and feeding time is straightforward: feeding time increases as toughness increases. However, when considering median toughness, the relationship with feeding time may depend upon body mass, such that smaller primates increase their feeding time in response to an increase in median dietary toughness, whereas larger primates may feed for shorter periods of time as toughness increases. Our results emphasize the need for additional studies quantifying the mechanical and chemical properties of primate diets so that they may be meaningfully compared to research on feeding behavior and jaw morphology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Primates' Socio-Cognitive Abilities: What Kind of Comparisons Makes Sense?

    Science.gov (United States)

    Byrnit, Jill T

    2015-09-01

    Referential gestures are of pivotal importance to the human species. We effortlessly make use of each others' referential gestures to attend to the same things, and our ability to use these gestures show themselves from very early in life. Almost 20 years ago, James Anderson and colleagues presented an experimental paradigm with which to examine the use of referential gestures in non-human primates: the object-choice task. Since then, numerous object-choice studies have been made, not only with primates but also with a range of other animal taxa. Surprisingly, several non-primate species appear to perform better in the object-choice task than primates do. Different hypotheses have been offered to explain the results. Some of these have employed generalizations about primates or subsets of primate taxa that do not take into account the unparalleled diversity that exists between species within the primate order on parameters relevant to the requirements of the object-choice task, such as social structure, feeding ecology, and general morphology. To examine whether these broad primate generalizations offer a fruitful organizing framework within which to interpret the results, a review was made of all published primate results on the use of gazing and glancing cues with species ordered along the primate phylogenetic tree. It was concluded that differences between species may be larger than differences between ancestry taxa, and it is suggested that we need to start rethinking why we are testing animals on experimental paradigms that do not take into account what are the challenges of their natural habitat.

  8. Cranial vault thickness in primates: Homo erectus does not have uniquely thick vault bones.

    Science.gov (United States)

    Copes, Lynn E; Kimbel, William H

    2016-01-01

    Extremely thick cranial vaults have been noted as a diagnostic characteristic of Homo erectus since the first fossil of the species was identified, but relatively little work has been done on elucidating its etiology or variation across fossils, living humans, or extant non-human primates. Cranial vault thickness (CVT) is not a monolithic trait, and the responsiveness of its layers to environmental stimuli is unknown. We obtained measurements of cranial vault thickness in fossil hominins from the literature and supplemented those data with additional measurements taken on African fossil specimens. Total CVT and the thickness of the cortical and diploë layers individually were compared to measures of CVT in extant species measured from more than 500 CT scans of human and non-human primates. Frontal and parietal CVT in fossil primates was compared to a regression of CVT on cranial capacity calculated for extant species. Even after controlling for cranial capacity, African and Asian H. erectus do not have uniquely high frontal or parietal thickness residuals, either among hominins or extant primates. Extant primates with residual CVT thickness similar to or exceeding H. erectus (depending on the sex and bone analyzed) include Nycticebus coucang, Perodicticus potto, Alouatta caraya, Lophocebus albigena, Galago alleni, Mandrillus sphinx, and Propithecus diadema. However, the especially thick vaults of extant non-human primates that overlap with H. erectus values are composed primarily of cortical bone, while H. erectus and other hominins have diploë-dominated vault bones. Thus, the combination of thick vaults comprised of a thickened diploë layer may be a reliable autapomorphy for members of the genus Homo. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Disease-associated mitochondrial mutations and the evolution of primate mitogenomes.

    Directory of Open Access Journals (Sweden)

    William Corrêa Tavares

    Full Text Available Several human diseases have been associated with mutations in mitochondrial genes comprising a set of confirmed and reported mutations according to the MITOMAP database. An analysis of complete mitogenomes across 139 primate species showed that most confirmed disease-associated mutations occurred in aligned codon positions and gene regions under strong purifying selection resulting in a strong evolutionary conservation. Only two confirmed variants (7.1%, coding for the same amino acids accounting for severe human diseases, were identified without apparent pathogenicity in non-human primates, like the closely related Bornean orangutan. Conversely, reported disease-associated mutations were not especially concentrated in conserved codon positions, and a large fraction of them occurred in highly variable ones. Additionally, 88 (45.8% of reported mutations showed similar variants in several non-human primates and some of them have been present in extinct species of the genus Homo. Considering that recurrent mutations leading to persistent variants throughout the evolutionary diversification of primates are less likely to be severely damaging to fitness, we suggest that these 88 mutations are less likely to be pathogenic. Conversely, 69 (35.9% of reported disease-associated mutations occurred in extremely conserved aligned codon positions which makes them more likely to damage the primate mitochondrial physiology.

  10. The last fossil primate in North America, new material of the enigmatic Ekgmowechashala from the Arikareean of Oregon.

    Science.gov (United States)

    Samuels, Joshua X; Albright, L Barry; Fremd, Theodore J

    2015-09-01

    Primates were common in North America through most of the Eocene, but vanished in the Chadronian, about 35 million years ago. In the Arikareean, about 6 million years later, the enigmatic primate Ekgmowechashala appeared in the Great Plains and Oregon. This taxon shows little resemblance to other North American primates and its phylogenetic position has long been debated. New material of this taxon allows a revised assessment of its age and how it is related to other primates. Recently collected Ekgmowechashala specimens from the Turtle Cove Member of the John Day Formation in Oregon are described. These specimens are compared to previously collected material from South Dakota and Nebraska, as well as other fossil primates from North America and Asia. Study of the John Day material allows diagnosis of a new, distinct species. Comparison of Ekgmowechashala to a pair of recently described Asian primates, Muangthanhinius and Bugtilemur, suggests that it is a strepsirrhine adapiform, rather than an omomyid. The well-defined stratigraphy and dated marker beds of the Turtle Cove Member provide a refined age for Ekgmowechashala occurrences in Oregon, during the Oligocene (early Arikareean). The age and morphology of these ekgmowechashaline taxa suggest that the group originated in Asia and dispersed to North America in the Oligocene, after the extinction of other primates in North America. Contemporaneous occurrences of Ekgmowechashala in Oregon and the Great Plains indicate the last non-human primates vanished in North America about 26 million years ago. © 2015 Wiley Periodicals, Inc.

  11. Animal continuities. Arguments against human/non-human animal dichotomy

    Directory of Open Access Journals (Sweden)

    Javier Ignacio Vernal

    2011-07-01

    Full Text Available At present, there is still a deep need to differentiate the members of the species Homo sapiens from the individuals belonging to the rest of the animal kingdom. As a consequence of this need arises the dichotomy human/non-human animal based on artificial and groundless differences that leads to actions always harmful to the non-human animals. In this work we want to show, on the one hand, that many of the characteristics proposed as specifically human are shared by at least some non-human animal species, and on the other hand, that specifically human characteristics do exist, but from this fact does not follow that we should draw a sharp line between human and non-human animals. We reject the speciesist and segregationist perspective that establishes that only human beings possess a singular position in nature. Every animal species has its own characteristics and, therefore, there would be no place for a human exception, but there would be as many exceptions as animal species exist in the nature. Instead of the abyss established between human animals and non-human animals, we defend the perspective of the animal continuum, which allows recognizing the characteristics that we share with other animal species and, therefore, promotes the end of the speciesism.

  12. A comparison of antemortem tooth loss in human hunter-gatherers and non-human catarrhines: implications for the identification of behavioral evolution in the human fossil record.

    Science.gov (United States)

    Gilmore, Cassandra C

    2013-06-01

    Middle and Late Pleistocene fossil hominin specimens with severe antemortem tooth loss are often regarded as evidence for the precocious evolution of human-like behaviors, such as conspecific care or cooking, in ancient hominin species. The goal of this project was to ask whether the theoretical association between antemortem tooth loss and uniquely human behaviors is supported empirically in a large skeletal sample of human hunter-gatherers, chimpanzees, orangutans, and baboons. Binomial regression modeling in a Bayesian framework allows for the investigation of the effects of tooth class, genus, age, and sex on the likelihood of tooth loss. The results strongly suggest that modern humans experience more antemortem tooth loss than non-human primates and identify age in years as an important predictor. Once age is accounted for, the difference between the humans and the closest non-human genus (chimpanzees) is less pronounced; humans are still more likely on average to experience antemortem tooth loss though 95% uncertainty envelopes around the average prediction for each genus show some overlap. These analyses support theoretical links between antemortem tooth loss and modern human characteristics; humans' significantly longer life history and a positive correlation between age and antemortem tooth loss explain, in part, the reason why humans are more likely to experience tooth loss than non-human primates, but the results do not exclude behavioral differences as a contributing factor. Copyright © 2013 Wiley Periodicals, Inc.

  13. Referential alarm calling behaviour in New World primates

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    Cristiane CÄSAR, Klaus ZUBERBÜHLER

    2012-10-01

    Full Text Available There is relatively good evidence that non-human primates can communicate about objects and events in their environment in ways that allow recipients to draw inferences about the nature of the event experienced by the signaller. In some species, there is also evidence that the basic semantic units are not individual calls, but call sequences and the combinations generated by them. These two findings are relevant to theories pertaining to the origins of human language because of the resemblances of these phenomena with linguistic reference and syntactic organisation. Until recently, however, most research efforts on the primate origins of human language have involved Old World species with comparatively few systematic studies on New World monkeys, which has prevented insights into the deeper phylogenetic roots and evolutionary origins of language-relevant capacities. To address this, we review the older primate literature and very recent evidence for functionally referential communication and call combinations in New World primates. Within the existing literature there is ample evidence in both Callitrichids and Cebids for acoustically distinct call variants given to external disturbances that are accompanied by distinct behavioural responses. A general pattern is that one call type is typically produced in response to a wide range of general disturbances, often on the ground but also including inter-group encounters, while another call type is produced in response to a much narrower range of aerial threats. This pattern is already described for Old World monkeys and Prosimians, suggesting an early evolutionary origin. Second, recent work with black-fronted titi monkeys has produced evidence for different alarm call sequences consisting of acoustically distinct call types. These sequences appear to encode several aspects of the predation event simultaneously, notably predator type and location. Since meaningful call sequences have already been

  14. Theories about evolutionary origins of human hepatitis B virus in primates and humans

    Directory of Open Access Journals (Sweden)

    Breno Frederico de Carvalho Dominguez Souza

    2014-09-01

    Conclusion: Some hypotheses about the evolutionary origins of human hepatitis B virus have been debated since the ‘90s. One theory suggested a New World origin because of the phylogenetic co-segregation between some New World human hepatitis B virus genotypes F and H and woolly monkey human hepatitis B virus in basal sister-relationship to the Old World non-human primates and human hepatitis B virus variants. Another theory suggests an Old World origin of human hepatitis B virus, and that it would have been spread following prehistoric human migrations over 100,000 years ago. A third theory suggests a co-speciation of human hepatitis B virus in non-human primate hosts because of the proximity between the phylogeny of Old and New World non-human primate and their human hepatitis B virus variants. The importance of further research, related to the subject in South American wild fauna, is paramount and highly relevant for understanding the origin of human hepatitis B virus.

  15. Abduction: Can non-human animals make discoveries?

    DEFF Research Database (Denmark)

    Vitti-Rodrigues, Mariana; Emmeche, Claus

    2017-01-01

    The aim of this paper is to investigate the relationship between information and abductive reasoning in the context of problem-solving, focusing on non-human animals. Two questions guide our investigation: (1) What is the relation between information and abductive reasoning in the context of human...... and non-human animals? (2) Do non-human animals perform discovery based on inferential processes such as abductive reasoning? In order to answer these questions, we discuss the semiotic concept of information in relation to the concept of abductive reasoning and, more specifically, to the notion...... of manipulative abduction proposed by Magnani (2009). Finally, we investigate a case study of corvids’ intelligence, namely, their capacity of causal cognition....

  16. Feeding rate as valuable information in primate feeding ecology.

    Science.gov (United States)

    Nakagawa, Naofumi

    2009-04-01

    In this review I outline studies on wild non-human primates using information on feeding rate, which is defined as the food intake per minute on a dry-weight basis; further, I summarize the significance of feeding rate in primate feeding ecology. The optimal foraging theory has addressed three aspects of animal feeding: (1) optimal food patch choice, (2) optimal time allocation to different patches, and (3) optimal food choice. In order to gain a better understanding of these three aspects, the feeding rate itself or its relevance indices (e.g., rates of calorie and protein intake) could be appropriate measures to assess the quality of food and food patches. Moreover, the feeding rate plays an essential role in estimation of total food intake, because it varies greatly for different food items and the feeding time is not a precise measure. The feeding rate could also vary across individuals who simultaneously feed on the same food items in the same food patch. Body size-dependent and rank-dependent differences in the feeding rate sometimes cause individuals to take strategic behavioral options. In the closing remarks, I discuss the usefulness of even limited data on feeding rate obtained under adverse observational conditions in understanding primate feeding ecology.

  17. Primates in biomedical research and their maintenance in captivity. I primati nella ricerca biomedica ed il loro allevamento in cattivita

    Energy Technology Data Exchange (ETDEWEB)

    Monaco, V.

    1983-01-01

    This conference is intended to provide to biologists, phychologists, zoologists etc., some criteria on use of non-human primates in biomedical research and to assess their value in procedures and tests of products by a pharmaceutical industry (i.e., poliomyelitis vaccine). After a review of scientific achievements during last decades and of the possibility of development of use of primates for medical experimentation, a numerical estimation of the subjects employed in different countries and of the basic needs as indicated by OMS and EEC is reported. In an attempt to promote a programme for production of primates in Italy, this communication describes the project of primates breeding by using areas near electro-nuclear power stations. 5 refs.

  18. Estimating thumb–index finger precision grip and manipulation potential in extant and fossil primates

    Science.gov (United States)

    Feix, Thomas; Kivell, Tracy L.; Pouydebat, Emmanuelle; Dollar, Aaron M.

    2015-01-01

    Primates, and particularly humans, are characterized by superior manual dexterity compared with other mammals. However, drawing the biomechanical link between hand morphology/behaviour and functional capabilities in non-human primates and fossil taxa has been challenging. We present a kinematic model of thumb–index precision grip and manipulative movement based on bony hand morphology in a broad sample of extant primates and fossil hominins. The model reveals that both joint mobility and digit proportions (scaled to hand size) are critical for determining precision grip and manipulation potential, but that having either a long thumb or great joint mobility alone does not necessarily yield high precision manipulation. The results suggest even the oldest available fossil hominins may have shared comparable precision grip manipulation with modern humans. In particular, the predicted human-like precision manipulation of Australopithecus afarensis, approximately one million years before the first stone tools, supports controversial archaeological evidence of tool-use in this taxon. PMID:25878134

  19. A simpler primate brain: the visual system of the marmoset monkey

    Directory of Open Access Journals (Sweden)

    Samuel Gavan Solomon

    2014-08-01

    Full Text Available Humans are diurnal primates with high visual acuity at the centre of gaze. Although primates share many similarities in the organisation of their visual centres with other mammals, and even other species of vertebrates, their visual pathways also show unique features, particularly with respect to the organization of the cerebral cortex. Therefore, in order to understand some aspects of human visual function, we need to study non-human primate brains. Which species is the most appropriate model? Macaque monkeys, the most widely used non-human primates, are not an optimal choice in many practical respects. For example, much of the macaque cerebral cortex is buried within sulci, and is therefore inaccessible to many imaging techniques, and the postnatal development and lifespan of macaques are prohibitively long for many studies of brain maturation, plasticity and ageing. In these and several other respects the marmoset, a small New World monkey, represents a more appropriate choice. Here we review the visual pathways of the marmoset, highlighting recent work that brings these advantages into focus, and identify where additional work needs to be done to link marmoset brain organisation to that of macaques and humans. We will argue that the marmoset monkey provides a good subject for studies of a complex visual system, which will likely allow an important bridge linking experiments in animal models to humans.

  20. Developmental parallelism in primates.

    Science.gov (United States)

    Sikorska-Piwowska, Z M; Dawidowicz, A L

    2017-01-01

    The authors examined a large random sample of skulls from two species of macaques: rhesus monkeys and cynomolgus monkeys. The skulls were measured, divided into age and sex groups and thoroughly analysed using statistical methods. The analysis shows that skulls of young rhesuses are considerably more domed, i.e. have better-developed neurocrania, than their adult counterparts. Male and female skulls, on the other hand, were found to be very similar, which means that sexual dimorphism of the rhesus macaque was suppressed. Both of these patterns are known from the human evolutionary pattern. No such parallelism to the development of Homo sapiens was found in the cynomolgus monkeys. The authors conclude that mosaic hominisation trends may have featured in the evolution of all primates. This would mean that apes were not a necessary step on the evolutionary way leading to the development of Homo sapiens, who may have started to evolve at an earlier stage of monkeys.

  1. Brains, Genes and Primates

    Science.gov (United States)

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  2. Visuomotor cerebellum in human and nonhuman primates.

    Science.gov (United States)

    Voogd, Jan; Schraa-Tam, Caroline K L; van der Geest, Jos N; De Zeeuw, Chris I

    2012-06-01

    In this paper, we will review the anatomical components of the visuomotor cerebellum in human and, where possible, in non-human primates and discuss their function in relation to those of extracerebellar visuomotor regions with which they are connected. The floccular lobe, the dorsal paraflocculus, the oculomotor vermis, the uvula-nodulus, and the ansiform lobule are more or less independent components of the visuomotor cerebellum that are involved in different corticocerebellar and/or brain stem olivocerebellar loops. The floccular lobe and the oculomotor vermis share different mossy fiber inputs from the brain stem; the dorsal paraflocculus and the ansiform lobule receive corticopontine mossy fibers from postrolandic visual areas and the frontal eye fields, respectively. Of the visuomotor functions of the cerebellum, the vestibulo-ocular reflex is controlled by the floccular lobe; saccadic eye movements are controlled by the oculomotor vermis and ansiform lobule, while control of smooth pursuit involves all these cerebellar visuomotor regions. Functional imaging studies in humans further emphasize cerebellar involvement in visual reflexive eye movements and are discussed.

  3. 7 CFR 993.108 - Non-human consumption outlet.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... consumption outlet means any livestock feeder or manufacturer of inedible syrup, industrial alcohol, animal feed, or other product for non-human use, who has established, to the satisfaction of the committee...

  4. Captivity humanizes the primate microbiome.

    Science.gov (United States)

    Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

    2016-09-13

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

  5. Captivity humanizes the primate microbiome

    Science.gov (United States)

    Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M.; Al-Ghalith, Gabriel A.; Travis, Dominic A.; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E.; Johnson, Timothy J.; Knights, Dan

    2016-01-01

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome. PMID:27573830

  6. Heart transplant survival in non-human primates : T cell-directed immunosuppressive therapy and regulatory T cells for promotion of heart transplant survival in non-human primates

    NARCIS (Netherlands)

    E.M. Dons (Eefje)

    2013-01-01

    textabstractHeart transplantation significantly enhances the life expectancy of adult patients suffering heart failure, and infants born with malformations of their heart. However, there are many hurdles such as rejection of the transplanted organ, or side effects of the immunosuppressive drugs,

  7. Species association of hepatitis B virus (HBV in non-human apes; evidence for recombination between gorilla and chimpanzee variants.

    Directory of Open Access Journals (Sweden)

    Sinéad Lyons

    Full Text Available Hepatitis B virus (HBV infections are widely distributed in humans, infecting approximately one third of the world's population. HBV variants have also been detected and genetically characterised from Old World apes; Gorilla gorilla (gorilla, Pan troglodytes (chimpanzee, Pongo pygmaeus (orang-utan, Nomascus nastusus and Hylobates pileatus (gibbons and from the New World monkey, Lagothrix lagotricha (woolly monkey. To investigate species-specificity and potential for cross species transmission of HBV between sympatric species of apes (such as gorillas and chimpanzees in Central Africa or between humans and chimpanzees or gorillas, variants of HBV infecting captive wild-born non-human primates were genetically characterised. 9 of 62 chimpanzees (11.3% and two from 11 gorillas (18% were HBV-infected (15% combined frequency, while other Old world monkey species were negative. Complete genome sequences were obtained from six of the infected chimpanzee and both gorillas; those from P. t .ellioti grouped with previously characterised variants from this subspecies. However, variants recovered from P. t. troglodytes HBV variants also grouped within this clade, indicative of transmission between sub-species, forming a paraphyletic clade. The two gorilla viruses were phylogenetically distinct from chimpanzee and human variants although one showed evidence for a recombination event with a P.t.e.-derived HBV variant in the partial X and core gene region. Both of these observations provide evidence for circulation of HBV between different species and sub-species of non-human primates, a conclusion that differs from the hypothesis if of strict host specificity of HBV genotypes.

  8. Genome-wide identification of human- and primate-specific core promoter short tandem repeats.

    Science.gov (United States)

    Bushehri, A; Barez, M R Mashhoudi; Mansouri, S K; Biglarian, A; Ohadi, M

    2016-08-01

    Recent reports of a link between human- and primate-specific genetic factors and human/primate-specific characteristics and diseases necessitate genome-wide identification of those factors. We have previously reported core promoter short tandem repeats (STRs) of extreme length (≥6-repeats) that have expanded exceptionally in primates vs. non-primates, and may have a function in adaptive evolution. In the study reported here, we extended our study to the human STRs of ≥3-repeats in the category of penta and hexaucleotide STRs, across the entire human protein coding gene core promoters, and analyzed their status in several superorders and orders of vertebrates, using the Ensembl database. The ConSite software was used to identify the transcription factor (TF) sets binding to those STRs. STR specificity was observed at different levels of human and non-human primate (NHP) evolution. 73% of the pentanucleotide STRs and 68% of the hexanucleotide STRs were found to be specific to human and NHPs. AP-2alpha, Sp1, and MZF were the predominantly selected TFs (90%) binding to the human-specific STRs. Furthermore, the number of TF sets binding to a given STR was found to be a selection factor for that STR. Our findings indicate that selected STRs, the cognate binding TFs, and the number of TF set binding to those STRs function as switch codes at different levels of human and NHP evolution and speciation. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Crop Damage by Primates: Quantifying the Key Parameters of Crop-Raiding Events

    Science.gov (United States)

    Wallace, Graham E.; Hill, Catherine M.

    2012-01-01

    Human-wildlife conflict often arises from crop-raiding, and insights regarding which aspects of raiding events determine crop loss are essential when developing and evaluating deterrents. However, because accounts of crop-raiding behaviour are frequently indirect, these parameters are rarely quantified or explicitly linked to crop damage. Using systematic observations of the behaviour of non-human primates on farms in western Uganda, this research identifies number of individuals raiding and duration of raid as the primary parameters determining crop loss. Secondary factors include distance travelled onto farm, age composition of the raiding group, and whether raids are in series. Regression models accounted for greater proportions of variation in crop loss when increasingly crop and species specific. Parameter values varied across primate species, probably reflecting differences in raiding tactics or perceptions of risk, and thereby providing indices of how comfortable primates are on-farm. Median raiding-group sizes were markedly smaller than the typical sizes of social groups. The research suggests that key parameters of raiding events can be used to measure the behavioural impacts of deterrents to raiding. Furthermore, farmers will benefit most from methods that discourage raiding by multiple individuals, reduce the size of raiding groups, or decrease the amount of time primates are on-farm. This study demonstrates the importance of directly relating crop loss to the parameters of raiding events, using systematic observations of the behaviour of multiple primate species. PMID:23056378

  10. Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice.

    Science.gov (United States)

    Cokorinos, Emily C; Delmore, Jake; Reyes, Allan R; Albuquerque, Bina; Kjøbsted, Rasmus; Jørgensen, Nicolas O; Tran, Jean-Luc; Jatkar, Aditi; Cialdea, Katherine; Esquejo, Ryan M; Meissen, John; Calabrese, Matthew F; Cordes, Jason; Moccia, Robert; Tess, David; Salatto, Christopher T; Coskran, Timothy M; Opsahl, Alan C; Flynn, Declan; Blatnik, Matthew; Li, Wenlin; Kindt, Erick; Foretz, Marc; Viollet, Benoit; Ward, Jessica; Kurumbail, Ravi G; Kalgutkar, Amit S; Wojtaszewski, Jørgen F P; Cameron, Kimberly O; Miller, Russell A

    2017-05-02

    The AMP-activated protein kinase (AMPK) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. We evaluated two distinct direct activators of AMPK: a non-selective activator of all AMPK complexes, PF-739, and an activator selective for AMPK β1-containing complexes, PF-249. In cells and animals, both compounds were effective at activating AMPK in hepatocytes, but only PF-739 was capable of activating AMPK in skeletal muscle. In diabetic mice, PF-739, but not PF-249, caused a rapid lowering of plasma glucose levels that was diminished in the absence of skeletal muscle, but not liver, AMPK heterotrimers and was the result of an increase in systemic glucose disposal with no impact on hepatic glucose production. Studies of PF-739 in cynomolgus monkeys confirmed translation of the glucose lowering and established activation of AMPK in skeletal muscle as a potential therapeutic approach to treat diabetic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Activation of skeletal muscle AMPK promotes glucose disposal and glucose lowering in non-human primates and mice

    DEFF Research Database (Denmark)

    Cokorinos, Emily C; Delmore, Jake; Reyes, Allan R

    2017-01-01

    for AMPK β1-containing complexes, PF-249. In cells and animals, both compounds were effective at activating AMPK in hepatocytes, but only PF-739 was capable of activating AMPK in skeletal muscle. In diabetic mice, PF-739, but not PF-249, caused a rapid lowering of plasma glucose levels that was diminished...... in the absence of skeletal muscle, but not liver, AMPK heterotrimers and was the result of an increase in systemic glucose disposal with no impact on hepatic glucose production. Studies of PF-739 in cynomolgus monkeys confirmed translation of the glucose lowering and established activation of AMPK in skeletal...

  12. Jaw-opening reflex and corticobulbar motor excitability changes during quiet sleep in non-human primates

    DEFF Research Database (Denmark)

    Yao, Dongyuan; Lavigne, Gilles J.; Lee, Jye-Chang

    2013-01-01

    Study Objective: To test the hypothesis that the reflex and corticobulbar motor excitability of jaw muscles is reduced during sleep. Design: Polysomnographic recordings in the electrophysiological study. Setting: University sleep research laboratories. Participants and Interventions: The reflex...... and corticobulbar motor excitability of jaw muscles was determined during the quiet awake state (QW) and quiet sleep (QS) in monkeys (n = 4). Measurements and Results: During QS sleep, compared to QW periods, both tongue stimulation-evoked jaw-opening reflex peak and root mean square amplitudes were significantly......-evoked activity in the jaw motor system is depressed during QS....

  13. Assessment of social cognition in non-human primates using a network of computerized automated learning device (ALDM) test systems.

    Science.gov (United States)

    Fagot, Joël; Marzouki, Yousri; Huguet, Pascal; Gullstrand, Julie; Claidière, Nicolas

    2015-05-05

    Fagot & Paleressompoulle(1) and Fagot & Bonte(2) have published an automated learning device (ALDM) for the study of cognitive abilities of monkeys maintained in semi-free ranging conditions. Data accumulated during the last five years have consistently demonstrated the efficiency of this protocol to investigate individual/physical cognition in monkeys, and have further shown that this procedure reduces stress level during animal testing(3). This paper demonstrates that networks of ALDM can also be used to investigate different facets of social cognition and in-group expressed behaviors in monkeys, and describes three illustrative protocols developed for that purpose. The first study demonstrates how ethological assessments of social behavior and computerized assessments of cognitive performance could be integrated to investigate the effects of socially exhibited moods on the cognitive performance of individuals. The second study shows that batteries of ALDM running in parallel can provide unique information on the influence of the presence of others on task performance. Finally, the last study shows that networks of ALDM test units can also be used to study issues related to social transmission and cultural evolution. Combined together, these three studies demonstrate clearly that ALDM testing is a highly promising experimental tool for bridging the gap in the animal literature between research on individual cognition and research on social cognition.

  14. Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.

    Science.gov (United States)

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

    2009-12-11

    Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 1970s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRPs) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 x 10(6)pfu of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine.

  15. Regulation of EGF and Prostaglandin Expression during Neonatal Gastrointestinal Injury in a Non-Human Primate Explant Model

    Science.gov (United States)

    2017-05-05

    FHsIm7- d Prosta.gim:lin E.’q)IcSLoO During Neon tal Gastro!:n.r.e:;t!na.llDjury: Line M8ER: FOml 3D39 r 1 :2. DYE8 DA-E Ap ill? 2017 15. ACe\\" edo . N\\’l...efficiently replicates in vivo tissue behavior allowing for testing of confounding variables within the. same tissue and translation to an in vivo

  16. Tools, treats, toys : what human and non-human primates remember about their past and plan for their future

    NARCIS (Netherlands)

    Dekleva, M.

    2011-01-01

    Whether humans are the only species capable of re-experiencing past personal episodes and imagining potential future events has been questioned. A major obstacle previously hindering investigation of other species was that humans typically report these abilities verbally. In the past 20 years,

  17. The NMDAr antagonist ketamine interferes with manipulation of information for transitive inference reasoning in non-human primates.

    Science.gov (United States)

    Brunamonti, Emiliano; Mione, Valentina; Di Bello, Fabio; De Luna, Paolo; Genovesio, Aldo; Ferraina, Stefano

    2014-09-01

    One of the most remarkable traits of highly encephalized animals is their ability to manipulate knowledge flexibly to infer logical relationships. Operationally, the corresponding cognitive process can be defined as reasoning. One hypothesis is that this process relies on the reverberating activity of glutamate neural circuits, sustained by NMDA receptor (NMDAr) mediated synaptic transmission, in both parietal and prefrontal areas. We trained two macaque monkeys to perform a form of deductive reasoning - the transitive inference task - in which they were required to learn the relationship between six adjacent items in a single session and then deduct the relationship between nonadjacent items that had not been paired in the learning phase. When the animals had learned the sequence, we administered systemically a subanaesthetic dose of ketamine (a NMDAr antagonist) and measured their performance on learned and novel problems. We observed impairments in determining the relationship between novel pairs of items. Our results are consistent with the hypothesis that transitive inference premises are integrated during learning in a unified representation and that reducing NMDAr activity interferes with the use of this mental model, when decisions are required in comparing pairs of items that have not been learned. © The Author(s) 2014.

  18. Repeated intravenous injections in non-human primates demonstrate preclinical safety of an anti-inflammatory phosphorus-based dendrimer.

    Science.gov (United States)

    Fruchon, Séverine; Mouriot, Sébastien; Thiollier, Thibaud; Grandin, Clément; Caminade, Anne-Marie; Turrin, Cédric-Olivier; Contamin, Hugues; Poupot, Rémy

    2015-05-01

    Dendrimers are nanosized hyperbranched polymers synthesized through an iterative step-by-step process; their size and structure are perfectly controlled, and they are widely used for biomedical purposes. Previously, we showed that a phosphorous-based dendrimer capped with anionic AzaBisPhosphonate groups (so-called ABP dendrimer) has immunomodulatory and anti-inflammatory properties toward the human immune system. It dramatically inhibits the onset and development of experimental arthritis in a mouse model relevant for human rheumatoid arthritis, a chronic inflammatory disease of auto-immune origin. In this article, we demonstrate in an unprecedented study that cynomolgus macaques repeatedly injected with the ABP dendrimer displayed no adverse response. Indeed, biochemical, haematological, clotting and immunological parameters remained with a normal physiological range during the study. Moreover, quantification of serum cytokines and histopathological analyses failed to reveal any noticeable lesion or noteworthy non-physiological occurrence. These results strengthen the potential of the ABP dendrimer as an innovative drug-candidate for the treatment of inflammatory diseases and favor the regulatory preclinical development of the molecule.

  19. 6-methylprednisolone does not impair anti-thymocyte globulin (ATG) immunosuppressive activity in non-human primates

    NARCIS (Netherlands)

    Preville, [No Value; Sick, E; Beauchard, S; Ossevoort, M; Tiollier, J; Revillard, JP; Jonker, Margreet

    2001-01-01

    Background: Induction treatments with anti-thymocyte globulin (ATG) in solid organ transplantation may enhance the efficacy of maintenance immunosuppressive therapy. Since ATG can trigger Fas (CD95) mediated T cell apoptosis, a process antagonized in vitro by corticosteroids, an important issue is

  20. Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.

    Directory of Open Access Journals (Sweden)

    Alexander Strom

    Full Text Available Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE-infected female cynomolgus monkeys (Macaca fascicularis. The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c. infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001 which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

  1. Open-Source, Low Cost, Free-Behavior Monitoring, and Reward System for Neuroscience Research in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Tyler Libey

    2017-05-01

    Full Text Available We describe a low-cost system designed to document bodily movement and neural activity and deliver rewards to monkeys behaving freely in their home cage. An important application is to studying brain-machine interface (BMI systems during free behavior, since brain signals associated with natural movement can differ significantly from those associated with more commonly used constrained conditions. Our approach allows for short-latency (<500 ms reward delivery and behavior monitoring using low-cost off-the-shelf components. This system interfaces existing untethered recording equipment with a custom hub that controls a cage-mounted feeder. The behavior monitoring system uses a depth camera to provide real-time, easy-to-analyze, gross movement data streams. In a proof-of-concept experiment we demonstrate robust learning of neural activity using the system over 14 behavioral sessions.

  2. The effects of a calorie-reduced diet on periodontal inflammation and disease in a non-human primate model.

    Science.gov (United States)

    Branch-Mays, Grishondra L; Dawson, Dolphus R; Gunsolley, John C; Reynolds, Mark A; Ebersole, Jeffrey L; Novak, Karen F; Mattison, Julie A; Ingram, Donald K; Novak, M John

    2008-07-01

    Low-calorie diets are commonplace for reducing body weight. However, no information is available on the effects of a reduced-calorie diet on periodontal inflammation and disease. The purpose of this study was to evaluate the clinical effects of a long-term calorie-restriction (CR) diet on periodontitis in an animal model of periodontitis. Periodontitis was induced in 55 young, healthy, adult rhesus monkeys (Macaca mulatta) by tying 2.0 silk ligatures at the gingival margins of maxillary premolar/molar teeth. Animals on a CR diet (30% CR; N = 23) were compared to ad libitum diet controls (N = 32). Clinical measures, including the plaque index (PI), probing depth (PD), clinical attachment level (CAL), modified gingival index (GI), and bleeding on probing (BOP) were recorded at baseline and 1, 2, and 3 months after ligature placement. Significant effects of CR were observed on the development of inflammation and the progression of periodontal destruction in this model. Compared to controls, CR resulted in a significant reduction in ligature-induced GI (P Periodontal destruction, as measured by CAL, progressed significantly more slowly in the CR animals than in the controls (P periodontal breakdown associated with an acute microbial challenge.

  3. Impact of obesity severity and duration on pancreatic β- and α-cell dynamics in normoglycemic non-human primates.

    Science.gov (United States)

    Guardado-Mendoza, R; Jimenez-Ceja, L; Majluf-Cruz, A; Kamath, S; Fiorentino, T V; Casiraghi, F; Velazquez, A O C; DeFronzo, R A; Dick, E; Davalli, A; Folli, F

    2013-08-01

    Obesity is associated with high insulin and glucagon plasma levels. Enhanced β-cell function and β-cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons. Pancreatic β- and α-cell volumes were measured in 51 normoglycemic baboons divided into six groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters. Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater increase in RIαV. Baboons' body weights correlated with serum levels of interleukin-6 and tumor necrosis factor-α soluble receptors, demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β- and α-cell viability and replication. In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV), whereas have minimal effects on the β cells. This study suggests that an increase in the α-cell mass may precede the loss of β cells and the transition to overt hyperglycemia and diabetes.

  4. Delivering Prolonged Intensive Care to a Non-human Primate: A High Fidelity Animal Model of Critical Illness.

    Science.gov (United States)

    Poliquin, P Guillaume; Biondi, Mia; Ranadheera, Charlene; Hagan, Mable; Bello, Alexander; Racine, Trina; Allan, Mark; Funk, Duane; Hansen, Gregory; Hancock, B J; Kesselman, Murray; Mortimer, Todd; Kumar, Anand; Jones, Shane; Leung, Anders; Grolla, Allen; Tran, Kaylie N; Tierney, Kevin; Qiu, Xiangguo; Kobasa, Darwyn; Strong, James E

    2017-04-26

    Critical care needs have been rising in recent decades as populations age and comorbidities increase. Sepsis-related admissions to critical care contribute up to 50% of volume and septic shock carries a 35-54% fatality rate. Improvements in sepsis-related care and mortality would have a significant impact of a resource-intensive area of health care delivery. Unfortunately, research has been hampered by the lack of an animal model that replicates the complex care provided to humans in an intensive care unit (ICU). We developed a protocol to provide full ICU type supportive care to Rhesus macaques. This included mechanical ventilation, continuous sedation, fluid and electrolyte management and vasopressor support in response to Ebolavirus-induced septic shock. The animals accurately recapitulated human responses to a full range of ICU interventions (e.g. fluid resuscitation). This model can overcome current animal model limitations by accurately emulating the complexity of ICU care and thereby provide a platform for testing new interventions in critical care and sepsis without placing patients at risk.

  5. Brazilian Firms

    Directory of Open Access Journals (Sweden)

    Vicente Lima Crisóstomo

    2016-01-01

    Full Text Available This work makes an analysis of the determinants of Corporate Social Responsibility (CSR of Brazilian firms, as proxied by firm membership of the ISE Index of BM&FBOVESPA. Besides other proposed determinants of CSR present in the literature (firm size, profitability, growth opportunities, the work examines ownership concentration and the persistence on CSR status. Logit regression estimates have been run for a sample of 1649 firm-year observations in the period 2006-2011. The findings show that CSR of Brazilian firms is inversely correlated to its ownership concentration indicating that controlling voting shareholders may not see social concerns as a priority. Besides, firms tend to maintain their present CSR status. The results also indicate that leading CSR firms are larger, face more growth opportunities, and are persistent in their superior CSR situation.

  6. Processing pitch in a non-human mammal (Chinchilla laniger)

    Science.gov (United States)

    Shofner, William P.; Chaney, Megan

    2013-01-01

    Whether the mechanisms giving rise to pitch reflect spectral or temporal processing has long been debated. Generally, sounds having strong harmonic structures in their spectra have strong periodicities in their temporal structures. We found that when a wideband harmonic tone complex is passed through a noise vocoder, the resulting sound can have a harmonic structure with a large peak-to-valley ratio, but with little or no periodicity in the temporal structure. To test the role of harmonic structure in pitch perception for a non-human mammal, we measured behavioral responses to noise-vocoded tone complexes in chinchillas using a stimulus generalization paradigm. Animals discriminated either a harmonic tone complex or an iterated rippled noise from a 1-channel vocoded version of the tone complex. When tested with vocoded versions generated with 8, 16, 32, 64 and 128 channels, responses were similar to those of the 1-channel version. Behavioral responses could not be accounted for based on harmonic peak-to-valley ratio as the acoustic cue, but could be accounted for based on temporal properties of the autocorrelation functions such as periodicity strength or the height of the first peak. The results suggest that pitch perception does not arise through spectral processing in non-human mammals, but rather through temporal processing. The conclusion that spectral processing contributes little to pitch in non-human mammals may reflect broader cochlear tuning than that described in humans. PMID:22985274

  7. Dental maturation, eruption, and gingival emergence in the upper jaw of newborn primates

    Science.gov (United States)

    Smith, Timothy D.; Muchlinksi, Magdalena N.; Jankord, Kathryn D.; Progar, Abbigal J.; Bonar, Christopher J.; Evans, Sian; Williams, Lawrence; Vinyard, Christopher J.; DeLeon, Valerie B.

    2015-01-01

    In this report we provide data on dental eruption and tooth germ maturation at birth in a large sample constituting the broadest array of non-human primates studied to date. Over 100 perinatal primates, obtained from natural captive deaths, were screened for characteristics indicating premature birth, and were subsequently studied using a combination of histology and micro-CT. Results reveal one probable unifying characteristic of living primates: relatively advanced maturation of deciduous teeth and M1 at birth. Beyond this, there is great diversity in the status of tooth eruption and maturation (dental stage) in the newborn primate. Contrasting strategies in producing a masticatory battery are already apparent at birth in strepsirrhines and anthropoids. Results show that dental maturation and eruption schedules are potentially independently co-opted as different strategies for attaining feeding independence. The most common strategy in strepsirrhines is accelerating eruption and the maturation of the permanent dentition, including replacement teeth. Anthropoids, with only few exceptions, accelerate mineralization of the deciduous teeth, while delaying development of all permanent teeth except M1. These results also show that no living primate resembles the altricial tree shrew (Tupaia) in dental development. Our preliminary observations suggest that ecological explanations, such as diet, provide an explanation for certain morphological variations at birth. These results confirm previous work on perinatal indriids indicating that these and other primates telegraph their feeding adaptations well before masticatory anatomy is functional. Quantitative analyses are required to decipher specific dietary and other influences on dental size and maturation in the newborn primate. PMID:26425925

  8. Dental maturation, eruption, and gingival emergence in the upper jaw of newborn primates.

    Science.gov (United States)

    Smith, Timothy D; Muchlinski, Magdalena N; Jankord, Kathryn D; Progar, Abbigal J; Bonar, Christopher J; Evans, Sian; Williams, Lawrence; Vinyard, Christopher J; Deleon, Valerie B

    2015-12-01

    In this report we provide data on dental eruption and tooth germ maturation at birth in a large sample constituting the broadest array of non-human primates studied to date. Over 100 perinatal primates, obtained from natural captive deaths, were screened for characteristics indicating premature birth, and were subsequently studied using a combination of histology and micro-CT. Results reveal one probable unifying characteristic of living primates: relatively advanced maturation of deciduous teeth and M1 at birth. Beyond this, there is great diversity in the status of tooth eruption and maturation (dental stage) in the newborn primate. Contrasting strategies in producing a masticatory battery are already apparent at birth in strepsirrhines and anthropoids. Results show that dental maturation and eruption schedules are potentially independently co-opted as different strategies for attaining feeding independence. The most common strategy in strepsirrhines is accelerating eruption and the maturation of the permanent dentition, including replacement teeth. Anthropoids, with only few exceptions, accelerate mineralization of the deciduous teeth, while delaying development of all permanent teeth except M1. These results also show that no living primate resembles the altricial tree shrew (Tupaia) in dental development. Our preliminary observations suggest that ecological explanations, such as diet, provide an explanation for certain morphological variations at birth. These results confirm previous work on perinatal indriids indicating that these and other primates telegraph their feeding adaptations well before masticatory anatomy is functional. Quantitative analyses are required to decipher specific dietary and other influences on dental size and maturation in the newborn primate. © 2015 Wiley Periodicals, Inc.

  9. Brazilian energy

    Energy Technology Data Exchange (ETDEWEB)

    O`Shaughnessy, H.

    1997-04-01

    Brazilian Energy provides all the information necessary for energy companies to invest and operate in Brazil, including: a review of Brazil`s natural resources; an assessment of privatisation strategies at the federal, state and regional level; an analysis of the electricity industry and the future for Electrobras; an analysis of the oil industry and, in particular, Petrobras; a discussion of the fuel alcohol industry; the discovery of local natural gas, its prospects and the involvement of the auto industry; an assessment of the problems facing the coal industry and its future; a discussion of the regulatory framework for the newly privatised companies; the importance of intra-regional energy links and the booming membership of Mercosur; the difficulties experienced by foreign investors doing business in Brazil; brief profiles of the key energy companies; profiles of key people influencing the privatisation process in Brazil. Brazilian energy is essential reading for those wishing to advise and assist Brazil in this period of change and development, as well as those who wish to invest or become key players in the Brazilian energy sector. (author)

  10. A molecular phylogeny of living primates.

    Directory of Open Access Journals (Sweden)

    Polina Perelman

    2011-03-01

    Full Text Available Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb from 186 primates representing 61 (~90% of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.

  11. A Molecular Phylogeny of Living Primates

    Science.gov (United States)

    Perelman, Polina; Johnson, Warren E.; Roos, Christian; Seuánez, Hector N.; Horvath, Julie E.; Moreira, Miguel A. M.; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C.; Silva, Artur; O'Brien, Stephen J.; Pecon-Slattery, Jill

    2011-01-01

    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (∼8 Mb) from 186 primates representing 61 (∼90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species. PMID:21436896

  12. Color vision in primates: Neurobiology and behavior

    OpenAIRE

    Skalníková, Petra

    2015-01-01

    Trichromacy is the condition that involves three independent channels for processing color information based on three different cone types. Most mammals have dichromatic vision, trichromacy appears in primates of the Old World (including human) and partly in the New Wold primates. This thesis focuses on the mechanisms of trichromatic vision, its evolution in primates and the comparison of the primates of the Old and New World. The neuronal mechanisms underlying both trichromatic and dichromat...

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

    Directory of Open Access Journals (Sweden)

    Fabio ePaglieri

    2014-02-01

    Full Text Available 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 offer 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.

  14. 42 CFR 71.53 - Nonhuman primates.

    Science.gov (United States)

    2010-10-01

    ... nonhuman primates that is suspected of being yellow fever, monkeypox, or Marburg/Ebola disease. (3... member of their staff suspected of having an infectious disease acquired from nonhuman primates. (f) Disease control measures. Upon receipt of evidence of exposure of nonhuman primates to a communicable...

  15. Cutaneous thermoreceptors in primates and sub-primates.

    Science.gov (United States)

    Iggo, A

    1969-02-01

    1. Cutaneous thermoreceptors were examined electrophysiologically in primates (monkey, baboon) and in sub-primates (dog and rat) by recording from single units dissected from peripheral nerves.2. Thermal stimuli were delivered from thermodes in contact with the skin.3. Primate ;cold' receptors had spot-like receptive fields and were found in both hairy and glabrous skin. The conduction velocities of the axons ranged from 0.6 to 15.3 m/sec.4. The discharge from the primate receptors characteristically appeared in bursts with intervals of silence within the range temperatures of 18-40 degrees C. Static and dynamic sensitivity curves were established, with maxima about 30 degrees C.5. Cold receptors in the lip of the dog had maximal sensitivity at 31-37 degrees C. The axons were myelinated with conduction velocities less than 20 m/sec.6. ;Warm' receptors, with maximal sensitivity at 40 degrees C and non-myelinated axons, were abundant in the scrotal nerve of the rat. The ;cold' receptors had maximal responses at 23-28 degrees C.7. The ;spurious' thermoreceptor behaviour of slowly adapting mechanoreceptors is described and the way in which they may distort integrated potential records from whole nerves is analysed.

  16. Efferent influences on the bioelectrical activity of the retina in primates.

    Science.gov (United States)

    Ortiz, Gonzalo; Odom, J Vernon; Passaglia, Christopher L; Tzekov, Radouil T

    2017-02-01

    The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.

  17. Primate ABO Gene is under Weak Positive Selection

    Directory of Open Access Journals (Sweden)

    Eliane Santos EVANOVICH

    2012-05-01

    Full Text Available ABO locus presents three main alleles: A, B and O. A and B encode glycosyltransferases that catalyze the addiction of an N-GalNac and D-galactose to a precursor substance (H substance, producing A and B antigens, while the O allele does not produce a functional protein. The presence of A and B antigens have been associated to resistance against infectious agents which could use them as attachment factors increasing the virulence of some parasitic agents. As these antigens are not restrict to humans, analyses them in others species, for instance non-human primates, may be crucial to understand the relationship between pathogens and ABO phenotypes. Despite of the relevance of this issue, in the last decade few studies have addressed, mainly in New World Monkeys (NWM, natural reservoir of tropical diseases in Amazon Region. In order to understand the evolution of the ABO system in the primates, it has been obtained the partial sequence of the most important exon of ABO gene (exon 7, in platyrrhini families: Atelidae, Pithecidae and Cebidae. Then, it has been compared the sequences obtained those present in the literature, and measured the selective pressure. The present results shown that residues 266 and 268 are also crucial to distinguish A and B phenotypes in the platyrrhines, such as in catarrhines, and the 266 codon is under positive selection, although the most site codons are under action of purifying selection.

  18. The collective action problem in primate territory economics.

    Science.gov (United States)

    Willems, Erik P; Hellriegel, Barbara; van Schaik, Carel P

    2013-05-22

    Group-living animals often do not maintain territories, but instead have highly overlapping ranges, even though in principle these are economically defendable. We investigate whether this absence of range defence reflects a collective action problem, since a territory can be considered a public good. In a comparative analysis comprising 135 primate species, we find a positive association between range overlap and group size, controlling for economic defendability and phylogenetic non-independence. We subsequently demonstrate that groups with multiple adults of both sexes suffer levels of range overlap twice as high as groups with only a single adult representative of either sex, consistent with the presence of a collective action problem. Finally, we reveal that this collective action problem can be overcome through philopatry of the larger sex. These results suggest that a social complication of group living is a stronger determinant of between-group relations among social animals than ecological factors, but also that collective defence is still achieved where the dominant sex is philopatric and effective defence is critical to reproductive success and survival. In addition, our findings support the idea that human-like warfare, defined as escalated collective territorial conflict, has an evolutionary basis reflected by cases of convergent evolution among non-human primates.

  19. Identification and molecular characterization of novel primate bocaparvoviruses from wild western lowland gorillas of Moukalaba-Doudou National Park, Gabon.

    Science.gov (United States)

    Nze-Nkogue, Chimene; Horie, Masayuki; Fujita, Shiho; Inoue, Eiji; Akomo-Okoue, Etienne-François; Ozawa, Makoto; Ngomanda, Alfred; Yamagiwa, Juichi; Tsukiyama-Kohara, Kyoko

    2017-09-01

    Bocaparvoviruses have been studied extensively owing to their ability to cause respiratory illness or gastroenteritis in humans. Some bocaparvoviruses have been detected in non-human primates (gorillas and chimpanzees), but the diversity and evolution of these viruses are not fully understood. In this study, we collected 107 fecal samples from wild western lowland gorillas in Moukalaba-Doudou National Park in Gabon to investigate the presence of bocaparvoviruses. Using a combination of pan-bocaparvovirus PCR and individual identification by microsatellite genotyping, we found that two samples from two apparently healthy infant gorillas were positive for bocaparvovirus. Sequencing and phylogenetic analyses revealed that the two gorilla bocaparvovirus strains are nearly identical and are closely related to viruses in the species Primate bocaparvovirus 2 (with 86.0% nucleotide identity to a human bocavirus 2 isolate). To our knowledge, this is the first report showing the presence of a non-human primate bocaparovirus within Primate bocaparvovirus 2. Our findings provide novel insights into the diversity and evolution of bocaparvoviruses and highlight the importance of surveying these viruses for the safe management of gorilla-based ecotourism. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Are we making the grade? Practices and reported efficacy measures of primate conservation education programs.

    Science.gov (United States)

    Kling, Katherine J; Hopkins, Mariah E

    2015-04-01

    Conservation education is often employed alongside primate conservation efforts with the aim of changing knowledge, attitudes, and behaviors toward non-human primates. Recommended best-use practices include longevity, use of program incentives, collaboration among educators, and adaptive program assessment, among others. This study surveys primate conservation education programs (PCEPs) to assess the frequency of suggested best-use practices, and to investigate impacts on program efficacy. Online surveys were collected from PCEPs in 2013-2014 (N = 43). The majority of programs reported lengths of 5-10 years, with participant involvement ranging widely from a day to several years. Non-economic and economic incentives were distributed by approximately half of all programs, with programs that provided economic incentives reporting positive participant attitude changes more frequently than those that did not (P = 0.03). While >70% of PCEPs consulted with community leaders, local teachers, and research scientists, only 45.9% collaborated with other conservation educators and only 27% collaborated with cultural experts such as cultural anthropologists. Programs that collaborated with other conservation educators were more likely to report reductions in threats to primates, specifically to bushmeat hunting and capture of primates for the pet trade (P = 0.07). Formal program evaluations were employed by 72.1% of all programs, with the majority of programs using surveys to assess changes to participant attitudes and knowledge. Formal evaluations of participant behavior, community attitudes and behaviors, and threats to primate populations were less common. While results indicate that PCEPs follow many suggested best-use practices, program impacts may be enhanced by greater discussion of economic incentivization, increased collaboration between conservation educators, and improved commitment to adaptive evaluation of changes to behaviors in addition to attitudes and

  1. Reading wild minds: A computational assay of Theory of Mind sophistication across seven primate species.

    Science.gov (United States)

    Devaine, Marie; San-Galli, Aurore; Trapanese, Cinzia; Bardino, Giulia; Hano, Christelle; Saint Jalme, Michel; Bouret, Sebastien; Masi, Shelly; Daunizeau, Jean

    2017-11-01

    Theory of Mind (ToM), i.e. the ability to understand others' mental states, endows humans with highly adaptive social skills such as teaching or deceiving. Candidate evolutionary explanations have been proposed for the unique sophistication of human ToM among primates. For example, the Machiavellian intelligence hypothesis states that the increasing complexity of social networks may have induced a demand for sophisticated ToM. This type of scenario ignores neurocognitive constraints that may eventually be crucial limiting factors for ToM evolution. In contradistinction, the cognitive scaffolding hypothesis asserts that a species' opportunity to develop sophisticated ToM is mostly determined by its general cognitive capacity (on which ToM is scaffolded). However, the actual relationships between ToM sophistication and either brain volume (a proxy for general cognitive capacity) or social group size (a proxy for social network complexity) are unclear. Here, we let 39 individuals sampled from seven non-human primate species (lemurs, macaques, mangabeys, orangutans, gorillas and chimpanzees) engage in simple dyadic games against artificial ToM players (via a familiar human caregiver). Using computational analyses of primates' choice sequences, we found that the probability of exhibiting a ToM-compatible learning style is mainly driven by species' brain volume (rather than by social group size). Moreover, primates' social cognitive sophistication culminates in a precursor form of ToM, which still falls short of human fully-developed ToM abilities.

  2. Reading wild minds: A computational assay of Theory of Mind sophistication across seven primate species.

    Directory of Open Access Journals (Sweden)

    Marie Devaine

    2017-11-01

    Full Text Available Theory of Mind (ToM, i.e. the ability to understand others' mental states, endows humans with highly adaptive social skills such as teaching or deceiving. Candidate evolutionary explanations have been proposed for the unique sophistication of human ToM among primates. For example, the Machiavellian intelligence hypothesis states that the increasing complexity of social networks may have induced a demand for sophisticated ToM. This type of scenario ignores neurocognitive constraints that may eventually be crucial limiting factors for ToM evolution. In contradistinction, the cognitive scaffolding hypothesis asserts that a species' opportunity to develop sophisticated ToM is mostly determined by its general cognitive capacity (on which ToM is scaffolded. However, the actual relationships between ToM sophistication and either brain volume (a proxy for general cognitive capacity or social group size (a proxy for social network complexity are unclear. Here, we let 39 individuals sampled from seven non-human primate species (lemurs, macaques, mangabeys, orangutans, gorillas and chimpanzees engage in simple dyadic games against artificial ToM players (via a familiar human caregiver. Using computational analyses of primates' choice sequences, we found that the probability of exhibiting a ToM-compatible learning style is mainly driven by species' brain volume (rather than by social group size. Moreover, primates' social cognitive sophistication culminates in a precursor form of ToM, which still falls short of human fully-developed ToM abilities.

  3. Advances in primate stable isotope ecology-Achievements and future prospects.

    Science.gov (United States)

    Crowley, Brooke E; Reitsema, Laurie J; Oelze, Vicky M; Sponheimer, Matt

    2016-10-01

    Stable isotope biogeochemistry has been used to investigate foraging ecology in non-human primates for nearly 30 years. Whereas early studies focused on diet, more recently, isotopic analysis has been used to address a diversity of ecological questions ranging from niche partitioning to nutritional status to variability in life history traits. With this increasing array of applications, stable isotope analysis stands to make major contributions to our understanding of primate behavior and biology. Most notably, isotopic data provide novel insights into primate feeding behaviors that may not otherwise be detectable. This special issue brings together some of the recent advances in this relatively new field. In this introduction to the special issue, we review the state of isotopic applications in primatology and its origins and describe some developing methodological issues, including techniques for analyzing different tissue types, statistical approaches, and isotopic baselines. We then discuss the future directions we envision for the field of primate isotope ecology. Am. J. Primatol. 78:995-1003, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  4. Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary–gonadal axis of primates

    Directory of Open Access Journals (Sweden)

    A Daniel Bird

    2017-09-01

    Full Text Available Steroid hormones play clinically important and specific regulatory roles in the development, growth, metabolism, reproduction and brain function in human. The type 1 and 2 11-beta hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 2 have key roles in the pre-receptor modification of glucocorticoids allowing aldosterone regulation of blood pressure, control of systemic fluid and electrolyte homeostasis and modulation of integrated metabolism and brain function. Although the activity and function of 11β-HSDs is thought to be understood, there exists an open reading frame for a distinct 11βHSD-like gene; HSD11B1L, which is present in human, non-human primate, sheep, pig and many other higher organisms, whereas an orthologue is absent in the genomes of mouse, rat and rabbit. We have now characterised this novel HSD11B1L gene as encoded by 9 exons and analysis of EST library transcripts indicated the use of two alternate ATG start sites in exons 2 and 3, and alternate splicing in exon 9. Relatively strong HSD11B1L gene expression was detected in human, non-human primate and sheep tissue samples from the brain, ovary and testis. Analysis in non-human primates and sheep by immunohistochemistry localised HSD11B1L protein to the cytoplasm of ovarian granulosa cells, testis Leydig cells, and gonadatroph cells in the anterior pituitary. Intracellular localisation analysis in transfected human HEK293 cells showed HSD1L protein within the endoplasmic reticulum and sequence analysis suggests that similar to 11βHSD1 it is membrane bound. The endogenous substrate of this third HSD enzyme remains elusive with localisation and expression data suggesting a reproductive hormone as a likely substrate.

  5. Comparison of the social systems of primates and feral horses: data from a newly established horse research site on Serra D'Arga, northern Portugal.

    Science.gov (United States)

    Ringhofer, Monamie; Inoue, Sota; Mendonça, Renata S; Pereira, Carlos; Matsuzawa, Tetsuro; Hirata, Satoshi; Yamamoto, Shinya

    2017-06-05

    Horses are phylogenetically distant from primates, but considerable behavioral links exist between the two. The sociality of horses, characterized by group stability, is similar to that of primates, but different from that of many other ungulates. Although horses and primates are good models for exploring the evolution of societies in human and non-human animals, fewer studies have been conducted on the social system of horses than primates. Here, we investigated the social system of feral horses, particularly the determinant factors of single-male/multi-male group dichotomy, in light of hypotheses derived from studies of primate societies. Socioecological data from 26 groups comprising 208 feral horses on Serra D'Arga, northern Portugal suggest that these primate-based hypotheses cannot adequately explain the social system of horses. In view of the sympatric existence of multi- and single-male groups, and the frequent intergroup transfers and promiscuous mating of females with males of different groups, male-female relationships of horses appear to differ from those of polygynous primates.

  6. Epidemiology and molecular relationships of Cryptosporidium spp. in people, primates, and livestock from Western Uganda.

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    Stephanie J Salyer

    Full Text Available Cryptosporidium is one of the most common parasitic diarrheal agents in the world and is a known zoonosis. We studied Cryptosporidium in people, livestock, and non-human primates in the region of Kibale National Park, Uganda. Land use change near the park has resulted in fragmented forest patches containing small, remnant populations of wild primates that interact intensively with local people and livestock. Our goal was to investigate risk factors for Cryptosporidium infection and to assess cross-species transmission using molecular methods.Diagnostic PCR revealed a prevalence of Cryptosporidium of 32.4% in humans, 11.1% in non-human primates, and 2.2% in livestock. In the case of humans, residence in one particular community was associated with increased risk of infection, as was fetching water from an open water source. Although 48.5% of infected people reported gastrointestinal symptoms, this frequency was not significantly different in people who tested negative (44.7% for Cryptosporidium, nor was co-infection with Giardia duodenalis associated with increased reporting of gastrointestinal symptoms. Fecal consistency was no different in infected versus uninfected people or animals. DNA sequences of the Cryptosporidium oocyst wall protein gene placed all infections within a well-supported C. parvum/C. hominis clade. However, the only two sequences recovered from primates in the core of the park's protected area fell into a divergent sub-clade and were identical to published sequences from C. parvum, C. hominis, and C. cuniculus, suggesting the possibility of a separate sylvatic transmission cycle.Cryptosporidium may be transmitted frequently among species in western Uganda where people, livestock, and wildlife interact intensively as a result of anthropogenic changes to forests, but the parasite may undergo more host-specific transmission where such interactions do not occur. The parasite does not appear to have strong effects on human or

  7. Detection of arboviruses of public health interest in free-living New World primates (Sapajus spp.; Alouatta caraya captured in Mato Grosso do Sul, Brazil

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    Paulo Mira Batista

    2013-12-01

    Full Text Available Introduction A sero-epidemiological survey was undertaken to detect the circulation of arboviruses in free-living non-human primates. Methods Blood samples were obtained from 16 non-human primates (13 Sapajus spp. and three Alouatta caraya that were captured using terrestrial traps and anesthetic darts in woodland regions in the municipalities of Campo Grande, Aquidauana, Jardim, Miranda and Corumbá in the State of Mato Grosso do Sul, Brazil. The samples were sent to the Instituto Evandro Chagas (IEC in Ananindeua, Pará, Brazil, to detect antibodies against 19 species of arboviruses using a hemagglutination inhibition test (HI. Results Of the 16 primates investigated in the present study, five (31.2% were serologically positive for an arbovirus. Of these five, two (12.5% exhibited antibodies to the Flavivirus genus, one (6.2% exhibited a monotypic reaction to Cacipacoré virus, one (6.2% was associated with Mayaro virus, and one (6.2% was positive for Oropouche virus. Conclusions Based on the positive serology observed in the present study, it was possible to conclude that arboviruses circulate among free-living primates. The viruses in the areas studied might have been introduced by infected humans or by primates from endemic or enzootic areas. Studies of this nature, as well as efficient and continuous surveillance programs, are needed to monitor viral activities in endemic and enzootic regions.

  8. Primate Experiments on SLS-1

    Science.gov (United States)

    Aochi, J.

    1985-01-01

    Experiments to study how certain body systems are affected by the space environment are described. These experiments are to be conducted on space shuttle flights. How weightlessness affects two body systems of primates are the prime concern. Thermoregulation and fluid and electrolyte homeostasis are the two systems concerned. The thermoregulation project will provide data on how body temperature and circadian rhythms are affected in a weightlessness environment and the homeostasis in fluids and electrolyte levels will address the problem of body fluid shifts.

  9. Assessing Anxiety in Nonhuman Primates

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    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

  10. Cellular scaling rules for primate brains

    OpenAIRE

    Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.

    2007-01-01

    Primates are usually found to have richer behavioral repertoires and better cognitive abilities than rodents of similar brain size. This finding raises the possibility that primate brains differ from rodent brains in their cellular composition. Here we examine the cellular scaling rules for primate brains and show that brain size increases approximately isometrically as a function of cell numbers, such that an 11× larger brain is built with 10× more neurons and ≈12× more nonneuronal cells of ...

  11. Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

    Science.gov (United States)

    Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

    2016-11-01

    Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.

  12. Functional divergence of the brain-size regulating gene MCPH1 during primate evolution and the origin of humans

    Science.gov (United States)

    2013-01-01

    Background One of the key genes that regulate human brain size, MCPH1 has evolved under strong Darwinian positive selection during the evolution of primates. During this evolution, the divergence of MCPH1 protein sequences among primates may have caused functional changes that contribute to brain enlargement. Results To test this hypothesis, we used co-immunoprecipitation and reporter gene assays to examine the activating and repressing effects of MCPH1 on a set of its down-stream genes and then compared the functional outcomes of a series of mutant MCPH1 proteins that carry mutations at the human- and great-ape-specific sites. The results demonstrate that the regulatory effects of human MCPH1 and rhesus macaque MCPH1 are different in three of eight down-stream genes tested (p73, cyclinE1 and p14ARF), suggesting a functional divergence of MCPH1 between human and non-human primates. Further analyses of the mutant MCPH1 proteins indicated that most of the human-specific mutations could change the regulatory effects on the down-stream genes. A similar result was also observed for one of the four great-ape-specific mutations. Conclusions Collectively, we propose that during primate evolution in general and human evolution in particular, the divergence of MCPH1 protein sequences under Darwinian positive selection led to functional modifications, providing a possible molecular mechanism of how MCPH1 contributed to brain enlargement during primate evolution and human origin. PMID:23697381

  13. Dynamics of the primate ovarian surface epithelium during the ovulatory menstrual cycle.

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    Wright, Jay W; Jurevic, Leigh; Stouffer, Richard L

    2011-06-01

    Epithelial ovarian cancer (EOC) risk correlates strongly with the number of ovulations that a woman experiences. The primary source of EOC in women is the ovarian surface epithelium (OSE). Mechanistic studies on the etiology of OSE transformation to EOC cannot be realistically performed in women. Selecting a suitable animal model to investigate the normal OSE in the context of ovulation should be guided by the model's reproductive similarities to women in natural features that are thought to contribute to EOC risk. We selected the non-human primate, rhesus macaque, as a surrogate to study the normal OSE during the natural menstrual cycle. We investigated OSE morphology and marker expression, plus cell proliferation and death in relation to menstrual cycle stage and ovulation. OSE cells displayed a morphological range from squamous to columnar. Cycle-independent parameters and cycle-dependent changes were observed for OSE histology, steroid receptor expression, cell death, DNA repair and cell adhesion. Contrary to findings in non-primates, primate OSE cells were not manifestly cleared from the site of ovulation, nor were proliferation rates affected by ovulation or stage of the menstrual cycle. DNA repair proteins were more highly expressed in OSE than in other ovarian cells. This study identifies significant differences between primate and non-primate OSE. In contrast to established views, ovulation-induced death and proliferation are not indicated as prominent contributors to EOC risk, but disruption of OSE cadherin-mediated adhesion may be, as could the loss of ovary-mediated chronic suppression of proliferation and elevation of DNA repair potential.

  14. The next step for stress research in primates: To identify relationships between glucocorticoid secretion and fitness.

    Science.gov (United States)

    Beehner, Jacinta C; Bergman, Thore J

    2017-05-01

    Glucocorticoids are hormones that mediate the energetic demands that accompany environmental challenges. It is therefore not surprising that these metabolic hormones have come to dominate endocrine research on the health and fitness of wild populations. Yet, several problems have been identified in the vertebrate research that also apply to the non-human primate research. First, glucocorticoids should not be used as a proxy for fitness (unless a link has previously been established between glucocorticoids and fitness for a particular population). Second, stress research in behavioral ecology has been overly focused on "chronic stress" despite little evidence that chronic stress hampers fitness in wild animals. Third, research effort has been disproportionately focused on the causes of glucocorticoid variation rather than the fitness consequences. With these problems in mind, we have three objectives for this review. We describe the conceptual framework behind the "stress concept", emphasizing that high glucocorticoids do not necessarily indicate a stress response, and that a stress response does not necessarily indicate an animal is in poor health. Then, we conduct a comprehensive review of all studies on "stress" in wild primates, including any study that examined environmental factors, the stress response, and/or fitness (or proxies for fitness). Remarkably, not a single primate study establishes a connection between all three. Finally, we provide several recommendations for future research in the field of primate behavioral endocrinology, primarily the need to move beyond identifying the factors that cause glucocorticoid secretion to additionally focus on the relationship between glucocorticoids and fitness. We believe that this is an important next step for research on stress physiology in primates. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Evolutionary history of lorisiform primates.

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    Rasmussen, D T; Nekaris, K A

    1998-01-01

    We integrate information from the fossil record, morphology, behavior and molecular studies to provide a current overview of lorisoid evolution. Several Eocene prosimians of the northern continents, including both omomyids and adapoids, have been suggested as possible lorisoid ancestors, but these cannot be substantiated as true strepsirhines. A small-bodied primate, Anchomomys, of the middle Eocene of Europe may be the best candidate among putative adapoids for status as a true strepsirhine. Recent finds of Eocene primates in Africa have revealed new prosimian taxa that are also viable contenders for strepsirhine status. Plesiopithecus teras is a Nycticebussized, nocturnal prosimian from the late Eocene, Fayum, Egypt, that shares cranial specializations with lorisoids, but it also retains primitive features (e.g. four premolars) and has unique specializations of the anterior teeth excluding it from direct lorisiform ancestry. Another unnamed Fayum primate resembles modern cheirogaleids in dental structure and body size. Two genera from Oman, Omanodon and Shizarodon, also reveal a mix of similarities to both cheirogaleids and anchomomyin adapoids. Resolving the phylogenetic position of these Africa primates of the early Tertiary will surely require more and better fossils. By the early to middle Miocene, lorisoids were well established in East Africa, and the debate about whether these represent lorisines or galagines is reviewed. Neontological data are used to address the controversial branching sequences among extent lorisid clades. Data from the skin and scent glands, when integrated with other lines of evidence, suggest that Asian and African lorisines share a common lorisine ancestry. The hypothesis of an African clade containing both pottos and galagos to the exclusion of Asian lorisines is less tenable. True galagines are found in the fossil record of Namibia, while true lorisines are known from the Miocene of Asia. The hypothetical branching sequences can

  16. Bion 11 mission: primate experiments

    Science.gov (United States)

    Ilyin, E. A.; Korolkov, V. I.; Skidmore, M. G.; Viso, M.; Kozlovskaya, I. B.; Grindeland, R. E.; Lapin, B. A.; Gordeev, Y. V.; Krotov, V. P.; Fanton, J. W.; hide

    2000-01-01

    A summary is provided of the major operations required to conduct the wide range of primate experiments on the Bion 11 mission, which flew for 14 days beginning December 24, 1996. Information is given on preflight preparations, including flight candidate selection and training; attachment and implantation of bioinstrumentation; flight and ground experiment designs; onboard life support and test systems; ground and flight health monitoring; flight monkey selection and transport to the launch site; inflight procedures and data collection; postflight examinations and experiments; and assessment of results.

  17. The evolution of neocortex in primates.

    Science.gov (United States)

    Kaas, Jon H

    2012-01-01

    We can learn about the evolution of neocortex in primates through comparative studies of cortical organization in primates and those mammals that are the closest living relatives of primates, in conjunction with brain features revealed by the skull endocasts of fossil archaic primates. Such studies suggest that early primates had acquired a number of features of neocortex that now distinguish modern primates. Most notably, early primates had an array of new visual areas, and those visual areas widely shared with other mammals had been modified. Posterior parietal cortex was greatly expanded with sensorimotor modules for reaching, grasping, and personal defense. Motor cortex had become more specialized for hand use, and the functions of primary motor cortex were enhanced by the addition and development of premotor and cingulate motor areas. Cortical architecture became more varied, and cortical neuron populations became denser overall than in nonprimate ancestors. Primary visual cortex had the densest population of neurons, and this became more pronounced in the anthropoid radiation. Within the primate clade, considerable variability in cortical size, numbers of areas, and architecture evolved. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. A mitogenomic phylogeny of living primates.

    Science.gov (United States)

    Finstermeier, Knut; Zinner, Dietmar; Brameier, Markus; Meyer, Matthias; Kreuz, Eva; Hofreiter, Michael; Roos, Christian

    2013-01-01

    Primates, the mammalian order including our own species, comprise 480 species in 78 genera. Thus, they represent the third largest of the 18 orders of eutherian mammals. Although recent phylogenetic studies on primates are increasingly built on molecular datasets, most of these studies have focused on taxonomic subgroups within the order. Complete mitochondrial (mt) genomes have proven to be extremely useful in deciphering within-order relationships even up to deep nodes. Using 454 sequencing, we sequenced 32 new complete mt genomes adding 20 previously not represented genera to the phylogenetic reconstruction of the primate tree. With 13 new sequences, the number of complete mt genomes within the parvorder Platyrrhini was widely extended, resulting in a largely resolved branching pattern among New World monkey families. We added 10 new Strepsirrhini mt genomes to the 15 previously available ones, thus almost doubling the number of mt genomes within this clade. Our data allow precise date estimates of all nodes and offer new insights into primate evolution. One major result is a relatively young date for the most recent common ancestor of all living primates which was estimated to 66-69 million years ago, suggesting that the divergence of extant primates started close to the K/T-boundary. Although some relationships remain unclear, the large number of mt genomes used allowed us to reconstruct a robust primate phylogeny which is largely in agreement with previous publications. Finally, we show that mt genomes are a useful tool for resolving primate phylogenetic relationships on various taxonomic levels.

  19. Modeling olfactory bulb evolution through primate phylogeny.

    Science.gov (United States)

    Heritage, Steven

    2014-01-01

    Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution.

  20. Spectrum of Infantile Esotropia in Primates: Behavior, Brains and Orbits

    Science.gov (United States)

    Tychsen, Lawrence; Richards, Michael; Wong, Agnes; Foeller, Paul; Burhkalter, Andreas; Narasimhan, Anita; Demer, Joseph

    2009-01-01

    Introduction Recent studies of human infants have described a spectrum of early-onset esotropia, from small-variable-angle to large heterotropias.1 We report here a similar spectrum of early-onset esotropia in infant monkeys, with emphasis on the relationship between visuomotor deficits, central nervous system (CNS) circuitry and orbital anatomy. Methods Eye movements were recorded in macaque monkeys with natural, infantile-onset esotropia (n=7) and in control monkeys (n=2) to assess alignment, latent nystagmus, dissociated vertical deviation (DVD), and pursuit/optokinetic nystagmus (OKN) asymmetries. Acuity was measured by preferential-looking technique or spatial sweep VEP (SSVEP). Geniculo-striate pathways were then analyzed with neuroanatomic tracers and metabolic labels. Extraocular muscles were examined by high-resolution magnetic resonance imaging (MRI) and anatomic sectioning of whole orbits. Results Esotropia ranged from 4-13.5° (7-24 prism diopters [PD]) with fixation preference (if any) varying idiosyncratically (as in human). Severity of ocular motor dysfunction (i.e. nystagmus velocity, DVD amplitude, pursuit-OKN nasal bias index), increased as the magnitude of esotropia angle. Animals with greater ocular motor deficits tended to have greater visual area V1 (striate cortex) neuroanatomic deficits, evident as fewer binocular horizontal connections in V1. Orbital MRI/anatomic analysis showed no difference in horizontal rectus cross sectional areas, muscle paths, innervation densities or cytoarchitecture compared to normal animals. Conclusion The infantile esotropia spectrum in non-human primates is remarkably similar to that reported in human infants. Concomitant esotropia in these primates cannot be ascribed to abnormalities of the extraocular muscles or orbit. These findings, combined with epidemiologic studies of human, suggest that perturbations of CNS binocular pathways in early development are the primary cause of the infantile esotropia syndrome

  1. Properties of virion transactivator proteins encoded by primate cytomegaloviruses

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    Barry Peter A

    2009-05-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1 genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action. Results The UL82 homolog encoded by simian cytomegalovirus (SCMV, strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All

  2. Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates

    OpenAIRE

    Weber, B.; Scherman, J.; Emmert, M. Y.; Gruenenfelder, J.; Verbeek, R.; Bracher, M.; Black, M.; Kortsmit, J.; Franz, T.; Schoenauer, R.; Baumgartner, L.; Brokopp, C.; Agarkova, I.; Wolint, P.; Zund, G.

    2011-01-01

    Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven...

  3. Trypanoxyuris (Paraoxyuronema lagothricis (Nematoda: Oxyuridae in Lagothrix cana (Primates: Atelidae from Brazil Trypanoxyuris (Paraoxyuronema lagothricis (Nematoda: Oxyuridae em Lagothrix cana (Primates: Atelidae no Brasil

    Directory of Open Access Journals (Sweden)

    Hudson Alves Pinto

    Full Text Available During necropsy of a specimen of Lagothrix cana (É. Geoffroy, 1812 (Primates: Atelidae from the Brazilian Amazon, pinworms were found in the large intestine. The intensity of infection was 64 parasites (17 males and 47 females and there were no gross pathological changes related to parasitism. After morphological analysis the parasites were identified as Trypanoxyuris (Paraoxyuronema lagothricis (Buckley, 1931 (Nematoda: Oxyuridae. This is the first record of this oxyurid species in primates in Brazil.Durante a necropsia de Lagothrix cana (É. Geoffroy, 1812 (Primates: Atelidae oriundo da Amazônia brasileira, oxiurídeos foram encontrados no intestino grosso. A intensidade de infecção foi de 64 parasitos (17 machos e 47 fêmeas, não havendo alterações patológicas macroscópicas relacionadas ao parasitismo. Após análise morfológica os parasitos foram identificados como Trypanoxyuris (Paraoxyuronema lagothricis (Buckley, 1931 (Nematoda: Oxyuridae. Este é o primeiro relato desta espécie de oxiurídeo em primatas no Brasil.

  4. Impending extinction crisis of the world’s primates: Why primates matter

    Science.gov (United States)

    Estrada, Alejandro; Garber, Paul A.; Rylands, Anthony B.; Roos, Christian; Fernandez-Duque, Eduardo; Di Fiore, Anthony; Nekaris, K. Anne-Isola; Nijman, Vincent; Heymann, Eckhard W.; Lambert, Joanna E.; Rovero, Francesco; Barelli, Claudia; Setchell, Joanna M.; Gillespie, Thomas R.; Mittermeier, Russell A.; Arregoitia, Luis Verde; de Guinea, Miguel; Gouveia, Sidney; Dobrovolski, Ricardo; Shanee, Sam; Shanee, Noga; Boyle, Sarah A.; Fuentes, Agustin; MacKinnon, Katherine C.; Amato, Katherine R.; Meyer, Andreas L. S.; Wich, Serge; Sussman, Robert W.; Pan, Ruliang; Kone, Inza; Li, Baoguo

    2017-01-01

    Nonhuman primates, our closest biological relatives, play important roles in the livelihoods, cultures, and religions of many societies and offer unique insights into human evolution, biology, behavior, and the threat of emerging diseases. They are an essential component of tropical biodiversity, contributing to forest regeneration and ecosystem health. Current information shows the existence of 504 species in 79 genera distributed in the Neotropics, mainland Africa, Madagascar, and Asia. Alarmingly, ~60% of primate species are now threatened with extinction and ~75% have declining populations. This situation is the result of escalating anthropogenic pressures on primates and their habitats—mainly global and local market demands, leading to extensive habitat loss through the expansion of industrial agriculture, large-scale cattle ranching, logging, oil and gas drilling, mining, dam building, and the construction of new road networks in primate range regions. Other important drivers are increased bushmeat hunting and the illegal trade of primates as pets and primate body parts, along with emerging threats, such as climate change and anthroponotic diseases. Often, these pressures act in synergy, exacerbating primate population declines. Given that primate range regions overlap extensively with a large, and rapidly growing, human population characterized by high levels of poverty, global attention is needed immediately to reverse the looming risk of primate extinctions and to attend to local human needs in sustainable ways. Raising global scientific and public awareness of the plight of the world’s primates and the costs of their loss to ecosystem health and human society is imperative. PMID:28116351

  5. Perspectives on object manipulation and action grammar for percussive actions in primates.

    Science.gov (United States)

    Hayashi, Misato

    2015-11-19

    The skill of object manipulation is a common feature of primates including humans, although there are species-typical patterns of manipulation. Object manipulation can be used as a comparative scale of cognitive development, focusing on its complexity. Nut cracking in chimpanzees has the highest hierarchical complexity of tool use reported in non-human primates. An analysis of the patterns of object manipulation in naive chimpanzees after nut-cracking demonstrations revealed the cause of difficulties in learning nut-cracking behaviour. Various types of behaviours exhibited within a nut-cracking context can be examined in terms of the application of problem-solving strategies, focusing on their basis in causal understanding or insightful intentionality. Captive chimpanzees also exhibit complex forms of combinatory manipulation, which is the precursor of tool use. A new notation system of object manipulation was invented to assess grammatical rules in manipulative actions. The notation system of action grammar enabled direct comparisons to be made between primates including humans in a variety of object-manipulation tasks, including percussive-tool use. © 2015 The Author(s).

  6. Perspectives on object manipulation and action grammar for percussive actions in primates

    Science.gov (United States)

    Hayashi, Misato

    2015-01-01

    The skill of object manipulation is a common feature of primates including humans, although there are species-typical patterns of manipulation. Object manipulation can be used as a comparative scale of cognitive development, focusing on its complexity. Nut cracking in chimpanzees has the highest hierarchical complexity of tool use reported in non-human primates. An analysis of the patterns of object manipulation in naive chimpanzees after nut-cracking demonstrations revealed the cause of difficulties in learning nut-cracking behaviour. Various types of behaviours exhibited within a nut-cracking context can be examined in terms of the application of problem-solving strategies, focusing on their basis in causal understanding or insightful intentionality. Captive chimpanzees also exhibit complex forms of combinatory manipulation, which is the precursor of tool use. A new notation system of object manipulation was invented to assess grammatical rules in manipulative actions. The notation system of action grammar enabled direct comparisons to be made between primates including humans in a variety of object-manipulation tasks, including percussive-tool use. PMID:26483528

  7. In utero recombinant adeno-associated virus gene transfer in mice, rats, and primates

    Directory of Open Access Journals (Sweden)

    Marrero Luis

    2003-09-01

    Full Text Available Abstract Background Gene transfer into the amniotic fluid using recombinant adenovirus vectors was shown previously to result in high efficiency transfer of transgenes into the lungs and intestines. Adenovirus mediated in utero gene therapy, however, resulted in expression of the transgene for less than 30 days. Recombinant adenovirus associated viruses (rAAV have the advantage of maintaining the viral genome in daughter cells thus providing for long-term expression of transgenes. Methods Recombinant AAV2 carrying green fluorescent protein (GFP was introduced into the amniotic sac of fetal rodents and nonhuman primates. Transgene maintenance and expression was monitor. Results Gene transfer resulted in rapid uptake and long-term gene expression in mice, rats, and non-human primates. Expression and secretion of the reporter gene, GFP, was readily demonstrated within 72 hours post-therapy. In long-term studies in rats and nonhuman primates, maintenance of GFP DNA, protein expression, and reporter gene secretion was documented for over one year. Conclusions Because only multipotential stem cells are present at the time of therapy, these data demonstrated that in utero gene transfer with AAV2 into stem cells resulted in long-term systemic expression of active transgene roducts. Thus, in utero gene transfer via the amniotic fluid may be useful in treatment of gene disorders.

  8. Estimating thumb-index finger precision grip and manipulation potential in extant and fossil primates.

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    Feix, Thomas; Kivell, Tracy L; Pouydebat, Emmanuelle; Dollar, Aaron M

    2015-05-06

    Primates, and particularly humans, are characterized by superior manual dexterity compared with other mammals. However, drawing the biomechanical link between hand morphology/behaviour and functional capabilities in non-human primates and fossil taxa has been challenging. We present a kinematic model of thumb-index precision grip and manipulative movement based on bony hand morphology in a broad sample of extant primates and fossil hominins. The model reveals that both joint mobility and digit proportions (scaled to hand size) are critical for determining precision grip and manipulation potential, but that having either a long thumb or great joint mobility alone does not necessarily yield high precision manipulation. The results suggest even the oldest available fossil hominins may have shared comparable precision grip manipulation with modern humans. In particular, the predicted human-like precision manipulation of Australopithecus afarensis, approximately one million years before the first stone tools, supports controversial archaeological evidence of tool-use in this taxon. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  9. Special issue: Comparative biogeography of Neotropical primates.

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    Lynch Alfaro, Jessica W; Cortés-Ortiz, Liliana; Di Fiore, Anthony; Boubli, Jean P

    2015-01-01

    New research presented in this special issue of Molecular Phylogenetics and Evolution on the "Phylogeny and Biogeography of Neotropical Primates" greatly improves our understanding of the evolutionary history of the New World monkeys and provides insights into the multiple platyrrhine radiations, diversifications, extinctions, and recolonizations that have taken place over time and over space in the Neotropics. Here, we synthesize genetic and biogeographic research from the past several years to construct an overarching hypothesis for platyrrhine evolution. We also highlight continuing controversies in Neotropical primate biogeography, such as whether the location of origin of platyrrhines was Africa or Asia; whether Patagonian fossil primates are stem or crown platyrrhines; and whether cis- and trans-Andean Neotropical primates were subject to vicariance through Andes mountain building, or instead diversified through isolation in mountain valleys after skirting around the Andes on the northwestern coast of South America. We also consider the role of the Amazon River and its major tributaries in shaping platyrrhine biodiversity, and how and when primates from the Amazon reached the Atlantic Forest. A key focus is on primate colonizations and extirpations in Central America, the Andes, and the seasonally dry tropical forests and savannas (such as the Llanos, Caatinga, and Cerrado habitats), all ecosystems that have been understudied up until now for primates. We suggest that most primates currently inhabiting drier open habitats are relatively recent arrivals, having expanded from rainforest habitats in the Pleistocene. We point to the Pitheciidae as the taxonomic group most in need of further phylogenetic and biogeographic research. Additionally, genomic studies on the Platyrrhini are deeply needed and are expected to bring new surprises and insights to the field of Neotropical primate biogeography. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Comparing primate crania: The importance of fossils.

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    Fleagle, John G; Gilbert, Christopher C; Baden, Andrea L

    2016-10-01

    Extant primate crania represent a small subset of primate crania that have existed. The main objective here is to examine how the inclusion of fossil crania changes our understanding of primate cranial diversity relative to analyses of extant primates. We hypothesize that fossil taxa will change the major axes of cranial shape, occupy new areas of morphospace, change the relative diversity of major primate clades, and fill in notable gaps separating major primate taxa/clades. Eighteen 3D landmarks were collected on 157 extant and fossil crania representing 90 genera. Data were subjected to a Generalized Procrustes Analysis then principal components analysis. Relative diversity between clades was assessed using an F-statistic. Fossil taxa do not significantly alter major axes of cranial shape, but they do occupy unique areas of morphospace, change the relative diversity between clades, and fill in notable gaps in primate cranial evolution. Strepsirrhines remain significantly less diverse than anthropoids. Fossil hominins fill the gap in cranial morphospace between extant great apes and modern humans. The morphospace outlined by living primates largely includes that occupied by fossil taxa, suggesting that the cranial diversity of living primates generally encompasses the total diversity that has evolved in this Order. The evolution of the anthropoid cranium was a significant event allowing anthropoids to achieve significantly greater cranial diversity compared to strepsirrhines. Fossil taxa fill in notable gaps within and between clades, highlighting their transitional nature and eliminating the appearance of large morphological distances between extant taxa, particularly in the case of extant hominids. © 2016 Wiley Periodicals, Inc.

  11. Oligocene primates from China reveal divergence between African and Asian primate evolution.

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    Ni, Xijun; Li, Qiang; Li, Lüzhou; Beard, K Christopher

    2016-05-06

    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. Copyright © 2016, American Association for the Advancement of Science.

  12. The Automated Primate Research Laboratory (APRL)

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    Pace, N.; Smith, G. D.

    1972-01-01

    A description is given of a self-contained automated primate research laboratory to study the effects of weightlessness on subhuman primates. Physiological parameters such as hemodynamics, respiration, blood constituents, waste, and diet and nutrition are analyzed for abnormalities in the simulated space environment. The Southeast Asian pig-tailed monkey (Macaca nemistrina) was selected for the experiments owing to its relative intelligence and learning capacity. The objective of the program is to demonstrate the feasibility of a man-tended primate space flight experiment.

  13. Jean-Jacques Petter. Primates

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    Bruno Simmen

    2010-12-01

    Full Text Available Voici un magnifique ouvrage grand format sur les Primates dont l’auteur principal est le regretté Jean Jacques Petter, l’un des spécialistes historiques des prosimiens de Madagascar. Ce livre, publié à titre posthume, a une histoire que nous découvrons dans la préface d’Yves Coppens. A l’origine pensé et rédigé par Jean-Jacques Petter, qui a été professeur au Muséum National d’Histoire Naturelle, l’ouvrage interrompu à sa mort en 2002 a été remis en chantier sous l’impulsion de sa femme Arlet...

  14. Nodule worm infection in humans and wild primates in Uganda: cryptic species in a newly identified region of human transmission.

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    Ghai, Ria R; Chapman, Colin A; Omeja, Patrick A; Davies, T Jonathan; Goldberg, Tony L

    2014-01-01

    Soil-transmitted helminths (STHs) are a major health concern in tropical and sub-tropical countries. Oesophagostomum infection is considered endemic to West Africa but has also been identified in Uganda, East Africa, among primates (including humans). However, the taxonomy and ecology of Oesophagostomum in Uganda have not been studied, except for in chimpanzees (Pan troglodytes), which are infected by both O. bifurcum and O. stephanostomum. We studied Oesophagostomum in Uganda in a community of non-human primates that live in close proximity to humans. Prevalence estimates based on microscopy were lower than those based on polymerase chain reaction (PCR), indicating greater sensitivity of PCR. Prevalence varied among host species, with humans and red colobus (Procolobus rufomitratus) infected at lowest prevalence (25% and 41% by PCR, respectively), and chimpanzees, olive baboons (Papio anubis), and l'hoest monkeys (Cercopithecus lhoesti) infected at highest prevalence (100% by PCR in all three species). Phylogenetic regression showed that primates travelling further and in smaller groups are at greatest risk of infection. Molecular phylogenetic analyses revealed three cryptic clades of Oesophagostomum that were not distinguishable based on morphological characteristics of their eggs. Of these, the clade with the greatest host range had not previously been described genetically. This novel clade infects humans, as well as five other species of primates. Multiple cryptic forms of Oesophagostomum circulate in the people and primates of western Uganda, and parasite clades differ in host range and cross-species transmission potential. Our results expand knowledge about human Oesophagostomum infection beyond the West African countries of Togo and Ghana, where the parasite is a known public health concern. Oesophagostomum infection in humans may be common throughout Sub-Saharan Africa, and the transmission of this neglected STH among primates, including zoonotic

  15. Transmission of MDR MRSA between primates, their environment and personnel at a United States primate centre.

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    Soge, Olusegun O; No, David; Michael, Karen E; Dankoff, Jennifer; Lane, Jennifer; Vogel, Keith; Smedley, Jeremy; Roberts, Marilyn C

    2016-10-01

    MDR MRSA isolates cultured from primates, their facility and primate personnel from the Washington National Primate Research Center were characterized to determine whether they were epidemiologically related to each other and if they represented common local human-associated MRSA strains. Human and primate nasal and composite environmental samples were collected, enriched and selected on medium supplemented with oxacillin and polymyxin B. Isolates were biochemically verified as Staphylococcus aureus and screened for the mecA gene. Selected isolates were characterized using SCCmec typing, MLST and WGS. Nasal cultures were performed on 596 primates and 105 (17.6%) were MRSA positive. Two of 79 (2.5%) personnel and two of 56 (3.6%) composite primate environmental facility samples were MRSA positive. Three MRSA isolates from primates, one MRSA from personnel, two environmental MRSA and one primate MSSA were ST188 and were the same strain type by conventional typing methods. ST188 isolates were related to a 2007 ST188 human isolate from Hong Kong. Both MRSA isolates from out-of-state primates had a novel MLST type, ST3268, and an unrelated group. All isolates carried ≥1 other antibiotic resistance gene(s), including tet(38), the only tet gene identified. ST188 is very rare in North America and has almost exclusively been identified in people from Pan-Asia, while ST3268 is a newly reported MRSA type. The data suggest that the primate MDR MRSA was unlikely to come from primate centre employees. Captive primates are likely to be an unappreciated source of MRSA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. The prevalence of Microfilaria spp. in primates of colombian zoos

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    Rosmery Ladino De La Hortúa

    2007-06-01

    Full Text Available The prevalence of Microfilaria spp in 266 human and non human primates of Colombian zoos located